Irinotecan, oxaliplatin plus bolus 5-fluorouracil and low dose folinic acid every 2 weeks: a feasibility study in metastatic colorectal cancer patients.
OBJECTIVE
Irinotecan or oxaliplatin combined with 5-fluorouracil (5-FU) +/- folinic acid (FA) has changed the treatment standards for metastatic colorectal cancer (CRC). The oxaliplatin and irinotecan combination has reported consistent activity. The purpose of this phase II study was to assess the efficacy and safety of the simultaneous administration of a triple chemotherapy combination of oxaliplatin, irinotecan, 5-FU bolus, and FA.


METHODS
Eligible patients had metastatic CRC with no prior oxaliplatin or irinotecan-based chemotherapy. Treatment consisted of oxaliplatin 85 mg/m2 followed by irinotecan 150 mg/m2, repeated every 15 days, with 5-FU 500 mg/m2 bolus and FA 20 mg/m2 on days 1, 8, and 15. An early amendment suppressed the day 8 5-FU/FA.


RESULTS
Twenty-six eligible treated patients receiving 253 doses were assessed for toxicity. Myelosuppression was the most frequent toxicity; grade 3 to 4 neutropenia and febrile neutropenia occurred in 50% and 15% of patients, respectively. The treatment schedule modification, omitting the 5-FU dosing on day 8, considerably improved treatment compliance, reducing the incidence of febrile neutropenia, diarrhea, and asthenia. Among the 25 patients evaluable for efficacy, 10 had objective responses including 1 complete response (CR) (4%) and 9 partial responses (PR) (36%), giving an overall response rate of 40%. Median time to progression was 6.20 months [95% confidence interval (CI), 5.44-6.96]. Median overall survival was 12.95 months.


CONCLUSIONS
The administration of a triple combination produced promising objective responses with acceptable toxicity but does not seem to produce an evident benefit in time-related parameters.
Martinez
Justina
J
Hospital Britanico, Buenos Aires, Argentina.
Martin
Claudio
C
Chacon
Matias
M
Korbenfeld
Ernesto
E
Bella
Santiago
S
Senna
Susana
S
Richardet
Eduardo
E
Coppola
Federico
F
Bas
Carlos
C
Hidalgo
Jorge
J
Escobar
Emiliano
E
Reale
Monica
M
Smilovich
Andres M
AM
Wasserman
Ernesto
E
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*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin