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.
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.
Trimbos
J Baptist
JB
Department of Gynecology, Leiden University Medical Center, The Netherlands. J.B.M.Z.Trimbos@lumc.nl
Parmar
Mahesh
M
Vergote
Ignace
I
Guthrie
David
D
Bolis
Giorgio
G
Colombo
Nicoletta
N
Vermorken
Jan B
JB
Torri
Valter
V
Mangioni
Constantino
C
Pecorelli
Sergio
S
Lissoni
Andrea
A
Swart
Ann Marie
AM
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007391:International Cooperation; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin