Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

L. T. Vahdat, C. Balmaceda, K. Papadopoulos, D. Frederick, D. Donovan, E. Sharpe, E. Kaufman, D. Savage, A. Tiersten, G. Nichols, J. Haythe, A. Troxel, K. Antman, C. S. Hesdorffer

Research output: Contribution to journalArticle

Abstract

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m2), the second melphalan (180 mg/m2) and the third consisted of cyclophosphamide 6000 mg/m2 (1500 mg/m2/day × 4), thiotepa 500 mg/m2 (125 mg/m2/day × 4) and carboplatin 800 mg/ml (200 mg/m2/day × 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR* and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalBone marrow transplantation
Volume30
Issue number3
DOIs
StatePublished - Jan 1 2002

Keywords

  • Breast cancer
  • Multicycle chemotherapy
  • Stem cell transplant
  • Tandem transplants

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Vahdat, L. T., Balmaceda, C., Papadopoulos, K., Frederick, D., Donovan, D., Sharpe, E., Kaufman, E., Savage, D., Tiersten, A., Nichols, G., Haythe, J., Troxel, A., Antman, K., & Hesdorffer, C. S. (2002). Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer. Bone marrow transplantation, 30(3), 149-155. https://doi.org/10.1038/sj.bmt.1703592