Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer.
BACKGROUND
Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m(-2) per day on days 3-16 every 3 weeks.


METHODS
Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m(-2) and an S-1 dose of 80 mg m(-2).


RESULTS
In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1-72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8-12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind.


CONCLUSIONS
Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer.
Yoshioka
T
T
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba ward, Sendai 980-8575, Japan. ytakashi@med.id.yamagata-u.ac.jp
Kato
S
S
Gamoh
M
M
Chiba
N
N
Suzuki
T
T
Sakayori
N
N
Kato
S
S
Shibata
H
H
Shimodaira
H
H
Otsuka
K
K
Kakudo
Y
Y
Takahashi
S
S
Ishioka
C
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin