Background: All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging. Methods: Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan–Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were twosided. Results: After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.44 to 1.08; P = .10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P = .02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 [95% CI = 1.08 to 4.96]; P = .03 and HR = 1.82 [95% CI = 1.02 to 3.24] P = .04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 [95% CI = 1.04 to 2.95]; P = .03 and HR = 1.78 [95% CI = 1.15 to 2.77]; P = .009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen. Conclusion: Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.

Impact of Adjuvant Chemotherapy and Surgical Staging in Early-Stage Ovarian Carcinoma: European Organisation for Research and Treatment of Cancer–Adjuvant ChemoTherapy in Ovarian Neoplasm Trial / J.B. Trimbos, I. Vergote, G. Bolis, J.B. Vermorken, C. Mangioni, C. Madronal, M. Franchi, S. Tateo, G. Zanetta, G. Scarfone, L. Giurgea, P. Timmers, C. Coens, S. Pecorelli. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 95:2(2003 Jan), pp. 113-125.

Impact of Adjuvant Chemotherapy and Surgical Staging in Early-Stage Ovarian Carcinoma: European Organisation for Research and Treatment of Cancer–Adjuvant ChemoTherapy in Ovarian Neoplasm Trial

G. Bolis;G. Scarfone;
2003

Abstract

Background: All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging. Methods: Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan–Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were twosided. Results: After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.44 to 1.08; P = .10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P = .02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 [95% CI = 1.08 to 4.96]; P = .03 and HR = 1.82 [95% CI = 1.02 to 3.24] P = .04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 [95% CI = 1.04 to 2.95]; P = .03 and HR = 1.78 [95% CI = 1.15 to 2.77]; P = .009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen. Conclusion: Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.
Ovarian diseases ; Female genital diseases ; Malignant tumor ; Platinum II Complexes ; Human ; Surgery ; Clinical stage ; Prognosis ; Adjuvant treatment ; Phase III trial ; Chemotherapy ; Antineoplastic agent ; Postoperative ; Therapeutic protocol ; Carboplatin ; Alkylating agent ; Cisplatin ; Early stage ; Ovary ; Carcinoma
Settore MED/40 - Ginecologia e Ostetricia
gen-2003
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/46502
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