Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas

[摘要] Patients:Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease.Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids.Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity inpre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective responserate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of theadjuvant setting.Methods:Dol-10 was given intravenously at a dose of 400 μg/m2and repeated every 21 days. Toxicities were assessed usingthe Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cyclesto assess response [Miller AB, et al.Cancer1981; 47(1): 207].Results:Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significantgastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objectiveresponses in 12 patients treated with Dol-10.Discussion:Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced ormetastatic soft tissue sarcomas.

[学科分类] 肿瘤学