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. 2023 May 26:e30436.
doi: 10.1002/pbc.30436. Online ahead of print.

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

Sapna Oberoi  1   2 , Amria Qumseya  3 , Wei Xue  3 , Douglas J Harrison  4 , Erin R Rudzinski  5 , Suzanne L Wolden  6 , Roshni Dasgupta  7 , Rajkumar Venkatramani  8 , Abha A Gupta  9
Affiliations

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

Sapna Oberoi et al. Pediatr Blood Cancer. .

Abstract

Background: 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, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) in children with intermediate-risk (IR) RMS.

Methods: The feasibility phase of the COG IR-RMS trial, ARST1431 (NCT02567435), assigned 10 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 less than 40% of patients developed a priori defined nonhematological dose-limiting toxicities (DLTs).

Results: Ten patients (seven males and three females; median age = 4.5 years [range: 0.2-14.4 years]) with IR-RMS were enrolled and received dose level 1 of temsirolimus. Eight patients had FOXO1-negative disease, while two had FOXO1-positive disease. Two patients had metastatic disease. Of 10 patients, two developed DLTs: grade 3 oral mucositis and pneumonitis. Four patients (40%) had grade 4 neutropenia. No treatment-related mortality occurred. The median duration of the completion of the feasibility phase was 12.1 weeks (range: 11.7-15 weeks).

Conclusions: Weekly temsirolimus at 15 mg/m2 /dose during VAC/VI chemotherapy was feasible and well tolerated. The efficacy of this regimen is currently being tested in a phase III randomized trial against VAC/VI chemotherapy alone in the ARST1431 trial.

Keywords: children; mTOR inhibitor; rhabdomyosarcoma; temsirolimus.

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Conflict of interest statement

Conflict of Interests: Authors have no conflicts to declare

Figures

Figure 1
Figure 1
Treatment schema: Schedule of vincristine, dactinomycin, cyclophosphamide, irinotecan and temsirolimus delivered from week 1 to week 12
See this image and copyright information in PMC

References

    1. Ognjanovic S, Linabery AM, Charbonneau B, Ross JA. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005. Cancer. 2009;115(18):4218–4226. - PMC - PubMed
    1. Haduong JH, Heske CM, Allen-Rhoades W, et al. An update on rhabdomyosarcoma risk stratification and the rationale for current and future Children’s Oncology Group clinical trials. Pediatr Blood Cancer. 2022;69(4):e29511. - PMC - PubMed
    1. Gartrell J, Pappo A. Recent advances in understanding and managing pediatric rhabdomyosarcoma. F1000Res. 2020;9. - PMC - PubMed
    1. Arndt CA, Stoner JA, Hawkins DS, et al. Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children’s oncology group study D9803. J Clin Oncol. 2009;27(31):5182–5188. - PMC - PubMed
    1. Hawkins DS, Chi YY, Anderson JR, et al. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children’s Oncology Group. J Clin Oncol. 2018;36(27):2770–2777. - PMC - PubMed