| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 107 === Osteosarcoma (OGS) is a cancerous tumor derived from bone, which is most prevalent in children, teenagers and young adults. The current standard treatment of OGS includes surgical resection and chemotherapy. According to 2019 National Comprehensive Cancer Network guideline of bone tumor, MAP, consisted of high dose methotrexate (M), adriamycin (doxorubicin, A) and platinum (cisplatin, P), is the first line therapy. However, severe hepatotoxicity associated with MAP, especially high dose methotrexate (HD-MTX) is more often encountered in Taiwanese than Western patients. MTX serum level is continuing monitored after infusion to avoid adverse effects. The elevated alanine aminotransferase (ALT) should be ≤ 200U in 7 days before executing the next step of chemotherapy. To ensure equivalent efficacy and reduce the incidence of hepatotoxicity, the chemotherapeutic protocols for OGS were optimized in 2003 at Taipei Veterans General Hospital (TVGH). In TVGH OGS protocol HD-MTX courses were reduced and high dose ifosfamide were added. Additionally, some co-medications during chemotherapy are usually prescribed to reduce cancer related complications. However, it has been reported that proton-pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX) and non-steroidal anti-inflammatory drugs (NSAIDs) have drug-drug interactions (DDIs) with MTX. The DDIs may cause delayed elimination of MTX. Based on the study of Hung et al., it has been reported that there is no significant difference in outcome between MAP and TVGH OGS protocol. However, the safety of HD-MTX treatment remains uncertain. Therefore, the aim of the study is to investigate: (1) whether the optimize protocol could reduce the risk of hepatotoxicity, (2) whether ALT level could decrease ≤ 200U in 7 days, (3) whether these co-medications (PPIs or TMP-SMX or NSAIDs) would affect the efficacy and safety of HD-MTX treatment.
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