	On screen, Patrick Dempsey cares for patients as Dr Derek Shepherd in 

. When cameras stop rolling, Dempsey is still busy caring for patients—as founder of the Patrick Dempsey Center for Cancer Hope & Healing in Maine and a tireless advocate for adults and children with the disease. “My awakening to the realities of cancer began in 1997, when my mom was diagnosed with ovarian cancer,” Dempsey said in an interview over Skype.

	Amanda Dempsey survived her cancer and 2 relapses, and Dempsey said the experience educated him on the struggle patients with cancer face in navigating the maze of treatment options and payment concerns and the support community groups provide. This served as the genesis for the center, which has taken an integrative approach to care since opening in 2008 as a wing of the Central Maine Comprehensive Cancer Center.

	The staff of oncology social workers and volunteers—many cancer survivors&mdash;provide education and support services to local patients and their families. Dempsey said patients with cancer not only deal with the disease, they also “worry about paying their bills, spending time with their children.” Family members are under stress, too, he said. Dempsey believes “you have to treat the whole person, emotionally, physically, and mentally.” He said meeting patients’ psychosocial needs positively affects their health. “We’ve noticed a huge change in attitude when people get a message or reiki or yoga. That human touch and caring makes a big difference for people.”

	In addition to providing massage therapy and lessons on stress management, the staff explains treatment concerns and financial issues and provides counseling for patients and their partners. The center recently established the Healing Tree Children’s Program to provide emotional support for children with cancer and those dealing with a relative’s diagnosis, said Dempsey. “Play therapy...lets them work out their feelings in a very safe and nurturing way.”

	Last year, the Patrick Dempsey Center helped more than 75,000 people. “All the care we give is free,” Dempsey said. To raise money, he lends his name to the 2-day Dempsey Challenge, which consists of walks, runs, and a 100-mile bicycle race. Last year’s inaugural event raised $1 million, and Dempsey said early registrations suggest this year’s event, on October 1-2, is on track to beat those totals. The Amgen-sponsored fundraiser also features the Festival in the Park, which hosts a Health and Wellness Expo that provides educational materials touting the benefits of cancer prevention and screening. Dempsey is a strong proponent of screening, which he emphasized saves lives through early detection.

	“People need to be aware that they need to get screened. If there is a family history, go in and get your screenings early.” As for prevention, Dempsey said we need to pay attention to our environment. He also encourages everyone to “look at what’s going into our bodies with the foods we are eating and how they are grown.” In line with this philosophy, Dempsey stopped smoking the night before the Patrick Dempsey Center opened its doors.

	When it comes to the fi ght against cancer, Dempsey said he is disappointed in the government on several levels. “Nobody’s working together. It seems like everyone’s in it for themselves.” He encouraged the nation to unite and recharge the fight against cancer. “I really do think what came out of this meeting is that we do have to rally around and fight for treating the whole person,” Dempsey said. Learn about the Patrick Dempsey Center for Cancer Hope & Healing at 

Articles

That human touch and caring makes a big difference for people

Mom's Cancer Lands Patrick Dempsey a New Role

	A drug that delivers paclitaxel in a novel way has yielded favorable results in a phase II trial of patients with advanced esophageal cancer, prompting the company developing the drug to plan a phase III trial. No tumors were found in 38% of patients with advanced esophageal cancer who received paclitaxel poliglumex (CT-2103; Opaxio) as part of a combination regimen before surgery, according to research presented in a poster session.

	Paclitaxel poliglumex links paclitaxel to the biodegradable polymer polyglutamate to form a new chemical, said Cell Therapeutics Inc (CTI), the drug’s manufacturer. Based on preclinical studies, the drug distributes preferentially to tumors. This allows significantly more of the active chemotherapy agent to localize in the tumor and reduces toxic effects to normal organs.

	In the phase II, single-arm study, paclitaxel poliglumex was administered with cisplatin and radiation to 40 patients (median age, 62 y) prior to surgery. There were 37 cases of adenocarcinoma and 3 of squamous cell carcinoma of the esophagus or gastroesophageal junction. Doses of paclitaxel poliglumex at 50 mg/m2 and cisplatin at 25 mg/m2 were given weekly for 6 weeks, along with a 50.4 Gy-dose of radiation. Resection occurred 4 to 6 weeks aft er treatment.

	Pathologic complete response was observed in 12 of the 37 patients (32%) who had their esophagus surgically removed. The remaining 3 patients (7.5%) declined surgery aft er complete endoscopic response. One patient required a feeding tube and one needed total outside nutrition support. No treatment-related deaths were reported, though 1 patient died during surgery fr om multisystem organ failure. No grade 4 hematologic adverse events were observed; grade 3 neutropenia, esophagitis, and allergic reaction each occurred in 6% of patients; 8% of patients developed nausea, and 3% reported fatigue.

	“Opaxio significantly improved the pathologic complete response rate that has been shown in previous phase III trials using standard chemotherapy plus radiation,” said investigator Kimberly Perez, MD, of the Warren Alpert School of Medicine at Brown University, in a press release. She also noted that the drug was well tolerated.

