Memorial Sloan Kettering Cancer Center, New York, NY
Heather D. Magnan , Anita Price , Alexander J. Chou , Elyn Riedel , Leonard H. Wexler , Srikanth R. Ambati , Emily Kanaya Slotkin , Gary Ulaner , Shakeel Modak , Michael P. La Quaglia , Paul A. Meyers
Background: DSRCT is a rare tumor with a dismal prognosis in the setting of current treatment options. Preclinical data suggested that VEGF-dependent angiogenesis is important for DSRCT tumor biology and that targeting angiogenesis with bevacizumab in combination with irinotecan was more effective than treatment with irinotecan alone. This pilot study was designed to explore the safety and feasibility of adding ITB to the existing “P6- like” regimen used to treat DSRCT. Methods: Fifteen patients with newly diagnosed DSRCT were enrolled onto this single-institution study. They began treatment with 2 cycles of irinotecan (20 mg/m2/dose x 10 days) and temozolomide (100 mg/m2/dose x 5 days). Bevacizumab 10 mg/kg q2 weeks was added after sufficient time had passed from initial biopsy or surgery. Patients were then treated with cycles of alkylator based chemotherapy (3 cycles of cyclophosphamide, doxorubicin, vincristine and 3 cycles of ifosfamide, etoposide). An initial surgical resection was performed after cycle 5 and a second resection or second look surgery after cycle 8. Toxicity was graded according to CTCAE v.4.0. Secondary efficacy objectives were assessed using RECIST 1.1 criteria and the Kaplan Meir method. Results: 14 of 15 patients completed planned protocol therapy. One patient was taken off study due to complications associated with surgery after cycle 5 of chemotherapy. Stopping rules for unacceptable toxicity were not met. No patients experienced toxicity attributed to bevacizumab, and surgical morbidity was no greater than expected. Grade 3 diarrhea associated with irinotecan was experienced by 2 patients. Expected toxicities with “P6-like” cycles included grade 3/4 hematologic toxicity and admissions for febrile neutropenia in all patients. Response rate to the ITB cycles was 27% (95% CI 8-55%) and to the 5 pre-resection cycles was 73% (95% CI 45-92%). Median time to progression was 18.1 months. Overall survival at 1 year was 100% and 3 years 61% (95% CI 25-84%). Conclusions: The combination of ITB is active in patients with DSRCT, and it is feasible to combine these agents with standard chemotherapy without greater than expected toxicity. Clinical trial information: NCT01189643
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