Pharmacological treatment for uterine leiomyosarcomas

Gadducci, Angiolo; Guerrieri, Maria Elena

doi:10.1517/14656566.2015.985205

Cited by 14 publications

(8 citation statements)

References 115 publications

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“…In addition, trabectedin results in 30% PFS rate at 6 months with 12-month OS rate of more than 50% in pretreated patients with U-LMS. Taken together, the response rate, PFS, and OS with trabectedin are comparable with published outcomes on other single agents (doxorubicin, ifosfamide, and gemcitabine) in this indication [ 118 ].…”

Section: Discussionsupporting

confidence: 80%

Management Strategies in Advanced Uterine Leiomyosarcoma: Focus on Trabectedin

Amant

Lorusso

Mustea

et al. 2015

Sarcoma

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The treatment of advanced uterine leiomyosarcomas (U-LMS) represents a considerable challenge. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made postoperatively. Whilst a total abdominal hysterectomy is the cornerstone of management of early disease, the role of routine adjuvant pelvic radiotherapy and adjuvant chemotherapy is less clear, since they may improve local tumor control in high risk patients but are not associated with an overall survival benefit. For recurrent or disseminated U-LMS, cytotoxic chemotherapy remains the mainstay of treatment. There have been few active chemotherapy drugs approved for advanced disease, although newer drugs such as trabectedin with its pleiotropic mechanism of actions represent an important addition to the standard front-line systemic therapy with doxorubicin and ifosfamide. In this review, we outline the therapeutic potential and in particular the emerging evidence-based strategy of therapy with trabectedin in patients with advanced U-LMS.

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Section: Discussionsupporting

confidence: 80%

Management Strategies in Advanced Uterine Leiomyosarcoma: Focus on Trabectedin

Amant

Lorusso

Mustea

et al. 2015

Sarcoma

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“…Surgical resection of localized disease is a well‐established therapeutic strategy . In the event tumors have metastasized, hormonal therapy and cytotoxic chemotherapeutic agents such as gemcitabine , docetaxel , anthracyclines , ifosfamide , temozolomide , trabectedin , eribulin , and many other cytotoxic agents provide modest antitumor activity . In contrast, novel targeted therapeutic agents have not widely used for the treatment of advanced LMS.…”

Section: Introductionmentioning

confidence: 99%

Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical Center for targeted therapy experience

et al. 2016

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Advanced stage leiomyosarcoma (LMS) is incurable with current systemic antitumor therapies. Therefore, there is clinical interest in exploring novel therapeutic regimens to treat LMS. We reviewed the medical records of 75 consecutive patients with histologically confirmed metastatic LMS, who had been referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. To lay the foundation for potential phase I trials for the treatment of advanced LMS, we analyzed tumor response and survival outcome data. The frequent hotspot gene aberrations that we observed were the TP53 mutation (65%) and RB1 loss/mutation (45%) detected by Sequenom or next‐generation sequencing. Among patients treated with gene aberration‐related phase I trial therapy, the median progression‐free survival was 5.8 months and the median overall survival was 15.9 months, significantly better than in patients without therapy (1.9 months, P = 0.001; and 8.7 months, P = 0.013, respectively). Independent risk factors that predicted shorter overall survival included hemoglobin <10 g/dL, body mass index <30 kg/m2, serum albumin <3.5 g/dL, and neutrophil above upper limit of normal. The median survivals were 19.9, 7.6, and 0.9 months for patients with 0, 1 or 2, and ≥3 of the above risk factors, respectively (P < 0.001). A prognostic scoring system that included four independent risk factors might predict survival in patients with metastatic LMS who were treated in a phase I trial. Gene aberration‐related therapies led to significantly better clinical benefits, supporting that further exploration with novel mechanism‐driven therapeutic regimens is warranted.

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“…Pazopabib is the only approved targeted therapy for uterine leiomyosarcoma [82]. ICON6 is the first trial to demonstrate a significant improvement in both PFS and OS with an oral TKI, such as cediranid, in recurrent platinum-sensitive epithelial ovarian cancer [89,90].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the results of phase II and III trials of the European Organization for Research and Treatment of Cancer [EORTC], pazopanib is considered to be a novel treatment option for non adypocitic STSs, including leiomyosarcoma, and it is the only approved targeted therapy for uterine leiomyosarcoma [82].…”

Section: Uterine Sarcomasmentioning

confidence: 99%