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Randomized Controlled Trial
. 2009 Nov 1;27(31):5182-8.
doi: 10.1200/JCO.2009.22.3768. Epub 2009 Sep 21.

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

Carola A S Arndt  1 , Julie A Stoner, Douglas S Hawkins, David A Rodeberg, Andrea A Hayes-Jordan, Charles N Paidas, David M Parham, Lisa A Teot, Moody D Wharam, John C Breneman, Sarah S Donaldson, James R Anderson, William H Meyer
Affiliations
Randomized Controlled Trial

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

Carola A S Arndt et al. J Clin Oncol. .

Abstract

Purpose: The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).

Patients and methods: Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided alpha level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC.

Results: A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups.

Conclusion: For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. VAC, vincristine, dactinomycin, and cyclophosphamide; VAC/VTC, VAC alternating with vincristine, topotecan, and cyclophosphamide; PM + ICE, paramenegeal rhabdomyosarcoma with intracranial extension.
Fig 2.
Fig 2.
Treatment schema: randomized schedule of either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC) at weeks 3, 9, 21, 27, 33, and 39. Doses of drugs for children age 3 years and older were vincristine (V) 1.5 mg/m2 (top dose, 2 mg) × 1 day; dactinomycin (A) 0.045 mg/kg × 1 day (maximum dose, 2.5 mg); topotecan (T) 0.75 mg/m2 × 5 days; cyclophosphamide (C*) 2.2 g/m2 × 1 dose (with mesna uroprotection); cyclophosphamide (C†) 250 mg/m2/dose for 5 days.
Fig 3.
Fig 3.
Outcome by treatment regimen. (A) Failure-free survival; (B) overall survival. VAC, vincristine, dactinomycin, and cyclophosphamide; VAC/VTC, VAC alternating with vincristine, topotecan, and cyclophosphamide.
Fig 4.
Fig 4.
Failure-free survival by risk group stratum (all therapy groups combined). Alv, alveolar; UDS, undifferentiated sarcoma; Emb, embryonal; PM + ICE, parameningeal rhabdomyosarcoma with intracranial extension.
See this image and copyright information in PMC

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