Adjuvant Chemo Offers 8-9% Benefit

Optimal Surgery Most Valuable

Excerpt from MEDSCAPE (Great Debates in Gynecologic Oncology), Case 3: Use of Sensitivity Assays in Ovarian Cancer

Case 3 Discussant 1: Bob Nagourney, MD

Discussant 2: Maurie Markman, MD

"Dr. Nagourney: "With the exception of gestational carcinoma, we today in medial oncology have virtually no disease that has a 100% response rate. In fact, in an analysis of all tumor types, the average response rate across the board in human tumors is in the range of 35% to 40%.

If you look at the GOG 111 as the gold standard for platinum/paclitaxel, the achievement of complete remission in that study by pathological assessment was 26%. And we know that that corresponds very closely to the 29% 5-year survival for patients with advanced ovarian cancer. So I think the question is, do we really feel that we should rest on our laurels with 26% of pathological complete remissions"?

Adjuvant Chemotherapy Improves Survival In Early-Stage Ovarian Cancer

-- Results from two large European studies suggest that adjuvant chemotherapy immediately after surgery for early-stage ovarian cancer can increase some patients' chances of both overall and recurrence-free survival. The findings are reported in three articles in the January 15 issue of the Journal of the National Cancer Institute.

As many as 50% of patients with early-stage ovarian cancer relapse after surgery, and these subsequent tumor recurrences are often resistant to treatment. Adjuvant chemotherapy has been used to prevent recurrence; however, definitive data are lacking on the effectiveness of adjuvant therapy, and there is no information available about which patients may benefit the most. In addition, previous trials have been too small to provide clear answers.

In the early 1990s, two large randomized clinical trials were initiated to compare survival between patients treated with adjuvant chemotherapy immediately after surgery for early-stage ovarian cancer and patients who received no additional treatments until clinically indicated.

In the Adjuvant ChemoTherapy in Ovarian Neoplasm (ACTION) trial, a team of researchers from the European Organisation for Research and Treatment of Cancer (EORTC) randomly assigned 448 patients from across Europe to either adjuvant platinum-based chemotherapy or observation following surgery. This trial also examined the impact of completeness of surgical staging on survival.

One-third of the patents received optimal surgical staging for their cancers. This meant that clinicians performed all the requirements to determine the extent of the disease, or its stage. The remaining two-thirds of patients received nonoptimal surgical staging.

At 5 years, there was no statistically significant difference in overall survival between patients who were treated with adjuvant chemotherapy and patients who were in the observation group. However, recurrence-free survival was statistically significantly improved, with 76% of patients treated with adjuvant chemotherapy surviving without a recurrence, compared with 68% of patients in the observation arm.

Moreover, the authors found that among patients who did not receive adjuvant chemotherapy, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival. In contrast, optimal staging was not associated with any survival benefit in patients who received adjuvant chemotherapy. Adjuvant chemotherapy appeared to only benefit patients whose cancers were not optimally staged.

"This finding suggests that adjuvant chemotherapy in early-stage ovarian cancer may work predominantly by affecting small-volume or microscopic tumor implants or metastases that remain unnoticed at the time of surgical staging," the authors write.

They add that the observed benefit of adjuvant chemotherapy primarily in nonoptimally staged patients suggests a benefit of adjuvant chemotherapy predominantly in patients with unrecognized residual disease.

In a second trial, the International Collaborative Ovarian Neoplasm (ICON1) study, collaborators randomly assigned 477 patients to receive either adjuvant chemotherapy immediately after surgery for early-stage ovarian cancer or no immediate adjuvant chemotherapy. (Information on the completeness of surgical staging was not collected in this trial.)

At 5 years, women who received adjuvant chemotherapy had a 9% greater overall survival and an 11% greater recurrence-free survival than women who did not receive immediate adjuvant therapy.

In a separate paper, researchers reported findings from a combined analysis of the two trials. Similar to the ICON1 trial, the combined analysis found that 5-year overall survival was 8% greater in the adjuvant chemotherapy arm than in the observation arm.

The analysis also found that 5-year recurrence-free survival was 11% better in the adjuvant chemotherapy arm than in the observation arm.

In an accompanying editorial, Robert C. Young, M.D., of the Fox Chase Cancer Center in Philadelphia, says that the trials add important information on adjuvant chemotherapy but do not address which patients can be spared unnecessary adjuvant chemotherapy.

He recommends that future trials focus on identifying patients who do not require additional therapy while also seeking to improve therapy in patients who do. "Selecting only high-risk patients for additional treatment can narrow the use of chemotherapy, and this approach should be used until such time as a randomized trial can demonstrate that good prognosis, early-stage patients benefit from such therapy," he writes.

January 15, 2003(Journal of the National Cancer Institute)

Thanks to

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