More than 3 Cycles May Not Reduce Recurrence Risk

Gynecological Cancers

Therapy longer than three cycles may not reduce recurrence risk

Going beyond three cycles of adjuvant chemotherapy for ovarian cancer should depend on a patient’s response and on toxicity.

By Tammy Dotts

Staff Writer

NEW ORLEANS — Continuing adjuvant chemotherapy beyond three cycles may not decrease the risk of recurrence for patients with early-stage ovarian cancer.

In a study presented here at the annual meeting of the Society of Gynecologic Oncologists, six cycles of carboplatin (Paraplatin, Bristol-Myers Squibb) and paclitaxel modestly but not significantly improved the rate of cancer recurrence while causing significantly more toxicity.

Looking for improvement

Standard chemotherapy consists of three cycles, although previous studies have suggested clinical benefit from additional cycles. To determine whether there was additional benefit, Jeffrey Bell, MD, from Riverside Methodist Hospitals in Columbus, Ohio, and his colleagues began a randomized phase-3 study.

Within six weeks of surgery, 457 patients were randomized to three or six cycles. Doses were the same in each arm: 175 mg/m2 of paclitaxel followed by carboplatin at an area under the curve of 7.5. Three hundred twenty-two patients were evaluable. Twenty-three percent of patients were excluded from analysis because of incomplete surgical staging.

Bell and his colleagues chose the recurrence rate as the primary measure of therapeutic benefit. Benefit would occur if the four-year recurrence-free survival rate increased from 80% to 89%.

Similar results

Toxicity was significantly different between the two arms. Neurotoxicity, granulocytopenia and anemia were significantly higher with six cycles of chemotherapy, compared with three cycles.

The probability of recurrence at five years was 27% with three cycles and 19% with six cycles. This represented a 31% lower risk of recurrence with six cycles but was not significant, according to the study.

Overall survival at five years also slightly increased with six cycles of therapy: 84% compared with 79% with three cycles. The difference was not significant, according to the study.

Because a high proportion of patients had been excluded from the study, Bell analyzed survival for all patients. The results were similar to the original analysis with a lack of significant difference between the two arms. Six cycles of therapy reduced the risk of recurrence by 23%. The five-year overall survival was 80% with three cycles and 84% with six cycles.

A question of significance

“What doctors need to remember is that statistical significance is not always the same as clinical significance,” Bell told Hem/Onc Today. “We use data from studies to guide practice, but we need to remember that they’re just guidelines. A lack of statistical significance does not mean that a treatment doesn’t have benefit in the real world.”

He added that other studies have shown a trend for significant improvement with six cycles of therapy. Before this trial, Bell treated his own patients with a standard four cycles of therapy. Now, he plans to treat with three or four cycles and then reevaluate the patient.

“If the patient is responding and has no toxicity, then I might continue therapy but with no more than six cycles,” he said.

For more information:

Bell J, Brady M, Lage J, et al. A randomized phase III trial of three versus six cycles of carboplatin and paclitaxel as adjuvant treatment in early stage ovarian epithelial carcinoma: a Gynecologic Oncology Group study.

Abstract #1. Presented at the Society of Gynecologic Oncologists 34th Annual Meeting on Women’s Cancer. Jan. 31-Feb. 4, 2003. New Orleans, March 2003

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