[Studies on an appropriate intra thoracic administration of cisplatin and sodium thiosulfate in malignant pleural...

Twenty-eight patients with malignant pleural effusion received instillation of cisplatin (CDDP) into the pleural cavity to examine the pharmacokinetics and side effects of CDDP Thirteen patients received high-dose CDDP (120 mg/m2-160 mg/m2) in combination with sodium thiosulfate (STS), while 15 others received CDDP alone (80 mg/m2). Total Pt and non-protein-bound Pt (free Pt) concentrations in the pleural effusion and plasma were determined by flameless atomic absorption spectrometry. In one patient, Pt concentrations of intact CDDP and STS-bound CDDP were determined using high performance liquid chromatography and flameless atomic absorption spectrometry. Instillation of CDDP at 160 mg/m2 into the pleural cavity was achieved by concurrent use of STS in the large dose (STS 20 g/m2 1 hr later, totalling 625-fold molar ratio to CDDP). When CDDP was combined with STS, there was alleviation in hematological, renal and auditory toxicity but not in nausea, vomiting or anorexia. When CDDP was instillated into the pleural cavity at 150 mg/m2 (in combination with STS equivalent to 200-fold molar ratio to CDDP), a high Pt concentration of intact CDDP could be maintained in the pleural effusion over a prolonged period of time, recording 8.80 micrograms/ml even as late as 12 hr after instillation. On the other hand nearly all of the free Pt concentration for the first 2 hr was considered to be due to intact CDDP. Once systemically administered, STS quickly moved into the pleural effusion, binding with CDDP in the pleural cavity and thus probably reducing its anti-tumor effect. STS did not greatly affect the plasma concentration of total Pt when it was administered at a 100-fold molar ratio to CDDP, yielding only p poor effect. Our findings suggest that malignant pleural effusion could be effectively treated by the instillation of CDDP 80 mg/m2 into the pleural cavity.