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- Title
New drugs in sarcoma.
- Authors
Miron, Lucian
- Abstract
Sarcoma is the term used for cancers of connective tissue. Soft tissue sarcomas (STS) in adult are a complex group of neoplasms. The STS biology has made major advancements in understanding of the biology and drivers of several sarcomas. Doxorubicin and ifosfamide are the most effective single drugs for metastatic non-GIST adult soft tissue sarcomas. As single drugs or in combination, anthracyclines yeld the best response rates for metastatic sarcomas (rates of 10% to 25% for each drug in various studies). Ifosfamide is particularly active in synovial sarcoma, and myxoid liposarcoma appears to be less active in leiomyosarcomas. Dacarbazine has modest activity against leiomyosarcoma, paclitaxel is active against angiosarcomas and desmoid tumors, and sunitinib and cediranib against alveolar soft part sarcoma. The combination of temozololamid and bevacizumab has activity in solitary fibrous tumors. The recently impoved understanding of biology of certain connective tissue tumors has led to clinical introduction of new molecules in the management of disease. Pazopanib is an oral multikinase inhibitor that was approved for the treatment of patients with locally advanced or metastatic STS after treatment with standard chemotherapy. Pazopanib is approved for the treatment of advanced or metastatic non-GIST soft tissue sarcoma (excluding liposarcoma) after the treatment with chemotherapy. Trabectidin is a citotoxic agent that binds to the minor grove in DNA and affects DNA, RNA and protein synthesis. Trabectedin was approved for the use in patients with unresectable or metastatic leiomyosarcoma or liposarcoma after prior treatment with anthracycline-containing regimens. Eribulin is an antimitotic agent that inhibits microtubule function and demonstrated improvement in overall survival compared to dacarbazine in patients pretreated, with locally advanced or metastaic leiomyosarcoma or liposarcoma. Olaratumab (Lartruvo) is a monoclonal antibody developed for the treatment of solid tumors. It is directed against the platelet-derived growth factor receptor alpha (PDGF). Olaratumab is used in combination with doxorubicin for the treatment of adults with advanced soft-tissue sarcoma (STS) who cannot be cured by cancer surgery or radiation therapy, and who have not been previously treated with doxorubicin. In a randomised controlled trial with 133 STS patients, olaratumab plus doxorubicin improved the median of progressionfree survival from 4.1 to 6.6 months as compared to doxorubicin alone (p=0.0615, narrowly missing statistical significance), and overall survival from 14.7 to 26.5 months (p=0.0003, highly significant). On October 19, 2016, the U.S. Food and Drug Administration granted accelerated approval to olaratumab for the treatment of patients with STS not amenable to curative treatment with radiotherapy or surgery, and with a histologic subtype for which an anthracyclinecontaining regimen is appropriate. The mTOR inhibitors have been studied in several sarcoma studies, with relatively limited success, with the exception of perivascular epitheloid cell tumors, wich are rare malignancies characterized by the activation of the mTOR pathway. Everolimus is an inhibitor of mTOR with indication in the treatment of patients with angiomyolipomas, resulted in an objective tumor response rate of 42% using 10 mg everolimus daily, compared to 0% using placebo. There are a number of ongoing trials in sarcomas investigating immunoterapy, including checkpoint inhibitors, as well as T-cell therapy. Tyrosine kinase inhibitors, including imatinib, pexidarartinib, pazopanib and axitinib, have been shown to impact the immune microenvironment within tumors. Subsets of sarcomas overexpress Her2, which has been targeted using chimeric antigen receptor (CAR) T cell. In the last years, there have been seen remarcable growth in the novel treatment strategies for sarcomas, with an increased emphasis on understanding genetic and molcular biology of various sarco
- Subjects
CANCER treatment; SARCOMA; DRUG development; DOXORUBICIN
- Publication
Oncolog-Hematolog, 2017, Issue 40, p46
- ISSN
2066-8716
- Publication type
Article