Second-Generation Monoclonal Antibody Demonstrates Benefit in Treatment-Resistant Follicular Lymphoma

Results from early-stage, preliminary (phase I) data presented by a team of University of Alabama researchers suggests that a second-generation, highly targeted monoclonal antibody may offer new hope for patients with follicular lymphoma (a particularly difficult to treat subtype of non-Hodgkin’s lymphoma) who have failed other treatments.

In all, 22 immune-cell variant patients have enrolled in the study and received regular treatment with the experimental agent AME-133v. Of the participants, 20 had received unsuccessful prior treatment with rituximab (Rituxan) and 19 had also had chemotherapy. For the dose escalation phase of the study, 20 of the 22 participating patients were eligible to be evaluated. Researchers reported that the agent was well tolerated at all dosages. Only two (10%) participants reported anything beyond minor (grade I) adverse events. For the interim analysis of clinical benefit, 16 of the 22 subjects were evaluable. Of 16 patients that have been analyzed so far, four (25%) have attained either a partial response (PR) or a complete response (CR) to the novel therapy AME- 133v. Two of the four responding subjects demonstrated PR and two showed CR.

Commenting on the results, Andres Forero, MD, the study’s lead investigator, University of Alabama, Birmingham, Comprehensive Cancer Center, stated, “These first results suggest that AME- 133v provides a mechanism of action that may be more potent and ultimately more effective than the treatments we have on hand for a subset of patients with this cancer (who demonstrate immune cell variation or mutation). Monoclonal antibodies were the first successful targeted therapy for cancer, and we have now moved on to a whole new class of second-generation antibodies for the treatment of many different lymphomas. This is an exciting time.”

According to Dr. Forero, the interim results are robust enough to warrant continued study. “Given these encouraging (phase I) results, patients are currently being enrolled in a phase II study,” he reported.

The majority of patients in the study (20 of 22) either did not initially respond to—or relapsed after&mdash;the use of rituximab, the first monoclonal antibody therapy approved for use in lympho- ma treatment. AME-133v is a second-generation therapy that is believed to be a more specific treatment for follicular lymphoma in general, compared with rituximab, but is also thought to offer particular benefits for those patients who have a variant in the immune cells needed to attack the cancer.

Although treatment with rituximab as a single agent has resulted in significant responses in patients with almost every subtype of B-cell lymphoma, including follicular lymphoma, recent evidence has shown that some patients with effector immune cells that carry a mutation in the receptor protein FcγRIIIa 158-F do not have the same response. This is an issue that is related to the patient’s own biological makeup, not to the cancer cells themselves, he adds. There are three different classes of Fcγ receptors to which the monoclonal antibody binds on leukocyte effector cells—T helper cells&mdash;that direct other immune cells to the antigen. Response to rituximab depends on variants in the receptors these helper cells use.

AME-133v is an anti-CD20 antibody engineered to bind more strongly to these variant receptors. In preclinical studies, it demonstrated a 10-fold improvement in killing power of human B cells, compared with rituximab, researchers reported.

“AME-133v appears to be capable of binding with high specificity to cell-surface antigens, resulting in targeted killing of malignant cells, relative sparing of normal tissues, and low toxicity,” Dr. Forero concluded.

The data were presented during a recent poster session at the annual meeting of the American Association for Cancer Research in San Diego.

Gum Disease and Human Papillomavirus Linked to Tongue Cancer

The presence of gum disease in conjunction with human papillomavirus (HPV) can markedly increase tongue cancer risk, according to a new study conducted by researchers at the University at Buffalo School of Dental Medicine.

Previous studies have found that periodontitis, which destroys connective tissue and bone supporting the teeth, and HPV, each pose increased risks of cancer in the head, neck or tongue. The University of Buffalo research, however, is the first to suggest that the two conditions may work in tandem.

In a study of 30 patients newly diagnosed with squamous cell carcinoma on the base of the tongue, 63% (19 patients) had tumors testing positive for a common type of HPV. In addition, 90% of the patients with HPV-positive tumors had periodontitis, and 79% of patients whose tumors showed no presence of HPV did not have periodontitis.

“Evidence of periodontitis—HPV synergy has important practical implications, because there is a safe treatment for periodontitis but no treatment for HPV infection. If these results are confirmed by other studies, this has tremendous relevance in predicting and intervening in the initiation and prognosis of HPV-related diseases, including head and neck cancers,” stated lead investigator Mine Tezal, MD, Department of Oral Diagnostic Sciences, University of Buffalo, in a prepared statement released when these data were announced.

Dr. Tezal added that “persistence of HPV infection is the strongest risk factor for carcinogenesis. Thus, the identification of factors that influence the persistence of HPV infection is critical to facilitate efforts to prevent head and neck cancers. This study implicates that chronic inflammation and co-infection with oral bacteria may be significant factors in the natural history of HPV infection.”

Most people contract HPV infection at least once in their lives, but one’s immune system often fights it off without incident.

Dr. Tezal presented the findings during the annual meeting of the American Association of Dental Research in Dallas.

Researchers Penetrate Key Ewing’s Sarcoma Mystery

Disclosing a discovery that sheds light on the mechanisms of Ewing’s Sarcoma and is likely to be applicable to advances in the treatment of the disease, Georgetown University Medical Center researchers have identified a molecule that disrupts the oncogene that causes Ewing’s sarcoma, a cancer that strikes children and young adults and can cause tumors to grow anywhere in the body.

According to the research findings of the Georgetown team, Ewing’s sarcoma occurs when there’s an exchange of DNA between two chromosomes, a process called translocation. The EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11, creating a new gene called EWS-FLI1, which produces the fusion protein that causes the cancer.

If further research shows that this newly identified molecule is effective, it could offer the first targeted therapy to treat Ewing’s sarcoma, the researchers said. The molecule works through a so-called protein—protein interaction and could provide a model upon which to design other therapies.

“I think this holds really wonderful promise as a unique way of targeting fusion proteins,” stated lead investigator Jeffrey Toretsky, MD, Lombardi Comprehensive Cancer Center, Georgetown University, Washington D.C. “People thought it wasn’t possible to have a small molecule that can bind between flexible proteins, but we have shown that it can be done,” explained Dr. Toretsky, who noted that the study was conducted in laboratory cells, so further research is needed before the molecule can be tested in humans.

The study was presented by Dr. Toretsky at the annual meeting of the American Association for Cancer Research in San Diego.

The current standard treatment regimen for Ewing’s sarcoma involves a combination of five different chemotherapy drugs. Although the therapy is somewhat efficacious (an estimated 60% to 70% of patients survive over time), many patients experience lingering health effects from the multiple lines of chemotherapy required.

Case Western Reserve University School of Medicine

For the past few decades, incidence of both throat cancer and obesity has been on the rise. These two increases may not exist independently of each other, according to new research data from Case Western Reserve University School of Medicine scientists. The Case Western study team makes the case that the two health conditions, which, at first glance, appear to be completely unrelated to one another, may actually be intimately connected. In fact, the Case Western researchers are asserting that our weight-gain as a society may very well be a prime mover fueling the increase in throat cancer.

