Dose escalation of mitoxantrone given with thiotepa and autologous bone marrow transplantation for metastatic breast cancer.
High-dose chemotherapy given with autologous bone marrow support has resulted in significant tumor responses in the majority of patients with metastatic breast cancer, a minority of which are durable. To improve on these results, we are developing high-dose preparative regimens which may be given in successive cycles, each with autologous bone marrow transplantation (ABMT), over a short duration. In this report, 44 patients with metastatic breast cancer were treated with thiotepa (total dose: 900 mg/m2) and mitoxantrone (MT), administered in a dose-escalation fashion, with ABMT. The dose-limiting non-hematologic toxicity of mitoxantrone was cardiotoxicity, with the maximum tolerated dose being 50 mg/m2 Mucositis and pneumonia were also frequent treatment-related side-effects. The overall tumor response rate was 49% in this heavily pre-treated group of patients. We are currently evaluating the toxicity and efficacy of tandem non-cross-resistant transplant regimens, using the MT combination for the second cycle of therapy, in patients with metastatic breast cancer sensitive to standard dose chemotherapy.
Bowers
C
C
Saint Louis University Medical Center, MO 63110-0250.
Adkins
D
D
Dunphy
F
F
Harrison
B
B
LeMaistre
C F
CF
Spitzer
G
G
D000328:Adult; D001853:Bone Marrow / Q000473:pathology / Q000502:physiology; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D011014:Pneumonia / Q000139:chemically induced; D013852:Thiotepa / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D013997:Time Factors
D013852:Thiotepa; D008942:Mitoxantrone