Clinical Abstracts From Overseas: May 25, 2010

Norway

Preoperative Chemoradiotherapy Improves Outcomes in Advanced Rectal Cancer

As in many areas of medicine, standards of care sometimes precede the actual evidence proving their value. In order to prove the value of preoperative radiotherapy with preoperative chemotherapy in patients with rectal cancer whose tumors are too large for surgery, Norwegian researchers conducted a phase III study. Do the preoperative treatments help make these tumors resectable or can patients be similarly helped without the additional cytotoxic treatment? The results confirmed that the standard of care, in this case, is on target.

Two hundred seven patients with T4 primary rectal tumors or local recurrent tumors were enrolled in the randomized investigation. In total, 98 patients were assigned to receive 50 Gy of preoperative radiotherapy and preoperative fluorouracil and leucovorin chemotherapy, in addition to 16 weeks of chemotherapy postsurgery, and 109 patients received 50 Gy of radiotherapy alone preoperatively, along with postoperative chemotherapy.

More patients in the combined therapy group underwent an R0 resection than in the radiotherapy group alone (84% vs 68%, respectively). A complete pathologic response was noted by the researchers in 16% of those receiving combined therapy compared with 7% given radiotherapy only. The Table illustrates some of the key outcomes measures.

In terms of side effects, the chemotherapy group experienced significantly more grade 3 or 4 toxicities (29% in the preoperative chemotherapy radiotherapy group vs 6% in the preoperative radiotherapy group).

The investigators concluded that the use of preoperative radiotherapy and concurrent chemotherapy resulted in better efficacy and improved outcomes for patients with initially nonresectable rectal tumors than for patients without preoperative chemotherapy treatment.

Braendengen M, Tveit KM, Berglund A, et al. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer.

2008;26:3687-3694.

J Clin Oncol.

Japan

Does CD55 Expression Have Prognostic Significance in Breast Cancer?

A breast cancer cell line that possesses a relatively high percentage of CD55 gene expression was found in vitro to be resistant to aptosis compared with cells that demonstrated less CD55 expression. Researchers from Osaka University and Kansai Medical University, Japan, sought to determine if tumors with high CD55 expression had worse prognosis in vivo.

Using an immunodeficient mouse model, the researchers injected breast cancer cell lines with low (≤1% of tumor cells) and high expression (>1% of tumor cells) of CD55 genes. They subsequently examined clinical samples from 74 mice with breast cancer.

The scientists noted that of breast cancer tumors sampled, 50 (67%) were revealed to express CD55-high cells. In these samples, tumor volume was greater than in mice with CD55-low expressing cells. They believe that CD55 expression may be directly linked to cells’ ability to organize into tumors (i.e., tumorigenic potential). In studying mice in which the tumors were removed, the investigators also found that the CD55-high tumors were more likely to relapse than the CD55- low tumors (P = .001).

Although these findings need to be confirmed in humans, they believe that CD55 expression, even by small proportions of cells, has an effect on prognosis in breast cancer.

Ikeda J, Morii E, Liu Y, et al. Prognostic significance of CD55 expression in breast cancer.

2008;14:4780-4786.

Clin Cancer Res.

Switzerland

Treating Advanced Pancreatic Cancer with Gemcitabine and Capecitabine

Options are few for patients with metastatic pancreatic cancer, although gemcitabine has been shown to delay disease progression somewhat. Swiss oncologists considered the use of capecitabine in combination with gemcitabine in an attempt to obtain a survival benefit.

In this phase III study, 319 patients were randomized to receive either oral capecitabine 650 mg/m² bid for 14 consecutive days plus infused gemcitabine 1 g/m² on the first and eighth day of a continuing 3-week cycle or infused gemcitabine 1 g/ m² once weekly for seven weeks, then once weekly for three weeks of a cycle lasting four weeks. The latter regimen was continued for a maximum of 24 weeks (or until disease advanced).

Nineteen percent of those receiving the combination and 20% receiving gemcitabine alone experienced a clinical benefit response, according to the physicians. The response lasted for 9.5 weeks in the combined therapy group compared with 6.5 weeks in the monotherapy group (P < .02).

The investigators assessed patient quality of life, finding that patients did not rate their quality of life differently by assigned treatment. However, quality of life ratings improved in both groups of patients for a short time.

They concluded that oral capecitabine added to gemcitabine provided only limited benefit (duration of clinical response) compared with gemcitabine monotherapy.

Bernhard J, Dietrich D, Scheithauer W, et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: A randomized multicenter phase III clinical trial— SAKK 44/00-CECOG/PAN.1.3.001.

2008;26:3695-3701.

J Clin Oncol.

Italy

Prolonged Infusion of Gemcitabine Monotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer

In an effort to improve clinical responses in patients with advanced non—small cell lung cancer, Italian researchers tested a prolonged infusion of gemcitabine 10 mg/m²/min.

This phase II study was not randomized or controlled. Fifty-one patients (median age, 76 yr) with at least stage IIIB disease were eligible for the study. Additionally, only patients who were chemotherapy-naïve were included in the investigation. Patients were given a total dose of 1,200 mg/m² on the first and eighth days of the 21-day cycle. Patients received a maximum of six cycles or until they experienced severe toxicity or disease progression.

The investigators reported two complete responses and seven partial responses (17% total response rate). Median time to disease progression was 16.1 weeks, and overall survival was 41.3 weeks.

