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Maurie Markman, M.D., Vice President for Clinical Research |
More than 50 years ago, in the earliest days of the “modern chemotherapeutic” era, oncologists attempted to administer antineoplastic agents directly into the peritoneal cavity as treatment for nearby malignancies, including ovarian cancer. However, this strategy was soon abandoned when it was shown that systemic drug delivery produced similar improvement without the local toxic effects, like severe abdominal pain, that were commonly associated with the drugs available for regional treatment at that time.
In the late 1970s, there was renewed interest in intraperitoneal treatment based on theoretical modeling studies showing that malignant cells in the peritoneal cavity could be exposed to much larger concentrations of anticancer agents—10- to 1000-fold greater than with systemic treatment—if direct drug instillation was used.
Multiple phase I and II clinical trials in the 1980s and early 1990s confirmed the safety (e.g., limited abdominal pain), major pharmacokinetic advantage (e.g., 10- to 20-fold for cisplatin; 1000+ fold for paclitaxel), and biological activity (e.g., tumor shrinkage, surgically documented complete responses) of the regional administration of a number of anticancer agents for ovarian cancer. But while these data were of considerable scientific interest, the trials did not establish the superiority of intraperitoneal delivery, compared with standard intravenous drug delivery.
However, over the past decade, the results of three large, multi-institution, randomized phase III trials have now convincingly demonstrated improved survival in advanced ovarian cancer from intraperitoneal delivery. Studies have shown that the intraperitoneal administration of cisplatin, a member of the most important class of agents used in ovarian cancer, results in a statistically significant improvement in both the time to disease progression and in overall survival for women with advanced ovarian cancer. The most recently reported trial, conducted by the Gynecologic Oncology Group, revealed a 17-month improvement in median survival associated with this approach compared with intravenous delivery of the cytotoxic agents.
Much remains to be learned about this novel strategy for the management of ovarian cancer, including refining the drugs and dosages and defining the best method of delivery (e.g., types of catheters and the optimal surgical placement technique). Critically important clinical research efforts at many institutions, including M. D. Anderson, will seek to determine the optimal use of this “old,” yet highly innovative, management strategy that has now been shown to prolong the lives of women with this very difficult malignancy.For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call the M. D. Anderson Information Line at (800) 392-1611 (in the United States) or (713) 792-3245 (in Houston and outside the United States).
Other articles in OncoLog, October 2005 issue:
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