Scientific Publications Database
Article Title: OV21/PETROC: A Randomized Gynecologic Cancer Intergroup Phase II Study of Intraperitoneal Versus Intravenous Chemotherapy Following Neoadjuvant Chemotherapy and Optimal Debulking Surgery in Epithelial Ovarian CancerAuthors: Provencher, D. M.; Gallagher, C. J.; Parulekar, W. R.; Ledermann, J. A.; Armstrong, D. K.; Brundage, M.; Gourley, C.; Romero, I.; Gonzalez-Martin, A.; Feeney, M.; Bessette, P.; Hall, M.; Weberpals, J. I.; Hall, G.; Lau, S. K.; Gauthier, P.; Fung-Kee-Fung, M.; Eisenhauer, E. A.; Winch, C.; Tu, D.; MacKay, H. J.
Journal: OBSTETRICAL & GYNECOLOGICAL SURVEY Volume 73 Issue 4
Date of Publication:2018
Abstract:
The use of neoadjuvant chemotherapy (NACT) prior to surgical debulking is increasingly used for advanced epithelial ovarian cancer (EOC). In women with EOC, the principal site of disease is the peritoneal cavity. As a means of increasing the dose intensity delivered to the tumor, intraperitoneal (IP) chemotherapy has been investigated. Three randomized clinical trials and a meta-analysis have demonstrated improved survival for women with stage III EOC who-following optimal, primary debulking surgery-received a combination of intravenous (IV) and IP chemotherapy. Updated data from Gynecologic Oncology Group trial 172 (GOG 172), themost recent of these trials, reported continued benefit for womenwho had received the experimental arm. However, the use of IP/IV chemotherapy for advanced-stage EOC remains controversial. There has been a continuing debate on the impact of drug scheduling on the benefits of IP and concern over the toxicity of IP cisplatin used in the positive studies, compared with IV carboplatin.OV21/PETROC was a multicenter, multistage, randomized phase II study designed to evaluate the role of IP chemotherapy following NACT and optimal debulking surgery in women with EOC. Eligible patients with histologically confirmed stage IIB-IVA EOC were treated with platinum- based IV NACT followed by optimal (<1 cm) debulking surgery and randomized to 3 treatment arms: (1) IV carboplatin and paclitaxel; (2) IP cisplatin and IV/IP paclitaxel, or (3) IP carboplatin and IV/IP paclitaxel. The primary study outcome measure was PD9 defined as the proportion of patients with disease progression or death due to any cause occurring within 9 months of randomization. Secondary outcome measures included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QOL).Between 2009 and 2015, 275 patients were randomized to arm 1(IValone), 72 to arm 2 (IP cisplatin-based regimen), and 102 to arm 3 (IP carboplatin-based regimen). Because patients in the IP cisplatin-based arm failed to meet the preset efficacy rule, this arm was discontinued after the first stage of the study. In the final analysis, the IV carboplatin/paclitaxel (arm 1) was compared with IP carboplatin, IV/IP paclitaxel (arm 3). In the intention-to-treat population, PD9 was lower in the IP carboplatin arm compared with the IV carboplatin arm: 24.5% (95% confidence interval [CI], 16.2%-32.9%) versus 38.6% (95% CI, 29.1%-48.1%), P = 0.065. The study was underpowered to detect differences in PFS and OS: for PFS, the hazard ratio was 0.82 (with a 95% CI of 0.57-1.17; P = 0.27), and for OS, the hazard ratio was 0.80 (with a 95% CI of 0.47-1.35; P = 0.40). The IP carboplatin-based regimen (arm 3) was well tolerated with no detriment in QOL or increase in toxicity compared with IVadministration alone (arm 1).These findings show that in women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery subsequent use of an IP carboplatin-based regimen is well tolerated and improves PD9 compared with IV carboplatin-based chemotherapy.