Interval compressed vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide in patients with advanced Ewing’s and other Small Round Cell Sarcomas

Jeremy Whelan,Atia Khan,Maria Michelagnoli,Christian Rothermundt,Beatrice Seddon,Sandra Strausss,Palma Dileo,Anand Sharma

doi:10.1186/2045-3329-2-12

Jeremy Whelan, Atia Khan + Show 6 more

Open Access

https://doi.org/10.1186/2045-3329-2-12

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Abstract

BackgroundTo evaluate tolerability and maintenance of dose intensity of 2 weekly treatment with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide (VDC/IE) in patients with advanced small round cell sarcomas including Ewing family tumours (EFT), desmoplastic small round cell tumours (DSRCT) and undifferentiated high grade round cell sarcomas (UHGRCS).MethodsRetrospective review of 16 patients treated at a single centre with VDC/IE. Dose received, treatment delay, toxicity and clinical outcome were recorded for each cycle up to a maximum of 14 cycles.ResultsA total 193 cycles of VDC/IE were administered to 10 patients with EFT, 4 with DSRCT and 2 with UHGRCS. Median age was 22 years with 75% over 18 years. Metastases were present in 14 patients. The mean duration of each cycle was 16.7 days. Febrile neutropenia occurred in 14 % of cycles, and grade 3/4 haematologic toxicity including anaemia and thrombocytopenia in 16 % and 11 % of cycles respectively. Seven patients had a dose reduction. Five patients discontinued VDC/IE early due to toxicity.ConclusionsThis schedule of VDC/IE is feasible in patients with EFT and DSRCT including adults and those with metastases. Its comparison with other standard regimens for these diseases is justified.

Highlights

To evaluate tolerability and maintenance of dose intensity of 2 weekly treatment with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide (VDC/IE) in patients with advanced small round cell sarcomas including Ewing family tumours (EFT), desmoplastic small round cell tumours (DSRCT) and undifferentiated high grade round cell sarcomas (UHGRCS)
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
In preparation for a planned randomized comparison in Europe of first line treatment for EFT between VIDE and VDC/IE, we retrospectively examined the feasibility of interval compressed VDC/IE in patients with metastatic EFT

Summary

Introduction

To evaluate tolerability and maintenance of dose intensity of 2 weekly treatment with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide (VDC/IE) in patients with advanced small round cell sarcomas including Ewing family tumours (EFT), desmoplastic small round cell tumours (DSRCT) and undifferentiated high grade round cell sarcomas (UHGRCS). The Ewing’s family of tumours (EFT) are the second most common malignant bone tumour seen in children and young people [1,2]. They are characterized by small round blue cells with immunohistochemical staining for CD99 and neural markers. The family of small round blue cell sarcomas includes desmoplastic small round cell tumour (DSRCT), a rare soft tissue sarcoma characteristically presenting in young males with extensive multifocal intraabdominal disease. To contend with a lack of recent survival improvement or new agents with major activity, investigators have concentrated on investigating the benefits of scheduling and dose intensity

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