Feasibility of combining temsirolimus to vincristine, dactinomycin, cyclophosphamide, and vincristine and irinotecan chemotherapy for children with intermediate-risk rhabdomyosarcoma: A report from Children’s Oncology Group

Oberoi S, Qumseya A, Xue W, Harrison DJ, Rudzinski ER, Wolden SL, Dasgupta R, Venkatramani R, Gupta AA. Feasibility of combining temsirolimus to vincristine, dactinomycin, cyclophosphamide, and vincristine and irinotecan chemotherapy for children with intermediate-risk rhabdomyosarcoma: A report from Children’s Oncology Group. Pediatr Blood Cancer. 2023 May 26;:e30436. doi: 10.1002/pbc.30436. [Epub ahead of print] PubMed PMID: 37243336; PubMed Central PMCID: PMC10676447.

Temsirolimus has shown in vivo activity against rhabdomyosarcoma (RMS). We aimed to determine the feasibility of incorporating temsirolimus within the standard Children’s Oncology Group (COG) chemotherapy backbone of vincristine, actinomycin-D, cyclophosphamide (VAC) alternating with vincristine, irinotecan (VI) in children with intermediate-risk (IR) RMS. The feasibility phase of the COG IR-RMS trial, ARST1431(NCT02567435), assigned ten patients to receive 15 mg/m2/dose (Dose Level 1) of temsirolimus on days 1, 8 and 15 of each of three weekly VAC and VI cycles for the first 12 weeks of induction chemotherapy. The primary endpoint of the feasibility phase was to establish the safe dose and safety of combining temsirolimus with VAC/VI. The combination regimen was deemed feasible if < 40% of patients developed a priori defined non-hematological dose-limiting toxicities (DLTs).