Oxaliplatin/Gemcitabine Effective in Advanced Pancreatic Cancer

March 2, 2005

This special “annual highlights” supplement to Oncology News International (ONI)is a compilation of selected news on important advances in the management ofgastrointestinal cancers over the past year, as reported in ONI. Guest Editor, Dr.James L. Abbruzzese, comments on the reports included herein and discussesdevelopments in the clinical management of GI cancers, with a look at the impactof targeted agents with cytotoxic chemotherapy, first-line and adjuvant therapies foradvanced disease, and the role of statins and COX-2 inhibitors in prevention.

NEW ORLEANS-Comparedwith gemcitabine (Gemzar)alone, the combination of oxaliplatin(Eloxatin) and gemcitabine improvesboth response rates and progressionfreesurvival in patients with nonresectableor metastatic pancreatic cancer,according to Christophe Louvet,MD, of the Hpital Saint-Antoine,Paris. Dr. Louvet presented the finalresults of a phase III trial at the 40thAnnual Meeting of the American Societyof Clinical Oncology (abstract4008).Pancreatic cancer has the lowest5-year survival rate of all cancers, between1% and 4%. There are currentlyfew options for patients with advanceddisease, with most chemotherapy treatmentsshowing only modest tumorshrinkage. A phase II trial of combinedgemcitabine/oxaliplatin hadshown clinical benefit in 40% of patients,with acceptable toxicity (Louvetet al: J Clin Oncol 20:1512-1518,2002), and accordingly prompted evaluationin a phase III trial.The multicenter trial randomized313 patients either to gemcitabine (givenas a 1,000 mg/m2 weekly infusionfor 7 weeks and, after a 1-week break,for 3 of the following 4 weeks) or togemcitabine given at the same dosageon day 1, followed the next day by aninfusion of oxaliplatin (100 mg/m2),with this combination then repeatedat 2-week intervals. Patients were stratifiedas to performance status, treatmentcenter, and type of disease (locallyadvanced vs metastatic).Study ResultsOverall response rate was 26.8% inthe combined arm, compared with17.3% in the gemcitabine-alone arm(P = .044). Significant improvementswere also seen in overall clinical benefit(38.2% vs 26.9%; P = .03) and progression-free survival (median 5.8months vs 3.7 months; P = .0038).Overall survival showed a trend in favorof the combination treatment, witha median of 9 months vs 7.1 months inthe gemcitabine-alone arm, corresponding to a 27% increase, but thisresult did not reach statistical significance(P = .13). Both of these figureswere superior to those that had beenprojected at the beginning of the study(8 and 6 months, respectively).Dr. Louvet pointed out that someblurring of the difference betweentreatments may have resulted fromthe second-line therapies to which patientsin both arms had subsequentaccess, including platinum-based therapies.ToxicitiesCompared with gemcitabine alone,the combined treatment showed a significantincrease in several grade 3-4toxicities, including thrombocytopenia,vomiting, and neurological symptoms,but overall these were manageableand considered acceptable, hesaid.Further studies are underway toassess the relative contributions ofgemcitabine and oxaliplatin in thecombined regimen. Dr. Louvet saidthat new approaches, including targeteddrugs such as inhibitors of EGFRand VEGF, are projected as furtherenhancements of the gemcitabine/oxaliplatincombination.