Phase II study of doxorubicin and thalidomide in patients with refractory aggressive fibromatosis

Invest New Drugs. 2018 Feb;36(1):114-120. doi: 10.1007/s10637-017-0542-0. Epub 2017 Nov 23.

Abstract

Background To evaluate the efficacy and safety of doxorubicin (ADM) combined with thalidomide (THA) as a first-line treatment for patients with refractory aggressive fibromatosis (AF). Patients and Methods Eligible patients were treated with ADM 30 mg/m2 on days 1-2 and THA 200 mg nightly on days 1-21 every 3 weeks for a maximum of six cycles. THA was then continued for a total of 1 year. The primary end point was response rate (RR). Results Fifteen patients were enrolled in the study. No patient had a complete response, but five patients had partial responses, resulting in a RR of 33%. Eight patients (53%) had stable disease and two patients (13%) had progressive disease, and the disease control rate was 87%. The median progression free survival (mPFS) was 20.6 months (95% confidence interval, 14.5-26.7 months). Patients with below normal baseline serum albumin levels had significantly inferior mPFS compared with those with normal baseline serum albumin (1.4 months versus 23.7 months, P = 0.045). Grade 3/4 toxicities included leukopenia (33%), neutropenia (60%), febrile neutropenia (7%), nausea (7%), and vomiting (6.6%). Conclusions ADM plus THA was well-tolerated and effective as a first-line treatment for patients with refractory AF. However, patients with hypoalbuminemia at baseline had inferior clinical outcomes, and further studies are needed to investigate this issue.

Keywords: Aggressive fibromatosis; Beta-catenin; Doxorubicin; Hypoalbuminemia; Thalidomide.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Doxorubicin / therapeutic use*
  • Female
  • Fibromatosis, Aggressive / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Thalidomide / therapeutic use*
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Thalidomide
  • Doxorubicin