Dacarbazine in combination with bevacizumab for the treatment of unresectable/metastatic melanoma: a phase II study.
The combined treatment of dacarbazine with an antiangiogenic drug such as bevacizumab may potentiate the therapeutic effects of dacarbazine in metastatic melanoma (MM). Preliminary antitumour activity of dacarbazine plus bevacizumab is evaluated, together with the toxicity and safety profile, in MM patients. This prospective, open-label, phase II study included patients with previously untreated MM or unresectable melanoma. Patients received dacarbazine and bevacizumab until progressive disease or unacceptable toxicity. The primary efficacy variable was the overall response rate. The secondary efficacy parameters included duration of response, duration of stable disease, time to progression/progression-free survival, time to treatment failure and overall survival. The safety analysis included recordings of adverse events and exposure to study treatment. The intention-to-treat population included 37 patients (24 men and 13 women, mean age 54.2±13.1 years). Overall response rate was 18.9% (seven patients achieved a response) and clinical benefit was 48.6%. In patients who achieved a response, the median duration of response was 16.9 months and the median duration of stable disease was 12.5 months. The median time to progression/progression-free survival and time to treatment failure were 5.5 and 3.1 months, respectively. The median overall survival was 11.4 months. Almost all patients (94.6%) experienced at least one adverse event; however, no new area of toxicity of bevacizumab emerged. The dacarbazine/bevacizumab combination provides benefits compared with dacarbazine monotherapy in historical controls, with an acceptable safety profile. This combination appears to be a valid option in specific subgroups of patients, namely, those triple negative (BRAF, C-KIT and NRAS wild type) or with a BRAF mutation who have already received, or are not eligible for, immunomodulating or targeted agents.
aOncology of Melanoma Unit bEarly Drug Development for Innovative Therapies Division cDermatoncological Division dDepartment of Epidemiology and Biostatistics, European Institute of Oncology, Milan eRoche S.p.A., Monza, Italy.
Pier F
PF
Ferrucci
Ida
I
Minchella
Massimo
M
Mosconi
Sara
S
Gandini
Francesco
F
Verrecchia
Emilia
E
Cocorocchio
Claudia
C
Passoni
Chiara
C
Pari
Alessandro
A
Testori
Paola
P
Coco
Elisabetta
E
Munzone
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D057194:Intention to Treat Analysis; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D018906:Antineoplastic Agents, Alkylating; D000068258:Bevacizumab; D003606:Dacarbazine