High doses of intrapleural cisplatin in a case of malignant pleural mesothelioma. Clinical observations and pharmacokinetic analyses.
BACKGROUND: The authors report a feasibility study of intrapleural cisplatin in a patient with inoperable malignant pleural mesothelioma. METHODS: Total and filterable platinum in pleural effusion and in plasma were monitored for two intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted. Platinum concentrations in pleural effusion, plasma, and urine were determined by flameless atomic absorption spectroscopy. RESULTS: A lower peak of filterable platinum in plasma, a decrease in systemic filterable platinum exposure (AUC [area under the concentration-time curve]), and a greater pleural exposure to filterable platinum were observed after Course 2 compared with Course 1. After the second cycle of intrapleural treatment, the systemic AUC for filterable platinum was reduced by 40%. CONCLUSIONS: The authors' findings may have some implications for the clinical use of intrapleural chemotherapy with high doses of cisplatin. Both infusions of cisplatin were generally well tolerated by the patient and were associated with the local pharmacologic advantage of sustained exposure to cisplatin of the pleural cavity. No sign of myelosuppression, neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild nausea, vomiting, and prolonged anorexia. A transient presence of granular casts was the only observed nephrotoxic effect of cisplatin. Excellent local control of the disease with absence of recurrence of the effusion was observed.