Specifically, the rising incidence of throat cancer, also referred to as cancer of the esophagus or esophageal adenocarcinoma, may be related to the underlying cause behind rising American obesity rates: increasing intake of total and refined carbohydrates.

The researchers, all associated with Case Western Reserve University and University Hospitals of Cleveland, in Ohio, compared National Cancer Institute data for esophageal adenocarcinoma (1973—2001) and food consumption information from the National Nutrient Data Bank (1909–1997). The researchers found a trend toward higher intakes of refined carbohydrates; those with more starch and lower nutrient levels than carbohydrates obtained from whole grains and minimally processed foods.

The incidence of esophageal adenocarcinoma increased over the review period and “strongly correlated” with carbohydrate consumption. This cancer is also known to be strongly associated with gastroesophageal reflux disease (GERD), which, in turn, is associated with obesity and a high carbohydrate intake.

By contrast, they noted a decrease in the rates of squamous cell cancer of the esophagus, which is more closely associated with smoking rather than reflux disease and obesity.

“The similarity in these trends gives further evidence for the association of carbohydrate intake, obesity, and related measures with cancer,” stated lead investigator Cheryl L. Thompson, MD, Case Western Reserve University.

Dr. Thompson and colleagues cautioned, however, that such observations do not necessarily reflect individual risk for esophageal adenocarcinoma. Additional research is needed to assess individual risk from high intake of refined carbohydrates, added Dr. Thompson.

The findings, concluded researchers, highlight the importance of limiting refined carbohydrates in the American diet.

Preventive Colon Cancer Combo Radically Decreases Disease Risk

In newly released research, scientists from the University of Arizona are touting a new drug therapy combination that they assert has the potential to revolutionize colon cancer treatment.

The University of Arizona data demonstrated that the novel treatment—a combination of the drug DFMO (difluoromethylornithine) with sulindac (Clinoril), an anti-inflammatory medication&mdash; slashes the disease threat in high-risk patients by as much as 90%.

The drug regimen was evaluated in a preventive context: the study subject population who received the therapy did not yet have colon cancer but had all developed precancerous colon polyps, a major and significant risk factor for the eventual development of the disease.

Research findings indicated that overall, the likelihood of the development of more dangerous polyps was cut by 70% in patients who underwent combination therapy for a period of three years. In the highest risk group— patients who had large or multiple polyps&mdash; the risk of recurrence was decreased by 95%. The 95% drop in risk represents more than a doubling of preventive effect when compared with other known colon cancer therapies, including aspirin.

“This has really hit a home run,” said David S. Alberts, MD, director of the Arizona Cancer Center, where about 50 of the 300 patients in the study were tested and where much of the basic research and patient analysis was conducted.

“It is by a long shot the most effective therapy we have found to prevent this cancer, with very little toxicity,” Dr. Alberts said.

In a cautionary note, researchers warned that the DFMO-sulindac therapy faces at least two more years of clinical trials before it will be “ready for primetime” use in the United States.

“Although the five clinical trials we have completed show this therapy to be no more toxic than plain aspirin, we are always concerned about that issue and want further testing before this goes to the general population,” said study co-investigator Eugene Gerner, MD, University of Arizona Cancer Center, Tucson.

Results were presented at the annual meeting of the American Association for Cancer Research in San Diego.

Novel Drug Delivery System Driven by Spectacular Technology

At first glance, it sounds like something out of a futuristic science fiction film or an episode of `Star Trek’: cancer therapies delivered via tiny machines, so small that they fit inside the human cell. The seemingly unbelievable medical advance is not fictional, however. Rather, it is the result of research and development efforts led by a team from the Nano Machine Center at the University of California, Los Angeles’s NanoSystems Institute.

For such a complex technology, the “nanoimpeller” device has a relatively straightforward mechanism of action. Anticancer drugs are collected and stored inside the tiny pores of the microscopic machine, which then releases the drugs into cancer cells in response to light. The drugs continue to be released, in a steady, controlled manner, in response to continued directional lighting cues controlled remotely by the physician conducting the procedure, until the cancer cell dies. According to its creators, the nanoimpeller is the first light-powered nanomachine able to operate inside a living human cell.

To create the nanoimpeller, the researchers used mesoporous silica nanoparticles and coated the interiors of the pores with azobenzene, a chemical that changes characteristics when exposed to light.

Laboratory tests were conducted using a number of types of human cancer cells, including colon and pancreatic cancer cells. The nanoimpellers were loaded into the cancer cells in the dark. When light was directed at them, the nanoimpellers released their contents into the cells.

“The achievement here is gaining precise control of the amount of drugs that are released by controlling the light exposure. Controlled release to a specific location is the key issue, and the release is only activated by where the light is shining,” stated Fuyu Tamanoi, MD, Jonsson Comprehensive Cancer Center, UCLA.

Dr. Tamanoi and colleague Jeffrey Zink, MD, said this system “has potential applications for precise drug delivery and might be the next generation for novel platform for the treatment of cancers such as colon and stomach cancer. The fact that one can operate the mechanism by remote control means that one can administer repeated small-dosage releases to achieve greater control of the drug’s effect.”

The research was published on-line in the nanoscience journal 

Gene Therapy Yields First Product Candidate of its Kind

At the recent annual meeting of the American Society of Gene Therapy in Boston, it was announced that a gene therapy invented at The University of Texas M. D. Anderson Cancer Center has become the first treatment to succeed in a U.S. phase III clinical trial for cancer.

The trial showed that p53 expression in the patient’s tumor before treatment is a reliable biomarker for how to treat head and neck cancer. Patients with a favorable p53 profile who received the novel agent had a median survival of 7.2 months, compared with 2.7 months for those whose tumor expressed high levels of mutant p53 before treatment. Patients with this unfavorable profile were better off taking chemotherapy, resulting in median survival of 5.9 months. Patients treated with the gene therapy experienced far fewer harmful side effects such as pneumonia than those who received chemotherapy. The incidence of inflammation of the mouth lining and a decrease in white blood cells, for example, both dropped to zero for those receiving the agent.

“Cells become cancerous because p53 no longer functions. Restoring p53 works unlike any current cancer treatment because it treats the cancer genome. The important finding is that patients who benefit from treatment can be identified with the p53 biomarker. The biomarker will enable physicians to personalize treatment,” said the drug’s inventor Jack Roth, MD, professor in M. D. Anderson’s Department of Thoracic & Cardiovascular Surgery and Director of M. D. Anderson’s W.M. Keck Center for Innovative Cancer Therapies.

The modified adenovirus that expresses the tumor-suppressing gene p53 will be branded as Advexin and targeted at the treatment of endstage head and neck cancer. The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself. The therapy, if approved, will be marketed by Austin, Texas—based Introgen Therapeutics, Inc. Dr. Roth cofounded the company and the University of Texas System is a key shareholder.

