[Pharmacokinetic analysis of platinum in the continuous CDDP-CBDCA treatment; its relation to the changes of blood biochemistry].
Seven patients with recurrent gynecological malignancies (2 cervical, 2 endometrial, 3 ovarian) treated with CDDP at the initial chemotherapy were studied for the pharmacokinetic analysis of platinum (Pt) and changes of blood biochemistry in the continuous CDDP-CBDCA infusion therapy. All the patients were indwelled of the total parenteral nutrition catheter. A balloon type infuser (Baxter Inc., multiday type) was connected with the catheter and the drugs were infused continuously through it. CBDCA was infused continuously from day 1 through day 5 at a daily dose of 60 mg/m2, followed by continuous CDDP infusion from day 6 through day 30 at a daily dose of 2.5 mg/m2. All the patients received 3 courses of the treatment. The area under the [Pt]-time curve (AUC) of filterable Pt was as high as 60.98 +/- 8.20 mg.hr/ml (mean +/- SE), and that of total Pt 691.48 +/- 93.61 mg.hr/ml. However, the Cmax of filterable Pt was as low as around 400 ng/ml during day 1 to 6, and around 20 ng/ml during day 7 to day 30. As to the toxicity, only slight myelosuppression but no renal and gastrointestinal toxicity were observed in this therapy. The quality of life of the patients received this treatment were maintained well throughout of the therapy. Responders were evaluated as 1 CR, 2 PR, 2 NC and 1 PD. These data indicated that high AUC but low Cmax of filterable Pt by continuous CDDP-CBDCA therapy resulted in less toxicity. Further investigation was warranted to evaluate the efficacy of continuous CDDP-CBDCA therapy.
Chen
J T
JT
Hasumi
K
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001772:Blood Cell Count; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D010984:Platinum / Q000493:pharmacokinetics*; D014594:Uterine Neoplasms / Q000097:blood / Q000188:drug therapy*
D010984:Platinum; D003404:Creatinine; D016190:Carboplatin; D002945:Cisplatin