Metronomic Chemotherapy and Radiotherapy as Salvage Treatment in Refractory or Relapsed Pediatric Solid Tumours

Abstract

Metronomic chemotherapy (mctx) combined with radiation therapy (rt) is an emerging anticancer strategy. The aim of the present study was to assess the efficacy of mctx combined with rt as salvage treatment in children with refractory or relapsed solid malignancies. This prospective study enrolled patients with refractory or relapsed pediatric solid tumours from January 2013 to January 2015. Treatment consisted of 3-12 courses of mctx in all patients, followed by rt in patients who experienced local recurrence, distant metastases, or both. Each course of mctx consisted of oral celecoxib 100-400 mg twice daily (days 1-42), intravenous vinblastine 3 mg/m(2) weekly (weeks 1-6), oral cyclophosphamide 2.5 mg/m(2) daily (days 1-21), and oral methotrexate 15 mg/m(2) twice weekly (days 21-42). Statistical methods used were the log-rank test and binary logistic regression. A favourable disease response (partial response or stable disease) was seen in 49 of 64 patients (76.6%), with mild acute toxicity occurring in 41 (64%). After a median follow-up of 14 months, 1-year overall survival was 62%. Pattern of disease relapse (p < 0.0001), time from initial treatment to relapse (p = 0.0002), and response to treatment (p < 0.0001) significantly affected survival. Age was the only factor that significantly correlated with treatment toxicity (p = 0.002; hazard ratio: 3.37; 95% confidence interval: 1.53 to 7.35). Combining mctx with rt resulted in a favourable response rate, minimal toxicity, and 62% 1-year overall survival in patients with heavily pretreated recurrent disease. Patients with localized late recurrence or disease progression are the most likely to benefit from this regimen.