GRONINGEN, The Netherlands- Oxaliplatin(Drug information on oxaliplatin) (Eloxatin) added to a standard bolus fluorouracil(Drug information on fluorouracil)/folinic acid (5-FU/FA) regimen apparently increases response and progressionfree survival time in patients with metastatic colorectal cancer (abstract 3539), according to data presented at the 2004 Annual Meeting of the American Society of Clinical Oncology. The oxaliplatin-containing combination was associated with less grade 3-4 diarrhea and mucositis vs 5-FU/ FA in the randomized, phase III trial. Median overall survival time was approximately 14 months in patients treated with standard therapy or with the regimen containing oxaliplatin. "Despite a low treatment cross-over rate, overall survival in both groups was comparable," according to the Dutch Oxaliplatin Study Group. Reporting on behalf of the group were Geke Hospers, MD, PhD, University Hospital Groningen, and Michael Schaapveld, MD, Comprehensive Cancer Center North Netherlands, Groningen, Netherlands. Compared to Standard Tx The study included 302 patients with metastatic colorectal cancer enrolled between July 1999 and August 2002. As first-line treatment, patients received either:

• standard bolus administration of 5-FU 425 mg/m² on days 1 to 5, and FA 20 mg/m² on days 1 to 5 q4 wk; or
• oxaliplatin 85 mg/m² as a 2-hour infusion, FA 200 mg/m² as a 1-hour infusion, and 5-FU 2,600 mg/m² as a 24-hour infusion on day 1 q2wk.

Courses were continued until disease progression. The median number of courses received was six for 5-FU/ FA and eight for oxaliplatin/5-FU/FA. The median age of patients in the Dutch study was 63 years (range, 28- 80 years) and about 60% were male. Close to 95% of patients had a World Health Organization (WHO) performance score of 0 to 1. The primary site of disease was the colon in 75% of patients and the rectum in about 25%. About 10% of patients had previous adjuvant treatment. Data presented at ASCO represented a median follow-up of 13.2 months, with 18% of patients still alive. Response was confirmed in 31.2% of pa- tients on oxaliplatin/5-FU/FA, but in only 18.6% of the standard therapy arm. Overall survival time was 13.8 months in both arms, according to Dr. Hospers and Dr. Schaapveld. Progression- free survival time was longer in the oxaliplatin/5-FU/FA arm (6.7 months vs 5.6 months, P < .01). Rates of stable disease were 39.1% and 45%, respectively (see Table 1). Grade 3-4 Toxicities Differ Stomatitis/diarrhea was much more common in the standard 5-FU/FA arm, 22 cases vs 6 cases in the oxaliplatin/ 5-FU/FA arm (P < .001). There was a low (less than 10%) incidence of grade 3-4 vomiting and hematologic toxicity in both groups. Grade 3/4 sensory neuropathy, related to oxaliplatin, was seen in 10% of patients in the oxaliplatin/5-FU/FA arm. There was one toxic death, from septicemia, in the standard 5-FU/FA arm. "Immunologic side effects deserve attention," the investigators noted. In the oxaliplatin arm, 5% had grade 3-4 immunologic events; two cases were classical anaphylaxis and five were atypical, with thrombocytopenia, hemolysis, pulmonary and renal dysfunction, and the one toxic death. Second-line treatment was not specified in the study protocol, but about 14% of patients on standard therapy crossed over to treatment with oxaliplatin. Overall, about 60% of patients in either arm went on to receive second-line treatment.