Treatment outcomes for adult patients with localized osteosarcoma treated with chemotherapy without methotrexate at a public hospital in Brazil

ABSTRACT

Introduction: Standard treatment for pediatric patients with localized osteosarcoma includes high-dose methotrexate (HDMTX), and cure rates greater than 60% are observed. However, in adult patients, the toxicity profile limits the use of HDMTX and the drug is usually excluded from chemotherapy protocols for this group. We aimed to evaluate the outcomes of adult patients with localized osteosarcoma treated with chemotherapy without methotrexate. Methods: In this retrospective cohort, we evaluated adult patients with high-grade osteosarcoma who received chemotherapy treatment without methotrexate in a reference cancer center from 2007 to 2018. Outcomes analyzed were recurrence-free survival (RFS), overall survival (OS), and prognostic factors associated with overall survival. Results: A total of 48 patients had localized disease and received treatment with chemotherapy without methotrexate. The majority of them received chemotherapy with a combination of cisplatin and doxorubicin (n=42, 87.5%). Median age was 27 years (range 16.8-66.7). With a median follow-up of 29.2 months, median RFS was 29.9 months. Median OS was not reached. 5-year RFS and OS rates were 35.1% (95% CI: 20.3-50.2%) and 71.6% (95% CI: 52.3-84.2%), respectively. Patients who received cumulative doses of doxorubicin =375mg/m2 had better OS than those who received lower doses (HR 0.26, 95% CI: 0.07-0.94, p=0.041). Similarly, patients who received =6 cycles of neoadjuvant/adjuvant cisplatin tended to have better OS than those who received <6 cycles (HR 0.30, 95% CI: 0.081.09, p=0.069). Nineteen patients received less than 6 cycles of cisplatin and doxorubicin mainly because of grade 3 or 4 toxicities (11), disease progression (6), patient refusal (1), and physician choice (1). Conclusion: In our study, adult patients with localized highgrade osteosarcoma treated with chemotherapy without methotrexate had unfavorable outcomes. The cumulative doxorubicin dose and the number of cisplatin/doxorubicin cycles were associated with improved OS. The investigation of additional treatment strategies is of utmost importance to improve adult patients' outcomes.

RESUMO

Introdução: O tratamento padrão para pacientes pediátricos com osteossarcoma localizado inclui metotrexato em altas doses (HDMTX) e taxas de cura superiores a 60% são observadas. No entanto, em pacientes adultos, o perfil de toxicidade limita o uso de HDMTX e o medicamento geralmente é excluído dos protocolos de quimioterapia para esse grupo. Nosso objetivo foi avaliar os resultados de pacientes adultos com osteossarcoma localizado tratados com quimioterapia sem metotrexato. Métodos: Nesta coorte retrospectiva, avaliamos pacientes adultos com osteossarcoma de alto grau que receberam tratamento quimioterápico sem metotrexato em um centro de referência de câncer de 2007 a 2018. Os resultados analisados foram sobrevida livre de recorrência (SLR), sobrevida global (SG) e fatores prognósticos associados à sobrevida global. Resultados: Um total de 48 pacientes apresentou doença localizada e recebeu tratamento com quimioterapia sem metotrexato. A maioria deles recebeu quimioterapia com uma combinação de cisplatina e doxorrubicina (n=42, 87,5%). A idade média foi de 27 anos (intervalo de 16,8-66,7). Com um acompanhamento médio de 29,2 meses, o RFS médio foi de 29,9 meses. SG mediano não foi alcançado. As taxas de SLR e SG em 5 anos foram de 35,1% (IC 95%: 20,3-50,2%) e 71,6% (IC 95%: 52,3-84,2%), respectivamente. Pacientes que receberam doses cumulativas de doxorrubicina =375mg/m2 tiveram melhor SG do que aqueles que receberam doses mais baixas (HR 0,26, IC 95%: 0,07-0,94, p=0,041). Da mesma forma, os pacientes que receberam =6 ciclos de cisplatina neoadjuvante/adjuvante tenderam a ter melhor SG do que aqueles que receberam <6 ciclos (HR 0,30, IC 95%: 0,08-1,09, p=0,069). Dezenove pacientes receberam menos de 6 ciclos de cisplatina e doxorrubicina principalmente por causa de toxicidades de grau 3 ou 4 (11), progressão da doença (6), recusa do paciente (1) e escolha do médico (1). Conclusão: Em nosso estudo, pacientes adultos com osteossarcoma de alto grau localizado tratados com quimioterapia sem metotrexato tiveram resultados desfavoráveis. A dose cumulativa de doxorrubicina e o número de ciclos de cisplatina/ doxorrubicina foram associados à melhora da SG. A investigação de estratégias de tratamento adicionais é de extrema importância para melhorar os resultados dos pacientes adultos.

Keywords:

Osteosarcoma - Antineoplastic agents - Doxorubicin - Methotrexate.

Descritores:

Osteosarcoma - Agentes antineoplásicos - Doxorrubicina - Metotrexato.

Publication History

Received: 22 August 2020

Accepted: 05 March 2021

Article published online:
14 May 2021

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