	In the United States, the standard treatment regimen for esophageal cancer is 5-fluorouracil (5-FU) plus cisplatin chemotherapy with concurrent radiation. Investigators said this regimen is associated with a pathologic complete response rate of around 15%, with 40% of patients experiencing grade 3/4 inflammation and ulcers.

	"The important features of the current study are both the higher-than-historical pathological response rate—a potential excellent surrogate for long-term survival&mdash;and the dramatically lower side effects than would be expected from conventional neoadjuvant chemoradiotherapy with cisplatin and 5-FU," said Jack Singer, MD, chief medical officer of CTI, in a press release. Based on these data, CTI plans to meet with FDA officials before the end of the year to discuss a phase III registration study of Opaxio’s use in esophageal cancer. 

A drug that delivers paclitaxel in a novel way has yielded favorable results in a phase II trial of patients with advanced esophageal cancer, prompting the company developing the drug to plan a phase III trial.

ASCO 2010: Opaxio Highly Active in Esophageal Cancer

	Data from the phase III ZETA trial show that vandetanib (Zactima), a selective tyrosine kinase inhibitor, significantly slows the progression of advanced medullary thyroid carcinoma (MTC), a rare disease more diffi cult to treat than common thyroid cancers. In an interview with 

, Peter Langmuir, MD, executive director of medical science with AstraZeneca, which manufactures vandetanib, explained the rationale behind investigating vandetanib in this setting. “These patients can be cured with surgery, but it is ineffective or the disease recurs or they develop metastatic disease. There’s no effective treatment that is available.” Vandetanib inhibits tumor cell growth and migration by selectively targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, all of which are active in MTC.

	In ZETA, 331 people (median age, 50.7 y) with unresectable locally advanced or metastatic MTC were randomized 2:1 to receive vandetanib versus placebo between December 2006 and November 2007, with progression-fr ee survival (PFS) as the primary endpoint. Placebo was used as a comparator because there are no standard treatments for these patients. Patients in the vandetanib arm (n = 231) received 300-mg daily oral doses for a median of 90.1 weeks. At progression, patients in the placebo arm (n = 100) were allowed to cross over to the vandetanib arm, and the median duration on placebo was 39.9 weeks.

	Samuel A. Wells, MD, head of the Thyroid Clinical Research Program at the National Cancer Institute and lead author of the study abstract, presented findings during an oral session. He reported that median PFS was 19.3 months in the placebo arm, but this was not reached in the vandetanib arm at the point of data cutoff . Wells said this was statistically significant (hazard ratio, 0.46; 95% confidence interval, 0.31-0.69) and made vandetanib the first agent to demonstrate efficacy in advanced MTC in a phase III trial.

	Langmuir said PFS was not reached in the vandetanib arm because <50% of patients taking vandetanib (32%) had progressed at the time of cutoff compared with 51% of patients on placebo. Statistical modeling computed a probable median PFS of 30 months for vandetanib, indicating an 11-month advantage for the drug. “We see a similar magnitude of advantages for the secondary endpoints as well,” said Langmuir, noting that the overall response rate reached 45% in the vandetanib arm. “What’s more important is the duration of response,” he added. “What we see with vandetanib is a median duration of response close to 2 years.” Wells said the data on overall survival (OS) are “immature at this point.” Investigators decided not to evaluate OS until at least half the patients had died, and the mortality rate at the July 31, 2009, data cutoff date was only 15%.

	Wells said OS is a very important endpoint, but the fact that one-third of patients responded to vandetanib aft er crossing over fr om placebo could confound the OS outcome.

	Adverse events (AEs) of any grade were more common in the vandetanib arm than the placebo group, with diarrhea (56% vs 26%, respectively), rash (45% vs 11%, respectively), and nausea (33% vs 16%, respectively) as the most frequently reported AEs. These were generally manageable, said Wells. The discontinuation rate was only 12%, aft er a median duration of treatment of 1 year and 9 months.

	Langmuir noted that the prolonged duration of treatment suggests adverse effects were manageable. He said it was interesting that a study of vandetanib in lung cancer also had a 12% rate of discontinuation, but those patients had taken the drug for only 8 to 9 weeks.

	Langmuir said AstraZeneca plans to file for regulatory approval as soon as possible. “We’d like to make this drug available for patients because they don’t have options at this point and hopefully this drug will provide that need.” Abstract 5503.

Data from the phase III ZETA trial show that vandetanib (Zactima), a selective tyrosine kinase inhibitor, significantly slows the progression of advanced medullary thyroid carcinoma

ASCO 2010: Vandetanib Extends PFS in Medullary Thyroid Carcinoma

	In a phase III randomized trial, overall survival (OS) was more than 34% longer for patients with advanced melanoma who received the novel agent ipilimumab (MDX-010) with or without the glycoprotein 100 (gp100) peptide vaccine than for those who received the gp100 vaccine alone. Data for this pivotal trial were presented at ASCO’s Plenary Session.

