Pharmacokinetic study of two infusion schedules of irinotecan combined with cisplatin in patients with advanced gastric cancer.
OBJECTIVE
Irinotecan (CPT-11) in combination with cisplatin (CDDP) has shown promising antitumor activity for advanced gastric cancer, but the optimal administration schedule of CPT-11 is still controversial. To clarify the pharmacokinetic effects of different CPT-11 administration schedules, we compared two different regimens (continuous infusion of CPT-11 for 24 h and CPT-11 infusion for 90 min) combined with CDDP in patients with advanced gastric cancer.


METHODS
Five patients were treated with CPT-11 at a dose of 60 mg/m(2) delivered by continuous infusion for 24 h on day 1 and by a 90-min infusion on day 15, together with CDDP daily administered at a dose of 10 mg/m(2) on days 1-3 and days 15-17 for 4 weeks. The pharmacokinetics of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were investigated, as well as the toxicity of therapy.


RESULTS
Grade 3 leukopenia was observed in 1 patient after 24-hour infusion and in 1 patient after 90-min infusion of CPT-11. In addition, grade 3 thrombocytopenia was observed in 1 patient after the 90-min infusion. Other adverse reactions were mild, and the planned dose was delivered to all patients. The area under the plasma concentration-time curve of SN-38, the active metabolite from CPT-11, was increased by 24-hour infusion when compared with the 90-min infusion, and there was no increase in toxicity.


CONCLUSIONS
Protracted infusional CPT-11 combined with CDDP is a practical regimen, and may be appropriate for a future phase II trial.
Fujitani
Kazumasa
K
Department of Surgery, Osaka National Hospital, Osaka, Japan. fujitani@onh.go.jp
Tsujinaka
Toshimasa
T
Hirao
Motohiro
M
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin