Sequential Use of XELOX and XELIRI May Allow Greater Use of Oxaliplatin in Patients With Metastatic Colorectal Cancer

GUADALAJARA, SPAIN-Sequential cycling of XELOX (capecitabine [Xeloda]/oxaliplatin [Eloxatin]) and XELIRI (capecitabine/irinotecan [Camptosar]) provides good tumor control with a low rate of grade 3 neurosensory toxicity in patients with metastatic colorectal cancer, according to preliminary results of a phase II multicenter trial (abstract 3544). The investigators, who specifically wanted to evaluate the impact of sequential cycling on the dose-limiting neurosensory toxicity associated with oxaliplatin(Drug information on oxaliplatin), reported that "the low rate of grade 3 neurosensory toxicity is promising." Among the 33 enrolled patients, there were six cases each of grade 2 and 3 neurosensory adverse events in the group completing the first sequence of XELOX and eight grade 2 but no grade 3 adverse events in the group completing the first sequence of XELIRI. More common adverse events were anemia, diarrhea, nausea, vomiting, and asthenia (Table 1). Same Capecitabine(Drug information on capecitabine) Dose The XELOX treatment regimen for the ongoing study is oral capecitabine (1,000 mg/m² twice daily on days 1 to 14) with IV oxaliplatin (130 mg/m² on day 1). This is followed by the XELIRI regimen, which consists of the same dose of capecitabine but with 240 mg/m² of IV irinotecan(Drug information on irinotecan) on day 1. Thirty-two patients had completed the first sequence of XELOX, with 13 going on to complete XELIRI. Lead investigator Javier Cassinello, MD, of Hospital General in Guadalajara, Spain, reported that he expected most of those 32 patients will also complete the first cycle of XELIRI. Three patients completed the second sequence of XELOX, with two going on to complete the second sequence of XELIRI. Stop-and-Go Treatment Dr. Cassinello explained that the aim of the study was to test a "stopand- go treatment" with four cycles of XELOX, then stopping treatment and resuming with four cycles of XELIRI. "Then, if you can, restart treatment with oxaliplatin, knowing the neurosensory toxicity is coming down and you can start again with 100% of the oxaliplatin dose." This should allow the patient to receive more first-line treatment with oxaliplatin, which the investigators noted is the only platinum compound with clinical activity against metastatic colorectal cancer. The median age of patients was 69 (range 41-78 years). The Eastern Cooperative Oncology Group (ECOG) status was 0 for 33% of patients and ≥ 1 for 67%. The primary tumor site was the colon for 67% of patients, the rectum for 30%, and both sites for 3% of patients. Most patients (61%) had stage IV disease. Overall Response of 47% The overall response rate, based on intent-to-treat analysis, was 47% (95% confidence interval [CI]: 24.9%- 69.9%). That rate includes one patient with a complete response and eight patients with partial responses. Six patients had stable disease and four patients had progressive disease. Thirteen patients were not evaluable due to adverse events, loss of follow-up, or because treatment was ongoing. The median time to disease progression was 11.9 months (95% CI: 4.4-19.5). The median overall survival had not yet been reached at the time of this report.