CAPOX Clinical Benefit May Be Superior to Single-Agent Tx in Advanced Pancreatic Ca, German Researchers Report

BAD SODEN, Germany-Inadvanced/inoperable pancreatic cancer,capecitabine (Xeloda) plus oxaliplatin(Eloxatin) (CAPOX) has a clinicalbenefit rate that "seems to besuperior" to single-agent therapy andis better tolerated than other combinationregimens, according to earlyfindings reported by a team of Germanresearchers.In a multicenter phase II trial, theCAPOX regimen had a clinical benefitrate of 56%, and it was associated withless hematologic toxicity vs capecitabine/gemcitabine (Gemzar) (CAPGEM)and gemcitabine/oxaliplatin(GEMOX) (abstract 4108). However,all three treatment arms were "comparablywell tolerated," with a low incidenceof adverse events, accordingto Alexander Golf, MD, an oncologistand researcher in Bad Soden, Germany,who presented interim trial results."We think CAPOX is promising,and it's well tolerated," Dr. Golf said."Our primary objective was the timeto disease progression, which right nowis similar in all three arms."Capecitabine-containing combinationscould have a useful role inthe palliation of inoperable/advancedpancreatic cancer. While currentpalliative treatment for these poorprognosispatients is based on gemcitabineor fluorouracil (5-FU), oralcapecitabine is "at least as effective,better tolerated, and more convenient"vs intravenous 5-FU/leucovorinin first-line treatment of metastaticcolorectal cancer, the investigatorssaid.Protocol and Early FindingsAccrual has been completed in thestudy, with a total of 189 patients recruitedat 44 German centers betweenJune 2002 and May 2004. All patientswere naive to chemoradiotherapy andhad advanced/inoperable stage III/IVpancreatic cancer with an ECOG (EasternCooperative Oncology Group)performance status of 2 or less.Patients were randomized to CAPOX(capecitabine 1,000 mg/m² twicedaily on days 1-14, plus oxaliplatin130 mg/m² on day 1), CAPGEM(capecitabine 825 mg/m² twice dailyon days 1-14, plus gemcitabine 1,000mg/m² on days 1 and 8), or GEMOX(gemcitabine 1,000 mg/m² on days 1and 8, plus oxaliplatin 130 mg/m² onday 8). Cycles were repeated every 3weeks.The interim analysis at ASCO wasbased on 118 patients evaluable forsafety and 113 evaluable for response.Dr. Golf and colleagues said it was tooearly to draw reliable conclusions concerningtime to progression, the primaryendpoint of the trial, although itwas "similar" in the three groups.The clinical benefit rate (responseplus stable disease) was 56% for CAPOX,61% for CAPGEM, and 44% forGEMOX. "It seems that there's a littlebit less response in the GEMOX arm,but we do not have not all the datayet," Dr. Golf said.ToxicitiesThere were apparent differences betweenthe arms in toxicity. Grade 3/4hematologic toxicity was "rare" in theCAPOX arm, investigators said; bycontrast, anemia was more frequentin the CAPGEM arm, and thrombocytopeniawas more common withGEMOX. Gastrointestinal side effects(nausea and vomiting) were more frequentand more severe in the GEMOXarm, while neuropathy was primarilyseen with the oxaliplatin-containingregimens, and grade 3/4 infectionswere most common in the gemcitabine-containing regimens.Overall, however, the rate of clinicaladverse events was "acceptable andgenerally similar" across treatmentarms, said the investigators, who expectto complete the trial shortly.