Salvage chemotherapy using irinotecan and temozolamide in pediatric and adult populations with relapsed Ewing sarcoma.

Abstract

e22500 Background: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing Sarcoma (ES), although studies are largely limited to the paediatric population. We aimed to compare the tolerability and efficacy of IT between paediatric and adult patients. Methods: We retrospectively reviewed paediatric (< 18 years) and adult patients treated with salvage IT chemotherapy at two institutions from March, 2010 to June, 2018. Toxicities were graded according to common terminology criteria of adverse events (CTCAE v. 4.03) and compared using the Chi Square test. Responses were interpreted by Response Evaluation Criteria in Solid Tumors (RECIST). The Kaplan-Meyer method was used to estimate progression free survival (PFS); survival comparisons were carried out by the Log-rank test. Results: Fifty-three patients were included ( n= 16 paediatric; n= 37 adult). Median age was 20 (range, 5 – 45 years). A total 236 IT cycles were delivered (median = 4, range:1-7). IT was given as second-line ( n= 34; 64%) or ≥third-line ( n= 19; 36%). There was no difference in ≥grade 3/4 haematologic toxicity between paediatric and adult patients (31% vs. 35% respectively; p= 0.76), whilst febrile neutropenia was observed in two (4%) patients (one adults and one paediatric). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 19 (44%) had disease progression and 12 (28%) had stable disease. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.1 months, p = 0.001). Superior PFS for the paediatric population was observed in both, the second-line (6.2 vs. 2.2 months; p= 0.060) and ≥third-line setting (7.4 vs. 1.2 months, p= 0.014). Conclusions: IT is an effective salvage regimen for ES, with favourable toxicity and equally observed objective responses in paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in a larger prospective study.