GEMOX Shows Significant Clinical Benefit vs Gemcitabine in Advanced Pancreatic Cancer

NEW ORLEANS-In advanced pancreatic cancer, a gemcitabine(Drug information on gemcitabine) (Gemzar)/oxaliplatin (Eloxatin) combination provided a survival advantage of approximately 2 months over gemcitabine alone, based on increase in median survival vs standard-of-care gemcitabine alone in advanced pancreatic cancer, according to definitive results of a phase III randomized French-Italian trial. The gemcitabine/oxaliplatin (GEMOX) combination is the first to demonstrate a statistically significant difference in clinical benefit response vs the standard of care, said lead investigator Christophe Louvet, MD, PhD, of Hôpital St-Antoine, Paris, France (abstract 4008). Although the difference in overall survival was not statistically significant, investigators found that survival at 8 months-a prespecified study endpoint-was significant in favor of GEMOX. "I would never claim GEMOX is now the new standard of care," Dr. Louvet told ONI. "We will probably have better results with a combination of chemotherapy and new targeted drugs...I believe GEMOX in combina- tion with a targeted drug is a good way to proceed." The phase III trial was initiated following promising results in a 64-patient phase II trial, in which GEMOX was well tolerated and produced a 30% response rate, a median progression-free survival time of 5.3 months, and a median survival time of 9.2 months (J Clin Oncol 20:1512-1518, 2002). Superior Responses In the phase III trial, researchers randomized 313 patients to one of two regimens: gemcitabine given as a 30- minute infusion (1,000 mg/m² weekly for 7 weeks, followed by a 1-week rest period, then again every 3 of 4 weeks), and fixed-dose-rate gemcitabine plus oxaliplatin(Drug information on oxaliplatin) (gemcitabine 1,000 mg/m² in a 100-minute infusion, followed by a 2-hour oxaliplatin infusion at 100 mg/m² the next day, every 2 weeks). Both treatments were well tolerated, but there was a significant increase in grade 3/4 (mainly grade 3) thrombocytopenia in the GEMOX arm (14% vs 3.2% for gemcitabine alone). There was also a significant increase in vomiting with GEMOX, and, as investigators expected, increased peripheral neuropathy induced by oxaliplatin. The difference in the overall response rate and clinical benefit response were significant in favor of GEMOX (see Table 1), as was difference in progression-free survival time, favoring GEMOX (median, 5.8 months vs 3.7 months, P = .038). Overall survival time was 9.0 months for GEMOX, vs 7.1 months for gemcitabine (P = .13). For survival at 8 months, a prespecified analysis point, there was a significant difference in favor of GEMOX (56.5% vs 45.3%, P = .048). Overall, 52% of patients on GEMOX had at least one grade 3/4 toxicity, compared with 40% in the gemcitabine-alone arm; however, there was no difference in the number of serious adverse events related to therapy between the two arms, Dr. Louvet said. Second-Line Tx Allowed Hedy Lee Kindler, MD, commenting on the results, noted that response and survival were "better than expected" in both arms. One reason may have been the influence of second-line therapies. Second-line therapies were allowed in the GEMOX trial; notably, platinum-based therapy was received by 32.8% and 71.8% of patients in the GEMOX and gemcitabine arms, respectively. "We've never had active agents before, so we have never had to worry about this," said Dr. Kindler, an assistant professor of medicine at the University of Chicago, where she is medical director, Gastrointestinal Oncology, and director of the Mesothelioma Program.