Complex chemotherapy cocktails offers pluses, minuses in advanced endometrial cancer

Complex chemotherapy cocktails offer about one extra month of life to patients with end-stage endometrial cancer but also can result in severe, possibly fatal, side effects, according to the first systematic review of studies addressing the topic.

"The best drug treatment for women with advanced cancer of the womb is still not clear," concludes the review, led by Dr. Caroline Humber of Walsgrave Hospital in England.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The authors identified 11 randomized controlled trials with 2,288 participants. All compared one or more of the commonly used chemotherapy agents with an alternative drug, combination, or dosing schedule.

Six of the trials compared combinations of three or more drugs to simpler regimens. A combined analysis for all 1,135 women showed that the more intense treatments did a better job of controlling tumor growth, yet no drug combination stood out as superior.

But increasing the number of chemotherapy drugs also increased the likelihood of serious damage to the heart, kidneys, nerves, digestive system, blood cells and other body systems. The studies reported as many as 12 possible treatment-related deaths.

Among the drugs compared were paclitaxel, cisplatin, doxorubicin and 5-fluoracil.

Dr. Ira Horowitz, a gynecologic oncologist at Emory University, says that patients with advanced endometrial cancer are generally older and often have multiple health problems related to obesity and diabetes.

"When you're 60, 70, 80 years old with advanced endometrial cancer, it's much more difficult to tolerate the drugs and the side effects. …They may not get that payback for what it's going to take out of them."

The review authors had set out to answer the kinds of questions that patients ask when considering treatment options, says Humber. "They ask 'Will this make me live

longer? Will this make my cancer stay away for longer? Will it make me feel better? Will it help my symptoms?'" These questions remain largely unanswered. The authors could locate no studies that compared chemotherapy for advanced endometrial cancer with other options such as hormone therapy, comfort care or no treatment. Moreover, none of the studies examined symptom control and quality of life issues.

"It would be nice to know what the quality of life was," says Humber. "In other types of cancer that we treat, for example lung cancer, we do see very small gains in survival but absolutely enormous gains in quality of life reported by patients. ... But we don't know that for this condition."

The report says that collection of such patient-reported data should be a priority in future research.

"What ought to come out of this is that we need to continue to recruit patients into well-designed trials," says Humber. Yet, because of the relative rarity of the condition and the frequency of co-existing health problems, recruiting enough participants for a thorough study can be a long, slow process.

For example, Dr. David Scott Miller -- a professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center -- is leading a government-funded study that is seeking 900 participants. Miller and his colleagues will compare survival rates, quality of life and side effects of two widely used drug combinations. They aim to complete the study within five years.

"We hope [the Cochrane findings] might spur people to participate," says Miller. "There are about 6,000 or 7,000 women who are likely to die of endometrial cancer in the United States annually. Those patients would all be appropriate candidates for chemotherapy and for our trial." Because early-stage endometrial cancer can usually be cured by surgical removal of the uterus, advanced stages are relatively rare. About 50,000 deaths occur each year worldwide. The condition is most common in North America and Europe, and risk factors include obesity, hypertension, diabetes and hormone replacement therapy.