Oxaliplatin/Gemcitabine Effective in Advanced Pancreatic Cancer

NEW ORLEANS-Compared with gemcitabine(Drug information on gemcitabine) (Gemzar) alone, the combination of oxaliplatin(Drug information on oxaliplatin) (Eloxatin) and gemcitabine improves both response rates and progressionfree survival in patients with nonresectable or metastatic pancreatic cancer, according to Christophe Louvet, MD, of the Hôpital Saint-Antoine, Paris. Dr. Louvet presented the final results of a phase III trial at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 4008). Pancreatic cancer has the lowest 5-year survival rate of all cancers, between 1% and 4%. There are currently few options for patients with advanced disease, with most chemotherapy treatments showing only modest tumor shrinkage. A phase II trial of combined gemcitabine/oxaliplatin had shown clinical benefit in 40% of patients, with acceptable toxicity (Louvet et al: J Clin Oncol 20:1512-1518, 2002), and accordingly prompted evaluation in a phase III trial. The multicenter trial randomized 313 patients either to gemcitabine (given as a 1,000 mg/m² weekly infusion for 7 weeks and, after a 1-week break, for 3 of the following 4 weeks) or to gemcitabine given at the same dosage on day 1, followed the next day by an infusion of oxaliplatin (100 mg/m²), with this combination then repeated at 2-week intervals. Patients were stratified as to performance status, treatment center, and type of disease (locally advanced vs metastatic). Study Results Overall response rate was 26.8% in the combined arm, compared with 17.3% in the gemcitabine-alone arm (P = .044). Significant improvements were also seen in overall clinical benefit (38.2% vs 26.9%; P = .03) and progression- free survival (median 5.8 months vs 3.7 months; P = .0038). Overall survival showed a trend in favor of the combination treatment, with a median of 9 months vs 7.1 months in the gemcitabine-alone arm, corresponding to a 27% increase, but this result did not reach statistical significance (P = .13). Both of these figures were superior to those that had been projected at the beginning of the study (8 and 6 months, respectively). Dr. Louvet pointed out that some blurring of the difference between treatments may have resulted from the second-line therapies to which patients in both arms had subsequent access, including platinum-based therapies. Toxicities Compared with gemcitabine alone, the combined treatment showed a significant increase in several grade 3-4 toxicities, including thrombocytopenia, vomiting, and neurological symptoms, but overall these were manageable and considered acceptable, he said. Further studies are underway to assess the relative contributions of gemcitabine and oxaliplatin in the combined regimen. Dr. Louvet said that new approaches, including targeted drugs such as inhibitors of EGFR and VEGF, are projected as further enhancements of the gemcitabine/oxaliplatin combination.