Phase i trial of valproic acid and lenalidomide in patients with advanced cancer

Mehmet Asim Bilen, Siqing Fu, Gerald S Falchook, Chaan S. Ng, Jennifer J. Wheler, Maen Abdelrahim, Basak Erguvan-Dogan, David S. Hong, Apostolia M. Tsimberidou, Razelle Kurzrock, Aung Naing

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Purpose: The objectives of this study were to evaluate the tolerability and efficacy of valproic acid (VPA) and lenalidomide. Methods: In this 3+3 design study, VPA was administered daily on a 7-day-on, 7-day-off schedule, and lenalidomide was administered daily for 28 days. Because of the response noted during the dose-escalation phase, 12 additional patients with adenoid cystic carcinoma (ACC) received the maximum tolerated dose (MTD) in a dose-expansion phase. Results: Twenty-six patients with advanced cancer (14 men/12 women), median age of 56 years (range 38-70 years), and a median number of two prior therapies (range 0-12) were enrolled. The most common toxicities were fatigue, rash, neutropenia, thrombocytopenia, and change in mental status. Dose-limiting toxic (DLT) effects were grade III confusion (n = 3), somnolence (n = 1), and gait disturbance (n = 1). The MTD was reached at VPA 30 mg/kg and lenalidomide 25 mg. Although only two of the 12 patients from the dose-expansion phase had DLT during the first cycle at the MTD, during subsequent cycles the majority of patients required dose reduction of VPA to 5-20 mg/kg because of fatigue and drowsiness. No significant tumor reductions were noticed in patients with ACC, but seven of these patients had stable disease over four cycles. Of non-ACC patients, one patient with melanoma and one patient with parathyroid carcinoma had stable disease for six cycles and eight cycles, respectively. Conclusions: Lenalidomide combined with VPA was well tolerated. We recommend starting VPA at 5 mg/kg and titrating upward to 20 mg/kg. No significant tumor reductions were noticed in patients with ACC.

Original languageEnglish (US)
Pages (from-to)869-874
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Issue number4
StatePublished - 2015


  • Advanced cancer
  • Lenalidomide
  • Phase I
  • Toxicity
  • Valproic acid

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


Dive into the research topics of 'Phase i trial of valproic acid and lenalidomide in patients with advanced cancer'. Together they form a unique fingerprint.

Cite this