sirolimus and Desmoplastic-Small-Round-Cell-Tumor

Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. We report our experience with five patients treated with vinorelbine, cyclophosphamide, and temsirolimus (VCT). Median number of VCT courses delivered was 7 (range 4-14 courses), and partial response was observed in all patients. Median time to progression or relapse was 8.5 months (range 7-16 months). Neutropenia and mucositis were most common toxicities (n = 4 each).

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Desmoplastic Small Round Cell Tumor; Female; Humans; Male; Mucositis; Neoplasm Recurrence, Local; Neutropenia; Sirolimus; Vinblastine; Vinorelbine

Temsirolimus was combined with cixutumumab, a fully human IgG1 monoclonal antibody directed at the insulin growth factor-1 receptor (IGF-1R).. Patients received cixutumumab, 6 mg/kg i.v. weekly, and temsirolimus, 25 to 37.5 mg i.v. weekly (4-week cycles), with restaging after 8 weeks. Median follow-up was 8.9 months.. Twenty patients [17 with Ewing's sarcoma (EWS), 3 with desmoplastic small-round cell tumor (DSRCT)] were enrolled. Twelve patients (60%) were men with a median age of 24 years and six median prior systemic therapies in a metastatic setting. The most frequent toxicities were thrombocytopenia (85%), mucositis (80%), hypercholesterolemia (75%), hypertriglyceridemia (70%), and hyperglycemia (65%; mostly grade I-II). Seven of 20 patients (35%) achieved stable disease (SD) for more than 5 months or complete/partial (CR/PR) responses. Tumor regression of more than 20% (23%, 23%, 27%, 100%, 100%) occurred in five of 17 (29%) patients with EWS, and they remained on study for 8 to 27 months. One of six patients with EWS who previously developed resistance to a different IGF-1R inhibitor antibody achieved a CR. Four of the seven best responders developed grade III mucositis, myelosuppression, or hyperglycemia, which were controlled while maintaining drug dose.. Cixutumumab combined with temsirolimus was well-tolerated and showed preliminary evidence of durable antitumor activity in heavily pretreated EWS family tumors.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cohort Studies; Desmoplastic Small Round Cell Tumor; Female; Humans; Male; Neoplasm Grading; Prognosis; Receptor, IGF Type 1; Remission Induction; Sarcoma, Ewing; Sirolimus; TOR Serine-Threonine Kinases; Young Adult