Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 2, pp 251–258

Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors

  • John H. Strickler
  • Alexander N. Starodub
  • Jingquan Jia
  • Kellen L. Meadows
  • Andrew B. Nixon
  • Andrew Dellinger
  • Michael A. Morse
  • Hope E. Uronis
  • P. Kelly  Marcom
  • S. Yousuf  Zafar
  • Sherri T. Haley
  • Herbert I. Hurwitz
Original Article

DOI: 10.1007/s00280-012-1911-1

Cite this article as:
Strickler, J.H., Starodub, A.N., Jia, J. et al. Cancer Chemother Pharmacol (2012) 70: 251. doi:10.1007/s00280-012-1911-1

Abstract

Purpose

To define the maximum tolerated dose, clinical toxicities, and pharmacodynamics of bevacizumab, everolimus, and panobinostat (LBH-589) when administered in combination to patients with advanced solid tumor malignancies.

Experiment design

Subjects received 10 mg of panobinostat three times weekly, 5 or 10 mg everolimus daily, and bevacizumab at 10 mg/kg every 2 weeks. Dose-limiting toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. Protein acetylation was assessed in peripheral blood mononuclear cells (PBMC) both at baseline and on treatment.

Results

Twelve subjects were evaluable for toxicity and nine subjects for response. DLTs in cohort 1 included grade 2 esophagitis and grade 3 oral mucositis; DLTs in cohort -1 were grade 2 ventricular arrhythmia and grade 2 intolerable skin rash. Common adverse events were diarrhea (50 %), headache (33 %), mucositis/stomatitis (25 %), hyperlipidemia (25 %), and thrombocytopenia (25 %). There was 1 partial response; an additional 2 subjects had stable disease as best response. No consistent changes in protein acetylation in PBMC were observed in samples available from eight patients on treatment compared with baseline.

Conclusions

Bevacizumab, everolimus, and panobinostat in combination at the lowest proposed doses did not have an acceptable safety and tolerability profile and did not consistently inhibit HDAC activity; therefore, we do not recommend further evaluation.

Keywords

BevacizumabEverolimusPanobinostatPhase IAdvanced cancer

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • John H. Strickler
    • 1
  • Alexander N. Starodub
    • 1
    • 2
  • Jingquan Jia
    • 1
  • Kellen L. Meadows
    • 1
  • Andrew B. Nixon
    • 1
  • Andrew Dellinger
    • 1
  • Michael A. Morse
    • 1
  • Hope E. Uronis
    • 1
  • P. Kelly  Marcom
    • 1
  • S. Yousuf  Zafar
    • 1
  • Sherri T. Haley
    • 1
  • Herbert I. Hurwitz
    • 1
  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.Goshen Center for Cancer CareGoshenUSA