Mascarenhas L, et al. - Researchers assessed risk and response–based multi-agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. Randomization to a 6-week phase 2 window with 1 of 2 treatment schedules of irinotecan with vincristine (VI) (previously reported) was done in patients with RMS and measurable disease at first relapse with unfavorable-risk (UR) characteristics. Multi-agent chemotherapy (for 44 weeks) including the assigned VI regimen was continued in patients with at least a partial response to VI. They administered 31 weeks of multi-agent chemotherapy including tirapazamine (TPZ), at weeks 1, 4, 10, 19, and 28, in UR patients without measurable disease at study entry, without a radiographic response following the VI window, or declined VI window therapy. Same multi-agent chemotherapy without VI and TPZ was administered for 31 weeks in favorable-risk (FR) patients. Treatment with this multi-agent therapy resulted in a poor prognosis in patients with UR RMS at first relapse or disease progression, whereas a higher probability of being cured with second-line therapy was noted in FR patients.