[Importance of AUC of carboplatin in head and neck cancer].
Combination chemotherapy with Carboplatin (CBDCA) and 5-fluorouracil (5-FU) was given to 115 patients with head and neck cancer. The area under the blood concentration-time curve (AUC) of CBDCA was calculated by Calvert's formula for 111 of the 115 patients. A retrospective study was conducted to define the relationship between the clinical outcome of the combination chemotherapy and the AUC of CBDCA. The overall response rate was 58.4% in the 115 patients. The objective response rate for 103 patients with squamous cell carcinoma was 61.9% with eight (7.6%) with complete responses (CR) and 57 (54.3%) with partial responses. The mean AUC for the administration of 300 mg of CBDCA per m2 was 3.91 +/- 0.68 mg/ml.min in the patients with squamous cell carcinoma. Although, there was no statistically significant relationship between the AUC of CBDCA and therapeutic efficacy, all CRs were obtained at an AUC above 3. Thrombocytopenia was the major dose-limiting toxicity in this study. The magnitude of thrombocytopenia increased significantly with increase in AUC values. Severe thrombocytopenia did not seem to occur in the patients with an AUC under 4.5. From these results, the AUC was considered helpful for determining the CBDCA dose to prevent severe side effects. In respect of both therapeutic efficacy and toxicity, AUC values from 3 to 4.5 are recommended for neo-adjuvant chemotherapy with CBDCA and 5-FU. Prospective validation is necessary to settle the question of whether a higher AUC value within this range can improve the outcome.
Shimizu
T
T
Department of Otorhinolaryngology, University of Occupational and Environmental Health, School of Medicine, Kjtakyushu.
Yoshida
M
M
Makishima
K
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D012189:Retrospective Studies; D013810:Therapeutic Equivalency; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D016190:Carboplatin; D005472:Fluorouracil