High-dose biweekly intraperitoneal cisplatin: an effective way to increase cisplatin dose intensity

The amount of cisplatin (DDP) delivered per unit time (dose intensity, expressed in mg/m2/week) may be an important factor in determining the clinical outcome in tumors such as ovarian carcinoma. In this neoplasm, intraperitoneal chemotherapy is an effective form of treatment. In this trial we have explored the tactic of shortening the cycle interval as a way to increase the dose intensity of ip DDP. Sixteen patients with a variety of solid tumors received a total of 77 cycles of DDP 180 mg/m2 instilled ip concurrent with i.v. sodium thiosulfate at the dose of 4 g/m2 as loading dose, followed by 12 g/m2 over 6 hr. Each cycle was repeated every 2 weeks. The number of cycles delayed for 3 or more days was 28 (36%). The mean DDP dose intensity received by these patients was 77% of the planned dose or 69 mg/m2/week (confidence interval 95%, 60.5-77.5). The treatment was generally well tolerated: myelotoxicity was mild, only 1 patient had an increase in serum creatinine to > 2 mg/dl. Five patients (31%) developed symptoms of peripheral neuropathy. All patients were evaluable for response. The overall response rate (complete plus partial) in these heavily pretreated patients was 19%. When DDP is given in high doses by the ip route concurrently with systemic sodium thiosulfate, the dosing interval can be reduced to every 2 weeks permitting a marked increase in DDP dose intensity.