Super high-dose intraarterial cisplatin infusion under percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced uterine cervical carcinoma: I. Analysis for pharmacokinetics, tumor response, and toxicity of platinum.
The present study was designed to elucidate the clinical feasibility of a new intraarterial infusion system with an extracorporeal charcoal chemofiltration circuit, which is expected to achieve a super high-dose cisplatin pelvic perfusion with a limited systemic exposure to platinum. After inferior vena cava isolation was percutaneously achieved by balloon catheter technique, cisplatin (140-240 mg/m2) was administered by selective intrauterine arterial infusion, with inferior and superior gluteal arterial embolization. The platinum-containing blood was pumped through an extracorporeal charcoal chemofiltration circuit. Pharmacokinetics, tumor response, and toxicity of platinum under this system were studied in 14 patients with locally advanced uterine cervical carcinoma. Extracorporeal charcoal filters significantly (p < 0.05) reduced the prefilter area under concentration-time curve of plasma-free platinum by 86.7 +/- 5.2% at postfilter site and 76.3 +/- 6.6% at peripheral circulation, respectively. Although all adverse effects were mild under this system, tumor response and tissue platinum concentrations were augmented dose dependently with the administration of cisplatin. The extracorporeal chemofiltration system achieved a super high-dose cisplatin pelvic perfusion with the minimal adverse effects, allowing further cisplatin dose escalation with further augmented tumor response. This will contribute to the reduction in the extent of disease of locally advanced uterine cervical carcinoma.
Hamana
S
S
Department of Obstetrics and Gynecology, Kobe University School of Medicine, Kobe, Japan.
Motoyama
S
S
Takeuchi
S
S
Ku
Y
Y
Yoshida
S
S
Miyahara
Y
Y
Tateiwa
Y
Y
Maruo
T
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D010478:Chemotherapy, Cancer, Regional Perfusion; D002945:Cisplatin / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000493:pharmacokinetics; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin