title: Phase II randomised trial of raltitrexed-oxaliplatin vs raltitrexed-irinotecan as first-line treatment in advanced colorectal cancer.
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.
authors.affiliation: Service of Medical Oncology, La Paz, Paseo de la Castellana 261, Madrid 28046, Spain. jfeliu.hulp@salud.madrid.org
authors.forename: J
authors.initials: J
authors.lastname: Feliu
authors.forename: C
authors.initials: C
authors.lastname: Castañón
authors.forename: A
authors.initials: A
authors.lastname: Salud
authors.forename: J R
authors.initials: JR
authors.lastname: Mel
authors.forename: P
authors.initials: P
authors.lastname: Escudero
authors.forename: A
authors.initials: A
authors.lastname: Pelegrín
authors.forename: L
authors.initials: L
authors.lastname: López-Gómez
authors.forename: M
authors.initials: M
authors.lastname: Ruiz
authors.forename: E
authors.initials: E
authors.lastname: González
authors.forename: F
authors.initials: F
authors.lastname: Juárez
authors.forename: J
authors.initials: J
authors.lastname: Lizón
authors.forename: J
authors.initials: J
authors.lastname: Castro
authors.forename: M
authors.initials: M
authors.lastname: González-Barón
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; D000077146:Irinotecan; C068874:raltitrexed; D002166:Camptothecin