title: A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma.
abstract: BACKGROUND
  Tasisulam sodium (hereafter, tasisulam) is a novel anticancer agent that induces apoptosis through the intrinsic pathway and has antiangiogenic activity in preclinical models. Tasisulam demonstrated activity across a broad range of tumors, including melanoma. The primary objective of this phase 2 study was to determine the objective response rate (ORR) in patients who had received 1 previous systemic chemotherapy for unresectable/metastatic melanoma; secondary objectives were to evaluate the clinical response rate (CRR), progression-free survival (PFS), overall survival (OS), duration of response, safety, and pharmacokinetics.
  
  
  METHODS
  Tasisulam was administered intravenously on Day 1 of 21-day cycles according to a lean body weight-based dosing algorithm targeting a peak plasma concentration (C(max)) of 420 μg/mL.
  
  
  RESULTS
  In 68 enrolled patients, the median age was 59 years (range, 26-83 years). No patients had a complete response (CR), 8 patients had a partial response (PR), and 24 patients had stable disease (SD); the ORR (CR + PR) was 11.8%, and the CRR (CR + PR + SD) was 47.1%. The median PFS was 2.6 months, and the median OS was 9.6 months. The predominant treatment-related grade 3/4 toxicity was thrombocytopenia (20.6% of patients). Tasisulam exhibited a biexponential disposition with a predicted distribution half-life of 0.3 hours to 2.8 hours and a median terminal elimination half-life of 10 days (consistent with the turnover of albumin), suggesting that tasisulam is very tightly bound to albumin.
  
  
  CONCLUSIONS
  Tasisulam administered at a targeted C(max) of 420 μg/mL on Day 1 of 21-day cycles demonstrated activity and tolerable toxicity as second-line treatment in malignant melanoma. These results led to a registration trial in metastatic melanoma.
authors: Melanoma and Skin Cancer Program, University of Pittsburgh Medical Center, Pennsylvania, USA. kirkwoodjm@pmc.edu
authors: John M
authors: JM
authors: Kirkwood
authors: Rene
authors: R
authors: Gonzalez
authors: Douglas
authors: D
authors: Reintgen
authors: Philip R
authors: PR
authors: Clingan
authors: Robert R
authors: RR
authors: McWilliams
authors: Dinesh P
authors: DP
authors: de Alwis
authors: Annamaria
authors: A
authors: Zimmermann
authors: Michael P
authors: MP
authors: Brown
authors: Robert L
authors: RL
authors: Ilaria
authors: Michael J
authors: MJ
authors: Millward
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001835:Body Weight; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D001549:Benzamides; C534068:N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide; D013449:Sulfonamides