Adding Capecitabine to Gemcitabine Offers No Overall Survival Advantage, Though Could Benefit Some With Advanced Pancreatic Cancer

BASEL, SWITZERLAND- The combination of gemcitabine(Drug information on gemcitabine) (Gemzar)/capecitabine (Xeloda) (GemCap) failed to prolong survival more than gemcitabine (Gem) alone, although the combination was well tolerated and easily administered, Richard Herrmann, MD, of the University Hospital, Basel, Switzerland, reported (abstract LBA4010). The study was supported in part by Hoffmann- LaRoche and Eli Lilly. "Patients with good performance status achieved a significant gain in median survival of 2.6 months, or 35%, when treated with GemCap. Therefore, in patients with advanced cancer of the pancreas and good performance status, GemCap seems to be a good alternative to single-agent treatment," Dr. Herrmann said. A Multi-institutional Study Dr. Herrmann reported on a multiinstitutional study of patients with histologic or cytologic proof of primary inoperable or metastatic adenocarcinoma of the pancreas, a Karnofsky performance score (KPS) ≥ 60%, and no previous chemotherapy. Stratification factors included locally advanced/ metastatic disease, absence/presence of pain, institution, and a KPS of 60- 80 vs 90-100. The primary endpoint was overall survival, and secondary endpoints were quality of life, clinical benefit, objective tumor response (according to RECIST criteria), duration of response, time to disease progression, and toxicity. The investigators hypothesized that the median overall survival would be 5 months with gemcitabine and 7 months for combination gemcitabine/ capecitabine(Drug information on capecitabine). Better Results With Good Performance Status A total of 319 patients were randomized to receive GemCap (n = 160) or Gem (n = 159). The treatment protocol follows: GemCap-gemcitabine (1,000 mg/m² IV on days 1 and 8) and capecitabine (650 mg/m² twice daily on days 1-14 every 3 weeks) or gemcitabine (1,000 mg/m² weekly x 7, then 1 week rest, and then weekly x 3 every 4 weeks). Treatment continued for 6 months or until disease progression. Dr. Herrmann cautioned, "Please note that there are other versions of this regimen using higher doses of capecitabine and different schedules." Three hundred patients were evaluable for response (148 on GemCap, and 152 on Gem). The median overall survival was 8.4 months for the GemCap arm and 7.3 months for the Gem group (P = .314). Dr. Herrmann pointed out that survival in the gemcitabine-only group was 2 months longer than expected, rendering the difference between gemcitabine and combined gemcitabine/capecitabine insignifi- cant (Table 1). The confirmed response rate was 10.1% for GemCap vs 7.9% for Gem. The median duration of response was 7.4 months for GemCap vs 5.9 months for Gem, and the median time to disease progression was 4.8 months for GemCap vs 4.0 months for Gem. A multivariate Cox regression of overall survival showed that in patients with a KPS ≥ 90, those treated with GemCap had a significantly longer median overall survival of 10.1 months vs 7.5 months for Gem (P = .024). "Overall, GemCap does not improve overall survival as compared to the present standard gemcitabine. However (as indicated by subgroup analysis), in patients with a good performance status, a significant improvement in median overall survival of 2.6 months can be achieved," Dr. Herrmann said. In discussing this trial Eileen O"Reilly, MD (Memorial Sloan-Kettering Cancer Center, New York) said, "For now, the control arm of future trials should remain single-agent gemcitabine."