Integrating Irinotecan in standard chemotherapy: a novel dose density
combination for High-Risk pediatric Sarcomas
Abstract
BACKGROUND: Irinotecan is a drug active against pediatric sarcomas with
a toxicity profile that theoretically allows for its association with
more myelotoxic drugs. We examined the feasibility of a dose-density
strategy integrating irinotecan in standard chemotherapy regimens for
patients with high-risk sarcomas. METHODS: Between November 2013 and
January 2020, 23 patients < 21 years old with metastatic (11
children) or recurrent (12 children) sarcomas were treated with 9
IrIVA/IrVAC cycles. All newly-diagnosed patients received IrIVA
(ifosfamide 3g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on day 1,
actinomycin D 1.5 mg/m2 on day 1, irinotecan 20 mg/m2 for 5 consecutive
days starting on day 8). Two relapsed patients received IrIVA and 10
IrVAC (cyclophosphamide 1.5 g/m2 on day 1 instead of ifosfamide).
Feasibility was assessed in terms of toxicity and time to complete the
treatment. RESULTS: 17 rhabdomyosarcomas, 4 Ewing sarcomas, 2
desmoplastic round cell tumors received a total of 181 cycles (range
2-10). Grade 4 neutropenia occurred in 62.4% of the cycles. 13 patients
had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time
to complete the treatment was 195 days (range 170-231), 83.4% of cycles
were administered on time or with a delay <1 week. With a
median follow-up of 2.6 years (range 0.2-5.0), 12 patients are alive, 9
complete remissions, 3 with the disease. Conclusions: A dose density
strategy combining irinotecan with standard chemotherapy is feasible.
This approach will be investigated in the next trial coordinated by the
European pediatric Soft tissue sarcoma Study Group.