A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma
| Autor: | John M, Kirkwood, Rene, Gonzalez, Douglas, Reintgen, Philip R, Clingan, Robert R, McWilliams, Dinesh P, de Alwis, Annamaria, Zimmermann, Michael P, Brown, Robert L, Ilaria, Michael J, Millward |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Aged 80 and over Male Sulfonamides Skin Neoplasms Body Weight Angiogenesis Inhibitors Apoptosis Kaplan-Meier Estimate Middle Aged Thrombocytopenia Disease-Free Survival Drug Administration Schedule Treatment Outcome Antineoplastic Combined Chemotherapy Protocols Benzamides Humans Female Melanoma Algorithms Fatigue Aged |
| Zdroj: | Cancer. 117(20) |
| ISSN: | 1097-0142 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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