title: A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma.
abstract: BACKGROUND
  Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD).
  
  
  METHODS
  Patients aged 18 to 70 years with recurrent/refractory malignant solid tumors received aldoxorubicin at a dose of 230 mg/m(2) , 350 mg/m(2) , or 450 mg/m(2) (170 mg/m(2) , 260 mg/m(2) , or 335 mg/m(2) doxorubicin equivalents, respectively) by intravenous infusion once every 21 days for up to 8 consecutive cycles.
  
  
  RESULTS
  A total of 25 patients were enrolled, including 17 patients (68%) with advanced soft tissue sarcoma (STS). The MTD of aldoxorubicin was 350 mg/m(2) ; dose-limiting toxicities included grade 4 neutropenia and grade 3 febrile neutropenia (NCI CTCAE v4.0). Drug-related adverse events included myelosuppression, nausea, fatigue, alopecia, stomatitis, vomiting, and oropharyngeal pain. No clinically significant cardiac toxicities were reported. Seven patients (28%) had elevated serum troponin levels while taking part in the study, but these elevations were not clinically significant or associated with cardiac findings. A partial response was achieved in 20% of patients, and stable disease was reported in 40% of patients. The median progression-free survival was 4.80 months, and the median overall survival was 11.25 months. Among patients with STS who were treated at the MTD (13 patients), a partial response was achieved in 38% and stable disease in 46%; the median progression-free survival was 11.25 months and the median overall survival was 21.71 months.
  
  
  CONCLUSIONS
  Aldoxorubicin at a dose of 350 mg/m(2) administered once every 21 days for up to 8 cycles was found to be acceptably safe and demonstrated preliminary efficacy in patients with advanced solid tumors, including STS. Further investigation of aldoxorubicin is ongoing.
authors.affiliation: Sarcoma Oncology Center, Santa Monica, California.
authors.forename: Sant P
authors.initials: SP
authors.lastname: Chawla
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Chua
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hendifar
authors.forename: Doris V
authors.initials: DV
authors.lastname: Quon
authors.forename: Neelesh
authors.initials: N
authors.lastname: Soman
authors.forename: Kamalesh K
authors.initials: KK
authors.lastname: Sankhala
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wieland
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Levitt
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D004334:Drug Administration Schedule; D064147:Febrile Neutropenia / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D011355:Prodrugs; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000903:Antibiotics, Antineoplastic; D011355:Prodrugs; D004317:Doxorubicin
keywords: doxorubicin; maximum tolerated dose; prodrugs; serum albumin; soft tissue sarcoma