Vincristine/Irinotecan With or Without Temozolomide for Relapsed or Refractory Rhabdomyosarcoma

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In a European phase II trial (VIT-0910) reported in the Journal of Clinical Oncology, Defachelles et al found that the combination of vincristine/irinotecan with vs without temozolomide produced better outcomes—albeit with increased toxicity—in children and adults with relapsed or refractory rhabdomyosarcoma.

Study Details

In the open-label multicenter trial, 120 patients were randomly assigned between March 2012 and April 2018 to receive vincristine/irinotecan with (VIT group, n = 60) or without (VI group, n = 60) temozolomide. Patients received 21-day cycles combining vincristine at 1.5 mg/m2 once daily on days 1 and 8 and irinotecan at 50 mg/m2 once daily on days 1 to 5 with or without temozolomide at 125 mg/m2 once daily on days 1 to 5 and 150 mg/m2 once daily from cycle 2; treatment continued until disease progression or unacceptable toxicity.

Patients had a median age of 11 years (range = 0.75–45 years); 89% had relapsed rhabdomyosarcoma. The primary endpoint was objective response rate after two treatment cycles among patients enrolled at relapse.


Among patients enrolled at relapse, objective response after two treatment cycles was observed in 24 (44%) of 55 patients in the VIT group vs 18 (31%) of 58 in the VI group (adjusted odds ratio [OR] = 0.50, 95% confidence interval [CI] = 0.22–1.12, P = .09). Complete response was observed in five patients (11%) vs two (4%).


  • Vincristine/irinotecan with vs without temozolomide was associated with a numerically better objective response rate after two cycles.
  • The triplet regimen was associated with significantly improved overall survival.

Among all patients assessable for response over the entire duration of treatment, objective response was observed in 33 (57%) of 58 patients in the VIT group vs 22 (38%) of 58 in the VI group (adjusted OR = 0.40, 95% CI = 0.18–0.88, P = .023).

Median follow-up was 57 months. Among all patients, median progression-free survival was 4.7 months (95% CI = 4.1–8.5 months) in the VIT group vs 3.2 months (95% CI = 2.4–7.3 months) in the VI group (adjusted hazard ratio [HR] = 0.68, 95% CI = 0.46–1.01, P = .059), with a 1-year rate of 33% vs 28%. Median overall survival was 15.0 months (95% CI = 10.0–21.2 months) in the VIT group vs 10.3 months (95% CI = 7.1–12.6 months) in the VI group (adjusted HR = 0.55, 95% CI = 0.35–0.84, P = .006), with 1- and 2-year rates of 56% vs 43% and 33% vs 22%.

Adverse Events

Grade ≥ 3 adverse events occurred in 98% of those in the VIT group vs 78% of the VI group (P = .009), including a significantly higher incidence of grade ≥ 3 hematologic toxicity (81% vs 61%, P = .025). Grade ≥ 3 adverse events considered related to treatment occurred in 93% vs 69% (P = .002). Treatment-related serious adverse events occurred in 38% vs 19% (P = .023). No significant differences in grade ≥ 3 diarrhea (24% vs 17%, P = .33) or nausea/vomiting (26% vs 17%, P = .24) were observed. No treatment-related deaths occurred.

The investigators concluded, “The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed rhabdomyosarcoma, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.”

Anne-Sophie Defachelles, MD, of the Pediatric and AYA Oncology Unit, Centre Oscar Lambret, Lille, France, is the corresponding author for the Journal of Clinical Oncology article.  

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