VAC lock.

It’s been quite the summer for rhabdomyosarcoma (RMS). At ASCO, the EpSSG trial demonstrated improved overall and event-free survival (EFS) with the addition of maintenance chemo in patients with high-risk RMS. Now we have results from the COG ARST0531 trial, which randomized patients with intermediate risk RMS to either standard vincristine, dactinomycin, and cyclophosphamide (VAC) or a hybrid VAC/VI regimen where irinotecan replaced cyclophosphamide and/or dactinomycin in some cycles. The rationale for this trial was that VI demonstrated serious activity in recurrent and metastatic RMS. Problem is, VAC is the backbone of all backbones. It has endured challenger regimens and additional agents for decades. A secondary rationale was that a reduced overall dose of cyclophosphamide may reduce some of its significant long-term toxicities in kids (such as fertility). Once again, VAC stood strong with no demonstrated improvement in EFS with the addition of VI (59% versus 63% with VAC). But severe heme toxicity was less with VAC/VI. Not to mention, administration of lower doses of cyclophosphamide may allow for more outpatient chemo administration. TBL: VAC/VI was not “superior” to VAC for intermediate RMS, but it’s probably equally effective with less toxicity. Too bad the RMS protocol of this decade wasn’t one of non-inferiority design. | Hawkins, J Clin Oncol 2018