title: Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer.
abstract: The aim of this study is to test the hypothesis that antiangiogenic treatment with sunitinib consolidation can prolong remissions induced by taxane-based chemotherapy in women with metastatic breast cancer. The method involves a two-arm open-label (2:1 randomization) multicenter, randomized phase II trial evaluating the efficacy of sunitinib (arm A) versus no therapy (arm B) in patients with HER-2-negative metastatic breast cancer who achieved an objective response to taxane-based chemotherapy. The results of this study indicates that the primary endpoint of progression-free survival (PFS) > or =5 months was achieved in 10 of 36 patients (28%) in arm A and 4 of 19 patients (21%) in arm B. The median PFS was 2.8 and 3.1 months, respectively. A protocol amendment to the sunitinib dosing schedule was made because 53% (17/32) of patients treated at a starting dose of 50 mg (4 weeks on/2 weeks off) required dose reduction. Changing the starting dose to sunitinib 37.5 mg continuously resulted in dose reductions in 44% (7/16) of patients. Grades III-IV toxicity occurred in 69% of patients in arm A (fatigue 31%, musculoskeletal pain 11%, neutropenia and thrombopenia 8%) and 11% in arm B. The proof-of-principle study does not confirm the hypothesis that sunitinib consolidation therapy can lead to a predefined clinically relevant proportion of patients with PFS of > or =5 months after an objective response to taxanes. Furthermore, toxicity was significant.
authors.affiliation: Department of General Medical Oncology/Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. hans.wildiers@uzleuven.be
authors.forename: H
authors.initials: H
authors.lastname: Wildiers
authors.forename: C
authors.initials: C
authors.lastname: Fontaine
authors.forename: P
authors.initials: P
authors.lastname: Vuylsteke
authors.forename: M
authors.initials: M
authors.lastname: Martens
authors.forename: J L
authors.initials: JL
authors.lastname: Canon
authors.forename: W
authors.initials: W
authors.lastname: Wynendaele
authors.forename: C
authors.initials: C
authors.lastname: Focan
authors.forename: J
authors.initials: J
authors.lastname: De Greve
authors.forename: P
authors.initials: P
authors.lastname: Squifflet
authors.forename: R
authors.initials: R
authors.lastname: Paridaens
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001530:Belgium; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000077210:Sunitinib; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077210:Sunitinib; D043823:Taxoids; C508053:ERBB2 protein, human