Intraperitoneal Plus Intravenous Chemotherapy—an Underused Strategy—May Improve Survival in Advanced Ovarian Cancer
An observational study investigating the use and effectiveness of a combination regimen of intraperitoneal and intravenous chemotherapy in the treatment of advanced-stage ovarian cancer has found that although the dual approach substantially improved survival—81% of those treated with the combination therapy were alive 3 years after therapy, compared with 71% treated with intravenous chemotherapy alone—fewer than half of patients who could benefit from the dual therapy received it. The study by Wright et al is published in the Journal of Clinical Oncology.
Study Background and Methodology
The purpose of this prospective study was to explore whether combination intraperitoneal and intravenous chemotherapy performed as well in clinical practice as it did in GOG-172, a 2006 randomized clinical trial conducted by the Gynecologic Oncology Group, which demonstrated a 16-month improvement in median overall survival and led to a Clinical Announcement by the National Cancer Institute encouraging use of the combination method.
The researchers analyzed the medical records of 823 women treated for stage III ovarian cancer diagnosed at six National Comprehensive Cancer Network (NCCN) institutions. They examined the use of a combination regimen of intraperitoneal and intravenous chemotherapy administered to all patients diagnosed between 2003 and 2012 (N = 823) and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score–matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants to minimize selection bias.
The primary outcomes of interest included the proportion of patients receiving intraperitoneal and intravenous chemotherapy and overall survival. Secondary outcomes included chemotherapy completion, treatment-related toxicities, and site(s) of first disease recurrence.
Study Findings
The researchers found that the use of intraperitoneal and intravenous chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and plateaued thereafter. Between 2006 and 2012, adoption of intraperitoneal and intravenous chemotherapy varied by institution from 4% to 67% (P < .001), and 43% of patients received modified intraperitoneal and intravenous regimens at treatment initiation.
In the propensity score–matched sample, intraperitoneal and intravenous chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% vs 71%; hazard ratio [HR] = 0.68; 95% confidence interval [CI] = 0.47–0.99), compared with intravenous chemotherapy alone, but also more frequent alterations in the chemotherapy delivery route (adjusted rate discontinuation or change, 20.4% vs 10.0%; adjusted odds ratio [AOR] = 2.83; 95% CI = 1.47–5.47).
Treatment-Related Toxicities
The analysis also found that anemia rates were significantly higher in the intraperitoneal and intravenous vs the intravenous chemotherapy group (adjusted rates, 10.9% vs 5.0%; AOR = 2.20; 95% CI = 1.04–4.65), as were hospitalizations (adjusted rates, 14.4% vs 10.0%; AOR = 1.47; 95% CI = 0.82–2.64), although this latter difference was not statistically significant. Clinical complications did not otherwise differ by route.
Compared with those receiving intravenous chemotherapy alone, women who received intraperitoneal and intravenous chemotherapy were more likely to change treatments because of treatment-related toxicities (adjusted rates, 20.4% vs 10.0%; AOR = 2.83; 95% CI = 1.47–5.47) or for other reasons (eg, intraperitoneal port catheter complication; adjusted rates, 8.5% vs 4.0%; AOR = 2.14; 95% CI = 0.87–5.26), although this latter difference was not statistically significant.
Of the 41 patients who discontinued intraperitoneal and intravenous chemotherapy because of toxicities, 13 switched to a new intraperitoneal and intravenous chemotherapy regimen, 22 switched to intravenous chemotherapy, and 6 discontinued adjuvant treatment. Women treated with intraperitoneal and intravenous chemotherapy had higher odds of presenting with distant disease at first recurrence (adjusted rates, 58.8% vs 29.4%; AOR = 3.14; 95% CI = 1.34–7.36), compared with intravenous chemotherapy.
Improving Survival for Patients
“This is the first study to show that [intraperitoneal and intravenous] chemotherapy improves survival in the real world, outside of a clinical trial,” said Alexi A. Wright, MD, MPH, medical oncologist at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute and lead author of the study, in a statement. “Unfortunately, fewer than half of women who qualify for [intraperitoneal and intravenous] chemotherapy received the treatment. This suggests that increasing access to [intraperitoneal and intravenous] chemotherapy may improve ovarian cancer patients’ survival.”
Dr. Wright is the corresponding author of the Journal of Clinical Oncology article.
Funding for this study was provided by the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
