1. ¹Service of Medical Oncology, La Paz, Paseo de la Castellana 261, Madrid 28046, Spain
2. ²Service of Medical Oncology, Complejo Hospitalario de León, C/ Altos de Nava s/n, León, 24071, Spain
3. ³Service of Medical Oncology, H Arnau de Villanova, Avda. Alcalde Roure 80, Lérida 25006, Spain
4. ⁴Service of Medical Oncology, H Xeral, Doctor Severo Ochoa s/n, Lugo 27004, Spain
5. ⁵Service of Medical Oncology, H Lozano Blesa C/ San Juan Bosco 15, Zaragoza, 50009, Spain
6. ⁶Service of Medical Oncology, Virgen de la Salud, Avda. Barber 35, Toledo 45004, Spain
7. ⁷Service of Medical Oncology, H Punta de Europa, Ctra. De Getares s/n, Algeciras 11207, Spain
8. ⁸Service of Medical Oncology, H Virgen de las Nieves, Avda. Coronel Muñoz, Granada 18012, Spain
9. ⁹Service of Medical Oncology, H Nta. Señora del Prado, Ctra. De Madrid Km 114, Talavera 45600, Spain
10. ¹⁰Service of Medical Oncology, H San Juan, Ctra. Alicante-Valencia s/n, Alicante 03550, Spain

Correspondence: Dr J Feliu, E-mail: jfeliu.hulp@salud.madrid.org

Received 8 August 2005; Revised 7 October 2005; Accepted 10 October 2005; Published online 1 November 2005.

Abstract

The purpose of this phase II randomised trial was to determine which of two schemes, raltitrexed-irinotecan or raltitrexed-oxaliplatin, offered better activity and less toxicity in patients with advanced colorectal cancer (CRC). A total of 94 patients with previously untreated metastatic CRC were included and randomised to receive raltitrexed 3 mg m^-2 followed by oxaliplatin 130 mg m^-2 on day 1 (arm A), or CPT-11 350 mg m^-2 followed by raltitrexed 3 mg m^-2 (arm B). In both arms treatment was repeated every 3 weeks. Intent-to-treat (ITT) analysis showed an overall response rate of 46% (95% CI, 29.5–57.7%) for arm A, and 34% (95% CI, 19.8–48.4%) for arm B. Median time to progression was 8.2 months for arm A and 8.8 months for arm B. After a median follow-up of 14 months, 69% of patients included in arm A were still alive, compared to 59% of those included in arm B. Overall, 31 patients (65%) experienced some episode of toxicity in arm A and 32 patients (70%) in arm B, usually grade 1–2. The most common toxicity was hepatic, with 29 patients (60%) in arm A and 24 patients (62%) in arm B, and was grade 3–4 in four (8%) and four (9%) patients, respectively. In all, 14 patients (29%) from arm A and 24 patients (52%) from arm B had some grade of diarrhoea (P<0.03). Neurologic toxicity was observed in 31 patients (64%) in arm A, and was grade 3–4 in five patients (10%), while a cholinergic syndrome was detected in nine patients (19%) in arm B. There were no differences in haematologic toxicity. One toxic death (2%) occurred in arm A and three (6.5%) in arm B. In conclusion, both schemes have high efficacy as first-line treatment in metastatic CRC and their total toxicity levels are similar. Regimens with raltitrexed seem a reasonable alternative to fluoropyrimidines.