title: A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-alpha2a as first line treatment in metastatic melanoma.
abstract: Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon alpha-2a (IFN-alpha2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m days 1-5 every 4 weeks) and IFN-alpha2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab+/-IFN-alpha2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23% (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed > or =3 months after the last bevacizumab-DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.
authors.affiliation: Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland. pia.vihinen@tyks.fi
authors.forename: Pia P
authors.initials: PP
authors.lastname: Vihinen
authors.forename: Micaela
authors.initials: M
authors.lastname: Hernberg
authors.forename: Meri-Sisko
authors.initials: MS
authors.lastname: Vuoristo
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tyynelä
authors.forename: Marjut
authors.initials: M
authors.lastname: Laukka
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
authors.forename: Seppo
authors.initials: S
authors.lastname: Pyrhönen
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D010349:Patient Compliance; D011379:Prognosis; D011994:Recombinant Proteins; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D003606:Dacarbazine; D020780:Matrix Metalloproteinase 9