ASCOThe addition of irinotecan(Drug information on irinotecan), also known as CPT-11 (Camptosar), to standard first-line therapy significantly increased progression-free survival and antitumor response in patients with metastatic colorectal cancer, according to the preliminary results of a randomized, open-label phase III trial presented at the 35th Annual Meeting of the American Society of Clinical Oncology (ASCO). Irinotecan is currently FDA approved for second-line treatment of metastatic colorectal cancer.
At 6 months after the start of treatment, combination therapy with irino-tecan prevented tumor growth in 52% of patients treated, compared with 35% of those given standard therapy aloneie, fluorouracil(Drug information on fluorouracil) (5-FU) and leucovorinreported Leonard B. Saltz, MD, of the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center.
Median progression-free survival was 6.9 months in the triple-therapy arm vs 4.4 months for standard therapy (P = .001) and 4.2 months for irinotecan alone. Adding irinotecan to standard therapy also significantly increased the overall response rate: 51% vs 29%.
The 667 eligible study patients were randomized to one of three regimens: (1) irinotecan, 125 mg/m² weekly for 4 weeks followed by a 2-week rest, each irinotecan dose to be followed by leucovorin, 20 mg/m², and 5-FU, 500 mg/m² IV bolus, all drugs given weekly for 4 weeks on, 2 weeks off; (2) the standard Mayo Clinic regimen of leucovorin, 20 mg/m², and 5-FU, 425 mg/m², given daily for 5 days repeated every 4 weeks; or (3) irinotecan, 125 mg/m², given weekly for 4 weeks, repeated every 6 weeks.
Overall survival was not significantly different between the two key arms in the trial14.4 months for the irinotecan-containing combination and 12.6 months for the Mayo Clinic regimen at a median follow-up of approximately 12 months. Dr. Saltz pointed out, however, that a possible survival trend in favor of the irinotecan combination appeared at 18 months.
Toxicities in the triple-agent arm were predictable and manageable, occurring with a similar frequency and severity as with standard therapy. Furthermore, irinotecan had no detrimental impact on quality of life.
This CPT-11/5-FU/leucovorin bolus regimen can be considered a new standard treatment option for the first-line therapy of patients with metastatic colorectal cancer, Dr. Saltz commented. Evaluation of this combination regimen as adjuvant therapy for stage III colon cancer is now under way.
Preliminary results of an international phase III study presented at ASCO corroborated the results of the US trial. In the 387-patient trial, reported by Jean-Yves Douillard, MD, PhD, of Centre René-Gauducheau, Nantes, France, progression-free survival was 8.2 vs 4.3 months, and tumor response rates were 39% vs 22% in the triple combination (irinotecan, 5-FU, folinic acid) and standard therapy arms, respectively.
Median survival was 14 months in the 5-FU/leucovorin arm vs 17 months in the irinotecan combination arma clear survival benefit, Dr. Douillard said.