title: A role for maintenance therapy in managing sarcoma.
abstract: Despite the use of recommended chemotherapy regimens, patients with metastatic sarcomas have a poor prognosis. To date, the median overall survival for metastatic disease remains less than 18 months. First-line treatment of most metastatic sarcomas consists of chemotherapy with or without surgical excision of residual disease, followed by "watchful waiting" until disease progression or recurrence. According to the current treatment paradigm, recommended by United States and European clinical guidelines, chemotherapy is administered for a fixed number of cycles, and then a watchful waiting approach is taken once a best response is achieved. Single-agent doxorubicin remains the standard for treatment of most soft-tissue sarcomas (STS), as combination and dose-intense regimens have largely failed to improve survival. Combination chemotherapy is the standard treatment approach for osteosarcoma and Ewing's sarcoma, but outcomes are poor for patients with recurrent disease. In order to improve outcomes (in particular, progression-free survival [PFS] and overall survival [OS]), strategies shown to be effective in other solid malignancies, such as maintenance therapy and long-term treatment with targeted therapy, are being investigated in patients with advanced sarcomas. One potential promising approach is the use of mammalian target of rapamycin (mTOR) inhibitors for maintenance therapy. One such mTOR inhibitor, ridaforolimus (AP23573, MK-8669), is currently being evaluated in patients with advanced bone and STS in the ongoing Sarcoma mUlti-Center Clinical Evaluation of the Efficacy of riDaforolimus (SUCCEED) trial.
authors.affiliation: Département d'Oncologie Médicale & EAM Santé Individu Société, Centre Léon Bérard, 28 rue Laennec, F-69373 Lyon Cedex 08, France. ray@lyon.fnclcc.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: C515074:ridaforolimus; D004317:Doxorubicin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus