ASCOThe addition of 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 (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
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.