Efficacy and feasibility of treating adults with paediatric chemotherapy protocols in Ewing sarcoma, rhabdomyosarcoma and osteosarcoma - A systematic review by the Australia and New Zealand Sarcoma Association clinical practice guidelines working party.
This systematic review reports that pediatric chemotherapy protocols may improve survival in adults with rhabdomyosarcoma, while evidence for Ewing sarcoma and osteosarcoma is limited, and that adults generally receive lower chemotherapy exposure and experience different toxicity patterns than children.
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This systematic review reports that pediatric chemotherapy protocols may improve survival in adults with rhabdomyosarcoma, while evidence for Ewing sarcoma and osteosarcoma is limited, and that adults generally receive lower chemotherapy exposure and experience different toxicity patterns than children.
Research significance
The evidence supports an association between pediatric-protocol treatment and improved survival in one non-metastatic adult rhabdomyosarcoma cohort; inferentially, maintaining adequate chemotherapy exposure and including disease-specific agents could improve adult sarcoma outcomes, but this requires confirmation in prospective studies and careful toxicity assessment.
Source abstract
BACKGROUND: Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), and osteosarcoma (OSS) are rare in adults; efficacy and feasibility of treating adults with standard paediatric protocols (PP) are uncertain as chemotherapy protocols have been extrapolated from a paediatric population. METHODS: A systematic review was conducted for EWS, RMS, and OSS using the Population, Intervention, Comparison, and Outcome (PICO) framework. PICO 1 compared adults treated with PP vs personalised "adult protocols" (non-PP). PICO 2 compared adults vs children treated with PP. PP was defined as: VDC/IE, VIDE for EWS; IVA, VAC for RMS; and MAP for OSS. RESULTS: 14, 13 and 9 studies for EWS, RMS and OSS were identified; majority were retrospective. Compared with non-PP, PP was associated with improved survival in adults with RMS (5-year OS of 56.7% vs 39.5% in a non-metastatic cohort, multivariate analysis, p = 0.042). There was limited robust data directly comparing PP vs non-PP in adults with EWS and OSS. Acknowledging many potential confounders, adequate chemotherapy exposure may be associated with improved survival across EWS, RMS and OSS. Compared to children, adults had lower chemotherapy exposure and differential toxicities: more peripheral neuropathy, but similar or reduced haematological toxicity. CONCLUSION: The treatment of adults with EWS, RMS, and OSS remains an area of unmet need. Adequate chemotherapy exposure and inclusion of disease-specific therapeutic agents may be important elements in the optimal treatment of adults. Referral to a specialised sarcoma reference centre is strongly recommended.