TY - JOUR
T1 - Cyclophosphamide dose escalation in combination with vincristine and actinomycin-D (VAC) in gross residual sarcoma
T2 - A pilot study without hematopoietic growth factor support evaluating toxicity and response
AU - Ruymann, Frederick B.
AU - Vietti, Teresa
AU - Gehan, Edmund
AU - Wiener, Eugene
AU - Wharam, Moody
AU - Newton, William A.
AU - Maurer, Harold
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1995/11
Y1 - 1995/11
N2 - Purpose: The Intergroup Rhabdomyosarcoma Study (IRS) initiated an escalating-dose cyclophosphamide (Cyc) pilot without hematopoietic growth factor (HGF) support in combination with vincristine (Vcr) and actinomycin-D (Amd), known as VAC, to establish a Cyc dose with myelotoxicity comparable to an ifosfamide (Ifos), Vcr, and Amd combination regimen (VAI). A Cyc dose equivalent to Ifos was to be determined when comparable myelotoxicity was achieved. Patients and Methods: Patients with either rhabdomyosarcoma or undifferentiated soft-tissue sarcoma and gross residual (clinical group III) disease were eligible for the VAC pilot. Feasibility and toxicity were evaluated in the VAC pilot at each Cyc level before escalating the dose. Starting at CYC 1.2 g/m2dose escalation was planned at increments of 20–25% in cohorts of 8–10 patients until myelotoxicity at a severe or worse grade was seen in >90% of the patients. Results: One hundred nineteen eligible patients were evaluated for toxicity and response at four Cyc levels: 1.2, 1.5, 1.8, and 2.2 g/m2. Eight of 87 (9%) evaluable at 2.2 g/m2had a toxic death. Six of these were attributable to myelotoxicity. Patients age 1–3 years were most vulnerable. The overall complete response (CR) rate of 68% was poorly predicted by the weeks 8 and 20 CR rates of 20 and 40%, respectively. During the first year and overall, myelotoxicity at 2.2 g/m21 with VAC was comparable to Ifos 1.8 g/m25. Cyc was relatively more myelotoxic than Ifos in the second year of the VAC pilot. Based on actual amount of drug given, a standardized Ifos dose of 9.0 g/m2was equivalent to 2.1 g/m2of Cyc, giving an Ifos/Cyc ratio of 4.3. Conclusion: Myelotoxicity using 2.2 g Cyc/m2in a single intravenous infusion was dose limiting in this VAC pilot without HGF. In the first year and overall, myelotoxicity is comparable to that with VAI using Ifos at 9.0 g/m2. An ongoing IRS-IV randomized trial of VAC and VAI should provide a comparison of the efficacy of Ifos and Cyc in children and adolescents with embryonal or alveolar rhabdomyosarcoma and undifferentiated softtissue sarcomas.
AB - Purpose: The Intergroup Rhabdomyosarcoma Study (IRS) initiated an escalating-dose cyclophosphamide (Cyc) pilot without hematopoietic growth factor (HGF) support in combination with vincristine (Vcr) and actinomycin-D (Amd), known as VAC, to establish a Cyc dose with myelotoxicity comparable to an ifosfamide (Ifos), Vcr, and Amd combination regimen (VAI). A Cyc dose equivalent to Ifos was to be determined when comparable myelotoxicity was achieved. Patients and Methods: Patients with either rhabdomyosarcoma or undifferentiated soft-tissue sarcoma and gross residual (clinical group III) disease were eligible for the VAC pilot. Feasibility and toxicity were evaluated in the VAC pilot at each Cyc level before escalating the dose. Starting at CYC 1.2 g/m2dose escalation was planned at increments of 20–25% in cohorts of 8–10 patients until myelotoxicity at a severe or worse grade was seen in >90% of the patients. Results: One hundred nineteen eligible patients were evaluated for toxicity and response at four Cyc levels: 1.2, 1.5, 1.8, and 2.2 g/m2. Eight of 87 (9%) evaluable at 2.2 g/m2had a toxic death. Six of these were attributable to myelotoxicity. Patients age 1–3 years were most vulnerable. The overall complete response (CR) rate of 68% was poorly predicted by the weeks 8 and 20 CR rates of 20 and 40%, respectively. During the first year and overall, myelotoxicity at 2.2 g/m21 with VAC was comparable to Ifos 1.8 g/m25. Cyc was relatively more myelotoxic than Ifos in the second year of the VAC pilot. Based on actual amount of drug given, a standardized Ifos dose of 9.0 g/m2was equivalent to 2.1 g/m2of Cyc, giving an Ifos/Cyc ratio of 4.3. Conclusion: Myelotoxicity using 2.2 g Cyc/m2in a single intravenous infusion was dose limiting in this VAC pilot without HGF. In the first year and overall, myelotoxicity is comparable to that with VAI using Ifos at 9.0 g/m2. An ongoing IRS-IV randomized trial of VAC and VAI should provide a comparison of the efficacy of Ifos and Cyc in children and adolescents with embryonal or alveolar rhabdomyosarcoma and undifferentiated softtissue sarcomas.
KW - Cyclophosphamide
KW - Hyperfractionated radiotherapy
KW - Ifosfaraide
KW - Soft-tissue sarcoma
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U2 - 10.1097/00043426-199511000-00009
DO - 10.1097/00043426-199511000-00009
M3 - Article
C2 - 7583389
AN - SCOPUS:0028883876
SN - 1077-4114
VL - 17
SP - 331
EP - 337
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
IS - 4
ER -