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Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies.
Bone Marrow Transplant. 1994 Nov; 14(5):813-9.BM

Abstract

The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen-related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1-26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted.

Authors+Show Affiliations

Fred Hutchinson Cancer Research Center, Seattle, Washington.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7889015

Citation

Weaver, C H., et al. "Phase I Study of High-dose Busulfan, Melphalan and Thiotepa With Autologous Stem Cell Support in Patients With Refractory Malignancies." Bone Marrow Transplantation, vol. 14, no. 5, 1994, pp. 813-9.
Weaver CH, Bensinger WI, Appelbaum FR, et al. Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies. Bone Marrow Transplant. 1994;14(5):813-9.
Weaver, C. H., Bensinger, W. I., Appelbaum, F. R., Lilleby, K., Sandmaier, B., Brunvand, M., Rowley, S., Petersdorf, S., Rivkin, S., & Gooley, T. (1994). Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies. Bone Marrow Transplantation, 14(5), 813-9.
Weaver CH, et al. Phase I Study of High-dose Busulfan, Melphalan and Thiotepa With Autologous Stem Cell Support in Patients With Refractory Malignancies. Bone Marrow Transplant. 1994;14(5):813-9. PubMed PMID: 7889015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies. A1 - Weaver,C H, AU - Bensinger,W I, AU - Appelbaum,F R, AU - Lilleby,K, AU - Sandmaier,B, AU - Brunvand,M, AU - Rowley,S, AU - Petersdorf,S, AU - Rivkin,S, AU - Gooley,T, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 813 EP - 9 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 14 IS - 5 N2 - The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen-related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1-26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/7889015/Phase_I_study_of_high_dose_busulfan_melphalan_and_thiotepa_with_autologous_stem_cell_support_in_patients_with_refractory_malignancies_ L2 - https://medlineplus.gov/cancerchemotherapy.html DB - PRIME DP - Unbound Medicine ER -