Phase I trial of first-line bortezomib/thalidomide plus chemotherapy for induction and stem cell mobilization in patients with multiple myeloma

Ashraf Badros, Olga Goloubeva, Robert Fenton, Aaron P. Rapoport, Gorgun Akpek, Carolynn Harris, Kathleen Ruehle, Sandra Westphal, Barry Meisenberg

Research output: Contribution to journalArticle

Abstract

Background: In preclinical studies, bortezomib was shown to suppress tumor growth, sensitize malignant cells to apoptosis, and reverse chemotherapy resistance. Patients and Methods: We evaluated the addition of escalating doses of bortezomib 0.7, 1, and 1.3 mg/mg2 intravenously on days 1, 4, and 8 to DT-PACE (cisplatin 10 mg/m2, doxorubicin 10 mg/m2, cyclophosphamide 400 mg/m2, and etoposide 40 mg/m2 per day by intravenous continuous infusion on days 1-4) plus oral dexamethasone 40 mg on days 1-4 and thalidomide 200 mg on days 1-8 in newly diagnosed patients with multiple myeloma. Peripheral blood stem cells were collected after cycle 1. Twelve patients completed the study, and all received autologous stem cell transplantation (SCT). Results: Hematologic toxicities were predictable, with 3 episodes of neutropenic fever. Grade ≥ 2 nonhematologic toxicities included diarrhea (n = 1), deep vein thrombosis (n = 2), hypotension (n = 2), syncope (n = 1), and peripheral neuropathy (n = 3). The median number of CD34+ cells collected was 20.57 × 106 CD34+ cells/kg. After 2 cycles, 10 of 12 patients exhibited a partial response or better. Best response after autologous SGT, complete response/near complete response was exhibited in 9 patients, and partial response was exhibited in 3 patients. At a median of 20 months, 4 patients experienced relapse and 1 had died. Bortezomib/DT-PACE compared favorably with DT-PAGE with regard to leukapheresis days, total GD34+ cell collection, and engraftment. Conclusion: This novel strategy of simultaneous proteasome inhibition in combination with thalidomide and chemotherapy was effective and safe, allowing for adequate stem cell collection and early autologous SCT; its impact on overall survival, especially in patients with high-risk myeloma, awaits further investigation.

Original languageEnglish (US)
Pages (from-to)210-216
Number of pages7
JournalClinical Lymphoma and Myeloma
Volume7
Issue number3
Publication statusPublished - Nov 2006
Externally publishedYes

    Fingerprint

Keywords

  • Cisplatin
  • Cyclophosphamide
  • Doxorubicin
  • Engraftment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Hematology

Cite this

Badros, A., Goloubeva, O., Fenton, R., Rapoport, A. P., Akpek, G., Harris, C., ... Meisenberg, B. (2006). Phase I trial of first-line bortezomib/thalidomide plus chemotherapy for induction and stem cell mobilization in patients with multiple myeloma. Clinical Lymphoma and Myeloma, 7(3), 210-216.