Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation
| Autor: | Leisha A. Emens, Steven Piantadosi, Elizabeth M. Jaffee, Justin M. Asquith, Marina Laiko, Vered Stearns, Barbara A. Biedrzycki, Barry Kobrin, Silvia Petrik, John H. Fetting, Antonio C. Wolff, James M. Leatherman, Nancy E. Davidson, Mary L. Disis, Maithili M. Daphtary, Xiaobu Ye, Joy Levi |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Time Factors Receptor ErbB-2 medicine.medical_treatment Adoptive Immunotherapy Adoptive chemistry.chemical_compound ErbB-2 Antineoplastic Combined Chemotherapy Protocols Cancer Middle Aged Metastatic breast cancer Combined Modality Therapy Nitrogen mustard Treatment Outcome Oncology 6.1 Pharmaceuticals Female Immunotherapy Drug medicine.drug Receptor Biotechnology Adult Cyclophosphamide Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Breast Neoplasms Transfection Cancer Vaccines Drug Administration Schedule Cell Line Dose-Response Relationship Vaccine Related Breast cancer Immunity Clinical Research Breast Cancer Original Reports medicine Humans Doxorubicin Oncology & Carcinogenesis Immunization Schedule Aged Chemotherapy Dose-Response Relationship Drug business.industry Prevention Evaluation of treatments and therapeutic interventions Granulocyte-Macrophage Colony-Stimulating Factor medicine.disease Good Health and Well Being chemistry Immunology Immunization business |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 27, iss 35 |
| ISSN: | 1527-7755 |
| Popis: | Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting tumor vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance vaccine-induced immunity in patients with breast cancer. Patients and Methods We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting tumor vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity. Results Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received vaccine alone or with 200 mg/m2 CY. HER2-specific antibody responses were enhanced by 200 mg/m2 CY and 35 mg/m2 DOX, but higher CY doses suppressed immunity. Analyses revealed that CY at 200 mg/m2 and DOX at 35 mg/m2 is the combination that produced the highest antibody responses. Conclusion First, immunotherapy with an allogeneic, HER2-positive, GM-CSF–secreting breast tumor vaccine alone or with CY and DOX is safe and induces HER2-specific immunity in patients with metastatic breast cancer. Second, the immunomodulatory activity of low-dose CY has a narrow therapeutic window, with an optimal dose not exceeding 200 mg/m2. Third, factorial designs provide an opportunity to identify the most active combination of interacting drugs in patients. Further investigation of the impact of chemotherapy on vaccine-induced immunity is warranted. |
| Databáze: | OpenAIRE |
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