ADDITION OF IFOSFAMIDE AND ETOPOSIDE TO STANDARD CHEMOTHERAPY FOR ADULT PATIENTS WITH LOCALIZED OSTEOSARCOMA: A MATCHED-COHORT STUDY

Background Adult patients (pts) with localized osteosarcoma have poorer outcomes than pediatric patients in general. One factor that contributes to these poorer outcomes is the elevated toxicity rates with chemotherapy (CT) regimens containing high dose methotrexate in adult pts. Thus, a standard regimen frequently used as neoadjuvant/ adjuvant therapy for adult pts is cisplatin and doxorubicin. We aimed to evaluate the efficacy and safety of the addition of ifosfamide and etoposide (IE) to standard CT for adult pts with localized osteosarcoma. Methods We performed a matched-cohort study of adult pts treated for localized osteosarcoma in a single academic cancer center between Jun-2009 and Dec-2017. All pts who received neoadjuvant/ adjuvant IE in addition to standard CT were included in the analysis (IE group). For each patient in IE group, we selected one patient matched for stage, histologic subtype, age, and gender who received standard CT alone (Standard group). Standard CT consisted of cisplatin and doxorubicin. Overall survival (OS) and recurrence-free survival (RFS) were estimated with Kaplan-Meier method and curves were compared by log-rank test. Cox regression was used to obtain hazard-ratio (HR) and 95% confidence interval (CI). Results Six pts were identified in IE group, and six matched pts were included in standard group. Median age was 20.1 years (range 17-36). All pts had osteoblastic osteosarcoma. Most of them were male (N = 10, 83%), and had stage IIB (N = 4, 33%) or III (N = 6, 50%). With a median follow-up of 31.7 months, median RFS was 11.3 months in IE group in comparison with 31.8 months in standard group (HR 1.68, 95% CI 0.36 7.89; P = 0.505). Median OS was 44.4 vs 51.2 months, respectively (HR 1.57, 95% CI 0.29 – 8.46, P = 0.594). 5-year OS rates 33% in IE group and 40% in standard group. Grade ≥ 3 toxicities were mainly hematological and were numerically higher in IE group (83% vs 33%; P = 0.242). One grade 5 toxicity occurred in IE group due to sepsis. Conclusion In this small matched-cohort study, the addition of IE to standard CT for adult pts with localized osteosarcoma was not associated with improved RFS or OS. Additionally, it resulted in alarming rates of high-grade toxicities. Investigations of other treatment strategies are warranted to improve outcomes.