Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer

Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer

  1. Alexi A. Wright,
  2. Angel Cronin,
  3. Dana E. Milne,
  4. Michael A. Bookman,
  5. Robert A. Burger,
  6. David E. Cohn,
  7. Mihaela C. Cristea,
  8. Jennifer J. Griggs,
  9. Nancy L. Keating,
  10. Charles F. Levenback,
  11. Gina Mantia-Smaldone,
  12. Ursula A. Matulonis,
  13. Larissa A. Meyer,
  14. Joyce C. Niland,
  15. Jane C. Weeks and
  16. David M. O’Malley

+ Author Affiliations


  1. Alexi A. Wright, Angel Cronin, Dana E. Milne, Nancy L. Keating, Ursula A. Matulonis, and Jane C. Weeks, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA; Michael A. Bookman, University of Arizona Cancer Center, Tucson, AZ; Robert A. Burger, University of Pennsylvania; Gina Mantia-Smaldone, Fox Chase Cancer Center, Philadelphia, PA; David E. Cohn and David M. O’Malley, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Mihaela Cristea and Joyce C. Niland, City of Hope Comprehensive Cancer Center, Duarte, CA; Jennifer J. Griggs, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; and Charles F. Levenback and Larissa A. Meyer, The University of Texas MD Anderson Cancer Center, Houston, TX.
  1. Corresponding author: Alexi A. Wright, MD, Dana-Farber Cancer Institute, Dana 1133, 450 Brookline Ave, Boston, MA 02215; e-mail: alexi_wright@dfci.harvard.edu.
  1. Presented, in part, at the 50th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30-June 3, 2014.

Abstract

Purpose A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice.

INTRODUCTION

Several randomized clinical trials have demonstrated that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in women with optimally resected, stage III ovarian cancer, compared with IV chemotherapy alone.13 In 2006, the National Cancer Institute (NCI) issued a rare Clinical Announcement encouraging IP/IV chemotherapy use after the Gynecologic Oncology Group (GOG) conducted a randomized trial, GOG-172, that demonstrated a 16-month improvement in median overall survival.

To date, however, few studies have examined the impact of this announcement on the use of IP/IV chemotherapy in clinical practice or investigated whether the survival benefit in GOG-172 is representative of outcomes outside of clinical trials. This is important because fewer than 3% of adult patients with cancer enroll onto clinical trials, and trial participation may be associated with better survival outcomes,4,5 raising concerns about the generalizability of these findings.6

Several factors have been identified as potential barriers to integration of IP/IV chemotherapy into practice,7,8 including treatment-related toxicities, the absence of a standard regimen, patients’ preferences, and the inconvenience of an inpatient regimen.810 In addition, retrospective studies have documented higher rates of extra-abdominal cancer recurrences, raising concerns about whether IP/IV chemotherapy provides effective systemic control.11,12 Finally, some physicians may believe that alternate chemotherapy regimens (eg, dose-dense paclitaxel) offer comparable survival with fewer toxicities.13

In this study, we examined the use of IP/IV chemotherapy over time at six comprehensive cancer centers where structural barriers to IP/IV chemotherapy administration (eg, trained nursing staff and resource intensity)7,14 should be rare. In addition, we sought to characterize factors associated with IP/IV chemotherapy use and the regimens delivered, because physicians frequently modify the GOG-172 regimen to minimize toxicities.7,10,15 Finally, we examined outcomes associated with IP/IV chemotherapy, including chemotherapy completion, treatment-related toxicities, site(s) of first recurrence, and overall survival. We hypothesized that IP/IV chemotherapy would be associated with improved survival compared with IV chemotherapy, despite frequent modifications to the GOG-172 regimen.

PATIENTS AND METHODS

Purpose A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice.

Patients and Methods Prospective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in 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.

Results Use of IP/IV 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 IP/IV chemotherapy varied by institution from 4% to 67% (P < .001) and 43% of patients received modified IP/IV regimens at treatment initiation. In the propensity score–matched sample, IP/IV chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared with IV chemotherapy, but also more frequent alterations in chemotherapy delivery route (adjusted rates discontinuation or change, 20.4% v 10.0%; adjusted odds ratio, 2.83; 95% CI, 1.47 to 5.47).

Conclusion Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it. Increasing IP/IV chemotherapy use in clinical practice may be an important and underused strategy to improve ovarian cancer outcomes. Read that again- all we have to do is trqain and do it right and probably twice as many woman will live Dr Ryan- Outrageous and this the sort of thing NCI and American Cancer  Society goes after to fund the education and raise the clinical standards. Dr  Ryan

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