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Shorter-Duration Therapy Including Lower-Dose Cyclophosphamide Preserves Efficacy in Newly Diagnosed Low-Risk Rhabdomyosarcoma

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Key Points

  • A shorter-duration therapy including lower-dose cyclophosphamide with or without RT did not reduce failure-free survival.
  • Three-year failure-free survival was 89% and 3-year overall survival was 98%.

Intergroup Rhabdomyosarcoma Study Group (IRSG) studies have shown improved failure-free survival with VAC (vincristine, dactinomycin, and cyclophosphamide) given with a total cumulative cyclophosphamide dose of 26.4 g/m2 compared with VA (vincristine and dactinomycin) in patients with subset 1 low-risk embryonal rhabdomyosarcoma (stage 1/2, group I/II; or stage 1, group III orbit tumors).

In the Children’s Oncology Group ARST0331 study reported in the Journal of Clinical Oncology, Waterhouse and colleagues found that shorter-duration therapy with VAC, including lower-dose cyclophosphamide with or without radiation therapy, did not reduce failure-free survival in such patients.

Study Details

In the study, 271 newly diagnosed subset 1 patients were treated between September 2004 and August 2010 with four cycles of VAC with a cyclophosphamide cumulative dose of 4.8 g/m2 followed by four cycles of VA over 22 weeks. Patients with microscopic or gross residual disease at study entry also received radiotherapy.

Failure-free survival was the primary endpoint. Failure rate was compared with that [the expected rate] in a subgroup of patients in the IRSG low-risk rhabomyosarcoma study D9602 who received 45 weeks of VA and radiotherapy.

Failure-Free and Overall Survival

Median follow-up was 4.3 years. A total of 35 failures were observed compared with an expected 48.4 failures (P = .05). Estimated 3-year failure-free survival rate was 89% (95% confidence interval [CI] = 85%–92%) and 3-year overall survival rate was 98% (95% CI = 95%–99%).

Patients with paratesticular tumors (n = 118) had a better outcome (3-year failure-free and overall survival rates of 93% and 99%) than those with orbit tumors (n = 82, 86% and 97%) and those with tumors in all other sites combined (86% and 97%).

The 3-year cumulative incidence rates for any local, regional, or distant failures were 7.6%, 1.5%, and 3.4%.

No unexpected grade 4 toxicities and no deaths resulting from toxicity were observed.

The investigators concluded: “Shorter-duration therapy that included lower-dose cyclophosphamide and [radiotherapy] did not compromise [failure-free survival] for patients with subset-one low-risk [embryonal rhabdomyosarcoma].”

The study was supported by grants from the National Cancer Institute.

The authors indicated no potential conflicts of interest.

David O. Walterhouse, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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