Dr. Roth’s lab has been developing gene therapy for cancer since 1990. All basic and preclinical work on the modified adenovirus was done at M. D. Anderson. The first phase I clinical trial was conducted by Gary Clayman, MD, DDS, professor in M. D. Anderson’s Department of head and neck surgery. Dr. Clayman also enrolled patients in the phase II and III clinical trials conducted by Introgen.

Dr. Roth and colleagues deleted an important region of the adenovirus’ genome, preventing it from replicating. They installed a genomic segment that expresses p53. When injected into a tumor, the p53 adenovirus burrows into the cancer cell’s nucleus. However, instead of replicating in a typical viral manner, it expresses p53, resulting in cell death. Dr. Clayman’s phase I trial provided the first indicator that p53 expression in the tumor before treatment could be an accurate biomarker for p53 therapy.

The researchers are now focused on ways to deliver p53 and other tumor-suppressing genes systemically—through intravenous delivery. Advexin has to be injected straight into the tumor, but that’s not workable for many cancers. Head and neck cancer kills patients by recurring, not spreading to other organs, but most cancer deaths involve metastasis. By wrapping tumor-suppressing genes in tiny balls of fat, Roth and colleagues hope to be able to treat more invasive cancers. Injected nanoparticles gather mainly in tumors, where they are taken up and dissolved, leaving the tumor-suppressor gene at work in the cell.

Acupuncture May Play a Role in Alleviating Cancer Pain Symptoms

New data from a randomized, controlled trial found that acupuncture provided significant reductions in pain, dysfunction, and dry mouth in head and neck cancer patients after neck dissection. The study was led by David Pfister, MD, Chief of the Head and Neck Medical Oncology Service, and Barrie Cassileth, PhD, Chief of the Integrative Medicine Service, at Memorial Sloan-Kettering Cancer Center (MSKCC), New York City.

Seventy patients participated in the study and were randomized to receive either acupuncture or usual care, which includes recommendations of physical therapy exercises and the use of anti-inflammatory drugs. For all of the patients, at least three months had elapsed since their surgery and radiation treatments. The treatment group received four sessions of acupuncture over the course of approximately four weeks. Both groups were evaluated using the Constant-Murley scale, a composite measure of pain, function, and activities of daily living.

Pain and mobility improved in 39% of the patients receiving acupuncture, compared with a 7% improvement in the group that received usual care. An added benefit of acupuncture was significant reduction of reported xerostomia, or extreme dry mouth. This distressing problem, common among patients with cancer following radiotherapy in the head and neck, is addressed with only limited success by mainstream means.

“Chronic pain and shoulder mobility problems are common after such surgery, adversely affecting quality of life as well as employability for certain occupations,” stated Dr. Pfister. Nerve-sparing and other modified radical techniques that preserve certain structures without compromising disease control reduce the incidence of these problems but do not eliminate them entirely. Dr. Pfister added, “Unfortunately, available conventional methods of treatment for pain and dysfunction following neck surgery often have limited benefits, leaving much room for improvement.”

Acupuncture, a component of traditional Chinese medicine, originated more than 2,000 years ago. Treatment involves stimulation of one or more predetermined points on the body with needles, heat, pressure, or electricity for therapeutic effect. It is already being used in the palliative care of cancer to alleviate pain and chronic fatigue and to reduce postoperative chemotherapy-induced nausea and vomiting.

Articles

Academic research is fueling tremendous strides in oncology and biotechnology. The Academy delivers the latest news on biotech
and oncology research, providing a link between the clinical world of cancer care and the university researchers who are pushing the envelope of knowledge and discovery.

The Academy: June 9, 2010

Leaner, Refocused PDL BioPharma Poised to Make Oncology Play

After months of major reorganizations, upper-tier executive level shake-ups, and shareholder dissatisfaction, PDL Biopharma Inc., according to many analysts, is beginning to emerge from all the turmoil and change as a stronger, more streamlined and focused organization that has the potential to make an impact in the oncology sector. The once oversized and over-extended company had developed a reputation for enticing shareholders with all sorts of promise and potential, only to fall consistently short of expectations. A number of major moves over the past several months, however, have changed the face of the company and may change its fortunes.

Frustrated stakeholders have long lobbied for the company to sell off parts or put itself on the auction block in its entirety. Bowing both to shareholder pressure and the view of key company executives who believed the decision to be sound strategy, the company acquiesced, announcing last Fall that it would deal away or spin-off many of its more cumbersome, profit-draining divisions. It was not long before market watchers realized that PDL intended to be true to its word.

The fire sale began in earnest with the sale of PDL’s manufacturing facilities in late 2007. At the same time, the company began a sell-off of all of its commercialized products with the deal to cede its Busulfex IV franchise to Otsuka Pharmaceutical Co. for $200 million. The process was completed in early 2008. The 2008 transaction was conducted with EKR Therapeutics. The latter company purchased PDL’s cardiovascular product line for $85 million up front and $85 million in potential milestones. The deal includes the hypertension drug Cardene (nicardipine), heart attack drug Retavase (reteplase) and also ularitide, which is being developed for acute decompensated heart failure. In all, the sale of PDL’s commercial portfolio yielded roughly $357 million.

Next, PDL announced its intention to effectively split what was left of the company into two parts, spinning off its biotechnology assets into a separate publicly traded entity apart from its antibody humanization royalty assets and to capitalize the new biotechnology spin-off company with about $375 million in cash. The company said the initial infusion of money, along with potential milestone payments, royalties, and the sale of the company’s cardiovascular products will fund the biotech spinoff for about three years.

After the spinoff, the company said it will continue to hold rights to royalty revenue on all licensed products. It said it would distribute future revenue to stockholders and does not plan to make any acquisitions. PDL expects that revenue to range from $240 million to $260 million in 2008. This move is expected to be completed by the end of the year, at which point there will be a nimble, small-scale, responsive PDL research and development (R&D)—centered entity narrowly focused on lucrative markets such as oncology and a stand-alone company established for the purpose of accruing PDLs royalty-generating assets. According to a PDL spokesperson, the corporate restructuring is designed “to sharpen the Company’s focus on oncology clinical development efforts and to further reduce costs to extend its cash reserves.”

According to analysts, the entity that will exist to process royalties and other assets represents a distillation of what is generally acknowledged to be the most valuable piece of the company: the technology and underlying patents for creating humanized monoclonal antibodies. It forms the basis for many successful biotech drugs currently on the market, including Genentech’s cancer drugs Avastin (bevacizumab) and Herceptin (trastuzumab), and is behind Medimmune’s Synagis (palivizumab) and Biogen Idec’s Tysabri (natalizumab). Opting to license the technology to other companies instead of exclusively developing in-house products has provided PDL with a steady, stable revenue stream (from licenses and royalty revenue), that according to financial news website TheStreet.com, has the potential to reach $500 million annually within the next five years.