Two patients died as a result of treatment toxicity, and one patient experienced a stroke. Fatigue (44%) and hepatic toxicity (grade 2/3, 16%) were the other most common adverse events.

Based on the results of this study, the investigators did not recommend prolonged infusion of gemcitabine monotherapy over the use of other gemcitabine regimens in the treatment of elderly patients with advanced non—small cell lung cancer. They deemed the risk–benefit ratio too high to suggest widespread use, without additional evidence from larger studies.

Gridelli C, De Maio E, Barbera S, et al. The MILES- 2G phase 2 study of single-agent gemcitabine with prolonged constant infusion in advanced non—small cell lung cancer in elderly patients. Lung Cancer. 2008;61:67-72.

Multiple Sites in Asia

Adjuvant Chemoradiotherapy After Radical Gastrectomy and D2 Node Dissection for Adenocarcinoma

In parts of Asia, patients with gastric adenocarcinoma typically undergo D2 node dissection along with gastrectomy, whereas the standard of care in the United States is a radical gastrectomy with adjuvant chemoradiotherapy treatment (using the Intergroup 0116 protocol). Oncologists in Singapore conducted a noncontrolled, nonrandomized experiment to determine if this adjuvant therapy approach had clinical value in patients who underwent gastrectomy and D2- node dissection.

The investigators from Tan Tock Seng Hospital and National University Hospital treated 70 consecutive patients who had at least stage T3 gastric cancer with the Intergroup 0116 protocol (5-fluorouracil 425 mg/m2 and leucovorin 20 mg/m² during four cycles; during cycle 2, 45 Gy of radiotherapy administered over 5 wk).

The three-year overall survival rate was 61%. Disease-free survival for this period was 54%. Local disease control was established in 84% of patients. Thirty patients experienced recurrences, 17% of whom demonstrated local or regional disease.

They noted that toxicities caused by the adjuvant chemoradiotherapy altered therapeutic regimens in 37 patients (53%), with dose reductions in 18 patients and dose delays in 19. However, 94% of the patients completed the entire course of therapy.

Based on these results, the oncologists believe that the use of adjuvant chemoradiotherapy can provide good outcomes, with acceptable toxicity risk, in patients with gastric cancer who undergo D2 node dissections.

Leong CN, Chung HT, Lee KM, et al. Outcomes of adjuvant chemoradiotherapy after a radical gastrectomy and a D2 node dissection for gastric carcinoma. Cancer J. 2008;14:269-275.

England

Does Cancer in Childhood Predispose Women to Breast Cancer After Age 40?

It has been reported that girls with cancer have greater risk of breast cancer 10 to 20 years later. However, women normally experienced substantially increased breast cancer risk after age 40. What happens to the risk of women beyond age 40 who survived childhood cancer? A large English consortium of researchers published the results of their study recently in the International Journal of Cancer.

A registry of more than 8,000 childhood cancer survivors made up the study population, whose clinical status was reviewed beyond age 40. The researchers found that 81 childhood cancer survivors developed a primary breast tumor (37 would be expected to in the general population), yielding a standardized incidence ratio of 2.2. However, the incidence ratios were found to decrease as patients age (P <.001 for trend), to the point that women who do not have breast cancer by 50 years of age are actually less likely to develop it (standardized incidence ratio, 0.9).

This translates into a higher excess absolute risk until 40 years of age, with no further increase. The researchers specify that between the ages of 30 and 49 years, female survivors of childhood cancer experienced approximately one extra case of breast cancer per 1,000 survivors per year. The researchers did not provide evidence that certain childhood cancers predisposed women to breast cancer later in life.

They concluded that girls who survived childhood cancer had substantially increased relative risks of breast cancer until age 50 years, but their excess risk is not significant as they age.

Reulen RC, Taylor AJ, Winter DL, et al. Long-term population-based risks of breast cancer after childhood cancer. Int J Cancer. 2008;123:2156-2163.

Are Physicians Perpetuating Unreasonable Patient Expectations?

How often do clinicians provide clear information about patient prognosis when prescribing palliative treatment for incurable cancer? According to an article published by the BMJ, the answer is “not often enough,” and this has implications for patient consent.

By its very nature, palliative treatment for cancer is focused on relieving symptoms, slowing progression of disease, and/or improving quality of life, but patients are often misled into thinking it is a more active course of management, indicated authors from the University of Bristol, England.

They monitored the office visits of 37 patients and nine oncologists who first discussed palliative therapy for metastatic or locally advanced malignancies of the colon or rectum, lung, or pancreas. The researchers revealed that although the patients were told of the palliative benefits of the medications being prescribed, they did not discuss whether the medications would prolong their survival. During the office visits of eight patients (24%), a survival benefit was not discussed. For 18 patients (49%), the discussion of survival information was ambiguous and the physicians often used verbiage such as the treatment would “buy you some time,” offer “a few months extra.”

The researchers implied that patients do not have enough information regarding whether the therapies would actually prolong life to form a rational basis for informed decision making; yet, they worried that such a discussion would unintentionally strip the patient of any hope.

Audrey S, Abel J, Blazeby JM, et al. What oncologists tell patients about survival benefits of palliative chemotherapy and implications for informed consent: Qualitative study. BMJ. 2008;337:a752.