title: Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a phase II study.
abstract: The combination of Oxaliplatin (OXA) and Raltitrexed (RTX) may represent a more convenient regimen as compared with OXA + 5-FU with Folinic acid (FA) modulation regimens. The present trial has been designed to explore the activity and tolerability of this combination in untreated and pretreated patients with advanced colorectal cancer (ACC). OXA and RTX were administered at the dose of 130 mg/m2 as i.v. 3-hour infusion and 3 mg/m2 over a 15-minute i.v. infusion, respectively, repeated every 21 days. Fifty patients were enrolled between February 1999 and March 2001. A total of 293 cycles were administered, with a median number of 6 cycles (range 1-14) per patient. The median dose intensity for OXA and RTX was 100% (50-100) and 86% (21-100), respectively. Reasons for RTX dose reduction were increases in transaminase serum levels and a reduction in creatinine clearance. Myelotoxicity was limited. A transaminase increase was observed in 74% of patients (14% grade 3 and 10% grade 4). Peripheral sensorial neurotoxicity was the most frequent side-effect (88%), although its intensity was mild in most patients (grade I 48%, grade II 24%, grade III 16%). Of 46 evaluable patients, 3 CR, 5 PR, 22 S and 16 P were observed. The CR + PR remission rate, according to the intention to treat analysis, was 16% with a 95% confidence limit of 7.2%-29.1%; in patients not pretreated for advanced disease the CR + PR rate was 26%, while only 2 out of 27 pretreated patients responded to the treatment (7%). The median time to progression was 5 months (2-11). The median survival was not reached after a median follow-up of 14 months. One-year survival is 60%.
  
  
  CONCLUSIONS
  In this trial the OXA + RTX combination is confirmed to be active in ACC, although the level of activity seems to be lower than that of the other combination including OXA and 5-FU with or without FA modulation. The reasons for the low activity observed could at least in part be related to a reduction in the RTX dose intensity.
authors.affiliation: U.O. di Oncologia Medica, Dipartimento di Oncologia e Ematologia, Policlinico S. Orsola-Malpighi, via Albertoni 15, 40138 Bologna, Italy. martoni@orsola-malpighi.med.unibo.it
authors.forename: A
authors.initials: A
authors.lastname: Martoni
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.forename: C
authors.initials: C
authors.lastname: Pinto
authors.forename: A L
authors.initials: AL
authors.lastname: Gentile
authors.forename: S
authors.initials: S
authors.lastname: Nobili
authors.forename: P
authors.initials: P
authors.lastname: Dentico
authors.forename: A
authors.initials: A
authors.lastname: Marino
authors.forename: S
authors.initials: S
authors.lastname: Scicolone
authors.forename: B
authors.initials: B
authors.lastname: Angelelli
authors.forename: T
authors.initials: T
authors.lastname: Mazzei
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed