EXPERIENCE WITH INTRAPERITONEAL CISPLATIN AND ETOPOSIDE AND IV SODIUMTHIOSULFATE PROTECTION IN OVARIAN-CANCER PATIENTS WITH EITHER PATHOLOGICALLY COMPLETE RESPONSE OR MINIMAL RESIDUAL DISEASE

Background. High-dose platinum-based regimens can produce responses in patients not responding to standard chemotherapy. As in many ovarian cancer patients the disease remains confined to the peritoneal cavity, intraperitoneal (i.p.) chemotherapy has been applied as an alternativ e approach to increase drug exposure. The delivery of cytotoxic agents to the peritoneal cavity can lead to high drug concentrations intrape ritoneally with less systemic toxicity. This study aimed at evaluating the efficacy and toxicity of high-dose i.p. cisplatin plus etoposide and intravenous sodium thiosulphate protection in ovarian cancer. Pati ents and methods. Patients with either a pathologically complete respo nse (pCR) after first-line treatment or with persistent disease after first-line platinum-based chemotherapy or abdominal recurrences were e ligible. All intraabdominal lesions had to be < 2 cm at the start of i .p. treatment. The treatment consisted of etoposide 350 mg/m(2) i.p. f ollowed by cisplatin 200 mg/m(2) i.p. with intravenous sodium thiosulp hate (4 g/m(2) bolus, followed by 12 g/m(2) over six hours) protection . Four courses of i.p. treatment were administered in case of pCR and 6 courses otherwise, at four-weekly intervals. Results. The study comp rised 29 patients, six patients with pCR, 17 patients with persistent disease and six patients with abdominal recurrences. They received a t otal of 105 courses of treatment (65% of the scheduled number of cours es). Twelve patients completed scheduled treatment, illustrating its f easibility. In 17 patients treatment had to be prematurely stopped bec ause of inflow obstruction (seven patients), bowel perforation (two pa tients), renal toxicity (two patients), neurotoxicity (two patients), or malaise and vomiting (four patients). One patient with bowel perfor ation died of this complication. Severe nausea and vomiting occurred i n 51% of cycles. Leukopenia and thrombopenia grade 3 and 4 occurred in 30% and 6% of cycles, respectively. Ototoxicity of cisplatin was meas ured by serial tone audiography in 23 patients: only eight patients (3 5%) showed significant audiographic changes, although none of them dev eloped clinical hearing loss. Fifteen patients were evaluable for resp onse: four pCR, five PR, two SD, four PD. The median duration of Freed om from progression was 616 days and the median overall survival 1065 days from the start of treatment. Conclusions: High-dose i.p. treatmen t with cisplatin and etoposide can be associated with significant toxi cities. Major clinical problems are nausea, vomiting, and the formatio n of intraabdominal adhesions. Intravenous sodium thiosulphate effecti vely reduces the systemic toxicity of high-dose cisplatin. The value o f high-dose i.p, treatment is uncertain and its routine use cannot be recommended.