The stand-alone entity may exceed revenue-generation expectations: All of the existing royalty-producing drugs for PDL, developed by other companies but based on its patent for humanized monoclonal antibodies, are growing nicely—as seen with Genentech’s Avastin. Furthermore, new royalty-producing compounds could be on the market as early as this year: AstraZeneca just filed a marketing application with the Food and Drug Administration for respiratory tract infection treatment motavizumab. Finally, other royalty-producing drugs that just came to market, like Tysabri, should bring the new entity years of revenue growth.

In the words of one Wall Street analyst (quoted in a recent issue of 

) impressed with PDL’s recent maneuverings, “it’s hard to argue that PDL BioPharma isn’t trading at an incredible value right now.” According to a commentator on the website Motley Fool, “The most interesting upcoming event for Fools (potential investors) considering a stake in PDL is the breakup of the company. Investors should carefully monitor how the market chooses to value its royalty stream and R&D assets once they are divided. In asset-breakup cases like these, the market often incorrectly values at least one of the resulting spinoffs. In the confusion following a move like PDL’s, shrewd investors can make lots of money on the long or short side. Fools should track PDL closely once more news of the proposed spinoff is announced.”

Indeed, much of even the most boisterous shareholder grumblings have been quieted of late. It did not hurt that in May of this year, PDL delivered a $4.25-a-share special dividend payment to investors as part of the company’s plan to break apart and return cash to shareholders. (Much of the funding for this dividend came from PDL’s sale of the rights to its marketed drugs and biopharma manufacturing facilities.)

Newly stripped down and devoid of diversifications and distractions, PDLs future performance will depend on the progress of its pipeline (

). Its lead product candidate is satraplatin, a platinum-based compound intended for use as a chemotherapy treatment. Unlike other platinum-based drugs, satraplatin is administered orally. The ongoing phase I trial evaluating satraplatin in combination with radiation therapy in non—small-lung cancer is being conducted by the company. The remaining company is also developing a number of antibodies, currently in various stages of clinical trials, including aclizumab, which is being tested as a treatment for multiple sclerosis, volociximab, being studied for use against solid tumors, and multiple myeloma treatment candidate HuLuc63.The Company also has two kinase inhibitor compounds, RGB-344064 and RGB-286638 in pre-clinical development. Preclinical agent RGB-286638 is expected to enter clinical trials within the next few months.

The turbulence, difficulties, and challenges faced by PDL have been reflected in its stock price. Flying high at over $30 per share as recently as a year ago, the equity has been beaten down to the point where it is now hovering below $4 per share. A rally may be overdue, however, as numerous analysts and investment experts have deemed the stock to be undervalued and a good bargain.

Monoclonal Antibody Market Poised to Continue Remarkable Expansion 

According to numerous analysts, the oncology marketplace is likely to be increasingly dominated over the next decade by monoclonal antibody (MAB) therapies. The remarkable rise of the therapeutic category, which only several short years ago was looked upon as experimental and whose business prospects were far from certain, is being attributed to rapidly evolving development advances, applicability across multiple tumor types, and the proven, established success (both in terms of sales and efficacy) of the MABs that are currently on the market.

According to ‘Antibody Therapies in Oncology,’ a market report recently released by Pittsburgh-based Decision Resources, a research and advisory firm for pharmaceutical and health care issues, the MAB drug market will more than double to $16.7 billion in 2016. This dramatic rate of growth, states the report, will be fueled by the increasing use of currently available therapies and supplemented by the emergence of new MAB products currently in various stages of development.

Leaders among currently established MABs that, according to Decision Resources and a variety of other industry watchers, are likely to capture increasing marketshare in the years ahead include Genentech’s Avastin, ImClone’s Erbitux (cetuximab), and Genentech’s Rituxan (also marketed as Roche’s MabThera outside the U.S.) (rituximab).

The new Decision Resources report finds that another major driving force behind market growth of the MAB drug class through 2016 will be the label expansion of currently approved MABs into other patient populations as well as approvals in new indications in the United States, France, Germany, Italy, Spain, United Kingdom and Japan.

In 2006, Avastin held approvals in non—smallcell lung cancer and colorectal cancer. Since that time, of the cancers covered in the report, it has gained approval for breast cancer and renal cell carcinoma and is expected to be approved for prostate cancer and ovarian cancer. As is the case with other MABs’ mechanism of action, and applicability across multiple tumor types, even if and when only limited patient share is seen in some indications, it will likely be key to Avastin’s continued and sustained success.

While not as lucrative as Avastin in terms of revenue generation or as diverse in terms of its use across as many tumor types, Erbitux generates significant sales in colorectal cancer and squamous cell carcinoma of the head and neck. Also, Erbitux is expected to be approved for the treatment of non—smallcell lung cancer, which will dramatically boost its sales. Lastly, although the use of Rituxan/MabThera in non-Hodgkin’s lymphoma has reached saturation in many of the subtypes of the disease, this agent is forecasted to gain approval for chronic lymphocytic leukemia, allowing for increased prescribing in Europe where the cost-constrained environment limits off-label use.

Market sales will also be driven by the introduction of four new MABs by 2016: Genmab and GlaxoSmithKline’s ofatumumab for non- Hodgkin’s lymphoma and chronic lymphocytic leukemia, Medarex and Bristol-Myers Squibb’s ipilimumab for malignant myeloma, Genmab’s zanolimumab for T-cell lymphoma, and Genentech’s pertuzumab for breast cancer.

“These emerging MABs will contribute significant sales by 2016,” said Clair Gricks, PhD, analyst at Decision Resources, “They will provide new therapeutic options for patients with currently limited choices or will improve the efficacy of established agents when used in combination. The majority of market growth, however, will be driven by label expansions and increased uptake of currently marketed MABs.”

Physicians Financial News: June 8, 2010

Pegfilgrastim (Neulasta) is a covalent conjugate of recombinant methionyl human granulocyte colony-stimulating factor (G-CSF; filgrastim) and monomethoxypolyethylene glycol. Filgrastim is a water-soluble, 175—amino acid protein with a molecular weight of approximately 19 kD. Filgrastim is obtained from the bacterial fermentation of a strain of 

 transformed with a genetically engineered plasmid containing the human G-CSF gene. To produce pegfilgrastim, a 20-kD monomethoxypolyethylene glycol molecule is covalently bound to the n-terminal methionyl residue of filgrastim. The average molecular weight of pegfilgrastim is approximately 39 kD.

Pegfilgrastim is a longer-acting form of filgrastim (Neupogen), Amgen’s original leukocyte- stimulating agent. Pegfilgrastim requires only one injection per chemotherapy cycle, while filgrastim may require daily injections for up to 14 days following chemotherapy.

