Cancer Treatment Today

The Ewing’s family of tumours (EFT) are the second most common malignant bone tumour seen in children and young people. Histologically, they are characterized by small round blue cells with immunohistochemical staining for CD99 and neural markers.

This is the so called VAC/ IE regimen. In North America, alternative approaches to dose optimization have been explored. The Children’s Oncology Group (COG) study, INT-0154, using a regimen of vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE), randomized patients to an increased treatment intensity by higher doses of cyclophosphamide and ifosfamide and a decreased length of treatment to 11 cycles over 30 weeks in the test arm compared with a standard 17 cycles over 48 weeks but with equivalent total drug doses in each arm. There was no survival improvement but more toxicity in the dose intense arm. In contrast a survival advantage has been reported in the preliminary results from a further COG study of patients with localized EFT, AEWSOO31, randomizing between a standard three weekly schedule and an ‘interval compressed’ two weekly schedule of VDC/IE, the latter made possible by growth factor support.

NCCN recommends VAC/IE (vincristine, doxorubicin [Adriamycin], and cyclophosphamide alternating with ifosfamide and etoposide) is the preferred regimen for localized disease  and VAC (vincristine, doxorubicin, and cyclophosphamide) is the preferred regimen for patients with metastatic disease, but ti does nto negate VAC/IE.
ESMO recommends a treatment protocol of three to six cycles of multi-agent chemotherapy (doxorubicin, cyclophosphamide, ifosfamide, vincristine, dactinomycin, and etoposide), followed by local therapy and another six to 10 cycles of chemotherapy.

Jeremy Whelan et al, Interval compressed vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide in patients with advanced Ewing’s and other Small Round Cell Sarcomas. Clinical Sarcoma Research20122:12

Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Bone Cancer. Version 1.2017. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. August 29, 2016; Accessed: September 9, 2016.

25.[Guideline] ESMO/European Sarcoma Network Working Group. Bone sarcomas: ESMO Clinical Practice Guidelines