Phase ii randomised trial of raltitrexed-oxaliplatin vs raltitrexed- irinotecan as first-line treatment in advanced colorectal cancer

• Published in: British journal of cancer Vol. 93; no. 11; pp. 1230 - 1235
• Main Authors: FELIU, J, CASTANON, C, LIZON, J, CASTRO, J, GONZALEZ-BARON, M, SALUD, A, MEL, J. R, ESCUDERO, P, PELEGRIN, A, LOPEZ-GOMEZ, L, RUIZ, M, GONZALEZ, E, JUAREZ, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 28-11-2005
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Clinical Study; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Infusions, Intravenous; Irinotecan; Male; Medical sciences; Middle Aged; Organoplatinum Compounds - administration & dosage; Oxaliplatin; Quinazolines - administration & dosage; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Analysis; Thiophenes - administration & dosage; Treatment Outcome; Tumors; Antineoplastic agent; Rectal disease; Toxicity; Colorectal cancer; colorectal cancer raltitrexed; Raltitrexed; Randomization; Isomerases; Cancerology; Oxaliplatin; Phase II trial; Intestinal disease; Platinum II Complexes; Enzyme; Transferases; DNA topoisomerase; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; First line treatment; Colonic disease; Irinotecan; Alkylating agent; Methyltransferases; Digestive diseases; Comparative study
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602860

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.