title: Phase II study of amrubicin (SM-5887), a synthetic 9-aminoanthracycline, as first line treatment in patients with metastatic or unresectable soft tissue sarcoma: durable response in myxoid liposarcoma with TLS-CHOP translocation.
abstract: OBJECTIVE
  Amrubicin is a third generation synthetic 9-aminoanthracycline that specifically inhibits topoisomerase II. Amrubicin preferentially concentrates in tumor cells leading to tumor cell death without causing cardiac toxicity. This phase II multicenter study was done to evaluate the efficacy and tolerability of amrubicin in advanced soft tissue sarcoma (STS).
  
  
  METHODS
  24 eligible patients with chemotherapy-naive metastatic or unresectable STS were treated with amrubicin 40 mg/m(2) intravenously daily for three consecutive days in 21 days cycles with growth factor support. Patients continued to receive treatment, as long as it was tolerated, in the absence of significant disease progression. The disease was followed on imaging scans every 6 weeks. The primary endpoint of the study was the best overall response rate.
  
  
  RESULTS
  The best overall response rate was 13% in 23 evaluable patients. Median progression-free survival was 5.8 months, and median overall survival was 26 months. Grade 3 to 4 toxicities of febrile neutropenia and anemia occurred in 21% of treated patients. One patient with metastatic myxoid liposarcoma with TLS-CHOP translocation had a durable response and received 40 cycles of amrubicin. There was no significant cardiac toxicity.
  
  
  CONCLUSIONS
  Amrubicin has efficacy comparable to doxorubicin in adult STS, is well tolerated and has no significant cardiac toxicity up to a cumulative dose of 4800 mg /m(2). Topoisomerase II inhibition with amrubicin warrants further study as a potential 'targeted therapy' for TLS-CHOP-translocated myxoid liposarcoma. Results from this trial favor the use of amrubicin for the treatment of STS.
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA. sumati.gupta@hci.utah.edu.
authors.forename: Sumati
authors.identifier: http://orcid.org/0000-0001-6271-0831
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Intermountain Medical Center and LDS Hospital, 8th Ave & C St, Salt Lake City, UT, 84103, USA.
authors.forename: Launce
authors.initials: L
authors.lastname: Gouw
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wright
authors.affiliation: Sarcoma Oncology Center, 2811 Wilshire Blvd, Suite 414, Santa Monica, CA, 90403, USA.
authors.forename: Sant
authors.initials: S
authors.lastname: Chawla
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors.forename: Debbie
authors.initials: D
authors.lastname: Pitt
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Wade
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Boucher
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003710:Demography; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D018208:Liposarcoma, Myxoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D012509:Sarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D014057:Tomography, X-Ray Computed; D051742:Transcription Factor CHOP / Q000235:genetics*; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; C106030:TLS-CHOP fusion protein, human; D051742:Transcription Factor CHOP; C055866:amrubicin
keywords: Amrubicin; Clinical trial; DNA Topoisomerases; Human; Liposarcoma; Myxoid; Phase II; Sarcoma; TLSCHOP fusion protein; Type II