GEMOX Shows Significant Clinical Benefit vs Gemcitabine in Advanced Pancreatic Cancer

September 1, 2004

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

NEW ORLEANS-In advancedpancreatic cancer, a gemcitabine(Gemzar)/oxaliplatin (Eloxatin) combinationprovided a survival advantageof approximately 2 months overgemcitabine alone, based on increasein median survival vs standard-of-caregemcitabine alone in advanced pancreaticcancer, according to definitiveresults of a phase III randomizedFrench-Italian trial.The gemcitabine/oxaliplatin(GEMOX) combination is the first todemonstrate a statistically significantdifference in clinical benefit responsevs the standard of care, said lead investigatorChristophe Louvet, MD, PhD,of Hpital St-Antoine, Paris, France(abstract 4008). Although the differencein overall survival was not statisticallysignificant, investigators foundthat survival at 8 months-a prespecifiedstudy endpoint-was significantin favor of GEMOX."I would never claim GEMOX isnow the new standard of care," Dr.Louvet told ONI. "We will probablyhave better results with a combinationof chemotherapy and new targeteddrugs...I believe GEMOX in combina-tion with a targeted drug is a good wayto proceed." The phase III trial wasinitiated following promising resultsin a 64-patient phase II trial, in whichGEMOX was well tolerated and produceda 30% response rate, a medianprogression-free survival time of 5.3months, and a median survival time of9.2 months (J Clin Oncol 20:1512-1518,2002).Superior ResponsesIn the phase III trial, researchersrandomized 313 patients to one of tworegimens: gemcitabine given as a 30-minute infusion (1,000 mg/m2 weeklyfor 7 weeks, followed by a 1-week restperiod, then again every 3 of 4 weeks),and fixed-dose-rate gemcitabine plusoxaliplatin (gemcitabine 1,000 mg/m2in a 100-minute infusion, followed bya 2-hour oxaliplatin infusion at 100mg/m2 the next day, every 2 weeks).Both treatments were well tolerated,but there was a significant increasein grade 3/4 (mainly grade 3) thrombocytopeniain the GEMOX arm (14%vs 3.2% for gemcitabine alone). Therewas also a significant increase in vomitingwith GEMOX, and, as investigatorsexpected, increased peripheralneuropathy induced by oxaliplatin.The difference in the overall responserate and clinical benefit responsewere significant in favor ofGEMOX (see Table 1), as was differencein progression-free survival time,favoring GEMOX (median, 5.8months vs 3.7 months, P = .038). Overallsurvival time was 9.0 months forGEMOX, vs 7.1 months for gemcitabine(P = .13). For survival at 8 months,a prespecified analysis point, there wasa significant difference in favor ofGEMOX (56.5% vs 45.3%, P = .048).Overall, 52% of patients onGEMOX had at least one grade 3/4toxicity, compared with 40% in thegemcitabine-alone arm; however,there was no difference in the numberof serious adverse events related totherapy between the two arms, Dr.Louvet said.Second-Line Tx AllowedHedy Lee Kindler, MD, commentingon the results, noted that responseand survival were "better than expected"in both arms. One reason mayhave been the influence of second-linetherapies. Second-line therapies wereallowed in the GEMOX trial; notably,platinum-based therapy was receivedby 32.8% and 71.8% of patients in theGEMOX and gemcitabine arms, respectively."We've never had active agents before,so we have never had to worryabout this," said Dr. Kindler, an assistantprofessor of medicine at theUniversity of Chicago, where she ismedical director, Gastrointestinal Oncology,and director of the MesotheliomaProgram.