Second-line treatment with oxaliplatin + raltitrexed in patients with advanced colorectal cancer failing fluoropyrimidine/leucovorin-based chemotherapy.
BACKGROUND
To evaluate the efficacy and tolerance of combined raltitrexed and oxaliplatin in patients with advanced colorectal cancer pretreated with fluoropyrimidine leucovorin-based chemotherapy.


METHODS
Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within six months after withholding palliative chemotherapy with fluoropyrimidines leucovorin +/- irinotecan, participated in this study. Treatment consisted of oxaliplatin 130 mg/m2 and raltitrexed 3.0 mg/m2 both given on day 1 every three weeks for a total of eight courses unless prior evidence of progressive disease.


RESULTS
The overall objective response rate was 33.3% for all 36 evaluable patients (95% confidence interval (CI): 18.6%-51%). Seventeen additional patients (47.2%) had stable disease, and only seven (19.5%) progressed. The median progression-free survival was 6.5 months (range 1.2-14.0). After a median follow-up time of 12 months, 23 patients (63.8%) are still alive. The tolerance of treatment was acceptable with only 8 of 36 patients (22%) experiencing grade 3 or 4 neutropenia. Grade 3 non-haematological adverse reactions included peripheral sensory neuropathy in three, asthenia in one, diarrhea in two, and clinically insignificant increase in serum transaminases in two patients, respectively.


CONCLUSIONS
Our data suggest that the combination of oxaliplatin and raltitrexed has substantial antitumour activity in patients with progressive fluoropyrimidine leucovorin + irinotecan pretreated colorectal cancer. Because of its favorable toxicity profile and convenient three-weekly outpatient administration schedule, further evaluation of this regimen seems warranted.
Scheithauer
W
W
Department of Internal Medicine I, University Medical School, Vienna, Austria. werner.scheithauer@akh-wien.ac.at
Kornek
G V
GV
Schuell
B
B
Ulrich-Pur
H
H
Penz
M
M
Raderer
M
M
Lang
F
F
Schneeweiss
B
B
Lenauer
A
A
Depisch
D
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D016879:Salvage Therapy; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; D000077146:Irinotecan; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin