Vincristine, Ifosfamide, and Doxorubicin for Initial Treatment of Ewing Sarcoma in Adults

Abstract

Background: There are no clinical trials specifically addressing chemotherapy for adults with Ewing sarcoma (ES). Five-year event-free survival (EFS) of adults on pediatric studies of ES (44%-47%) is worse than that of children treated with the same therapy (69%). The object of this study was to review the results of therapy with vincristine, ifosfamide, and doxorubicin (VID) in the multidisciplinary treatment of adults with ES at our institution.

Materials and methods: Charts for adults treated for ES from 1995 to 2011 were retrospectively reviewed. Clinician-reported radiographic tumor response, type of local therapy, pathologic response, and survival data were collected.

Results: Seventy-one patients were identified who received VID as initial therapy. The median age was 25 (range: 16-64). Forty-two patients (59%) presented with a localized disease and 29 patients (41%) presented with a distant metastasis. Of all patients treated with VID, 83.6% showed a radiological response. Patients who presented with a localized disease had a 5-year overall survival (OS) of 68% (median not reached), compared with 10.3% (median: 1.9 years) in those who presented with distant metastases. Five-year EFS was 67%. The nine patients with a pelvic primary tumor had inferior 5-year OS (42%) to the 33 with primary tumors at other sites (75%). The 5-year OS of those who had greater than or equal to 95% necrosis after neoadjuvant VID (n = 20; 5-year OS: 84%) was superior to those who had less than 95% necrosis (n = 13; 5-year OS: 53%).

Conclusion: In adults with primary ES, VID combined with an adjuvant strategy based on post-treatment percent necrosis has favorable outcomes compared with historical adult controls.

Implications for practice: Ewing sarcoma (ES) is a rare tumor in adults, and there are no dedicated clinical trials in the adult population. Most therapy is modeled after the published pediatric studies, although the small numbers of adult patients included on those studies did significantly worse than the children. We modeled our treatment on other adult sarcomas and reviewed the charts of 71 adult patients with ES treated with vincristine, ifosfamide, and doxorubicin (VID). In adults with primary ES, VID combined with an adjuvant strategy based on post-treatment percent necrosis has favorable outcomes compared with historical adult controls.

Keywords: Adults; Doxorubicin; Ewing sarcoma; Ifosfamide; Vincristine.

Figure 1.

Flow chart of patient treatment characteristics. Abbreviations: ES, Ewing sarcoma; VID, vincristine, ifosfamide, and doxorubicin.

Figure 2.

Cumulative survival. (A): Overall survival (OS) of Ewing sarcoma patients receiving vincristine, ifosfamide, and doxorubicin (VID) for initial therapy stratified by the extent of disease (localized n = 42 vs. metastatic n = 29) at initial presentation. (B): Event‐free survival of patients presenting with a localized disease. (C): OS of patients presenting with localized disease stratified by percent necrosis after initial treatment with VID (≥95% necrosis n = 21 vs. <95% necrosis n = 13). (D): OS of patients presenting with a localized disease stratified by the site of primary (pelvic n = 9 vs. other n = 33). Abbreviation: Cum, cumulative.

Figure 3.

Examples of Ewing sarcoma (ES) histological responses. (A): Low power shows tumor has viable areas (darker blue) as well as areas of necrosis and hyalinization. The treatment effect was estimated to be 75% (H&E, 10x). (B): Poor responder at high power reveals viable ES (small round blue tumor). (C): Hypocellular hyalinized tissue with thin‐walled vessels, hemosiderin and scattered histiocytes. No residual tumor cells seen (H&E, 100x). (D): Extensive necrosis. No viable tumor cells seen (H&E, 100x).