Intraperitoneal Cisplatin and Carboplatin in the Management of Ovarian Cancer

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Abstract
In the early 1980’s, investigators at a number of institutions began to explore the intraperitoneal administration of cisplatin as therapy of ovarian cancer. Several factors provide strong support for these initial and subsequent clinical trials, including: 1. Ovarian cancer is a malignancy which tends to remain localized to the peritoneal cavity for most of its natural history (1,2). 2. Pharmacokinetic modeling studies have suggested that following intraperitoneal drug delivery it is possible to expose tumor within the cavity to significantly higher drug concentrations than possible following systemic administration (3). 3. Cisplatin is the single most active antineoplastic agent in the management of ovarian cancer (4). 4. Experimental data and retrospective evaluation of clinical trials have suggested that there is a relatively steep dose response curve for cisplatin against ovarian cancer (5,6). In addition, pre-clinical evaluation has demonstrated that resistance to cisplatin is often only “relative” with 2–4 fold increases in drug concentrations being capable of overcoming resistance in in vitro systems (7,8). 5. Unfortunately, the dose of cisplatin which can be administered systemically is limited by both the nephrotoxic and, most importantly, neurotoxic effects of the agent (9). Phase 1 trials of intraperitoneal cisplatin in ovarian cancer