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Experts consider ways to administer chemotherapy

On Jan. 4, the National Cancer Institute released an announcement encouraging patients with advanced ovarian cancer to undergo chemotherapy via the intravenous and intra peritoneal (directly into the abdominal cavity) route. The standard of care at this time is to administer chemotherapy by the intravenous route only. According to a study published in the Jan. 5 issue of the New England Journal of Medicine, additional intra peritoneal, or IP, chemotherapy extends the overall survival for advanced ovarian cancer patients by about a year.

At the last Chemotherapy Foundation Symposium in New York, Dr. Franco M. Muggia, professor of oncology at the Kaplan Comprehensive Cancer Center of New York University, noted that intra peritoneal chemotherapy dates to the 1970s. Several drugs were studied in phase II trials in the 1980s.

He quoted three phase III trials (identified as GOG 104, 144 and 172) conducted by the Gynecologic Oncology Group, or GOG, that favored combined intravenous and intra peritoneal chemotherapy over intravenous therapy alone.

The GOG 172 trial involved 429 patients with stage III ovarian cancer who had optimal tumor-reducing surgery. Patients were randomly assigned intravenous chemotherapy alone or a combination of intravenous and intra peritoneal chemotherapy. Patients who received the combined treatment realized an extra 12 months in overall survival and an extra 16 months of median survival compared with those who received intravenous chemotherapy alone.

Dr. Muggia said the results of the GOG 172 "make it impossible to walk away from that concept." The GOG 172, published in the Jan. 5 issue of the New England Journal of Medicine, was led by Dr. Debra Armstrong of the Johns Hopkins Kimmel Cancer Center.

While there are many proponents of the intra peritoneal therapy, two prominent medical ovarian cancer specialists don't agree with Dr. Muggia's assertions.

Dr. Robert Ozols, senior vice president of the Medical Science Division at the Fox Chase Cancer Center, said the reason for better survival of the GOG 172 patients must be explained. He wondered if the extended survival was because these patients got more chemotherapy, or if it could be attributed to the intra peritoneal route itself.

He also said the toxicities of IP therapy were unacceptable and that many patients were unable to complete six cycles of chemotherapy because of pain, catheter dysfunction and neurotoxicity. Another expert in ovarian cancer treatment, Dr. Robert C. Young, president of the Fox Chase Cancer Center, said that although several GOG studies showed a modest improvement with IP treatment, there were other studies that did not. He also questioned why the current major GOG studies do not have an IP arm, if it is indeed so good.

The concept of IP chemotherapy is based on the fact that most ovarian cancers recur within the peritoneal cavity, and the assumption that peritoneally delivered chemotherapy does not get into the systemic circulation. Hence it would not cause significant side effects commonly seen with high-dose intravenous chemotherapy.

This would make it possible to safely expose the tumor cells to high doses of chemotherapy that can be put into the peritoneal cavity and drained out through the same catheter used to deliver it.

Intra peritoneal chemotherapy requires the placement of a special catheter into the peritoneal cavity (preferably at the time of the original surgery). There must be an extra level of skill on the part of the oncologist to administer intra peritoneal chemotherapy and manage its side effects and those related to catheter dysfunction.

The complexity, cost and discomfort become a barrier to the widespread adaptation of intra peritoneal therapy. As strategies to manage treatment side effects and catheter-related problems are worked out, IP chemotherapy for advanced ovarian cancer may be more widely adapted.

With my surgical colleagues, I have conducted several successful intra peritoneal chemotherapies, both in the hospital and in outpatient settings. Initially we used the Tenkoff catheters that are used for peritoneal dialysis. Subsequently, special catheters were manufactured that had a larger bore than the intravenous catheters and also had side vents for easy diffusion of fluids.

Should IP therapy become the standard of care, it will be easy for us to build on our experience and make necessary adjustments for safe and effective treatment.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

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