Hyperthermic isolated regional perfusion with CDDP for bone and soft-tissue sarcoma of the lower limb: pharmacokinetics, thermal dose, toxicity, and feasibility.
The objectives of this study were to investigate the pharmacokinetics of cisplatin (CDDP) and the thermal dose, toxicity, and feasibility of hyperthermic isolated regional perfusion (HIRP) with CDDP for bone and soft-tissue sarcomas of the lower limb. A total of 43 patients were treated with HIRP using CDDP. The dose of CDDP administered was 62.9+/-11.8 mg/limb (20 mg/m(2) +20 approximately 30 mg). The mean highest CDDP concentration was 56.9 microg/ml as total platinum (tPt) and 49.0 microg/ml as free platinum (fPt). The tPt concentration remained higher than 10 microg/ml. The highest temperature within tumor was 42.3+/-1.4 degrees C on average. The complications of HIRP were grade II toxicity in 30 patients, grade III in 9, and grade IV in 4. The mean necrotic ratio in the resected specimen was 84.5%, and the effect was grade IV (no viable tumor cells) in 13 patients, grade III(>90% necrosis) in 12, grade II (50 to <90%) in 9, and grade I (<50%) in 4. We obtained favorable levels of platinum concentration of the perfusate using a lower CDDP dosage compared with previous studies of HIRP. Considering our results of the pharmacokinetics of CDDP and clinical efficacy, we propose a lower dosage of CDDP for HIRP in the treatment of osteosarcoma. Multimodality treatment of HIRP with preoperative chemotherapy and surgery is a relatively safe and reliable therapeutic option for patients with limb sarcomas, and our method offers excellent local control.
Abe
Satoshi
S
Department of Orthopaedic Surgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan. satoshi@med.teikyo-u.ac.jp
Tokizaki
Toru
T
Miki
Yuji
Y
Tateishi
Akio
A
Ogawa
Kazuhiko
K
Nakano
Hirotaka
H
Matsushita
Takashi
T
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects / Q000379:methods; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007866:Leg / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*; D013696:Temperature; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002945:Cisplatin