Both filgrastim and pegfilgrastim are colony-stimulating factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end-cell functional activation. Studies on cellular proliferation, receptor binding, and neutrophil function demonstrate that filgrastim and pegfilgrastim have the same mechanism of action. Pegfilgrastim has reduced renal clearance and prolonged persistence 

Pegfilgrastim was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMEA) in 2002 for reducing the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Dr. Ziad Atassi, University of Ulm, Ulm, Germany and colleagues evaluated the pharmacokinetics, safety, and efficacy of pegfilgrastim in 22 female patients with axillary metastatic breast cancer. Subjects received dose-dense chemotherapy consisting of 3x4 sequential single-drug cycles of epirubicin 90 mg/m

 on a q15d schedule. Pegfilgrastim was administered 24 hours after chemotherapy. Blood samples for pharmacokinetic studies were taken on days 8, 10, and 12 of each cycle. The mean pegfilgrastim serum level on day 1 of each cycle was 2.88 ng/mL, 1.66 ng/mL, and 0.51 ng/mL on days 1, 10, and 12 of each cycle, respectively. The minimum value was observed on day 12 of cycle 5. Pegfilgrastim remained bioavailable until day 12 of each cycle with absent cumulative effects. Four patients presented with a single grade 3 neutropenia event, and no cases of febrile neutropenia were noted at any cycle. Nine events of >grade 1 bone pain were noted. Considering the low adverse event rate, the investigators suggested that dose-dense chemotherapy with primary pegfilgrastim prophylaxis is a safe option for high-risk breast cancer patients.

Pegfilgrastim for the Treatment of Chemotherapy- Associated Myelosuppression in

Dr. Jessica A. Pollard and colleagues at the Fred Hutchinson Cancer Research Center, Seattle, Washington, reported their institutional experience with pegfilgrastim following doseintensive chemotherapy for solid tumors. Thirty-nine pediatric patients were included in this retrospective review. The median age of patients evaluated was 12 years (range, 0.17—23 yr) and the median weight was 50 kg (range, 4–107 kg). Primary diagnoses included osteosarcoma, Ewing’s sarcoma, rhabdomyosarcoma, soft tissue sarcoma, neuroblastoma, Hodgkin’s disease, and other solid tumors. A total of 141 chemotherapy courses with pegfilgrastim support were administered (median, 4 courses per patient). No adverse events related to pegfilgrastim were noted. Severe neutropenia occurred in 46% of courses. Overall, the median duration of severe neutropenia was 0 days (range, 0-8 days). Febrile neutropenia occurred in 28% of courses. Of particular interest were eight patients treated with interval-compressed (every 14 days) sarcoma chemotherapy. Of 51 courses administered, the median course duration was 15 days (range, 14–28 days). The investigators concluded that pegfilgrastim administration following dose intensive chemotherapy for solid tumors is safe and feasible in children, including those <45 kg. They noted that the frequency and duration of severe neutropenia, as well as the incidence of febrile neutropenia, were similar to historic data on filgrastim.

GROC plus Pegfilgrastim in Relapsed Aggressive Non-Hodgkin’s Lymphoma

A more effective and less toxic salvage regimen for relapsed aggressive non-Hodgkin’s lymphoma (NHL) is desirable for use before autologous stem cell transplant (ASCT). Gemcitabine (Gemzar) and oxaliplatin (Eloxatin) are active single agents in NHL and have modest myelosuppressive activity. Fernando Cabanillas, MD, Auxilio Mutuo Cancer Center, San Juan, Puerto Rico and colleagues performed a study to evaluate the gemcitabine, rituximab (Rituxan), oxaliplatin combination (GROC) administered every 14 days with pegfilgrastim support in patients with relapsed aggressive NHL (N = 37). Twelve patients were refractory to first-line therapy and 14 had partial response (PR) or progressive disease as best response to the preceding chemotherapy regimen. Doses were: rituximab, 375 mg/m

 on day 2, and pegfilgrastim, 6 mg on day 3. Median age of patients was 59 years. Overall response to GROC was 81%, with 40.5% of patients achieving complete remission and 40.5% achieving PR. At 2 years, overall survival (OS) was 33% and progression-free survival (PFS) was 29%. Among patients who were not refractory to the preceding chemotherapy regimen, the two-year PFS was 49% and 2-year OS was 52%. Despite the older age of patients receiving GROC, its toxicity appeared to be lower and its overall response rate was either similar or better. In 54% of patients, the response to GROC was better than to the preceding regimen. The investigators also noted that in 16 cases, PFS was longer with GROC than with the preceding regimen. The most common non-hematologic toxicities were reversible transaminitis, partially reversible neuropathy, and diarrhea. In this prospective study, GROC was an effective, dosedense salvage regimen even in patients with poor prognostic features such as older age. Furthermore, GROC appeared to be as effective as DHAP (dexamethasone, cisplatin, cytarabine), ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine, ICE [ifosfamide, carboplatin, etoposide]), and RICE (rituximab, ICE), but with considerably less hematologic and nonhematologic toxicity. Owing to the effectiveness and low toxicity profile of GROC, the investigators recommended further evaluation as a first salvage option for relapsed aggressive NHL.

Risk of Hospitalization With Pegfilgrastim Versus Filgrastim Prophylaxis

A retrospective cohort study was performed by Derek Weycker, PhD, Policy Analysis, Inc., Brookline, Massachusetts and colleagues using a U.S. health care claims database. The goal of the study was to determine whether the risk of hospitalization for neutropenic complications differs between pegfilgrastim and filgrastim in a real-world setting. The study population was made up of patients with cancer who underwent a course of chemotherapy over a threeyear period, and who also received pegfilgrastim or filgrastim during their first course. For each patient, each unique cycle of chemotherapy was identified, as was each cycle in which pegfilgrastim or filgrastim was administered by cycle day 5 (i.e., as prophylaxis). Risk of hospitalization for neutropenia, fever, or infection (“neutropenic complications”) was then examined on a cycle-specific basis, including all patient-cycles in which pegfilgrastim or filgrastim was administered as prophylaxis. A total of 15,763 patient-cycles were identified in which patients received prophylaxis either with pegfilgrastim (N = 14,570) or filgrastim (N = 1193). The crude risk of hospitalization for neutropenic complications was 4.8% for filgrastim and 3.1% for pegfilgrastim. The rates of all-cause hospitalization were 8.7% and 6.3%, respectively. Unadjusted and adjusted odds of hospitalization were consistently lower (by 28% to 36%) with pegfilgrastim than with filgrastim. The investigators concluded that the risk of hospitalization appears to be approximately one-third lower with pegfilgrastim than with filgrastim prophylaxis in patients with cancer receiving myelosuppressive chemotherapy in a real-world setting.

Presentations at this year’s ASCO meeting highlighted the advantages of pegfilgrastim in reducing the incidence of febrile neutropenia in patients receiving chemotherapy for a wide variety of solid tumors and hematologic malignancies, including osteosarcoma, Ewing’s sarcoma, rhabdomyosarcoma, soft tissue sarcoma, neuroblastoma, Hodgkin’s disease, NHL, and breast cancer.

