XELOX Safe, Effective as First-Line Therapy for Metastatic Colorectal Cancer

CHICAGO-In patients with metastatic colorectal cancer, the combination of oxaliplatin(Drug information on oxaliplatin) (Eloxatin) and capecitabine(Drug information on capecitabine) (Xeloda) (XELOX) compares favorably with oxaliplatin/fluorouracil (5-FU)/leucovorin (LV) regimens (eg, FOLFOX) as first-line therapy, according to a presentation at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 1023). XELOX offers the advantage of improved convenience. Oral capecitabine generates 5-FU preferentially in tumors. Because of its superior activity and improved safety, oral capecitabine has been replacing intravenous 5-FU/LV monotherapy in first-line metastatic colorectal cancer, noted Eric Van Cutsem, MD, PhD, University Hospital, Leuven, Belgium. Also, adding oxaliplatin to infused 5-FU/LV improves efficacy. Oxaliplatin and capecitabine have different mechanisms of action and have safety profiles that do not overlap. Furthermore, capecitabine requires only one clinic visit every 3 weeks. Therefore, substituting capecit- abine for 5-FU/LV should provide effective, safe, and convenient treatment, Prof. Van Cutsem said. To evaluate XELOX, the investigators enrolled 96 patients in an international phase II trial to receive intravenous oxaliplatin 130 mg/m² on day 1, followed by oral capecitabine 1,000 mg/m² twice daily (evening of day 1 through the morning of day 15) every 3 weeks. The patients (64% men, median age 64) had measurable metastatic colorectal cancer, Karnofsky performance status (KPS) greater than 70, life expectancy of 3 months or more, no prior chemotherapy with oxaliplatin, capecitabine, or irinotecan(Drug information on irinotecan) (Camptosar) in the metastatic setting, and no prior adjuvant therapy within 6 months of enrollment. Primary tumors were in the colon in 63% and in the rectum in 33% (4% both). More than half of the patients (54%) had more than one metastatic site (77% liver, 32% lung). Median number of cycles of therapy was nine (range 1 to 46), with 30% of patients continuing capecitabine monotherapy (median, two cycles) after oxaliplatin was stopped. Study Results
After a minimum follow-up of 24 months, the overall response rate was 55% (independent review assessment 45%). Median progression-free survival was 7.7 months, and median overall survival was 19.5 months, with 1-year survival of 71%. Subgroup evaluation (liver or lung metastases, prior adjuvant chemotherapy, KPS of 80 vs more than 80, age less than 60 vs 60 or more) revealed response rates (by investigator) consistently greater than 50%. Prof. Van Cutsem pointed out that the XELOX response rates compared favorably with those of other current 5-FU/LV (bolus/infusion) plus oxaliplatin regimens (de Gramont 50%, Goldberg 38%), as did progressionfree survival (de Gramont 8.2 months, Goldberg 8.8 months) and overall survival (de Gramont 16.2 months, Goldberg 18.6 months). Prof. Van Cutsem noted that 70% of the patients have received poststudy chemotherapy. The most common regimen was irinotecan with or without 5-FU. Sensory neuropathy (85%) and gastrointestinal disturbances (diarrhea 66%, nausea and vomiting 73%) were the most common treatment-related adverse events. Grade 3/4 diarrhea was seen in about 18% of patients, nausea/ vomiting in about 14%, and handoni foot syndrome in 3%. In view of the long duration of treatment, investigators considered it "impressive" that 50% of patients received full-dose capecitabine/oxaliplatin throughout. One death from respiratory failure was attributed to study treatment. This known, rare side effect of oxaliplatin occurred in a patient with pre-existing pulmonary fibrosis. Side effects of XELOX, as compared with the de Gramont and Goldberg regimens, were similar, but with much reduced neutropenia (7% XELOX vs 42% de Gramont/47% Goldberg). Prof. Van Cutsem concluded that as first-line therapy for metastatic colorectal cancer, XELOX offers high efficacy, good tolerability, and substantially improved convenience, compared with regimens combining oxaliplatin with infusional 5-FU. Phase III trials of XELOX vs FOLFOX are further assessing the potential for replacing 5-FU/LV as the backbone of colorectal cancer therapy.