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

BAD SODEN, Germany-In advanced/inoperable pancreatic cancer, capecitabine(Drug information on capecitabine) (Xeloda) plus oxaliplatin(Drug information on oxaliplatin) (Eloxatin) (CAPOX) has a clinical benefit rate that "seems to be superior" to single-agent therapy and is better tolerated than other combination regimens, according to early findings reported by a team of German researchers. In a multicenter phase II trial, the CAPOX regimen had a clinical benefit rate of 56%, and it was associated with less hematologic toxicity vs capecitabine/ gemcitabine(Drug information on gemcitabine) (Gemzar) (CAPGEM) and gemcitabine/oxaliplatin (GEMOX) (abstract 4108). However, all three treatment arms were "comparably well tolerated," with a low incidence of adverse events, according to Alexander Golf, MD, an oncologist and 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 time to disease progression, which right now is similar in all three arms." Capecitabine-containing combinations could have a useful role in the palliation of inoperable/advanced pancreatic cancer. While current palliative treatment for these poorprognosis patients is based on gemcitabine or fluorouracil(Drug information on fluorouracil) (5-FU), oral capecitabine is "at least as effective, better tolerated, and more convenient" vs intravenous 5-FU/leucovorin in first-line treatment of metastatic colorectal cancer, the investigators said. Protocol and Early Findings Accrual has been completed in the study, with a total of 189 patients recruited at 44 German centers between June 2002 and May 2004. All patients were naive to chemoradiotherapy and had advanced/inoperable stage III/IV pancreatic cancer with an ECOG (Eastern Cooperative Oncology Group) performance status of 2 or less. Patients were randomized to CAPOX (capecitabine 1,000 mg/m² twice daily on days 1-14, plus oxaliplatin 130 mg/m² on day 1), CAPGEM (capecitabine 825 mg/m² twice daily on days 1-14, plus gemcitabine 1,000 mg/m² on days 1 and 8), or GEMOX (gemcitabine 1,000 mg/m² on days 1 and 8, plus oxaliplatin 130 mg/m² on day 8). Cycles were repeated every 3 weeks. The interim analysis at ASCO was based on 118 patients evaluable for safety and 113 evaluable for response. Dr. Golf and colleagues said it was too early to draw reliable conclusions concerning time to progression, the primary endpoint of the trial, although it was "similar" in the three groups. The clinical benefit rate (response plus stable disease) was 56% for CAPOX, 61% for CAPGEM, and 44% for GEMOX. "It seems that there's a little bit less response in the GEMOX arm, but we do not have not all the data yet," Dr. Golf said. Toxicities There were apparent differences between the arms in toxicity. Grade 3/4 hematologic toxicity was "rare" in the CAPOX arm, investigators said; by contrast, anemia was more frequent in the CAPGEM arm, and thrombocytopenia was more common with GEMOX. Gastrointestinal side effects (nausea and vomiting) were more frequent and more severe in the GEMOX arm, while neuropathy was primarily seen with the oxaliplatin-containing regimens, and grade 3/4 infections were most common in the gemcitabine- containing regimens. Overall, however, the rate of clinical adverse events was "acceptable and generally similar" across treatment arms, said the investigators, who expect to complete the trial shortly.