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Key Words

Ovarian cancer, intraperitoneal chemotherapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Combined data from 60 randomized clinical trials of advanced ovarian cancer showed that multidrug chemotherapy using a platinum-based drug and a taxane-based drug delivered directly into the abdomen (intraperitoneal chemotherapy) can help women survive a median of 5.5 years.

Source

Journal of the National Cancer Institute, November 15, 2006 (see the journal abstract).
(J Natl Cancer Inst. 2006 Nov 15;98(22):1655-63)

Background

Early-stage ovarian cancer often causes no symptoms. Ovarian cancer is therefore usually diagnosed at a later stage, once it has spread outside of the ovaries. Chemotherapy is a mainstay for ovarian cancer treatment, because it can enter the bloodstream and kill cancer cells that have spread to other organs, and has been shown to extend survival.

However, even with the use of chemotherapy, ovarian cancer often recurs. For the last 40 years, clinical trials have tested different chemotherapy regimens against each other to find more effective combinations of drugs. Because many of these trials are small, and have tested many different combinations of drugs, no one trial alone has definitively answered the question of what regimen is most effective at extending survival for patients with ovarian cancer.

The Study

The study described in this summary was a meta-analysis, a type of study that combines data from many different trials. The investigators searched the major electronic databases of biomedical results as well as paper indexes to identify all of the clinical trials performed in the past 40 years that tested chemotherapy for ovarian cancer. They singled out all randomized clinical trials published in English, German, French, or Italian that compared at least two different chemotherapy regimens with each other, in at least five patients.

Each of these chemotherapy regimens was categorized according to several conditions.

• Whether it used a platinum-based drug, a taxane-based drug, both, or neither
• Whether it used one drug (monotherapy) or a combination of drugs
• Whether or not one or more of the drugs was given directly into the abdomen (intraperitoneal chemotherapy)

Investigators compared all chemotherapy regimens in all eligible trials both directly against each other in pairs, and in groups using a technique called multiple-treatment meta-analysis. Multiple-treatment meta-analysis compares different treatment regimens indirectly against each other. For example, if investigators know how much better regimen A is than regimen B, and how much better regimen B is than regimen C, they can use multiple-treatment meta-analysis to indirectly calculate how much better regimen A is than regimen C. Direct and indirect comparisons of treatment efficacy were compared to identify any discrepancies.

Results

The investigators identified 198 trials from their search that met the eligibility criteria for inclusion in the study. Of these, 60 trials had available data on survival after chemotherapy. These 60 studies were used for the final meta-analysis.

Direct comparisons showed differences in survival with different types of chemotherapy.

• For non-platinum and non-taxane drugs, combination therapy was better than monotherapy
• Monotherapy with a platinum-based drug was significantly better that monotherapy with a non-platinum, non-taxane drug
• Combination therapy including a platinum-based drug was better than monotherapy with any drug, and better than combination therapy that did not use either a platinum-based or taxane-based drug
• Combination therapy including both a platinum-based drug and a taxane-based drug was better than combination therapy including a platinum-based drug and a non-taxane drug
• Intraperitoneal administration improved survival for combination therapy with a platinum-based drug and a taxane-based drug

Multiple-treatment meta-analysis confirmed these comparisons. The investigators calculated a 92-percent likelihood that the most effective regimen for ovarian cancer was intraperitoneal administration of a platinum-based drug and a taxane-based drug.

Without effective treatment, women with advanced ovarian cancer can expect to survive about 2.5 years; with the most effective current treatments as identified in this meta-analysis, median survival is doubled to about 5.5 years.

Limitations

While newer treatment regimens including platinum-based drugs and taxane-based drugs increase survival, they also produce more side effects, caution the authors. Therefore, any chemotherapy regimen “should be tailored to the individual patients and balanced against tolerability.”

Comments

“Compared with the early days, when neither platinum nor taxanes were available and chemotherapy was clearly no better than supportive care for [extending survival]…median survival can now be more than doubled using currently available regimens,” state the authors. Even if intraperitoneal chemotherapy is not feasible for a particular patient, they explain, “survival can still be almost doubled with a combination of platinum and taxanes without intraperitoneal administration.”

“I think the take-home message of this analysis is that standard treatment should include both a platinum and a taxane, and that, where appropriate, intraperitoneal chemotherapy should be considered,” said Edward L. Trimble, M.D., M.P.H., of the National Cancer Institute’s Cancer Therapy Evaluation Program. “This meta-analysis supports the NCI Clinical Announcement that was put out in January 2006,” which recommends a combination of intravenous and intraperitoneal chemotherapy for the treatment of ovarian cancer (see a list of medical centers that perform intraperitoneal chemotherapy).

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