High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Ovarian Cancer: An Autologous Blood and Marrow Transplant Registry Report

3 October 2000 | Volume 133 Issue 7 | Pages 504-515

Background: Autologous transplantation is increasingly used to treat epithelial ovarian cancer. However, it is not clear which patients may benefit.

Objective: To determine overall and progression-free survival and factors associated with favorable outcome after autotransplantation for ovarian cancer.

Design: Observational cohort study.

Setting: 57 centers reporting to the Autologous Blood and Marrow Transplant Registry (ABMTR).

Patients: 421 women who received transplants between 1989 and 1996.

Interventions: High-dose chemotherapy using diverse regimens with hematopoietic stem-cell rescue.

Measurements: Primary outcomes were progression-free survival and overall survival. Multivariate analyses using Cox proportional-hazards regression considered the following factors: age, Karnofsky performance score, initial stage, histologic characteristics, previous therapy, remission status, extent of disease, graft source, transplant regimen, and year of transplantation.

Results: Most patients had extensive previous chemotherapy. Forty-one percent had platinum-resistant tumors, and 38% had tumors at least 1 cm in diameter. Only 34 patients (8%) received transplants as part of initial therapy. The probability of death within 100 days was 11% (95% CI, 8% to 14%). Two-year progression-free survival was 12% (CI, 9% to 16%), and 2-year overall survival was 35% (CI, 30% to 41%). Younger age, Karnofsky performance score of at least 90%, non–clear-cell disease, remission at transplantation, and platinum sensitivity were associated with better outcomes. Progression-free and overall survival were 22% (CI, 12% to 33%) and 55% (CI, 42% to 66%), respectively, for women with a high Karnofsky performance score and non–clear-cell, platinum-sensitive tumors.

Conclusions: Some subgroups of patients with ovarian cancer seem to have good outcomes after autotransplantation, although several biases may have affected these observations. Phase III trials are needed to compare such outcomes with outcomes of conventional chemotherapy.

Author and Article Information

From Loyola University Medical Center, Maywood, Illinois; Autologous Blood and Marrow Transplant Registry Statistical Center, Health Policy Institute, Medical College of Wisconsin, Milwaukee, Wisconsin; Case Western Reserve University, Cleveland, Ohio; University of Michigan Cancer Center, Ann Arbor, Michigan; Walt Disney Memorial Cancer Institute, Orlando, Florida; Princess Margaret Hospital, Toronto, Ontario, Canada; Sharp Health Care and the Sidney Kimmel Cancer Center, San Diego, California; University of North Carolina, Chapel Hill, North Carolina; and the Mayo Clinic, Rochester, Minnesota.

Grant Support: By Public Health Service grants P01-CA-40053 and U24-76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung, and Blood Institute (U.S. Department of Health and Human Services) and by grants from Alpha Therapeutic Corp.; Amgen, Inc.; anonymous donors; Baxter Fenwal/Nexell Therapeutics, Inc.; Berlex Laboratories; BioWhittaker, Inc.; BlueCross BlueShield; Bristol-Myers Squibb; Cell Therapeutics, Inc.; Centeon; Center for Advanced Studies in Leukemia; Chimeric Therapies, Inc.; Chiron Therapeutics; COBE BCT, Inc.; Eppley Foundation for Research; Fujisawa Healthcare, Inc.; Genentech, Inc.; Human Genome Sciences; Immunex Corp.; Kettering Family Foundation; Kirin Brewery Company; Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation; Mayer Ventures; Milstein Family Foundation; Milwaukee Foundation/Elsa Schoeneich Research Fund; Nexell Therapeutics, Inc.; NeXstar Pharmaceuticals, Inc; Novartis Pharmaceuticals; Orphan Medical; Ortho Biotech, Inc.; Pfizer, Inc.; Pharmacia & Upjohn; Roche Laboratories; SangStat Medical Corp.; Schering AG; Schering Oncology; Searle; SEQUUS Pharmaceuticals; SmithKline Beecham Pharmaceutical; SyStemix; TheraTechnologies; and United Resource Networks.

Requests for Single Reprints: Mary M. Horowitz, MD, MS, Statistical Center, Autologous Blood and Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226; e-mail, marymh{at}mcw.edu.

Current Author Addresses: Dr. Stiff: Division of Hematology/Oncology, Loyola University Medical Center, 2160 South First Avenue, Building 112, Room 240, Maywood, IL 60153.

Ms. Veum-Stone and Drs. Klein and Horowitz: Autologous Blood and Marrow Transplant Registry, Statistical Center, Health Policy Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226.

Dr. Lazarus: Department of Hematology/Oncology, Ireland Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-1736.

Dr. Ayash: Division of Hematology/Oncology, University of Michigan Medical Center, Cancer Center B1-212, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0914.

Dr. Edwards: Walt Disney Memorial Cancer Institute, 2501 North Orange Avenue, Suite 682, Orlando, FL 32804.

Dr. Keating: Department of Medical Hematology/Oncology, Princess Margaret Hospital, 610 University Avenue, Suite 5-211, Toronto, Ontario M5G 2M9, Canada.

Dr. Oblon: Blood and Marrow Program, Sharp Health Care and the Sidney Kimmel Cancer Center, 8008 Frost Street, Suite 300A, San Diego, CA 92123.

Dr. Shea: Division of Medical Oncology, University of North Carolina, Chapel Hill, CBB 3009 Old Clinic Building, Chapel Hill, NC 27599-0001.

Dr. Thomé: Hematology/Oncology, Mayo Clinic Rochester, Mayo E-12, Rochester, MN 55905.

Author Contributions: Conception and design: P.J. Stiff, H.M. Lazarus, L. Ayash, T.C. Shea, M.M. Horowitz.

Analysis and interpretation of the data: P.J. Stiff, J. Veum-Stone, H.M. Lazarus, J.R. Edwards, D.J. Oblon, T.C. Shea, S. Thomé, M.M. Horowitz.

Drafting of the article: P.J. Stiff, L. Ayash, T.C. Shea, S. Thomé, M.M. Horowitz.

Critical revision of the article for important intellectual content: P.J. Stiff, H.M. Lazarus, L. Ayash, J.R. Edwards, A. Keating, D.J. Oblon, T.C. Shea, S. Thomé, M.M. Horowitz.

Final approval of the article: P.J. Stiff, H.M. Lazarus, L. Ayash, J.R. Edwards, A. Keating, D.J. Oblon, T.C. Shea, S. Thomé, M.M. Horowitz.

Provision of study materials or patients: P.J. Stiff, L. Ayash, D.J. Oblon, T.C. Shea.

Statistical expertise: J. Veum-Stone, J.P. Klein, M.M. Horowitz.

Obtaining of funding: P.J. Stiff, M.M. Horowitz.

Administrative, technical, or logistic support: P.J. Stiff, M.M. Horowitz.

Collection and assembly of data: P.J. Stiff, J. Veum-Stone, M.M. Horowitz.