CHICAGO-In a randomized phase II trial studying patients with advanced colorectal cancer, capecitabine(Drug information on capecitabine) (Xeloda) combined with irinotecan(Drug information on irinotecan) (CPT-11, Camptosar), or with oxaliplatin(Drug information on oxaliplatin) (Eloxatin) showed substantial activity as first-line therapy. Both protocols exhibited good efficacy and had similar overall toxicity profiles. Axel Grothey, MD, senior attending oncologist, Martin-Luther-Universität, Halle-Wittenberg, Germany, presented the results (ASCO abstract 1022) at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO). This special supplement to Oncology News International also includes reports from more than 30 other presentations from the ASCO 2003 meeting. Previous studies have shown that capecitabine has comparable efficacy to bolus fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin in patients with advanced colorectal cancer. The phase II trial reported by Dr. Grothey compared the activity of the combination of capecitabine with irinotecan (CapIri) vs the combination of capecitabine with oxaliplatin (CapOx) as first-line therapy. No Previous Therapy for Metastatic Disease The trial randomized 161 patients, with 159 patients evaluable for safety and 144 patients evaluable for efficacy (see Table 1). Eligible patients had proven colorectal cancer with either inoperable and/or metastatic disease, with no previous therapy for metastatic disease and no adjuvant therapy within 6 months prior to the study. The age range was 18 to 75 years. Patients in the CapIri arm received capecitabine 1,000 mg/m2 bid on days 1 to 14, and irinotecan 100 mg/m2-subsequently reduced to 80 mg/m2-on days 1 and 8, followed by rest until day 22. Patients in the CapOx arm also received capecitabine 1,000 mg/m2 bid on days 1 to 14, with oxaliplatin 70 mg/m2 on days 1 and 8, followed by rest until day 22. The trial results indicate good efficacy with both protocols. Patients receiving CapIri demonstrated a response rate of 42.6%, and those receiving CapOx exhibited a response rate of 51.3%. In both treatment arms, just under 40% of patients experienced stable disease (39.7% with CapIri and 39.5% with CapOx), and progression-free survival was identical at 7.9 months. In addition, efficacy data are being collected for CapIri and CapOx as second-line therapy after cross-over. Toxicity Profiles Similar Toxicity profiles are similar in the two treatment arms with the exception of an unexpectedly high rate of early toxic deaths in the CapIri group. The incidence of grade 3/4 toxicities, according to National Cancer Institute Common Toxicity Criteria, was equal in both arms. Four of the first 40 patients in the CapIri arm died within the first 60 days after the onset of therapy, one due to septic diarrhea and neutropenia, two due to pulmonary embolism, and one of unknown causes. As a result of the early toxic deaths in the CapIri group, the irinotecan dose was reduced from 100 mg/m2 IV on days 1 and 8, to 80 mg/m2 on days 1 and 8 in the second phase of the trial. Subsequent early deaths were reduced to 1 in 39 patients. Dr. Grothey noted that the dose reduction did not compromise the efficacy of the CapIri treatment. "The response rate at the higher dose was 41.7% vs 43.8% at the reduced dose," he said. Ongoing Phase III Trial Dr. Grothey indicated that this phase II trial has served as the basis for an ongoing phase III German trial comparing infusional fluorouracil and leucovorin plus oxaliplatin (FUFOX) with CapOx as a first-line therapy for advanced colorectal cancer. Patients in the FUFOX arm receive 5-FU 2,000 mg/m2 and leucovorin 500 mg/m2 plus oxaliplatin 50 mg/m2 weekly x 4 every 5 weeks. Patients in the CapOx arm receive capecitabine 1,000 mg/m2 bid for days 1 to 14 plus oxaliplatin 70 mg/m2 on day 1 and 8, every 3 weeks.