monoclonal antibody therapy, cyclosporine, and paclitaxel in treating patients with recurrent or refractory metastatic breast cancer

Conditions: Breast Cancer

Summary: rationale: monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. combining monoclonal antibody therapy with cyclosporine and paclitaxel may be an effective treatment for metastatic breast cancer. purpose: phase i trial to study the effectiveness of radiolabeled monoclonal antibody therapy, cyclosporine, and paclitaxel in treating patients who have recurrent or refractory metastatic breast cancer.

objectives: * determine the maximum tolerated dose of yttrium y 90 monoclonal antibody m170 in combination with cyclosporine and paclitaxel in patients with recurrent or refractory metastatic breast cancer. * determine the preliminary efficacy of this regimen in these patients. outline: this is a dose-escalation study of yttrium y 90 monoclonal antibody m170 (y90 moab m170). patients receive filgrastim (g-csf) subcutaneously (sc) daily for 4 days prior to apheresis which continues daily for a maximum of 5 days. a minimum of 6 million cd34+ cells/kg must be harvested. patients receive oral cyclosporine every 12 hours on days -3 to 25. patients receive unlabeled monoclonal antibody (moab) m170 iv followed by a tracer dose of indium in 111 moab m170 iv on day 0. on day 7, patients receive unlabeled moab m170 iv followed by y90 moab m170 iv. patients in cohorts 2-4 also receive paclitaxel iv over 3 hours on day 9. if needed, patients undergo autologous peripheral blood stem cell transplantation on day 21 and receive g-csf sc daily until blood counts recover. cohorts of 3-6 patients receive escalating doses of y90 moab m170 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed monthly for 3 months, every 3 months for 1 year, and then every 6 months for 1 year. projected accrual: a total of 18-30 patients will be accrued for this study within 36 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed metastatic breast adenocarcinoma * residual or recurrent disease after first-line standard chemotherapy * clinical evidence of metastatic disease * tumor cells positive for m170 immunoreactivity * hama titer negative * hormone receptor status: * not specified patient characteristics: age: * 18 and over sex: * not specified menopausal status: * not specified performance status: * karnofsky 70-100% life expectancy: * not specified hematopoietic: * neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl renal: * creatinine less than 1.5 mg/dl cardiovascular: * lvef at least 50% by muga pulmonary: * fev1 at least 65% of predicted * fvc at least 65% of predicted * dlco at least 60% other: * no other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * see chemotherapy chemotherapy: * see disease characteristics * at least 1 prior chemotherapy regimen for advanced disease * prior high-dose chemotherapy with autologous stem cell transplantation is allowed if given at least 12 months prior to study and carmustine was not used * at least 4 weeks since prior chemotherapy endocrine therapy: * not specified radiotherapy: * at least 4 weeks since prior external beam radiotherapy * no prior radiotherapy to more than 25% of the total skeleton surgery: * not specified other: * no requirement for oral anticoagulants (low-dose warfarin for central line thrombosis prophylaxis allowed)

Keywords: stage iv breast cancer recurrent breast cancer