IP Chemotherapy Encouraged for Ovarian Cancer

Technique Increases Survival; Side Effects Being Addressed

Newly diagnosed patients with advanced ovarian cancer should know they have the option of receiving chemotherapy through a catheter (tube) placed in the abdomen, as well as a vein, if a majority of their tumors can be removed during surgery, cancer experts say.

The National Cancer Institute (NCI) is recommending that physicians discuss this treatment approach with their patients in response to a clinical trial that extended patient survival by nearly 16 months. In an announcement on the NCI website, officials encourage medical professionals to tell patients about the study, published in the Jan. 5, 2006 issue of The New England Journal of Medicine.

Several NCI-sponsored cancer centers, including M. D. Anderson, have begun offering the treatment that combines intravenous (IV) chemotherapy, drugs given through a catheter into a vein, and intraperitoneal (IP) chemotherapy, drugs given through a catheter into the abdomen, or peritoneal cavity.

"Now, when an eligible patient comes here, we are offering her a choice between IV chemotherapy (the standard treatment) or IV and IP chemotherapy," says Judith Wolf, M.D., associate professor in M. D. Anderson's Department of Gynecologic Oncology. Wolf began developing the new chemotherapy orders with her medical and nursing staff after learning of the latest study results several months ago.

Not all gynecologic oncologists offer IP chemotherapy, so patients interested in the treatment should ask their doctors if the treatment is available and recommended.

Benefits are greater with therapy combination

The traditional treatment for newly diagnosed stage III ovarian cancer includes surgery to remove the bulk of the tumor (meaning less than approximately 1 centimeter of cancer remains after surgery). The "debulking" is followed with administration of both a platinum drug [cisplatin (Platinol) or carboplatin (Paraplatin)] and a taxane drug [paclitaxel (Taxol) or docetaxel (Taxotere)].

In the latest study, which was conducted through the NCI's Gynecologic Oncology Group (GOG), 415 women with stage III debulked ovarian cancer were assigned randomly to either of two groups receiving six cycles of the following drugs every three weeks.

IV group- IV paclitaxel followed by IV cisplatin.

IP group- IV paclitaxel followed by IP cisplatin and IP paclitaxel.

The results showed a significant benefit in the IP group:

Median overall survival* - IV: 49.7 months; IP: 65.6 months.

Relapse-free survival- IV: 18.3 months; IP: 23.8 months.

(*The time in which half the patients were still alive)

IP along with IV chemotherapy is more effective because the IP route delivers a higher concentration of drug using the same dose to an area where most of the cancer develops and is likely to recur. The IP schedule involves one additional day of treatment (day 8), but the cycles are still 21 days apart.

Toxicity and infection problems being addressed

Eight published trial results, including the latest findings, have shown that IP therapy increases survival. However, they also show the therapy causes drug toxicity, catheter-related infections and other problems. These issues hindered the studies and prevented the treatment from gaining acceptance in the medical community, Wolf says.

In the latest study, only 42% of patients in the IP group were able to finish all six cycles due to problems with toxicity (such as abdominal pain) and catheter-related infection.

In a quality-of-life survey conducted throughout the study, patients in the IP group reported having worse quality of life than the IV group. However, there were no major differences in quality of life between the groups one year after treatment, according to the study researchers.

Although all of the IP patients did not complete the therapy, the entire group experienced a significant increase in survival compared to the IV group.

M. D. Anderson researchers are involved in studies to see if other drugs are as effective as the regimen used in the new study but with fewer side effects. They also plan to study the different types of catheters used to see which ones have fewer complications.

Meanwhile, precautions are being taken to help protect new M. D. Anderson patients receiving the treatment, Wolf says.

They include:

• Built-in dose reductions
• IP catheter training for medical staff
• Use of an NCI-recommended catheter

"We are using a central venous catheter for IP therapy," Wolf says. "This catheter is usually inserted into a vein either in the arm or under the collarbone. The same catheter is used to deliver IP therapy, except instead of inserting it into a vein in the arm or chest area, it is surgically inserted under the rib and used to infuse chemotherapy directly into the abdomen. Past studies have shown that the infection rate is lower with catheters that are placed under the skin."

Doctors may consider inserting the catheter during a patient's initial surgery, if possible, to avoid a second surgical procedure, she says.

Patients will want the option despite side effects

Despite the potential side effects of IP therapy, Wolf believes patients will want the treatment and will put pressure on medical institutions that were reluctant to offer it in the past.

"Ovarian cancer patients are very strong women," says Wolf, who chairs the National Ovarian Cancer Coalition (NOCC) board of directors. "They have access to the Internet, and they realize they have choices. I think they are going to demand this treatment, and things are going to change."

Ovarian cancer survivors are still concerned about toxicity, says NOCC President-elect April Donahue. One piece of advice she has for eligible patients is that they seek treatment from a gynecologic oncologist who is properly trained in IP therapy. Time will tell if the upcoming follow-up trials will reduce side effects, Donahue says.

Overall, however, she welcomes IP chemotherapy and thinks ovarian cancer patients will also. "We're giving women another 16 months, and I think that's great. We don't have a lot of hope some days, so this is giving a lot of people a lot of hope."