International Collaborative Ovarian Neoplasm Trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm Trial: Two Parallel Randomized Phase III Trials of Adjuvant Chemotherapy in Patients With Early-Stage Ovarian Carcinoma

• Published in: JNCI : Journal of the National Cancer Institute 2003-01, Vol.95 (2), p.105-112
• Main Authors: Trimbos, J Baptist, Parmar, Mahesh, Vergote, Ignace, Guthrie, David, Bolis, Giorgio, Colombo, Nicoletta, Vermorken, Jan B, Torri, Valter, Mangioni, Constantino, Pecorelli, Sergio, Lissoni, Andrea, Swart, Ann Marie
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Carcinoma - drug therapy; Carcinoma - pathology; Carcinoma - surgery; Chemotherapy; Chemotherapy, Adjuvant; Cisplatin - administration & dosage; Disease-Free Survival; Drug Administration Schedule; Female; Humans; International Cooperation; Medical sciences; Middle Aged; Neoplasm Staging; Odds Ratio; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Ovarian Neoplasms - surgery; Pharmacology. Drug treatments; Risk Factors; Survival Analysis; Treatment Outcome
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/95.2.105

Background: Adjuvant chemotherapy has been suggested as a possible strategy to improve survival in women with early-stage ovarian cancer; however, all randomized studies to date have been too small to answer this question reliably. Methods: We performed a preplanned combined analysis of two parallel randomized clinical trials (International Collaborative Ovarian Neoplasm 1 [ICON1] and Adjuvant ChemoTherapy In Ovarian Neoplasm [ACTION]) in early-stage ovarian cancer that compared platinum-based adjuvant chemotherapy with observation following surgery. Between November 1990 and January 2000, 925 patients (477 in ICON1 and 448 in ACTION) who had surgery for early-stage ovarian cancer were randomly assigned to receive platinum-based adjuvant chemotherapy (n = 465) or observation (n = 460) until chemotherapy was indicated. Kaplan–Meier analysis was used to compare overall and recurrence-free survival by treatment allocation. In subgroup analyses of pretreatment age, tumor stage, histologic cell type, and differentiation grade, the differences in relative size of effect were tested using a chi-square test for interaction or a chi-square test for trend. All tests of statistical significance were two-sided. Results: After a median follow-up of over 4 years, 245 patients had died or had a recurrence (ICON1: 133, ACTION: 112). Overall survival at 5 years was 82% in the chemotherapy arm and 74% in the observation arm (difference = 8% [95% confidence interval (CI) = 2% to 12%]; hazard ratio [HR] = 0.67, 95% CI = 0.50 to 0.90; P = .008). Recurrence-free survival at 5 years was also better in the adjuvant chemotherapy arm than it was in the observation arm (76% versus 65%, difference = 11% [95% CI = 5% to 16%]; HR = 0.64, 95% CI = 0.50 to 0.82; P = .001). Subgroup analyses provided no evidence of a difference in the size of effect of chemotherapy on survival in any pretreatment subcategory. Conclusions: Platinum-based adjuvant chemotherapy improved overall survival and recurrence-free survival at 5 years in this combined group of patients with early-stage ovarian cancer defined by the inclusion criteria of the ICON1 and ACTION trials.