Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma.
BACKGROUND
The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first-line treatment in metastatic colorectal carcinoma (CRC).


METHODS
A total of 140 patients received capecitabine at a dose of 1250 mg/m(2) twice daily on Days 2-15 and irinotecan at a dose of either 300 mg/m(2) on Day 1 (Arm A) or 150 mg/m(2) on Days 1 and 8 (Arm B) every 3 weeks. During the course of the study, enrollment was continued using lower doses of capecitabine (1000 mg/m(2) twice daily) and irinotecan (Arm A: 240 mg/m(2); Arm B: 120 mg/m(2)) to improve the safety profile of the combinations.


RESULTS
Efficacy was evaluable in 134 patients (68 in Arm A, 66 in Arm B). Objective responses were observed in 46% of the patients (8% complete response [CR]), including 47% in Arm A (9% CR; 38% partial response [PR]) and 44% in Arm B (8% CR; 36% PR). The median progression-free survival was 8.3 months in Arm A and 7.6 months in Arm B. Among the first 52 patients treated with the higher doses, the most frequent Grade 3-4 adverse event was diarrhea (27%). The lower doses adopted in the subsequent 88 patients led to better diarrhea control, particularly in Arm A, and significant reductions in the incidence of all-grade hand-foot syndrome and abdominal pain.


CONCLUSIONS
The capecitabine and irinotecan combination was a highly active first-line therapy in metastatic CRC. An acceptable safety profile was observed after dose reduction, particularly when irinotecan was administered on 1 day.
Bajetta
Emilio
E
Medical Oncology Unit B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via G. Venezian 1, 20133 Milan, Italy. emilio.bajetta@istitutotumori.mi.it
Di Bartolomeo
Maria
M
Mariani
Luigi
L
Cassata
Antonio
A
Artale
Salvatore
S
Frustaci
Sergio
S
Pinotti
Graziella
G
Bonetti
Andrea
A
Carreca
Ignazio
I
Biasco
Guido
G
Bonaglia
Luigi
L
Marini
Giovanni
G
Iannelli
Antonio
A
Cortinovis
Diego
D
Ferrario
Ermina
E
Beretta
Elena
E
Lambiase
Antonio
A
Buzzoni
Roberto
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin