Early initiation of chemotherapy following complete resection of advanced ovarian cancer associated with improved survival: NRG Oncology/Gynecologic Oncology Group study.
BACKGROUND
To determine whether time from surgery to initiation of chemotherapy impacts survival in advanced ovarian carcinoma.


METHODS
This is a post-trial ad hoc analysis of Gynecologic Oncology Group protocol 218, a phase III randomized, double-blind, placebo-controlled trial designed to study the antiangiogenesis agent, bevacizumab, in primary and maintenance therapy for patients with newly diagnosed advanced ovarian carcinoma. Maximum attempt at debulking was an eligibility criterion. Stage III patients, not stage IV, were required to have gross macroscopic or palpable residual disease following surgery. The survival impact of time from surgery to initiation of chemotherapy was studied using Cox regression models and stratified by treatment arm, residual disease and other clinical and pathologic factors.


RESULTS
One thousand seven hundred eighteen assessable patients were randomized (stage III (n = 1237); stage IV (n = 477), including those with complete resection (stage IV only, n = 81), low-volume residual (≤1 cm, n = 701), and suboptimal (>1 cm, n = 932). On multivariate analysis, time to chemotherapy initiation was predictive of overall survival (P < 0.001), with the complete resection group (i.e. stage IV) encountering an increased risk of death when time to initiation of chemotherapy exceeded 25 days (95% confidence interval 16.6-49.9 days).


CONCLUSIONS
Survival for women with advanced ovarian cancer may be adversely affected when initiation of chemotherapy occurs >25 days following surgery. Our analysis applies to stage IV only as women with stage III who underwent complete resection were not eligible for this trial. These results, however, are consistent with Gompertzian first-order kinetics where patients with microscopic residual are most vulnerable.


BACKGROUND
NCT00262847.
University of California, Irvine Medical Center, Orange, California ktewari@uci.edu.
K S
KS
Tewari
NRG Oncology/Gynecologic Oncology Group Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo.
J J
JJ
Java
University of California, Irvine Medical Center, Orange, California.
R N
RN
Eskander
Creighton University School of Medicine, St Joseph's Hospital and Medical Center, Phoenix.
B J
BJ
Monk
Obstetrics and Gynecology, University of Pennsylvania, Pennsylvania, USA.
R A
RA
Burger
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000401:mortality / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel
NRG Oncology/GOG; chemotherapy initiation; complete resection; ovarian cancer