Busulfan-containing pre-transplant regimens for the treatment of solid tumors
Ghalie, R.; Reynolds, J.; Valentino, L.A.; Manson, S.; Korenblit, A.D.; Feingold, J.M.; Adler, S.S.; Pruett, J.; Kaizer, H.
Bone Marrow Transplantation 14(3): 437-442
1994
ISSN/ISBN: 0268-3369 PMID: 7994269 Document Number: 423074
This study investigated the toxicity and efficacy of busulfan-containing pre-transplant regimens in patients with solid tumors. The majority of these patients were also treated on protocols involving two transplant courses aiming at further reducing tumor burden. Between October 1984 and November 1993, we treated 44 patients with recurrent breast cancer (n = 28), sarcoma (n = 10) or ovarian cancer (n = 6) with one of two busulfan-containing regimens. All patients except two had measurable disease prior to transplantation. Twenty-one patients had not received chemotherapy for metastatic disease. Of the remaining 23 patients treated with standard-dose chemotherapy, 14 had progressive disease. Busulfan 16 mg/kg was paired with cyclophosphamide 200 mg/kg (BuCY) or with etoposide 60 mg/kg (Bu-Vp). The Bu-Vp combination (32 courses) was used as the second preparative regimen in patients who had received thiotepa, carboplatin and cyclophosphamide for their first transplant. The BuCY regimen was used in 16 courses, either for single or for tandem transplant. Bone marrow cells only were used in 17 transplants and peripheral blood progenitor cells, with or without bone marrow, in 31 courses. Treatments were usually well tolerated. Common toxicities included mucositis, skin rash and veno-occlusive disease of the liver (fatal, in two). One patient developed generalized seizures during busulfan therapy. Hematologic recovery was significantly accelerated with peripheral progenitor cells and permitted the administration of closely spaced tandem transplants. Two patients receiving sequential transplants with BuCY experienced severe long-term neurologic and pulmonary toxicity. Objective responses were noted in 26 patients. Ten patients remain free of disease for 2-15+ months, all of whom received two transplants. In conclusion, busulfan appears to be an effective component of preparative regimens for patients with solid tumors. These regimens result in low overall toxicity. Evaluation of busulfan-containing regimens in less heavily pre-treated patients is desirable. Longer follow up is needed to confirm the role of tandem transplant for the treatment of patients with solid tumors.