Abstract | OBJECTIVE: A dose-escalation study of irinotecan (CPT-11) combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLTs) in advanced gastric cancer. METHODS: S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2 week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 40 mg/m(2)/day, stepping up to 60, 80, 100 or 120 mg/m(2)/day depending on the DLT. Courses were repeated every 5 weeks, unless disease progression or severe toxicity was observed. At a level of the RD, five patients were added to conduct a pharmacokinetic (PK) study. RESULTS: A total of 24 patients were entered in this study. The MTD of CPT-11 was considered to be 100 mg/m(2), because 50% of the patients (3/6) developed DLTs, diarrhea and rash. Therefore, the RD of CPT-11 was set at the dose immediately below 80 mg/m(2). The overall response rate (RR) by the criteria of the Japanese Research Society of Gastric Cancer was 58.3% (14/24) and the RR at the RD was 66.7% (6/9), suggesting promising clinical efficacy. There were no significant differences between the PK parameters of S-1 on days 10 and 15. CONCLUSIONS: S-1 with CPT-11 can be combined safely without CPT-11 effect on S-1 PK data and holds promise as an effective regimen for advanced gastric cancer.
|
Authors | Hiroya Takiuchi, Hiroyuki Narahara, Toshimasa Tsujinaka, Masahiro Gotoh, Sei-ichiro Kawabe, Ken-ichi Katsu, Hiroyasu Iishi, Masaharu Tatsuta, Kazumasa Fujitani, Hiroshi Furukawa, Tetsuo Taguchi, Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) |
Journal | Japanese journal of clinical oncology
(Jpn J Clin Oncol)
Vol. 35
Issue 9
Pg. 520-5
(Sep 2005)
ISSN: 0368-2811 [Print] England |
PMID | 16141295
(Publication Type: Clinical Trial, Phase I, Journal Article)
|
Chemical References |
- Drug Combinations
- Pyridines
- S 1 (combination)
- Tegafur
- Oxonic Acid
- Irinotecan
- Camptothecin
|
Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, pharmacokinetics, therapeutic use)
- Camptothecin
(administration & dosage, adverse effects, analogs & derivatives)
- Drug Combinations
- Female
- Humans
- Irinotecan
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasm Staging
- Oxonic Acid
(administration & dosage, adverse effects)
- Pyridines
(administration & dosage, adverse effects)
- Stomach Neoplasms
(drug therapy, pathology)
- Survival Rate
- Tegafur
(administration & dosage, adverse effects)
- Treatment Outcome
|