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Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma.

Publication ,  Journal Article
Voorhees, PM; Gasparetto, C; Moore, DT; Winans, D; Orlowski, RZ; Hurd, DD
Published in: Clin Lymphoma Myeloma Leuk
July 2017

INTRODUCTION/BACKGROUND: Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in preclinical models of multiple myeloma (MM). We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin (PLD) and bortezomib in relapsed/refractory MM. PATIENTS AND METHODS: Thirty-two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 to 11 or 1 to 14. RESULTS: The maximum tolerated dose of vorinostat was 400 mg on days 4 to 11. Neutropenia and thrombocytopenia attributable to protocol therapy were seen in 59% and 94% of patients, of which 37% and 47% were of grade 3 or higher severity, respectively. Constitutional and gastrointestinal adverse events of all grades were common, the majority of which were less than grade 3 in severity. The overall response rate (partial response rate or better) was 65% and the clinical benefit rate (minimal response rate or better) 74%. The overall response rate was 83%, 71%, and 45% for patients with bortezomib-naive, -sensitive, and -refractory MM, respectively. The median progression-free survival was 13.9 months and the 3-year overall survival 77%. Whole blood proteasome activity assays demonstrated a potential impact of vorinostat on the chymotryptic-like activity of the proteasome. CONCLUSION: Further evaluation of PLD, bortezomib, and deacetylase inhibitor combinations is warranted, with special attention directed toward strategies to improve tolerability.

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Published In

Clin Lymphoma Myeloma Leuk

DOI

EISSN

2152-2669

Publication Date

July 2017

Volume

17

Issue

7

Start / End Page

424 / 432

Location

United States

Related Subject Headings

  • Vorinostat
  • Proteasome Inhibitors
  • Polyethylene Glycols
  • Neoplasm Recurrence, Local
  • Multiple Myeloma
  • Middle Aged
  • Male
  • Hydroxamic Acids
  • Humans
  • Female
 

Citation

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Voorhees, P. M., Gasparetto, C., Moore, D. T., Winans, D., Orlowski, R. Z., & Hurd, D. D. (2017). Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk, 17(7), 424–432. https://doi.org/10.1016/j.clml.2017.05.007
Voorhees, Peter M., Cristina Gasparetto, Dominic T. Moore, Diane Winans, Robert Z. Orlowski, and David D. Hurd. “Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma.Clin Lymphoma Myeloma Leuk 17, no. 7 (July 2017): 424–32. https://doi.org/10.1016/j.clml.2017.05.007.
Voorhees PM, Gasparetto C, Moore DT, Winans D, Orlowski RZ, Hurd DD. Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2017 Jul;17(7):424–32.
Voorhees, Peter M., et al. “Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma.Clin Lymphoma Myeloma Leuk, vol. 17, no. 7, July 2017, pp. 424–32. Pubmed, doi:10.1016/j.clml.2017.05.007.
Voorhees PM, Gasparetto C, Moore DT, Winans D, Orlowski RZ, Hurd DD. Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2017 Jul;17(7):424–432.
Journal cover image

Published In

Clin Lymphoma Myeloma Leuk

DOI

EISSN

2152-2669

Publication Date

July 2017

Volume

17

Issue

7

Start / End Page

424 / 432

Location

United States

Related Subject Headings

  • Vorinostat
  • Proteasome Inhibitors
  • Polyethylene Glycols
  • Neoplasm Recurrence, Local
  • Multiple Myeloma
  • Middle Aged
  • Male
  • Hydroxamic Acids
  • Humans
  • Female