Dosage escalation study of S-1 and irinotecan in metronomic chemotherapy against advanced colorectal cancer.
The anti-angiogenic efficacy of chemotherapy would seem to be optimized by administering comparatively lower doses of drugs on a more frequent (daily, several times a week, or weekly) or continuous schedule, with no extended interruptions - sometimes referred to as 'metronomic' chemotherapy. This phase I study was performed to determine the recommended dosage (RD) of metronomic chemotherapy using oral fluoropyrimidine S-1 plus weekly irinotecan (CPT-11) in patients with previously untreated advanced or recurrent colorectal cancer. Patients received first-line chemotherapy consisting of 80 mg/m(2) of S-1 given on days 3 to 7, 10 to 14, and 17 to 21 with escalating dosages of CPT-11 (from 40 mg/m(2)) administered intravenously on day 1, 8, and 15 of a 28-day cycle. Standard patient eligibility criteria were used. Based on the concept of metronomic chemotherapy, dose limiting toxicity (DLT) was defined any toxicity that resulted in skipping of CPT-11 administration, or more than 5 days suspension in S-1 administration, in addition to the conventional criteria. If the maximum tolerated dosage (MTD) was defined as the maximum dosage at which no suspension of CPT-11 or S-1 administration occurred, the RD was considered to be the dosage one rank lower than the MTD. On the other hand, in the present study the MTD was defined as the dosage at which at least one suspension of CPT-11 or S-1 administration occurred, the MTD was considered to be the RD. Two of the first 3 patients at level 4 received 60 mg/m(2) of CPT-11 and 80 mg/m(2) of S-1 experienced a suspension in CPT-11 administration, thus level 4 was defined as the MTD and RD. Sixty mg/m(2) of CPT-11 and 80 mg/m(2) of S-1 were the indicated RD for the following phase II study of metronomic chemotherapy.
Ogata
Yutaka
Y
Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan. yogata@med.kurume-u.ac.jp
Sasatomi
Teruo
T
Akagi
Yoshito
Y
Ishibashi
Nobuya
N
Mori
Shinjirou
S
Shirouzu
Kazuo
K
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