Gemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy.

Prior studies showed clinical benefit with trabectedin in patients with sarcomas after failure of standard chemotherapy. This trial documents superior disease control with the q3 weeks 24-hour trabectedin regimen in liposarcomas and leiomyosarcomas, although the qwk 3-hour regimen also demonstrated activity relative to historical comparisons. Trabectedin may now be considered an important new option to control advanced sarcomas in patients after failure of available standard-of-care therapies.

Purpose: Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib.Experimental Design: Patients ≥10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily [body surface area (BSA) ≥ 1. ), or 100 mg twice daily (BSA < 1.0 m 2 ). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, plateletderived growth factor receptor α (PDGFRα), PDGFRβ, AKT, PTEN, FKHR, and β-catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR. Results: Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2-and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6%

ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy.

PURPOSE The purpose of this trial was to assess the efficacy of imatinib in patients with one of 10 different subtypes of advanced sarcoma. PATIENTS AND METHODS Eligible patients were treated daily with imatinib dosed at 300 mg twice a day (for body-surface area > or = 1.5 m(2)). The primary end point was response (clinical benefit response [CBR]), defined as complete (CR) or partial response (PR) at 2 months, or stable disease, CR, or PR at 4 months. Rules for early termination within each disease type were based on a Bayesian hierarchical probability model (BHM) accounting for correlation of the responses of the 10 subtypes. Available tissue samples were analyzed for molecules within the KIT/platelet-derived growth factor receptor (PDGFR) signal transduction pathway. Results One hundred eighty-five assessable patients with one of 10 subtypes of sarcoma were treated. One CR and three PRs were achieved. A CBR was achieved in 28 patients treated overall and by subtype: two angiosarcomas (n = 16), 0 Ewing (n = 13), one fibrosarcoma (n = 12), six leiomyosarcomas (n = 29), seven liposarcomas (n = 31), three malignant fibrous histiocytomas (n = 30), five osteosarcomas (n = 27), one malignant peripheral-nerve sheath tumor (n = 7), 0 rhabdomyosarcoma (n = 2), and three synovial sarcomas (n = 22). Variable expression and mutations within the KIT/PDGFR pathway were observed. CONCLUSION This is the first phase II study of a new agent in sarcoma to include sufficient patients with each of the common histologic subtypes to permit generalizable conclusions. The BHM is an effective method for studying rare diseases and their subtypes, when it is reasonable to assume that their response rates are exchangeable. Although rare dramatic responses were seen, imatinib is not an active agent in advanced sarcoma in these subtypes.

HDM has become an established and effective salvage regimen for children with relapsed neuroblastoma, as well as an effective consolidative treatment for children with high-risk disease (stage IV). HDM is emerging as an active and effective mode of treatment in patients with stage II and III myeloma. The favorable toxicity profile of HDM and the availability of PBPCs allows for repetitive therapy.

Results of this EAP are consistent with previous reports of trabectedin, demonstrating disease control despite a low incidence of objective responses in advanced STS patients after failure of standard chemotherapy. CLINICALTRIALS.GOV: NCT00210665.

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