Intraperitoneal Chemotherapy Extends Ovarian Cancer Survival by Year

/Home/About Cancer/Cancer Treatment Overviews/Chemotherapy/Intraperitoneal Chemotherapy

Intraperitoneal Chemotherapy Extends Ovarian Cancer Survival by Year
Published: January 04, 2006
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
MedpageToday

BALTIMORE, Jan. 4 - Chemotherapy delivered directly into the peritoneum in addition to intravenous therapy increased overall survival of women with advanced ovarian cancer by more than a year. Action Points
--------------------------------------------------------------------------------

Inform interested patients that the addition of intraperitoneal chemotherapy to standard intravenous chemotherapy may significantly prolong both progression-free and overall survival in women with optimally debulked stage III ovarian cancer.


Caution patients that intraperitoneal chemotherapy is associated with severe side effects, including serious fatigue, and hematologic, GI, metabolic, and neurologic toxic effects and a significant reduction in quality of life during therapy.
So dramatic were the findings of a Gynecologic Oncology Group study, reported in the Jan. 5 issue of the New England Journal of Medicine, that the National Cancer Institute plans to issue a clinical announcement endorsing the approach. The NCI will recommend a combination of IV and intraperitoneal chemotherapy to treat women with advanced ovarian cancer who have undergone optimal surgical debulking.


In the multicenter study, led by Deborah K. Armstrong, M.D., of Johns Hopkins here, overall survival for 205 women with surgically debulked stage III ovarian cancer, who received both intraperitoneal and intravenous chemotherapy, was a median of 65.6 months.


This was 25% longer than that of 210 women treated with conventional intravenous-only chemotherapy (49.7 months).


In addition, women who received chemotherapy via the abdominal route had 20% longer progression-free survival. This was 23.8 months compared with 18.3 months for women who received only IV chemotherapy.


"The rationale for intraperitoneal therapy in ovarian cancer is that the peritoneum, the predominant site of tumor, receives sustained exposure to high concentrations of antitumor agents while normal tissues, such as the bone marrow, are relatively spared," the investigators wrote.


Catheter-based delivery into the peritoneum of Taxol (paclitaxel) and Platinol (cisplatin) "allows us to bathe the entire abdominal area with a high concentration of chemotherapy for a long period of time, which appears to be better at destroying lingering cancer cells," Dr. Armstrong said.


The treatment strategy also relies on intravenous chemotherapy with the same two agents to target extraperitoneal metastases, Dr. Armstrong added.

The superior survival associated with adding intraperitoneal chemotherapy to IV treatment comes at a cost, however.


"The side effects of intraperitoneal chemotherapy included a high incidence of catheter-related complications, abdominal pain, metabolic abnormalities, and neuropathy," noted Stephen A. Cannistra, M.D., director of gynecologic medical oncology at Beth Israel Deaconess Medical Center in Boston, in an accompanying editorial.


About half of the patients randomized to receive intraperitoneal treatment completed only three or fewer of the six planned cycles because of toxicities, the majority of which were related to the use of the delivery catheter.


Eligible participants were women with stage III epithelial ovarian or peritoneal carcinoma with no residual mass greater than 1.0 cm in diameter after surgery, a Gynecologic Oncology Group performance status of 0 to 2 (with 0 being fully active and 4 completely disabled), normal blood counts, and adequate renal and hepatic function.


A total of 415 patients who were eligible for therapy were treated with 135 mg/m2 of Taxol IV over a 24-hour period, followed by either 75 mg/m2 of Platinol on day 2 (the intravenous-therapy group), or 100 mg/ m2 of intraperitoneal Platinol on day 2, and 60 mg/ m2 of intraperitoneal Taxol on day 8 (intraperitoneal-therapy group). Treatments were given every three weeks for up to six cycles.


The investigators found that intraperitoneal therapy was associated with significantly better progression-free and overall survival. The median duration of progression-free survival among patients receiving the intraperitoneal treatments was 23.8 months, compared with 18.3 months for those in the IV-only group (P = 0.05 by the log-rank test).


Median overall survival was also better among patients in the intraperitoneal group, at 65.6 months vs. 49.7 months among patients receiving only intravenous infusions (P = 0.03).


Quality of life, one of the safety endpoints "was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment, but not one year after treatment," the authors noted.


Grade 3 and 4 pain, fatigue, and hematologic, gastrointestinal, metabolic, and neurologic toxic effects occurred significantly more often in the intraperitoneal-therapy group than in the intravenous-therapy group (P ≤ 0.001). Only 42% of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy, and 48% completed only three or fewer cycles.


"Including this study, there are now three randomized trials showing that intraperitoneal chemotherapy has a clinical advantage in the treatment of ovarian cancer," the authors noted. "Although this advantage comes at the expense of increased toxicity and reduced quality of life during treatment, these results should encourage the use of intraperitoneal chemotherapy in patients with advanced ovarian cancer."


Dr. Cannistra agreed that given the survival advantage, many women who could benefit from intraperitoneal chemotherapy will choose to receive it, but "others will not be willing to do so," he wrote. "For these reasons, the decision to use intraperitoneal chemotherapy should be individualized."


Primary source: New England Journal of Medicine
Source reference:
Armstrong DK et al. Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer. N Engl J Med 2006;354:34-43. Click here for the abstract.

Additional source: New England Journal of Medicine
Source reference:
Cannistra SA. Intraperitoneal Chemotherapy Comes of Age.
N Engl J Med 2006;354:77-79. Click here for the abstract.


© 2004-2009 MedPage Today, LLC. All Rights Reserved.