	“Over the past 30 years, randomized clinical trials have repeatedly failed to demonstrate an improvement in OS in patients with advanced melanoma, which is an extremely difficult disease to treat,” said lead researcher Steven O’Day, MD, chief of research and director, Melanoma Clinic, The Angeles Clinic and Research Institute, Los Angeles, California. “These results are an exciting advance, both for patients with advanced melanoma and for the fi eld of cancer immunology.”

	Ipilimumab, a fully human monoclonal antibody, targets and blocks the cytotoxic T-lymphocyte— associated antigen 4 (CTLA-4) expressed on the surface of immune system T cells. CTLA-4 suppresses the immune system’s response to disease. Inhibiting this antigen with ipilimumab “triggers the T cells to attack the cancer,” O’Day told Oncology & Biotech News, who noted that the drug can be given on an outpatient basis as a 90-minute infusion. The gp100 vaccine is also an experimental treatment, and it is effective only in patients who are positive for the HLA-A0201 antigen. O’Day said investigators used it as a comparator because previous studies have found it to be more eff ective than the approved drug interleukin-2 (IL-2).

	Investigators at 125 centers in 13 countries accrued 676 HLA-A0201—positive patients with previously treated metastatic melanoma for the trial. Patients were randomized 3:1:1 to receive ipilimumab plus gp100 vaccine, ipilimumab alone, or gp100 vaccine alone. Median OS in both ipilimumab arms extended to 10 months compared with 6.4 months in the vaccine-only arm. In addition, patients who received ipilimumab had 1- and 2-year rates of survival that were nearly double those seen in patients treated only with vaccine (Table). O’Day said some ipilimumab-treated patients were still alive at 4.5 years’ follow-up. Combining the gp100 vaccine with ipilimumab appeared to have no eff ect on toxicity or survival.

	Ipilimumab’s side eff ects were generally mild to moderate and primarily immune related. However, severe side eff ects were observed in 10% to 15% of patients in the ipilimumab arms, and treatment-related deaths were also reported (2.1% in one ipilimumab group and 3.1% in the other). Approximately 1.5% of these deaths were immune related. “This is a powerful, immune-stimulating drug,” said O’Day. Other preliminary studies have shown that the adverse effects typically appear soon aft er initiating treatment with ipilimumab. The most common are gastrointestinal and skin reactions; less frequently, patients experience hepatitis, inflammation of the pituitary gland, eye inflammation, and nephritis.

	It has been more than a decade since the FDA approved a new drug for melanoma. “The only approved drugs are DTIC, which is not very effective at all, and high doses of IL-2, which most community doctors don’t give because of the side effects and the need for hospitalization,” O’Day said. “[Ipilimumab] does have some serious side effects that relate to the T cells attacking normal tissues, and there will be some learning curve for community oncologists since managing these is different fr om managing typical chemotherapy side eff ects.” O’Day added that different algorithms have been set up to help manage severe adverse effects. In most cases, the primary treatment is high-dose steroids, which have been found to reduce many of the severe immunosupressory effects.

	“There needs to be good communication between physician and patients about side effects and the need to manage them promptly,” advised O’Day, who said if the drug is approved, guidelines will be developed on how to do this so that the drug can be administered safely in the community setting.

	O’Day said another large, international randomized phase III trial has just fi nished investigating ipilimumab as first-line therapy in melanoma and results are anticipated within 6 to 12 months. “We’re also very interested in starting to study ipilimumab in combination with the Plexxikon BRAF drug [PLX4032], which has a very high rate of breaking the tumor up, somewhere in the order of 70% to 80%,” said O’Day. “There’s a lot of hope and interest in the research community about getting these drugs combined because they may be very synergistic together, but first we have to get both drugs on the market,” he added.

	Session discussant Vernon K. Sondak, MD, of the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, said he shared O’Day’s optimism about the “dramatic” data but that the study invites several questions. “Is the dose the right one? Has ipilimumab been compared with the right control? In light of these data, can we still be hopeful that ipilimumab can be combined with a vaccine to provide potent immunotherapy for patients?” Sondak said additional research should seek to answer these questions.

	This is the first trial to show a survival benefit in metastatic melanoma, and O’Day said he is hopeful that ipilimumab will go through the regulatory process rapidly and become available for patients in 2011. Following the ASCO meeting, the FDA granted priority review for the novel agent, which is manufactured by Bristol-Myers Squibb. Abstract 4.

In a phase III randomized trial, overall survival (OS) was more than 34% longer for patients with advanced melanoma who received the novel agent ipilimumab

July 2010 | Oncology & Biotech News

Mom's Cancer Lands Patrick Dempsey a New Role

ASCO 2010: Opaxio Highly Active in Esophageal Cancer

ASCO 2010: Vandetanib Extends PFS in Medullary Thyroid Carcinoma

ASCO 2010: Novel Therapy First to Extend Survival in Advanced Melanoma