MP 8.01.23

Hematopoietic Stem Cell Transplantation for Epithelial Ovarian Cancer

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Medical Policy
Section Therapy	Original Policy Date 12/01/99	Last Review Status/Date Reviewed with literature search/12:2008
Issue 12:2008		Return to Medical Policy Index

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Description

Policy

Policy Guidelines

Benefit Application

Rationale

Initially, this policy was based on a 1998 TEC Assessment, “High-dose chemotherapy with autologous stem cell support for epithelial ovarian cancer” (4) that reached the following conclusions:

The 1998 TEC Assessment did not identify any studies reporting outcomes of allogeneic transplants for patients with ovarian cancer. (4) A separate 1999 TEC Assessment evaluated the use of high-dose chemotherapy with allogeneic stem-cell support (HDC/AlloSCS) as a salvage therapy after a failed prior course of HDC/AuSCS. (5) There were no data regarding outcomes of this strategy as therapy for epithelial ovarian cancer.

Summary of the Literature Through 2008 on the Use of Stem-Cell Transplantation in Ovarian Cancer
Experience with high-dose chemotherapy in ovarian cancer comes primarily from registry data and phase II trials. (6-9) Over the last 20 years, more than 1,000 patients have been entered on transplant registries in Europe and in the U.S. (3, 6, 7) Many of the registry patients were treated in relapse, and others in nonrandomized studies using high-dose chemotherapy as first-line treatment. Case selection and retrospective review make the interpretation of the registries and nonrandomized data difficult. (3) Survival analyses from registry data and clinical trials suggested a possible benefit treating ovarian cancer patients with high-dose chemotherapy. (3)

 

However, as outlined below, none of the randomized trials that have been performed have provided evidence that high-dose chemotherapy with stem-cell transplant in ovarian cancer provides any outcome benefit, whether used as part of initial therapy or as a consolidation strategy.
Initial therapy
Mobus et al. reported on a trial of 149 patients with untreated ovarian cancer who were randomly assigned, after debulking surgery, to standard chemotherapy or sequential high-dose chemotherapy (HDC) and peripheral blood stem cell support. (3) This was the first randomized trial comparing HDC to standard CT as first-line treatment of ovarian cancer, and the investigators found no statistically significant difference in PFS or OS between the 2 treatment options. The median patient age was 50 years (range: 20–65) and FIGO stage was IIb/IIc in 4%, III in 78%, and IV in 17%. Seventy-six percent of patients in the HDC arm received all of the scheduled chemotherapy cycles. After a median follow-up of 38 months, progression-free survival was 20.5 months in the standard chemotherapy arm and 29.6 months in the HDC arm (hazard ratio [HR]: 0.84; 95% CI: 0.56–1.26; p =0.40). Median overall survival was 62.8 months in the standard chemotherapy arm and 54.4 months in the HDC arm (HR: 1.17; 95% CI: 0.71–1.94; p =0.54).
Consolidation therapy
Papadimitriou et al. reported on the use of HDC with stem cell support as consolidation therapy in patients with advanced epithelial ovarian cancer (FIGO stage IIC-IV). (2) Patients who achieved first clinical complete remission after conventional chemotherapy were randomly assigned to receive or not receive high-dose melphalan and autologous stem-cell transplant. A total of 30 patients were enrolled onto the trial. Of the 37 patients allocated to HDC, 11 did not receive the treatment either due to refusal or failure of peripheral blood stem-cell mobilization. In an intent-to-treat analysis, there were no significant differences between the 2 arms in time-to-disease progression (p =0.059) or OS (p =0.38).
Cure et al. reported on outcomes in advanced ovarian cancer patients randomized after second-look surgery to receive either high-dose chemotherapy with peripheral blood stem-cell support or conventional-dose maintenance chemotherapy. (10) Patients were younger than 60 years old with FIGO stage III-IV and disease sensitive to first-line chemotherapy. One-hundred ten patients were enrolled (n =57 high-dose and n =53 conventional-dose chemotherapy). Median follow-up was 60 months. No difference was seen in disease-free or overall survival between the 2 arms. Disease-free survival in the conventional- versus high-dose group was 12.2 months (95% CI: 7.3–17.1) versus 17.5 months (95% CI: 5.2–29.9) (p =0.22). Overall survival was 42.5 months (95% CI: 28.8-56.6) and 49.7 months (95% CI: 29.9–69.4), respectively (p =0.43).
National Comprehensive Cancer Network (NCCN) Guidelines
National Comprehensive Cancer Network clinical practice guidelines for ovarian cancer indicate that high-dose chemotherapy with peripheral blood stem cell transplantation is considered investigational for the treatment of ovarian cancer. (11)
National Cancer Institute Clinical Trials Database (PDQ®)
No Phase III trials investigating high-dose therapy for patients with ovarian epithelial cancer were identified in the 2008 National Cancer Institute database.

 

 

 

References:

1. Physician Data Query (PDQ), 2008. Ovarian epithelial cancer treatment (PDQ®). National Cancer Institute, U.S. National Institute of Health. Available online at: http://www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/HealthProfessional.
2. Papadimitriou C, Dafni U, Anagnostopoulos A et al. High-dose melphalan and autologous stem cell transplantation as consolidation treatment in patients with chemosensitive ovarian cancer: results of a single-institution randomized trial. Bone Marrow Transplant 2008; 41(6):547-54.
3. Mobus V, Wandt H, Frickhofen N et al. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: Intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol 2007; 25(27):4187-93.
4. 1998 TEC Assessments; Tab 6.
5. 1999 TEC Assessments; Tab 11.
6. Stiff PJ, Veum-Stone J, Lazarus HM et al. High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report. Ann Intern Med 2000; 133(7):504-15.
7. Ledermann JA, Herd R, Maraninchi D et al. High-dose chemotherapy for ovarian carcinoma: long-term results from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol 2001; 12(5):693-9.
8. Stiff PJ, Bayer R, Kerger C et al. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients. J Clin Oncol 1997; 15(4):1309-17.
9. Donato ML, Aleman A, Champlin RE et al. Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation. Bone Marrow Transplant 2004; 33(12):1219-24.
10. Cure H, Battista C, Guastalla JP et al. Phase III randomized trial of high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support as consolidation in patients (pts) with advanced ovarian cancer (AOC): 5-year follow-up of a GINECO/FNCLCC/SFGM-TC study. Abstract No: 5006. American Society for Clinical Oncology. 40th annual meeting. New Orleans, Louisiana. June 5-8, 2004.
11. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 1.2008. http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf .

Index

Policy History

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