Experimental Regimens Fail to Boost Pancreatic Survival

ATLANTA—A study comparing two experimental regimens with standard 30-minute gemcitabine (Gemzar) infusions for advanced pancreatic cancer found temporary improvements in tumor response, but no survival benefit, according to the ECOG 6201 trial, which was presented at the 42nd Annual Meeting of the American Society of Oncology (abstract LBA4004).

Smaller prior studies suggested that a fixed-dose gemcitabine regimen or adding oxaliplatin (Eloxatin) to standard gemcitabine improved survival substantially. "We sought to determine which of these was really the best," stated Elizabeth Poplin, MD, associate professor of Medicine at the Cancer Institute of New Jersey, New Brunswick. She noted that median survival with standard gemcitabine in advanced pancreatic cancer is 5.7 months, with 1-year survival of 18%.

The Protocol

In the ECOG 6201 trial, patients were randomized to one of three treatment arms: standard gemcitabine (GEM) infusion (1,000 mg/m² for 30 minutes, once weekly for 7 of the first 8 weeks, followed by the same infusion once weekly for 3 of the next 4 weeks); fixed-dose rate (FDR) gemcitabine (1,500 mg/m² for 150 minutes, once weekly for 3 out of every 4 weeks); or gemcitabine/oxaliplatin (GEMOX) (gemcitabine, 1,000 mg/m² for 30 minutes, once weekly, followed on the next day by oxaliplatin, 100 mg/m², with the cycle repeated every 14 days).

The 832 patients (mean age, about 62 years) had locally advanced or metastatic pancreatic adenocarcinoma. Prior adjuvant chemotherapy/radiotherapy was permitted, but not prior oxaliplatin or gemcitabine.

Response Rates

At the 8-week evaluation, 10% of the patients in the FDR group had a partial or complete tumor response, as did 9% of those on GEMOX. This compared favorably with 5% of those in the standard gemcitabine group, Dr. Poplin said. These positive short-term changes, however, did not translate into a significant survival benefit.

Dr. Poplin reported that by study end at 1 year, 87% of the patients had died, and none of the regimens had been more effective than the others in slowing the disease.

Median survival for the GEM group was 4.9 months, with 17% still alive at the 1-year mark. For the FDR group, the median survival was slightly increased to 6 months, and the 1-year survival was 21%. For the GEMOX patients, median survival was 5.9 months, with a 1-year survival of 21%.

"The experimental arms track very closely or overlap GEM for the first 4 to 5 months, and again at 18 to 20 months. Neither experimental treatment succeeded in achieving the hazard ratio goal of 0.75 or less, or the required

P value of .025. Neither arm meets the threshold of statistical significance," Dr. Poplin commented.

Furthermore, the modest gains in temporary tumor control were won at a cost in adverse effects, she said. Both experimental treatments had a heavier side effect burden than standard gemcitabine therapy. FDR induced more neutropenia, thrombocytopenia, and anemia, while GEMOX increased nausea, vomiting, and neuropathy.

Dr. Poplin pointed out that the extent of cancer at baseline influenced survival. Those patients with locally advanced disease had a mean survival of 9.1 months, compared with 5.4 months for those who had metastatic disease (P = .0001). However, differences between the various treatment groups were nonsignificant, she said.