Gemcitabine as adjuvant chemotherapy following complete resection for pancreatic cancer did not improve overall survival when compared with standard chemotherapy with fluorouracil plus folinic acid in a randomized, controlled, open-label phase III trial, according to a report in the Sept. 8 issue of JAMA.
In what they described as “the largest ever adjuvant trial conducted in pancreatic cancer,” median overall survival and median progression-free survival were essentially the same between the two chemotherapies, said Dr. John P. Neoptolemos of the University of Liverpool (England) and his associates.
These findings do not confirm the results of a much smaller study involving patients with nonresected advanced pancreatic cancer, in which gemcitabine (Gemzar) conferred a survival benefit compared with fluorouracil.
The 1,088 patients in the European Study Group for Pancreatic Cancer–3 (ESPAC-3) trial were treated at 159 centers in 17 countries after undergoing complete macroscopic resection for ductal adenocarcinoma of the pancreas. The study subjects had a life expectancy of at least 3 months and showed no evidence of malignant ascites, peritoneal metastasis, or spread to the liver or other abdominal or extra-abdominal organs.
A total of 551 patients were randomly assigned to receive 6 months of standard fluorouracil plus folinic acid and 537 to receive 6 months of gemcitabine in the open-label trial. Patients were followed for a median of 2 years.
At the time of data analysis, 753 (69%) of the study subjects had died. Median survival was 23 months for the fluorouracil group and 23.6 months for the gemcitabine group, a nonsignificant difference.
Interim survival estimates for the fluorouracil group were 79% at 12 months and 48% at 24 months. Comparable estimates for the gemcitabine group were 80% at 12 months and 49% at 24 months, again a nonsignificant difference.
Similarly, median progression-free survival was 14 months for both study groups. Interim progression-free survival rates for fluorouracil was 56% at 12 months and 31% at 24 months, which was not significantly different from 61% and 30%, respectively, with gemcitabine, Dr. Neoptolemos and his colleagues said (JAMA 2010;304:1073-81).
About twice as many patients receiving fluorouracil (14%) as those receiving gemcitabine (7.5%) reported serious adverse effects related to their treatment. Patients in the fluorouracil group reported significantly more stomatitis and diarrhea, while those in the gemcitabine group reported more hematologic toxicity.
Quality of life scores were similar between the two groups.
The investigators currently are conducting another study to compare combined gemcitabine plus capecitabine (Xeloda) (a fluoropyrimidine) against gemcitabine alone for pancreatic cancer.
In an editorial, Dr. Eileen M. O’Reilly of Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, said that even though gemcitabine did not prove superior to standard fluorouracil chemotherapy in this study, the findings provide a significant contribution by helping to firmly establish the value of adjuvant chemotherapy alone, rather than chemotherapy plus radiation, for resected pancreatic cancer.
It is now clear, she added, that both gemcitabine and fluorouracil offer a modest but real improvement in overall survival, with about twice as many patients who receive either adjuvant agent surviving for 5 years, compared with those who don’t receive either one.
The study by Neoptolemos et al also demonstrates that for patients unable to tolerate gemcitabine, there is now a clearly validated alternative with fluorouracil, she said (JAMA 2010;304:1124-5).
No financial conflicts of interest were reported by the study authors. This study was supported by Cancer Research UK, National Cancer Institute of Canada, Canadian Cancer Society, Fonds de Recherche de la Societe Nationale Francaise de Gastroenterologie, Fondazioone Italiana Malattie del Pancreas, Health and Medical Research Council of Australia, Cancer Councils of New South Wales, Queensland, Victoria, and South Austalia, and the UK National Institute for Health Research at Royal Marsden Hospital.
Dr. O’Reilly reported receiving research funding from Sanofi-Aventis and consulting fees from Genentech.