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A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma.(Melanoma)(Clinical report)

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 thi... Full description

Journal Title: Cancer Oct 15, 2011, Vol.117(20), p.4732(8)
Main Author: Kirkwood, John M.
Other Authors: Gonzalez, Rene , Reintgen, Douglas , Clingan, Philip R. , Mcwilliams, Robert R. , De Alwis, Dinesh P. , Zimmermann, Annamaria , Brown, Michael P. , Ilaria, Robert L. , Jr. , Millward, Michael J.
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0008-543X
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recordid: gale_ofa269848697
title: A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma.(Melanoma)(Clinical report)
format: Article
creator:
  • Kirkwood, John M.
  • Gonzalez, Rene
  • Reintgen, Douglas
  • Clingan, Philip R.
  • Mcwilliams, Robert R.
  • De Alwis, Dinesh P.
  • Zimmermann, Annamaria
  • Brown, Michael P.
  • Ilaria, Robert L. , Jr.
  • Millward, Michael J.
subjects:
  • Melanoma -- Drug Therapy
  • Melanoma -- Patient Outcomes
  • Melanoma -- Research
  • Antineoplastic Agents -- Dosage And Administration
  • Antineoplastic Agents -- Research
ispartof: Cancer, Oct 15, 2011, Vol.117(20), p.4732(8)
description: 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 (Cmax) 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 Cmax 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. Cancer 2011;. © 2011 American Cancer Society.
language: English
source:
identifier: ISSN: 0008-543X
fulltext: fulltext
issn:
  • 0008-543X
  • 0008543X
url: Link


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titleA phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma.(Melanoma)(Clinical report)
creatorKirkwood, John M. ; Gonzalez, Rene ; Reintgen, Douglas ; Clingan, Philip R. ; Mcwilliams, Robert R. ; De Alwis, Dinesh P. ; Zimmermann, Annamaria ; Brown, Michael P. ; Ilaria, Robert L. , Jr. ; Millward, Michael J.
ispartofCancer, Oct 15, 2011, Vol.117(20), p.4732(8)
identifierISSN: 0008-543X
subjectMelanoma -- Drug Therapy ; Melanoma -- Patient Outcomes ; Melanoma -- Research ; Antineoplastic Agents -- Dosage And Administration ; Antineoplastic Agents -- Research
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descriptionBACKGROUND: 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 (Cmax) 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 Cmax 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. Cancer 2011;. © 2011 American Cancer Society.
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