ORLANDO—Compared with the standard first-line chemotherapy treatment for advanced colorectal cancer, patients treated with the FOLFOX4 regimen containing the investigational agent oxaliplatin(Drug information on oxaliplatin) lived longer and had fewer side effects.

The FOLFOX4 regimen, also known as the de Gramont regimen, combines oxaliplatin with an infusion of fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin given over 2 days, while the standard therapy, the Saltz regimen (or IFL) consists of irinotecan(Drug information on irinotecan) (Camptosar) plus a brief injection of 5-FU/leucovorin. The study also contained a third arm consisting of oxaliplatin and irinotecan (IROX), also known as the Wasserman regimen.

Richard M. Goldberg, MD, professor of oncology, Mayo Clinic, presented the findings from the NCI-sponsored N9741 trial for the North Central Cancer Treatment Group at an oral session of the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 511).

Oxaliplatin Expanded Access Program Based on the interim analysis of N9741, accrual to all arms except FOLFOX4 has been discontinued. Patients already enrolled in one of the other two arms will be offered the option of switching to FOLFOX4. Sanofi-Synthelabo, Paris, the manufacturer of oxaliplatin, has submitted data on the use of oxaliplatin for second-line treatment of colorectal cancer to the US Food and Drug Administration for review. Until the agent is commercially available in the United States, the National Cancer Institute (NCI) is sponsoring an expanded access program known as a Treatment Referral Center (TRC) protocol. Patients and physicians may call the NCI Cancer Information Service at 1-800-4-CANCER for information on eligibility requirements and participating sites or visit the cancer website at http://cancer.gov/clinicaltrials/developments/oxaliplatin.  Sanofi-Synthelabo is also establishing an expanded access program for patients who have already received therapy for colorectal cancer. More information is available from the company at 1-877-435-6928 or at its website located at www.sanofi-synthelabous.com.

Doses for the three study regimens were as follows: IFL: irinotecan 125 mg/m² plus LV 20 mg/m² and 5-FU 500 mg/m²/d on days 1, 8, 15, and 22 every 6 weeks. FOLFOX4: oxaliplatin 85 mg/m² on day 1 plus LV 200 mg/m² and 5-FU 400 mg/m² bolus plus 600 mg/m² as a 22-hour infusion on days 1 and 2 every 2 weeks. IROX: oxaliplatin 85 mg/m² plus irinotecan 200 mg/m² on day 1 every 3 weeks.

After an analysis of deaths within 60 days of study entry, the starting dose of IFL was reduced. The current report, however, is based on patients enrolled before that reduction. The primary endpoint was time to progression.

A total of 795 patients were included in this phase III trial analysis (median age 61). They all had a histologic diagnosis of unresectable advanced colorectal cancer and ECOG performance status 0 to 2 with adequate organ function and life expectancy of 12 weeks or more. Minimum follow-up is 1 year.

Study Results