Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity.
Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity.
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作者：
Herzog J;von Klot-Heydenfeldt F;Jabar S;Ranft A;Rossig C;Dirksen U;Van den Brande J;D'Incalci M;von Luettichau I;Grohar PJ;Berdel WE;Burdach S
背景。临床前数据表明，trabectedin联合伊立替康治疗尤文氏肉瘤具有较强的协同效应。这可能是由于除了协同抑制EWS-FLI1下游靶点外，肿瘤细胞对喜树碱的超敏反应是trabectedin的作用。在人横纹肌肉瘤异种移植中也有很强的效果。过程。12例终末期难治性易位阳性肉瘤患者接受trabectedin和伊立替康治疗。8例患者有尤文氏肉瘤，4例患者有其他易位阳性肉瘤。结果。治疗开始后3个月生存率为0.75。根据RECIST标准，1例患者获得部分缓解，5例病情稳定，其余6例通过治疗取得进展。大多数患者出现明显的血液学毒性（3级和4级）。还发生可逆性肝毒性和腹泻。结论。我们在晚期肉瘤患者联合使用trabectedin和伊立替康的经验显示，在控制难治性实体瘤方面有很好的效果。虽然血液学毒性显著，但它是可逆的。治疗期间的生活质量得以维持。这些观察结果鼓励进行更大规模的临床试验。
Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.
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影响因子：
8.8
作者：
D'Incalci, M.;Badri, N.;Galmarini, C. M.;Allavena, P.
通讯作者：
Allavena, P.
影响因子：
3.2
作者：
Morland, B.;Platt, K.;Whelan, J. S.
通讯作者：
Whelan, J. S.
DOI：
10.1158/1078-0432.ccr-13-0901
发表时间：
2014-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Grohar PJ;Segars LE;Yeung C;Pommier Y;D'Incalci M;Mendoza A;Helman LJ
通讯作者：
Helman LJ
影响因子：
2.3
作者：
Riccardi, A;Meco, D;Riccardi, R
通讯作者：
Riccardi, R
影响因子：
3.2
作者：
Casey, Denise A.;Wexler, Leonard H.;Meyers, Paul A.
通讯作者：
Meyers, Paul A.