Capecitabine Shows Substantial Activity and Comparable Efficacy When Combined With Either Irinotecan or Oxaliplatin

CHICAGO-In a randomizedphase II trial studying patients withadvanced colorectal cancer, capecitabine(Xeloda) combined with irinotecan(CPT-11, Camptosar), or with oxaliplatin(Eloxatin) showed substantial activity asfirst-line therapy. Both protocols exhibitedgood efficacy and had similar overalltoxicity profiles.Axel Grothey, MD, senior attendingoncologist, Martin-Luther-Universitt,Halle-Wittenberg, Germany, presentedthe results (ASCO abstract 1022) at the39th Annual Meeting of the American Societyof Clinical Oncology (ASCO). Thisspecial supplement to Oncology News Internationalalso includes reports frommore than 30 other presentations fromthe ASCO 2003 meeting.Previous studies have shown thatcapecitabine has comparable efficacy tobolus fluorouracil (5-FU)/leucovorin inpatients with advanced colorectal cancer.The phase II trial reported by Dr. Grotheycompared the activity of the combinationof capecitabine with irinotecan (CapIri)vs the combination of capecitabine withoxaliplatin (CapOx) as first-line therapy.No Previous Therapy forMetastatic DiseaseThe trial randomized 161 patients, with159 patients evaluable for safety and 144patients evaluable for efficacy (see Table1). Eligible patients had proven colorectalcancer with either inoperable and/or metastaticdisease, with no previous therapyfor metastatic disease and no adjuvanttherapy within 6 months prior to the study.The age range was 18 to 75 years.Patients in the CapIri arm receivedcapecitabine 1,000 mg/m² bid on days 1 to14, and irinotecan 100 mg/m²-subsequentlyreduced to 80 mg/m²-on days 1and 8, followed by rest until day 22. Patientsin the CapOx arm also receivedcapecitabine 1,000 mg/m² bid on days 1 to14, with oxaliplatin 70 mg/m² on days 1and 8, followed by rest until day 22.

The trial results indicate good efficacywith both protocols. Patients receivingCapIri demonstrated a response rate of42.6%, and those receiving CapOx exhibiteda response rate of 51.3%. In bothtreatment arms, just under 40% of patientsexperienced stable disease (39.7%with CapIri and 39.5% with CapOx), andprogression-free survival was identical at7.9 months. In addition, efficacy data arebeing collected for CapIri and CapOx assecond-line therapy after cross-over.Toxicity Profiles SimilarToxicity profiles are similar in the twotreatment arms with the exception of anunexpectedly high rate of early toxic deathsin the CapIri group. The incidence ofgrade 3/4 toxicities, according to NationalCancer Institute Common Toxicity Criteria,was equal in both arms.Four of the first 40 patients in theCapIri arm died within the first 60 daysafter the onset of therapy, one due toseptic diarrhea and neutropenia, two dueto pulmonary embolism, and one of unknowncauses. As a result of the early toxicdeaths in the CapIri group, the irinotecandose was reduced from 100 mg/m² IV ondays 1 and 8, to 80 mg/m² on days 1 and 8in the second phase of the trial. Subsequentearly deaths were reduced to 1 in 39patients.Dr. Grothey noted that the dose reductiondid not compromise the efficacyof the CapIri treatment. "The responserate at the higher dose was 41.7% vs 43.8%at the reduced dose," he said.Ongoing Phase III TrialDr. Grothey indicated that this phaseII trial has served as the basis for an ongoingphase III German trial comparing infusionalfluorouracil and leucovorin plusoxaliplatin (FUFOX) with CapOx as afirst-line therapy for advanced colorectalcancer. Patients in the FUFOX arm receive5-FU 2,000 mg/m² and leucovorin500 mg/m² plus oxaliplatin 50 mg/m²weekly x 4 every 5 weeks. Patients in theCapOx arm receive capecitabine1,000 mg/m² bid for days 1 to 14 plusoxaliplatin 70 mg/m² on day 1 and 8, every3 weeks.