Outcomes investigations showed that non- Hodgkin's lymphoma patients with cancer with a range of comorbid conditions who receive primary pegfilgrastim prophylaxis may experience improved PFS and OS during chemotherapy. It also suggested that the risk of hospitalization appears to be significantly lower with pegfilgrastim than with filgrastim prophylaxis in patients with cancer receiving myelosuppressive chemotherapy.

Impact of Pegfilgrastim on Early All-Cause Mortality in Patients Receiving Cancer Chemotherapy

Gary H. Lyman, MD, MPH, FRCP, Duke University and the Duke Comprehensive Cancer Center, Durham, North Carolina, and colleagues performed a prospective observational study of 4,458 consecutive adult patients receiving cancer chemotherapy at 115 randomly selected U.S. practices to evaluate the effect of prophylactic colony-stimulating factors in cancer patients with multiple comorbid conditions. Pegfilgrastim was administered on an individual basis to 1,209 patients (including 620 as primary prophylaxis) starting in cycle 1. Patients receiving primary pegfilgrastim prophylaxis experienced better PFS (

 = 0.0079; HR = 0.41) than those without primary pegfilgrastim prophylaxis. In univariate analysis incorporating any use of pegfilgrastim as a time-dependent covariate, improvements in both PFS (

 < 0.0001; HR = 0.40) were observed. In multivariate analysis, pegfilgrastim use was associated with improved PFS (

 = 0.0120; HR = 0.44) after adjustment for other significant covariates (including Eastern Cooperative Oncology Group performance score, Charlson comorbidity index, age, body-mass index, cancer type, stage of disease, and year on study. The investigators concluded that cancer patients with a range of comorbid conditions who receive primary pegfilgrastim prophylaxis may experience improved PFS and OS during chemotherapy. 

New research presented at ASCO highlights advantages of pegfilgrastim in patients receiving chemotherapy for a wide variety of solid tumors and hematologic malignancies.

Pegfilgrastim for Reducing Incidence of Infection by Febrile Neutropenia

One of the most uncomfortable consequences of anticancer therapy is the development of oral mucositis. This painful condition develops in approximately 40% of patients treated with standard chemotherapy, 30%—60% of patients receiving radiation therapy for cancer of the head and neck, 70% of patients who undergo bone marrow transplantation and receive high-dose chemotherapy, and over 90% of patients receiving concomitant chemotherapy and localized radiation.

Oral mucositis is characterized by erythema, swelling, and ulceration of the mucous membranes. The consequences of this inflammation can greatly affect a patient’s health, quality of life, and anticancer therapy outcome. The disruption of the natural mucosal barrier can increase the risk of systemic infections. Furthermore, the intense pain associated with oral mucositis may impede the patient’s eating and oral hygiene activities which in turn can disrupt the efficacy of cancer therapy.

The economic consequences of oral mucositis are substantial. In patients receiving high-dose chemotherapy for stem-cell transplant, Sonis and colleagues

 observed that the increased infections, disruption of therapy, and increased need for hospitalization caused by oral mucositis added $43,000 per patient. Costs were also dependent on the level of oral mucositis. The authors estimated that for each 1 point rise in the oral mucositis assessment scale (OMAS), there was an additional $25,000 in costs. Similarly, in patients treated with standarddose chemotherapy, a large portion of the extra costs of mucositis arise from the increased need for hospitalization.

The best management option for oral mucositis however, is preventive therapy—a key component of which is recognizing which patients are at risk (see table 1).

Once it is established that the patient will likely develop oral mucositis, it is imperative that preventive/ educational measures be given to reduce the risk of developing mucositis or to reduce the severity of mucositis. Key educational material should include the importance of oral hygiene to reduce the risk of inflammation and nutritional advice to help the patient get the calories needed during therapy while reducing the discomfort of mucositis.

If the patient does develop oral mucositis, most treatment options are symptomatic to reduce pain (analgesic), swelling (cryotherapy), and/or inflammation (anti-inflammatory). One treatment option that has proven to be safe and effective at reducing the incidence, severity, and duration of oral mucositis is Caphosol

 (Supersaturated Calcium Phosphate Rinse).

				  Age (children and patients over 50 yr of age)

				  Tumor location (e.g., oral cavity, throat)

				  Chemotherapy (type of drug, dose and intensity,

				  Radiotherapy (location, fractioning,

- solution and is believed to promote healing of the mucosal lesions while helping to cleanse the oral cavity. In this manner, it reduces both the intensity and duration of mucositis in patients given high-dose chemotherapy. This was observed in a prospective, double-blind, randomized clinical trial by Papas and colleagues

 who compared Caphosol used at the initiation of cancer therapy in conjunction with proper oral hygiene with standard fluoride rinse in 95 patients undergoing hematopoietic stem-cell transplantation. During the course of treatment, oral mucositis was scored on a 6 point scale (0-no change; 1-erythema; 2-single ulcer < 1 cm; 3-a few ulcers approximately 1 cm; 4-multiple ulcers < 1 cm; 5-slough) and pain on a 0—100 visual analog scale (VAS). Inflammation (absolute neutrophil counts) and morphine intake were also measured during the study.

One interesting aspect of this study was that it acknowledged the importance of oral hygiene before beginning bone marrow transplant. Before transplant, patients in the Caphosol group received Caphosol and four topical fluoride treatments. After the transplant they received Caphosol at least four times daily. The comparator group was given a placebo gel with fluoride rinse prior to transplant and the fluoride rinse continued after transplant (at least 4 times daily).

The results of this study were very encouraging. As shown in Figure 1, the mean number of days patients experienced mucositis (days with score > 1) or ulcerations were significantly lower in patients receiving Caphosol compared with standard fluoride care. Patients given Caphosol also had significantly fewer days of pain and fewer days that required morphine (Figure 2). Further analysis showed the patients receiving Caphosol had fewer days of neutrophil engraftment, lower peak levels of mucositis and lower peak levels of pain.

The authors of this study concluded that Caphosol “should be considered in the treatment of of patients undergoing hematopeoitic stem-cell transplantation at high risk for mucositis.” The authors also noted that the encouraging results seen in this study with bone marrow transplant patients were similar to results reported at conferences with patients undergoing radiation and/or chemotherapy.

Oral mucositis is a costly consequence of cancer therapy that can impede the efficacy of anticancer therapy. Even small reductions in OMAS scores can reduce medical costs by the thousands while improving the patient’s quality of life. Therefore, every effort to reduce the severity and/or risk of getting mucositis should be undertaken by the patient as well as the patient’s oncologist, general practitioner, dentist, and other medical professionals.

Since most patients undergoing high-dose chemotherapies for solid tumors, bone marrow transplant, and radiation for head and neck cancer will develop oral mucositis, it is advised that these patients be part of an oral hygiene plan that cleans the oral cavity and promotes healing of the mucosal lesions. Using these simple preventive measures, the patient’s outcome and quality of life can greatly improve.

1. Naidu MUR, Ramana GV, Rani PU, et al: Chemotherapyinduced and/or radiation therapy—induced oral mucositis— 

    Complicating the treatment of cancer. 

