Chemotherapy immediately following autologous stem-cell transplantation in patients with advanced breast cancer

Zia Rahman, John Kavanagh, Richard Champlin, Richard Giles, Elie Hanania, Siqinq Fu, Zifei Zu, Rakesh Mehra, Frankie Holmes, Andrzej Kudelka, David Claxton, Claire Verschraegen, James Gajewski, Michael Andreeff, Shelly Heimfeld, Ronald Berenson, Debra Ellerson, Leslie Calvert, Eugene Mechetner, Tanya HolzmayerAndrew Dayne, Joy Hamer, Carlos Bachier, Jeffrey Ostrove, Donna Przepiorka, Barbara Burtness, Richard Cote, Robert Bast, Gabriel Hortobagyi, Albert Deisseroth

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Most patients relapse after high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) for metastatic breast cancer. Further chemotherapy immediately after hematopoietic recovery from ASCT is not given for fear of irreversibly damaging the newly engrafted stem cells. In a pilot chemoprotection trial, autologous CD34+ cells from patients with metastatic breast cancer were exposed to a replication-incompetent retrovital vector carrying MDR-1 cDNA and then reinfused after HDCT. Immediately on recovery, patients received multiple courses of escalating dose paclitaxel. All of the 10 patients tolerated reinfusion of modified cells without any toxicity and had myeloid engraftment within 12 days (range, 11-14). The bone marrow cells of three patients contained vector MDR-1-positive cells only at the time of the first course of posttransplant paclitaxel, indicating that the MDR-1 vector-modified cells had only short-term engrafting potential. A total of 83 courses of paclitaxel were administered starting at a median of 30 (range, 21-32) days from ASCT. The median dose of paclitaxel was 225 mg/m2 and the median interval between paclitaxel cycles of therapy was 21 (range, 20-41) days. Five of the six CR patients were able to receive all of the 12 courses of paclitaxel. Three patients who had achieved less than a complete response to the HDCT (2 patients) and partial response (1 patient) were converted to complete clinical responses during the 12 cycles of paclitaxel. No delayed toxicity or bone marrow failure was noted in these patients with a median follow-up of 2 years from ASCT. This is the first study of chemotherapy immediately after transplantation with autologous CD34+ cells. These data indicate that paclitaxel can be safely administered immediately after ASCT without any delayed toxicities. Paclitaxel given immediately after ASCT can further improve the response to pretransplant chemotherapy in patients with advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)2717-2721
Number of pages5
JournalClinical Cancer Research
Volume4
Issue number11
StatePublished - Nov 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Rahman, Z., Kavanagh, J., Champlin, R., Giles, R., Hanania, E., Fu, S., Zu, Z., Mehra, R., Holmes, F., Kudelka, A., Claxton, D., Verschraegen, C., Gajewski, J., Andreeff, M., Heimfeld, S., Berenson, R., Ellerson, D., Calvert, L., Mechetner, E., ... Deisseroth, A. (1998). Chemotherapy immediately following autologous stem-cell transplantation in patients with advanced breast cancer. Clinical Cancer Research, 4(11), 2717-2721.