High doses of intrapleural cisplatin in a case of malignant pleural mesothelioma. Clinical observations and pharmacokinetic analyses

Abstract

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.

Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies

“…In agreement with some recent reports, our results clearly demonstrate a pharmacological advantage for local cisplatin instillation in the thoracic cavity 13, 14, 25. The mean peak cisplatin levels and their mean AUCs were considerably higher in the pleural perfusion fluid than in the plasma.…”

Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure†

“…In addition, regional hyperthermia is suggested to increase the penetration depth and to enhance the cytotoxicity of the cytostatic drug as well as having its own antineoplastic effects by inducing the potent apoptosis of tumour cells [19,20]. Morphological and functional investigations showed no damage to the lung parenchyma from the hyperthermic pleural space perfusion with cisplatin [19,21].…”

Intraoperative adjuncts for malignant pleural mesothelioma

“…The safety and feasibility of IC were confirmed through phase I trials of ovarian carcinoma patients in the 1980s, engendering interest in IC as a treatment adjunct for intraperitoneal malignancies (3,4). Pharmacokinetics studies of intrapleural cisplatin and mitomycin following PD in the 1990s then showed consistently similar advantages in MPM, demonstrating that IC is a safe and effective form of treatment for MPM (5,6).…”