High-dose chemotherapy and autologous bone marrow or stem cell reconstitution for solid tumors.
High-dose chemotherapy--in conjunction with the transplantation of either mononuclear cells harvested from the marrow or CD 34+ cells harvested from the peripheral blood--has proved effective in curing certain patients with leukemia, lymphoma, and, to a lesser extent, multiple myeloma. Though the CD 34+ therapy is a relatively new treatment and the mononuclear cell therapy is more standard, both have been successfully used to reconstitute lethally damaged hematopoietic stem cells. Allogeneic transplants have been more effective than autologous transplants against tumors, but they also pose a greater hazard of death from complications, graft-versus-host disease, and infections. More currently, this approach has been used in patients with certain solid tumors, either in a metastatic or recurrent disease setting or as an adjuvant to surgery and/or standard doses of chemotherapy in patients with a known high risk of recurrence. Unfortunately, the majority of the studies about the impact of this therapy have been small and nonrandomized against standard therapy, and they have encompassed diverse populations of patients. This makes comparisons with contemporary standard--dose approaches--already problematic from a statistical point of view--even more dangerous because of the dissimilarity of the groups being compared. Particularly in the high-risk adjuvant setting, data suggest that those patients that meet the eligibility criteria for high-dose therapy and transplantation exhibit the prognostic factors for a positive outcome. When one compares these results with those of a more heterogeneous group of patients treated with conventional therapy, the conclusion might be drawn that high-dose therapy is superior to standard therapy, when a longer follow-up of the patients in the study will show this to be untrue. Thus there is a plea from clinicians and physicians conducting trials for prospective, randomized trials that would allow a fair comparison between high-dose therapy in combination with transplant procedures and a more conventional, standard chemotherapy, which is often less toxic and definitely less expensive. This article reviews the data for transplantation in four tumors: breast cancer, ovarian cancer, small-cell lung cancer, and germ cell testis cancer. There is such a small number of randomized trials that an attempt must be made to compare these small high-dose therapy studies with similar, though not identical, large studies of conventional therapy. This article attempts to make those comparisons, and several conclusions are drawn, which are detailed below. First, few data support the use of high-dose chemotherapy in any patient with recurrent and drug-resistant breast cancer or ovarian cancer. Similarly, few data support the use of high-dose approaches for patients with extensive small-cell lung cancer. For patients with metastatic breast cancer that has responded completely to conventional chemotherapy, no data suggest a survival advantage for the immediate consolidation of that response with high-dose chemotherapy. The only trial addressing this issue found that immediate transplantation led to a better disease-free survival rate, but overall survival, as compared with that of patients who received transplants at relapse, was not affected, and the study did not address the issue of the relative merits of conventional chemotherapy in either case. The only study of high-dose versus conventional chemotherapy was statistically underpowered, and it showed poorer-than-anticipated outcomes in the patients who received conventional therapy. Ongoing or recently completed trials will, it is hoped, address the many unanswered questions in this area. For patients with high-risk, non-metastatic breast cancer, no completed and analyzed phase III randomized studies address the relative merits of conventional versus high-dose therapy. (ABSTRACT TRUNCATED)
McGuire
W P
WP
University of Mississippi School of Medicine, Jackson Women's Cancer Center Medical Staff, Mercy Hospital, Baltimore, Maryland, USA.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000628:therapy; D018288:Carcinoma, Small Cell / Q000628:therapy; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy; D008297:Male; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000628:therapy; D011379:Prognosis; D013736:Testicular Neoplasms / Q000628:therapy; D014182:Transplantation, Autologous