2. Sonis ST, Oster G, Fuchs H, et al: Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell

3. Elting LS, Cooksley C, Chambers M, et al: The burdens of cancer therapy: Clinical and economic outcomes of

4. D’Hondt L, Lonchay C, Andre M, et al: Oral mucositis induced by anticancer treatments: Physiopathology and

5. Papas AS, Clark RE, Martuscelli G, et al: A prospective, randomized trial for the prevention of mucositis in patients

    undergoing hematopoietic stem cell transplantation. 

Oral mucositis is a costly consequence of cancer therapy that can impede the efficacy of anticancer therapy. Simple preventive measures can greatly improve the patientÃ¢ï¿½ï¿½s outcome and quality of life.

The Management of Oral Mucositis in Oncology 

Does Finasteride Prevent Prostate Cancer?

Finasteride has been used for many years in the treatment of benign prostatic hyperplasia (BPH) to improve the symptoms associated with enlarged prostate. However, it was not known if finasteride simply improved symptoms or actually helped prevent prostate cancer. Researchers from the Prostate Cancer Prevention Trial (PCPT) sought to determine the answer to this question, and found some encouraging results.

In this phase III trial, clinicians from the University of Texas Health Science Center, San Antonio, utilized a logistic regression model to evaluate men in the PCPT placebo group. In order to predict prostate cancer during the study’s subsequent seven years, prostate cancer risk at entry was assessed. No one was included if their prostate-specific antigen (PSA) level exceeded 3.0 ng/mL. The extent that finasteride may affect prostate cancer prevention was evaluated across risk and PSA strata.

Participants in each risk quintile experienced a significant reduction of prostate cancer risk with finasteride treatment. The risk of prostate cancer was cut by at least 28% 

 ≤ .05). Although the benefit of finasteride use did not appear to trend with increasing or decreasing overall risk, there did seem to be some association with baseline PSA level. For example, the odds ratio increased (smaller treatment effect of finasteride) from 0.60 for those with PSA levels below 0.7 ng/mL to 0.69 for men with PSA concentrations from 1.8 to 3.0 ng/mL. However, the treatment effect still continued to be statistically significant, even at the highest PSA concentration (

Likelihood of Cancer Decreased With Finasteride Use,

The risk of prostate cancer was significantly reduced by finasteride treatment, the researchers concluded, regardless of the level of this risk. That suggests, they added, that finasteride has both treatment and preventive effects, and all men should be made aware of the agent’s potential to reduce prostate cancer risk when they have PSA screenings.

Thompson IM, Tangen CM, Parnes HL, et al: Does the level of prostate cancer risk affect cancer prevention with finasteride?

Lapatinib Plus Trastuzumab for Patients With Progressing Metastatic HER-2—Positive Breast Cancer

Approximately 25% to 30% of patients with breast cancer are HER-2 positive, and this is a particularly aggressive form. Results from a first-ever randomized, multicenter, open-label phase III trial demonstrated that the combination of two targeted agents, lapatinib plus trastuzumab produced positive outcomes for women with HER-2 breast cancer.

The study group comprised 296 subjects with HER-2 positive breast cancer whose disease had progressed with the use of prior trastuzumab treatment. They were randomized to receive either treatment with lapatinib 1,000 mg/day plus trastuzumab 2 mg/kg weekly after a 4 mg/kg loading dose, or lapatinib 1,500 mg/day alone. All of the participants had previously received anthracycline and taxane therapy, and a median of six prior chemotherapy regimens.

The Figure shows that progression-free survival and clinical benefit rate at 24 weeks were significantly improved with the combination therapy, although the absolute difference in terms of time was limited. The researchers pointed out that response rate and overall survival were not different between groups. Generally, both treatment regimens were well tolerated although grades 1 and 2 diarrhea occurred more frequently in the combination therapy group (53% vs. 41%, 

 = .03). Symptomatic decreases in left ventricular ejection fraction were noted in the two patients in the combination group and in one in the monotherapy group. One patient receiving combination therapy died as a result of cardiac toxicity.

Progression-Free Survival Improved With Lapatnib + Trastuzumab

Treatment In HER2 + Metastatic Breast Cancer

PFS = Progression-free survival; OS = overall survival.

The investigators concluded that the combination of lapatinib and trastuzumab showed encouraging results in patients with metastatic breast cancer whose HER2-positive disease had progressed with the use of trastuzumab alone. They noted that the addition of lapatinib did not significantly change patients’ exposure to adverse events related to therapy.

O’Shaughnessy J, Blackwell KL, Burstein H, et al: A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. Presented at the 2008 annual meeting of the American Society of Clinical Oncology, Chicago, May 31, 2008.

Breast Cancer Risk Reduced With Raloxifene, but for Which Subgroups of Women?

The Raloxifene Use for The Heart (RUTH) trial originally enrolled more than 10,000 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors. In the original trial, the RUTH investigators found that although raloxifene reduced the risk of invasive breast cancer and vertebral fractures it did not reduce the risk of cardiovascular events over a median follow-up of 5.6 years. In this subgroup analysis, the RUTH researchers reported on the extent of breast cancer protection using raloxifene 60 mg.

Data from the original study revealed that raloxifene reduced the risk of invasive breast cancer by 44% (hazard ratio [HR] = 0.56) compared with women who did not take the drug. In the drill-down analysis, the RUTH researchers found that of the 5,044 women given raloxifene, 55% had a reduction in the risk of developing invasive estrogen receptor—positive breast cancer (HR = 0.45), compared with 5,057 women receiving a placebo. The clinicians pointed out that that corresponds to an absolute reduction in risk of 1.2 cases per 1,000 women treated for one year.

Raloxifene therapy did not appear to affect the risk of either invasive or noninvasive ER-negative breast cancer, according to the investigators. After adjusting for age, body mass index, prior hormone use, or baseline risk of breast cancer, the results were unaffected. In view of the side effects associated with raloxifene, they concluded that their findings of benefit being restricted to patients with ER-positive breast cancer can be an important consideration in the patient and clinician discussion of risk versus benefit of using raloxifene.

Grady D, Cauley JA, Geiger MJ, et al: Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk.

Erlotinib Treatment for the Elderly With Advanced Non—Small-Cell Lung Cancer

Survival after initial therapy fails for non—small-cell lung cancer (NSCLC) can be particularly grim. Previous research has determined that erlotinib can have positive effects in patients with NSCLC who failed first- or second-line treatment. A research group from the Department of Medical Oncology, Princess Margaret Hospital, Toronto, Canada, sought to determine whether age at time of treatment affects patients’ response to erlotinib.

A total of 731 patients enrolled in this double-blind study (National Cancer Institute of Canada Clinical Trials Group Study BR.21) and were randomly assigned to receive either erlotinib 150 mg daily or placebo. The clinicians analyzed endpoints including progression-free survival and overall survival, quality of life (QOL), drug exposure, response, and toxicity. Patients were stratified into two age groups of the elderly (≥ 70 yr [163 patients] or < 70 yr [568 patients]). The researchers assigned roughly two patients to receive erlotinib for every one patient in the placebo group.

