VDC-ICE treatment plan
The core treatment plan was adapted from published dosing and administration schedules. The plan consists of eight alternating cycles of VDC and ICE given intravenously. Cycles of VDC consist of cyclophosphamide 1800-2100 (higher dose for MRT) mg/m2given on day 1, doxorubicin 37.5 mg/m2 given days 1 and 2 (or a single dose on day 1), and vincristine 1.5 mg/m2 given days 1, 8, and 15 (or a single dose on day 1). Cycles of ICE consist of carboplatin at a target AUC of 6 mg/ml-min given on day 1, with ifosfamide 2000 mg/m2 and etoposide 100 mg/m2 given days 2, 3, and 4. Mesna was administered for bladder protection with all doses of cyclophosphamide or ifosfamide, per institutional standards. Growth factor with filgrastim or pegfilgrastim, and cardioprotection with dexrazoxane (dosed at 10 times the doxorubicin dose as 375 mg/m2), were administered per institutional standards to all patients. Cycles were three weeks in duration, with an allowable interruption of up to two weeks for surgical resection of the primary or residual tumor. Radiation therapy was recommended concurrently with chemotherapy. Modifications in chemotherapy doses or changes to the order of chemotherapy cycles (e.g., giving consecutive ICE cycles to avoid anthracyclines concurrently with radiation) were at the discretion of the patient’s oncologist. Supportive care often included aggressive and extended anti-emetic regimens and extended supplemental intravenous fluid replacement.