Gynecologic oncologists are advancing a treatment method that shows great promise in extending PFS and OS for women with certain advanced gynecologic cancers.
Intrabdominal infusions of carboplatin prove tolerable, are ready for phase-III investigation
Gynecologic oncologists are advancing a treatment method that shows great promise in extending progression-free and overall survival for women with certain advanced gynecologic cancers. Intraperitoneal (IP) infusion, in which chemotherapy agents are administered directly into the abdomen through an abdominal port, has been under investigation for many years, but the approach has not yet been widely accepted in the United States. Toxicity associated with the main IP agent, cisplatin, was one barrier to acceptance. Now the Gynecologic Oncology Group (GOG) is actively investigating IP treatment using carboplatin, a platinum-based chemotherapy agent that is thought to be significantly less toxic than cisplatin.
Two separate GOG phase-I studies helped establish dosing and safety data for abdominal administration of carboplatin. Gynecologic oncologists hope to find a more tolerable alternative to IP cisplatin, which, when combined with intravenous (IV) and IP paclitaxel, has been shown to extend progression-free and overall survival for women with advanced ovarian, fallopian tube or primary peritoneal cancers. Earlier studies indicated that carboplatin might be less toxic than cisplatin yet still extend survival. In one Japanese study, the length of progression-free survival doubled to 51 months in patients who received higher doses of carboplatin, compared to 25 months for patients who received lower doses.
The present studies provide additional useful data on carboplatin and the feasibility of IP infusion. Specifically, data relating to maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) derived from these studies will be implemented in advanced phase-III research trials.
The GOG studies looked into combinations of paclitaxel administered intravenously and carboplatin delivered directly into the abdomen. The study conducted by Dr. Gould and her colleagues also included a course of intraperitoneal paclitaxel on the eighth day of the treatment cycle.
Each of the studies concluded that IP carboplatin doses of area under the curve (AUC) 6 could be safely administered for six cycles, with intravenous paclitaxel dosages ranging from 135 mg/m2 (Gould) to 175 mg/m2 (Morgan). Both studies also indicated that adding growth factors to the regimen might counteract the toxic effects of the chemotherapy on blood cells.
Society of Gynecologic Oncologists