They reported significant differences between the treatment and control groups within each age cohort, but significant differences were not observed between the two age groups with regard to progression-free and overall survival (

). The age groups experienced similar response rates.

Survival Outcomes in Erlotinib and Control Groups, by Patient Age

Clinical Trial Reports: June 7, 2010

How Much Do Patients With Cancer Pay Out-of-Pocket for Care? 

The costs associated with oncologic therapies, particularly biologic agents, can be a stifling burden on patients, as many treatments cost thousands (even tens of thousands of dollars). Even with health insurance, many treatments are on coinsurance tiers, that is, the patient pays a percentage of total cost, unlike fixed copayments for conventional medications. With the influx of “high-deductible health plans,” which are less expensive than insurance offering first-dollar coverage, patients pay up to $5,000 before insurance payments contribute to the cost of care. Researchers from HealthCore in Wilmington, Delaware sought to determine how much patients with commercial insurance pay out-of-pocket when cancer is being treated.

The investigators retrospectively identified oncology claims from a managed care database. Four years of patient records (ending in 2006) were studied. Patients were included in the study if they had at least two medical claims for breast, colorectal, or lung cancer, or non- Hodgkin’s lymphoma. Patient-paid amounts and health plan payments were recorded for each year to detect trends.

A total of 74,630 patients were included in the study cohort. For these patients, health plan payments rose 57% from 2003 to 2006. However, the rise in out-of-pocket costs to the patient was even higher—109%, reaching $5,094 in 2006. Alarmingly, patient out-of-pocket expenses jumped 54% from 2005 to 2006, which may be ascribed to the expansion in high-deductible health plans.

The researchers found that the proportion of biologic drugs was still only 10% of the total costs. The remainder was for medical services, imaging studies, and other care.

Although this study covered a population with health insurance, it is a particularly worrisome trend that patients are paying far more out of their own wallets and purses than they were in the past for oncological care.

Willey VJ, Pollack MF, Lawless GD: Oncology health care and patient out-of-pocket cost trends in a commercially insured population. Presented at the 2008 annual meeting of the American Society of Community Oncology, Chicago, June 3, 2008.

Will Congress Mandate Minimum Hospital Stays for Breast Cancer?

A Congressional hearing in late May made it clear that health plans and insurers should be on their guard: U.S. Representatives don’t like the idea of drive-through breast cancer surgery, and are prepared to detour it.

Although 20 states already have minimum stay bills in place (no less than 48 hours for mastectomies or lumpectomies), breast cancer advocates claim that federal legislation is needed to bring the rest of the states in line. In remarks at the hearing, Representative Frank Pallone (D-NJ) said, “having access to appropriate medical care should not be dependent on the state you live in.” Representative Pallone chairs the important health subcommittee of the Congressional Energy and Commerce Committee.

A representative of the insurance industry’s trade organization, America’s Health Insurance Plans, Susan Pisano, countered that the health plans will cover longer stays, depending on medical necessity. “We do not think that it is a good idea on the state level or the federal level to be putting clinical guidelines into statute," she said.

The proposal, the Breast Cancer Patient Protect Action of 2007 (H.R. 119) has 219 sponsors and bipartisan support. A similar bill in the Senate (S.B. 459) has 19 sponsors at this time. Assuming a consensus conference passes this proposal and it lands on President George Bush’s desk, it is expected that the President will exercise his veto.

Dixon K: U.S. panel mulls minimum breast cancer hospital stay. Reuters May 21, 2008.

Bump in Oncology Costs Is Generally From Increased Utilization of Adjuvant Therapies

The cost to treat cancer has risen significantly, as more tools are at the disposal of clinicians, and more biopharmaceuticals have been approved, generally at higher cost compared with older therapies. The National Cancer Institute, Bethseda, Maryland, has attempted to quantify how these costs have increased over an 11-year period for four different common cancers.

Investigators evaluated 1992—2002 information from the Surveillance, Epidemiology, and End Results database on Medicare beneficiaries for the care of breast, colorectal, lung, and prostate cancer, starting from two months before diagnosis to 12 months postdiagnosis. Data obtained on nearly 307,000 patients revealed that average payments for lung cancer rose to $39,891 by 2002, up 22% after adjusted for inflation from 1991 (Figure). Interestingly, the average payment for initial prostate cancer care actually fell by $196, to a total of $18,261 in 2002.

Inflation-adjusted percent change in the cost of

Although the researchers noted that the vast majority of the payments were for hospital services, the use of adjuvant chemotherapy increased markedly for the cancers studied. The use of radiation therapy also increased for the breast, lung, and prostate cancer but not colorectal cancer.

Warren JL, Yabroff KR, Meekins A: Evaluation of trends in the cost of initial cancer treatment.

Oncology Case Drives Health Plans to Reinstate Cancelled Coverage for Californians

The case of a California hair salon owner who was undergoing cancer chemotherapy when her insurer, Health Net, cancelled her individual coverage in 2004, inflamed the Governor and the California Department of Managed Health Care. A jury awarded the woman $9 million this year, and it compelled insurers in the state to begin reconsidering their cancellation initiatives.

Health insurers have been reviewing the original applications of high-cost members to check if a mistake on the application or outright fraudulent information (e.g., withholding information about pre-existing medical conditions) could be grounds for canceling the policy. More than 5,000 coverage cancellations had been reported since 2004 (for reasons other than nonpayment of premiums), and virtually all involve individual, not group, policies.

Under a settlement brokered by the state regulator in the face of a glut of lawsuits for wrongful termination of coverage, Health Net and Kaiser Permanente will reinstate the health coverage of 1,092 Californians. If former enrollees accept the settlement, they will be able to seek up to $15,000 in reimbursement for uncovered medical expenses. Otherwise, they may opt to re-enroll for insurance but still take their claims individually to court. The Department of Managed Care is trying to come to similar terms with Blue Shield of California, PacifiCare, and Anthem Blue Cross, which terminated the policies of 4,000 members.

There are no regulations in California that currently codify when a health insurer can terminate a policy.

Girion L: 1,200 people to have canceled healthcare coverage restored.

Which Are the Best Insurers in Terms of Payment for Services?

A physician practice management consultant conducted a survey to determine which insurers paid claims most efficiently in 2006, and found that two national insurers were among the best, and apparently, getting better.

July 2008 | Oncology & Biotech News

The Academy: June 9, 2010

Physicians Financial News: June 8, 2010

Pegfilgrastim for Reducing Incidence of Infection by Febrile Neutropenia

The Management of Oral Mucositis in Oncology

Clinical Trial Reports: June 7, 2010

Reimbursement and Managed Care News: June 7, 2010

Clinical Abstracts From Overseas: June 7, 2010

New Angiogenesis Inhibitor May Be Effective Against a Broad Range of Cancers

ASCO Meeting Highlights

ASCO Coverage for Community Physicians