Feasibility of Treating Adults with Ewing or Ewing-Like Sarcoma with Interval-Compressed Vincristine, Doxorubicin, and Cyclophosphamide Alternating with Ifosfamide and Etoposide

Abstract

Vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) administered every 2 weeks demonstrated a superior event-free survival compared with 3-week dosing in a landmark pediatric trial and is now standard of care for younger patients. Only 12% of patients enrolled in that trial were over 18 years of age; thus, the feasibility of interval-compressed VDC/IE in adults remains poorly described. We conducted a retrospective analysis of our institutional experience using this regimen. Pharmacy administration records at Oregon Health and Science University were reviewed to identify patients with Ewing and Ewing-like sarcoma aged 18 years and older who received VDC/IE every 2 weeks. We identified 24 patients. Median age was 28 years (range 18-60 years). At diagnosis, 67% had localized disease. The most common primary sites were extremity (38%) and pelvis (17%); another 25% had extraosseous disease. The median interval between cycles was 15.0 days, with no difference between patients aged <30 years versus ≥30 years. The median number of admissions for toxicity per patient was two, primarily for febrile neutropenia. Early treatment discontinuation occurred in 17%. Dose reductions were minimal, with mean cumulative doses achieved comparable to original planned dose and no difference between patients aged <30 years versus ≥30 years. For adults with Ewing and Ewing-like sarcoma, administration of interval-compressed chemotherapy is feasible, without significant dose reductions required. Our results are comparable to prior studies involving a primarily pediatric population. For Ewing sarcoma, interval-compressed vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide administered every 2 weeks rather than every 3 weeks has been shown to improve event-free survival in pediatric patients. However, in adults, oncologists may be hesitant to pursue interval-compressed therapy because of concerns for feasibility. In the adult population in this study, a median interval between cycles of 15.0 days (mean 17.0 days) was achieved, comparable to the interval achieved in AEWS0031 (median 15.0, mean 17.3 days). Given that this was achieved without unexpected toxicity or substantial dose reductions and that clinical outcomes were favorable compared with adult historical controls, these results support the use of this regimen in adults.