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

Publication ,  Journal Article
Strickler, JH; Starodub, AN; Jia, J; Meadows, KL; Nixon, AB; Dellinger, A; Morse, MA; Uronis, HE; Marcom, PK; Zafar, SY; Haley, ST; Hurwitz, HI
Published in: Cancer Chemother Pharmacol
August 2012

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.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

August 2012

Volume

70

Issue

2

Start / End Page

251 / 258

Location

Germany

Related Subject Headings

  • Treatment Outcome
  • Sirolimus
  • Panobinostat
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Leukocytes, Mononuclear
  • Injections, Intravenous
 

Citation

APA
Chicago
ICMJE
MLA
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Strickler, J. H., Starodub, A. N., Jia, J., Meadows, K. L., Nixon, A. B., Dellinger, A., … Hurwitz, H. I. (2012). Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors. Cancer Chemother Pharmacol, 70(2), 251–258. https://doi.org/10.1007/s00280-012-1911-1
Strickler, John H., Alexander N. Starodub, Jingquan Jia, Kellen L. Meadows, Andrew B. Nixon, Andrew Dellinger, Michael A. Morse, et al. “Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors.Cancer Chemother Pharmacol 70, no. 2 (August 2012): 251–58. https://doi.org/10.1007/s00280-012-1911-1.
Strickler JH, Starodub AN, Jia J, Meadows KL, Nixon AB, Dellinger A, et al. Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors. Cancer Chemother Pharmacol. 2012 Aug;70(2):251–8.
Strickler, John H., et al. “Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors.Cancer Chemother Pharmacol, vol. 70, no. 2, Aug. 2012, pp. 251–58. Pubmed, doi:10.1007/s00280-012-1911-1.
Strickler JH, Starodub AN, Jia J, Meadows KL, Nixon AB, Dellinger A, Morse MA, Uronis HE, Marcom PK, Zafar SY, Haley ST, Hurwitz HI. Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors. Cancer Chemother Pharmacol. 2012 Aug;70(2):251–258.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

August 2012

Volume

70

Issue

2

Start / End Page

251 / 258

Location

Germany

Related Subject Headings

  • Treatment Outcome
  • Sirolimus
  • Panobinostat
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Leukocytes, Mononuclear
  • Injections, Intravenous