title: Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma.
abstract: Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate-refractory gastrointestinal stromal tumors). This single-institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty-eight patients were enrolled, and 35% were heavily pretreated (≥ 2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression-free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1 and 2.5 and 13.6 months, respectively. The 3-month progression-free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma and MFH were 75% and 69.2%, 60%, and 62.5% and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low-grade disease could have been included and the small numbers, a 3-month progression-free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted.
authors.affiliation: Sarcoma Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: S Tariq
authors.initials: ST
authors.lastname: Mahmood
authors.forename: Samuel
authors.initials: S
authors.lastname: Agresta
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Vigil
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.forename: Gina
authors.initials: G
authors.lastname: D'Amato
authors.forename: Ciara E
authors.initials: CE
authors.lastname: Calitri
authors.forename: Michelle
authors.initials: M
authors.lastname: Dean
authors.forename: Christopher
authors.initials: C
authors.lastname: Garrett
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schell
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappori
mesh_terms: D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D051677:Histiocytoma, Malignant Fibrous / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007890:Leiomyosarcoma / Q000188:drug therapy; D008080:Liposarcoma / Q000188:drug therapy; D008297:Male; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib