Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer

Background: Irinotecan (CPT-11) and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. Phase I studies have shown that single-agent full doses of both drugs can be safely combined. The aim of this...

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Veröffentlicht in:Annals of oncology 2003-07, Vol.14 (7), p.1121-1125
Hauptverfasser: Aparicio, J., Vicent, J. M., Maestu, I., Garcerá, S., Busquier, I., Bosch, C., Llorca, C., Díaz, R., Fernández-Martos, C., Galán, A.
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Sprache:eng
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Zusammenfassung:Background: Irinotecan (CPT-11) and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. Phase I studies have shown that single-agent full doses of both drugs can be safely combined. The aim of this multicenter study was to assess the efficacy and toxicity of the combination in patients with 5-fluorouracil (5-FU)-refractory ACC. Patients and methods: Between October 1999 and December 2000, 52 patients (31 males, 21 females) with a median age of 62 years (range 39–75) were included and received CPT-11 (350 mg/m2 as a 60-min infusion) plus raltitrexed (3 mg/m2 as a 15-min infusion, 1 h after CPT-11), with courses repeated every 21 days. Objective response was assessed after every three courses, and treatment maintained until tumor progression or unacceptable toxicity. Results: A total of 313 cycles were administered, with a median of six cycles per patient (range 1–14). Seven patients (13.5%) achieved a partial response and one a complete response (1.9%), for an overall intention-to-treat response rate of 15.4% (95% confidence interval 6.1% to 27.2%). The incidence of grade 3/4 toxicity was 23.1% for diarrhea, 21.2% for asthenia, 17.3% for neutropenia, 13.4% for emesis and 7.7% for infection. There were no treatment-related deaths. With a median follow-up of 20 months, median survival was 11.9 months and median time to progression was 4.6 months. Conclusions: CPT-11 plus raltitrexed is active in patients with 5-FU-refractory ACC, at the expense of moderate toxicity.
ISSN:0923-7534
1569-8041
DOI:10.1093/annonc/mdg285