Intraperitoneal drug delivery for ovarian cancer: why, how, who, what, and when?

In 1996, intraperitoneal (IP) administration of cisplatin plus intravenous (i.v.) cyclophosphamide proved superior to both drugs given intravenously at the same doses--which, at the time, was the standard treatment in the United States. The IP 'option' was not adopted, however, because the standard treatment had shifted to i.v. cisplatin plus paclitaxel.Two additional phase III trials by the Gynecologic Oncology Group (GOG) comparing IP versus i.v. cisplatin, but including other variables, have shown similar superior effects of the IP route on outcome, but with toxicities-particularly local tolerance and neuropathy--increased. An ongoing trial by the GOG is again looking into an IP versus i.v. comparison, and introducing in one of the IP arms the substitution of IP carboplatin for IP cisplatin. All three arms of this trial contain bevacizumab (Avastin). Two other trials comparing i.v. versus IP administration of platinums or platinums and paclitaxel have just been launched, led by Japanese and Canadian investigators, respectively. While awaiting additional data on the ongoing debate over IP versus i.v. therapy, it is important that we consider issues concerning why the IP route may be relevant, how can one increase the safety of this route, and who should be treated and with what drugs, particularly when faced with a patient outside the clinical trials setting. The underlying hypothesis for use of IP therapy is based on the existence of a dose-effect relationship for platinum drugs in ovarian cancer. We review the known data on this relationship, and explore why interest in platinum drugs has become the central focus of ovarian cancer treatment.