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Adding topotecan to standard VAC treatment did not improve outcomes in intermediate-risk rhabdomyosarcoma
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There was no improvement for failure-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin and cyclophosphamide alternated with vincristine, topotecan and cyclophosphamide compared with treatment with vincristine, actinomycin and cyclophosphamide alone.
Previous research had shown that topotecan, a topoisomerase I inhibitor, was active in patients with newly diagnosed stage IV rhabdomyosarcoma patients. This randomized clinical trial was initiated to compare outcomes in patients with intermediate-risk disease treated with the standard of care vincristine, actinomycin (Cosmegen, LundBeck;) and cyclophosphamide treatment (VAC) vs. VAC/vincristine, topotecan (Hycamtin, GlaxoSmithKline) and cyclophosphamide (VAT).
Researchers randomly assigned 264 patients to VAC and 252 patients to VAT treatment and nonrandomly assigned 101 patients with parameningeal rhabdomyosarcoma with intracranial extension to VAC and X-ray therapy. The median follow-up was 4.3 years.
The four-year failure-free survival rates were similar between the VAC (73%) and VAC/VTC (68%; P=.3) treatment groups. The relative hazard ratio was 1.19 (95% CI, 0.85-1.66) for VAC therapy vs. VAC/VTC therapy. OS was 79% in both treatment groups (P=.9).
No difference in effect was observed across risk groups, according to researchers. There was a slightly higher risk for failure in patients with stage II to stage III alveolar rhabdomyosarcoma or undifferentiated sarcoma treated with VAC/VTC compared with those treated with VAC (P=.05).
Overall, the most common grade-3 and grade-4 toxicities were febrile neutropenia, anemia, clinically documented infection, leucopenia, lymphopenia, neutropenia and thrombocytopenia. Patients in the VAC therapy group were more likely than patients in the VAC/VTC therapy group to develop febrile neutropenia (P=.04).
Another clinical trial comparing irinotecan — another topoisomerase inhibitor that also showed activity in early trials — is ongoing.
Arndt CAS. J Clin Oncol. 2009;doi:10.1200/JCO.2009.22.3768.