The use of intraperitoneal (IP) chemotherapy for the treatment of advanced ovarian cancer resulted in a survival benefit over intravenous chemotherapy, according to a pooled analysis of data from the Gynecologic Oncology Group (GOG) protocols 114 and 172.
The analysis looked at 876 patients with advanced ovarian cancer at a median follow-up of 10.7 years and found that the median overall survival with IP therapy was 61.8 months compared with 51.4 months for patients treated with intravenous chemotherapy. This difference resulted in a 23% decreased risk for death (adjusted hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.65–0.90; P = .002).
The benefit of IP chemotherapy extended beyond a decade. The probability of survival at 10 years was 19.3% for patients who received IP chemotherapy compared with 15.6% for patients who received intravenous chemotherapy (P = .004).
According to Devansu Tewari, MD, of Kaiser Permanente Irvine Medical Center in Irvine, California, and colleagues, the use of IP chemotherapy has not been widely accepted among clinicians in the United States, despite positive results from several clinical trials testing the treatment method.
“The long-term survival benefits described in this report may encourage more clinicians to adopt IP chemotherapy in the community,” Tewari and colleagues wrote in the Journal of Clinical Oncology. “In addition, IP therapy may be implemented as a quality measure at institutions with the expertise and support teams necessary to administer IP treatment.”
The researchers retrospectively analyzed data from patients assigned to intravenous chemotherapy (n = 436) or IP chemotherapy (n = 440) as part of GOG 114 and GOG 172. GOG 114 assigned patients to two different treatment arms: intravenous paclitaxel at a dose of 135 mg/m2 followed by intravenous cisplatin at a dose of 75 mg/m2 for 6 courses; or intravenous carboplatin for 2 courses followed by the intravenous paclitaxel dose on day 1 and IP cisplatin at 100 mg/m2 on day 8 for 6 courses. In GOG 172, patients received 135 mg/m2 of intravenous paclitaxel followed by either 75 mg/m2 of intravenous cisplatin or 100 mg/m2 of IP cisplatin on day 2 and 60 mg/m2 of IP paclitaxel on day 8 for 6 cycles.
In addition to the overall survival improvement, IP therapy was also associated with improved survival among those patients with gross residual disease (adjusted HR = 0.75; 95% CI, 0.62–0.92; P = .006).
“Nevertheless, it is important to note that those with gross residual disease had a 1.89-fold increase in risk of death (95% CI, 1.48–2.43; P < .001) compared with patients with no visible disease,” the researchers noted.
About 50% of patients in both study groups completed 6 cycles of IP therapy. The researchers found that the risk for death decreased by 12% for each cycle of IP chemotherapy that patients completed, and that the odds of completing IP therapy decreased about 5% for each increasing year of age at enrollment.
Other identified factors linked with decreased survival included clear/mucinous vs serous histology (adjusted HR = 2.79; 95% CI, 1.83–4.24; P < .001), gross residual disease vs no visible disease (adjusted HR = 1.89; 95% CI, 1.48–2.43; P < .001), and fewer vs more cycles of IP chemotherapy (adjusted HR = 0.88; 95% CI, 0.83–0.94; P < .001).
In an accompanying editorial, Michael A. Bookman, MD, of US Oncology Research in The Woodlands, Texas, and Mark F. Brady, PhD, of the NRG Oncology Statistical and Data Center in Buffalo, New York, wrote that the combined data in this analysis “clearly document a sustained impact on median overall survival favoring IP therapy by 10.4 months,” but also acknowledge that IP therapy is associated with “increased complexity, toxicity, and cost.”
“Important questions remain regarding patient selection (in terms of the extent of residual disease), mechanism of action, treatment modifications, timing, optimal number of IP cycles, and integration with targeted agents,” Bookman and Brady wrote. “Some of these questions will be addressed in the context of GOG-0252, and it remains to be seen whether better intravenous chemotherapy might match the outcomes previously associated with IP chemotherapy.”