Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: A Gynecologic Oncology Group study

https://doi.org/10.1016/j.ygyno.2013.04.001Get rights and content

Highlights

  • Survival for IP chemotherapy patients with no residual disease is unprecedented.

  • Prognostic factors include age, histology, and extent of residual disease.

  • More recurrences occur extraperitoneal for patients treated with IP chemotherapy.

Abstract

Objectives

To determine prognostic factors for survival in ovarian cancer patients treated with intraperitoneal (IP) chemotherapy using ancillary data from cooperative group clinical trials.

Methods

Data were collected from 428 patients with stage III ovarian cancer who underwent optimal surgical cytoreduction (< 1 cm) followed by IP paclitaxel/platinum chemotherapy. Primary endpoints were progression free survival (PFS) and overall survival (OS). Potential prognostic variables were included in Cox proportional hazard regression models. Multivariate analysis was conducted to identify independent prognostic factors.

Results

Median PFS was 24.9 months (95% CI, 23.0–29.2) and median OS was 61.8 months (95% CI, 55.5–69.8). Predictors for PFS were histology, surgical stage and residual disease. Age, histology, and residual disease were prognostic for OS. There were no differences in the hazard ratio for death or progression between patients with positive, negative, or unknown lymph node status. For patients receiving IP chemotherapy (n = 428), 36% of patients had no residual disease with median PFS of 43.2 months (95% CI 32.5–60.4) and median OS of 110 months (95% CI, 60.0–161.3).

Conclusions

Age, histology, and extent of residual disease were predictors of OS in stage III patients treated with IP chemotherapy following optimal cytoreduction. Patients with no residual disease following primary surgery that are treated with adjuvant platinum based IP chemotherapy have survival measures that exceed any rates previously seen in this population.

Introduction

Epithelial ovarian carcinoma (EOC) is the leading cause of death among patients with gynecologic malignancies with an estimated 22,240 new cases and 14,030 deaths for 2013 [1]. Unfortunately, most ovarian cancer patients present with advanced stages due to the absence of effective screening methods coupled with the natural biology of the disease [2]. In the absence of tools for screening or preventive strategies, the best approach for improving clinical outcome is to optimize management after diagnosis. Advances in survival have been achieved with aggressive cytoreductive surgery, followed by platinum and taxane-based chemotherapy, but the majority of patients will experience recurrence and ultimately die from their disease [3], [4]. The most promising improvements in survival in recent years have been identified thru clinical trials for patients treated with intraperitoneal (IP) chemotherapy [5], [6], [7]. Armstrong et al. documented the longest median survival to date at 66 months for stage III EOC patients treated with IP chemotherapy. The rationale for IP therapy is that higher concentrations of cytotoxic agents can be infused into the peritoneal cavity than would be tolerated systemically. This allows the predominant site of tumor to have sustained exposure to antitumor agents while normal tissues, such as the bone marrow, are relatively spared [8]. Drugs delivered by IP route penetrate only to a depth of a few millimeters beneath the tumor surface, so patients with small volume residual disease are expected to benefit the most [9]. It has not been determined whether IP chemotherapy is of benefit to patients with disease outside of the peritoneal cavity, specifically those with retroperitoneal disease.

There have been three large randomized clinical trials conducted by the Gynecology Oncology Group (GOG) which have demonstrated a clinically significant survival advantage associated with IP chemotherapy compared to intravenous (IV) chemotherapy. Table 1 summarizes patient eligibility, treatment arms, and overall survival (OS) data from the three trials. The objective of this ancillary data analysis was to review pooled data collected from GOG trials using IP chemotherapy and identify subsets of patients within this group that had better or worse clinical outcome measures.

Section snippets

Methods

The current study was a retrospective review of data collected from patients with stage III EOC treated with IP platinum and paclitaxel chemotherapy on randomized clinical trials conducted by the GOG: protocols 114 and 172. Data from GOG protocol 104 were not included in the final analysis because data collection forms were substantially different from those used for protocol 114 and 172 and did not provide detailed description of disease sites before and after surgery. Informed consent

Patient characteristics

Data from 845 patients enrolled in the IP and IV arms of GOG-114 and GOG-172 were included in this study. Table 2 summarizes the demographic and clinical characteristics for the 428 patients randomized to IP treatment. The median age was 57 years (range, 49 to 64), 91% were white, and 71% had a performance status of 0. Fifty percent of all patients had poorly differentiated tumors with only 6% of all tumors representing clear cell or mucinous histology. Eighty-three percent of patients had stage

Conclusion

This study represents a retrospective analysis of a large group of stage III EOC patients who received primary surgical cytoreduction to < 1 cm followed by IP platinum and paclitaxel chemotherapy during participation in cooperative group trials. A review of the similarities and differences between the experimental (IP) and control arms (IV) of these three trials will support that it is difficult to compare studies using different cytotoxic agents and dosing schedules. Experimental and control

Conflict of interest statement

The authors declare that there are no conflicts of interest to disclose.

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  • Cited by (0)

    Presented: Plenary presentation at Society of Gynecologic Oncologists Annual Meeting on March 27, 2012; Austin, TX.

    Invited presentation at Semi-Annual Gynecology Oncology Group Meeting on July 24, 2013; Boston, MA.

    This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), as well as the Ovarian Cancer Research Fund as a Young Investigator Award from the Gynecologic Oncology Group. The following institutions participated in this study: University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University, University of Minnesota Medical School, University of Southern California at Los Angeles, University of Mississippi Medical Center, Colorado Gynecologic Oncology Group P.C., University of California at Los Angeles, University of Washington, University of Pennsylvania Cancer Center, University of Miami School of Medicine, Milton S. Hershey Medical Center, Georgetown University Hospital, University of Cincinnati, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, University of Texas Southwestern Medical Center at Dallas, Indiana University School of Medicine, Wake Forest University School of Medicine, Albany Medical College, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, University of Kentucky, Eastern Virginia Medical School, The Cleveland Clinic Foundation, Johns Hopkins Oncology Center, State University of New York at Stony Brook, Eastern Pennsylvania GYN/ONC Center, P.C., Southwestern Oncology Group, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Columbus Cancer Council, University of Massachusetts Medical School, Fox Chase Cancer Center, Medical University of South Carolina, Women's Cancer Center, University of Oklahoma, University of Virginia Health Sciences Center, University of Chicago, University of Arizona Health Science Center, Tacoma General Hospital, Eastern Collaborative Oncology Group, Thomas Jefferson University Hospital, Mayo Clinic, Case Western Reserve University, Tampa Bay Cancer Consortium, North Shore University Hospital, Gynecologic Oncology Network, Ellis Fischel Cancer Center, and Fletcher Allen Health Care.

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