Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy again...Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy against various soft tissue sarcomas. However, its extravasation causes serious complications, such as tissue necrosis and a delay in the treatment of underlying diseases. Methods: We experienced a rare case in which trabectedin extravasation caused severe pectoralis major muscle necrosis. A 45-year-old man with multiple lung metastases of follicular dendritic cell sarcoma received 2.15 mg of trabectedin totally through a central venous access device (CVAD) system in the right precordium. Computed tomography showed extensive turbidity of subcutaneous fatty tissue and swelling of the pectoralis major muscle to the upper margin of the liver, and the creatine kinase level was elevated to 759 U/L (reference value from 54 to 286). We performed surgical debridement twice, and the CVAD was concomitantly removed;thereafter, the skin defect was reconstructed with a split skin mesh graft. Results: Histopathology showed extreme degeneration of striated muscle and fatty tissue. Unfortunately, disability of the right arm abducens persisted after treatment because of debridement around the right humerus muscle. Discussion: Several reports have described cases of the extravasation of trabectedin. A few have mentioned severe muscular degeneration similar to that shown in the present case. Because trabectedin is a strong vesicant cytotoxic agent, it is principally administered through a CVAD rather than peripheral vessels and is continued during the nighttime;this can lead to a delay in patients or attending doctors noticing any extravasation. We need to spread appropriate knowledge of this drug and make an effort to prevent severe complications like in the present case.展开更多
Epithelial ovarian cancer(OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response r...Epithelial ovarian cancer(OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer(ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.展开更多
Trabectedin and lurbinectedin are therapeutic antitumor pharmaceuticals approved by the Food and Drug Administration for treating soft tissue sarcomas and metastatic small cell lung cancer and have been facing synthes...Trabectedin and lurbinectedin are therapeutic antitumor pharmaceuticals approved by the Food and Drug Administration for treating soft tissue sarcomas and metastatic small cell lung cancer and have been facing synthesis challenges over the past three decades.In this report,the total synthesis of trabectedin,lurbinectedin,and renieramycin T were accomplished in 22-27 steps.The synthetic strategy features stereocontrolled Pictet-Spengler(PS)reaction leading to the multisubstituted tetrahydroisoquinoline fragment(DE ring),aldol condensation for C4-C10 bond formation,and a second PS cyclization with asymmetric oxomalonate for the fully substituted B ring,in which palladium complex-induced stereoselectivity is achieved via decarboxylative protonation anchoring the C1 stereocenter.The pentacyclic skeleton(A-E)was efficiently effectuated at a gramscale,displaying superior potential for further drug development.展开更多
曲贝替定（Yondelis R ，Trabectedin）是一种新的非铂类抗肿瘤药物，有独特的抗肿瘤机制，不良反应主要为可逆性肝脏损害。 Trabectedin的心脏毒性低，可以和蒽环类抗肿瘤药物联合应用，目前已应用于复发性卵巢癌的治疗。临床可选用的...曲贝替定（Yondelis R ，Trabectedin）是一种新的非铂类抗肿瘤药物，有独特的抗肿瘤机制，不良反应主要为可逆性肝脏损害。 Trabectedin的心脏毒性低，可以和蒽环类抗肿瘤药物联合应用，目前已应用于复发性卵巢癌的治疗。临床可选用的治疗方案有单药3周方案、单药周疗和联合蒽环类药物方案，其中联合方案疗效最好。Trabectedin对铂类敏感的复发性卵巢癌有较好的疗效，特别是对无铂间隔期（treatment-free interval，TFI）为6~12个月的复发性卵巢癌疗效显著，但对铂类耐药及难治性卵巢癌的疗效不明显。应用Trabectedin可延长TFI，为以后再次进行铂类药物治疗创造条件。展开更多
文摘Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy against various soft tissue sarcomas. However, its extravasation causes serious complications, such as tissue necrosis and a delay in the treatment of underlying diseases. Methods: We experienced a rare case in which trabectedin extravasation caused severe pectoralis major muscle necrosis. A 45-year-old man with multiple lung metastases of follicular dendritic cell sarcoma received 2.15 mg of trabectedin totally through a central venous access device (CVAD) system in the right precordium. Computed tomography showed extensive turbidity of subcutaneous fatty tissue and swelling of the pectoralis major muscle to the upper margin of the liver, and the creatine kinase level was elevated to 759 U/L (reference value from 54 to 286). We performed surgical debridement twice, and the CVAD was concomitantly removed;thereafter, the skin defect was reconstructed with a split skin mesh graft. Results: Histopathology showed extreme degeneration of striated muscle and fatty tissue. Unfortunately, disability of the right arm abducens persisted after treatment because of debridement around the right humerus muscle. Discussion: Several reports have described cases of the extravasation of trabectedin. A few have mentioned severe muscular degeneration similar to that shown in the present case. Because trabectedin is a strong vesicant cytotoxic agent, it is principally administered through a CVAD rather than peripheral vessels and is continued during the nighttime;this can lead to a delay in patients or attending doctors noticing any extravasation. We need to spread appropriate knowledge of this drug and make an effort to prevent severe complications like in the present case.
文摘Epithelial ovarian cancer(OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer(ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.
基金the financial support provided by National Science Foundation of China(grant nos.22125103 and 21971065)Science and Technology Commission of Shanghai Municipality(grant nos.22JC1401000,20XD1421500,and 20JC1416800).
文摘Trabectedin and lurbinectedin are therapeutic antitumor pharmaceuticals approved by the Food and Drug Administration for treating soft tissue sarcomas and metastatic small cell lung cancer and have been facing synthesis challenges over the past three decades.In this report,the total synthesis of trabectedin,lurbinectedin,and renieramycin T were accomplished in 22-27 steps.The synthetic strategy features stereocontrolled Pictet-Spengler(PS)reaction leading to the multisubstituted tetrahydroisoquinoline fragment(DE ring),aldol condensation for C4-C10 bond formation,and a second PS cyclization with asymmetric oxomalonate for the fully substituted B ring,in which palladium complex-induced stereoselectivity is achieved via decarboxylative protonation anchoring the C1 stereocenter.The pentacyclic skeleton(A-E)was efficiently effectuated at a gramscale,displaying superior potential for further drug development.
文摘曲贝替定（Yondelis R ，Trabectedin）是一种新的非铂类抗肿瘤药物，有独特的抗肿瘤机制，不良反应主要为可逆性肝脏损害。 Trabectedin的心脏毒性低，可以和蒽环类抗肿瘤药物联合应用，目前已应用于复发性卵巢癌的治疗。临床可选用的治疗方案有单药3周方案、单药周疗和联合蒽环类药物方案，其中联合方案疗效最好。Trabectedin对铂类敏感的复发性卵巢癌有较好的疗效，特别是对无铂间隔期（treatment-free interval，TFI）为6~12个月的复发性卵巢癌疗效显著，但对铂类耐药及难治性卵巢癌的疗效不明显。应用Trabectedin可延长TFI，为以后再次进行铂类药物治疗创造条件。
