Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer.
BACKGROUND
This phase Ib study evaluated volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin (Eli Lilly and Co., Indianapolis, IN) and paclitaxel (Taxol) in advanced, untreated non-small-cell lung cancer (NSCLC).


METHODS
Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in combination with carboplatin-paclitaxel chemotherapy and continued as maintenance therapy for patients with stable disease (SD) or better. Dose-limiting toxic effects, adverse events (AEs), pharmacokinetics, and anti-volociximab antibodies were assessed.


RESULTS
A maximum tolerated dose was not reached up to the maximum planned dose of 30 mg/kg. In 29 patients who received volociximab, the most common grade≥3 AEs were neutropenia (24%), hyponatremia (17%), and fatigue (10%). Three patients experienced volociximab-related serious AEs. No hemorrhages were observed. Of 33 patients enrolled, 8 (24%) achieved a partial response and 17 (52%) had SD. The median progression-free survival was 6.3 months (95% confidence interval 5.5-8.1). Levels of potential biomarkers of angiogenesis or metastasis were reduced following six cycles of treatment.


CONCLUSIONS
Volociximab combined with carboplatin and paclitaxel was generally well-tolerated and showed preliminary evidence of efficacy in advanced NSCLC.
Cancer Medicine/Thoracic Unit, Institut Gustave Roussy, Villejuif, France.
B
B
Besse
L C
LC
Tsao
D T
DT
Chao
Y
Y
Fang
J-C
JC
Soria
S
S
Almokadem
C P
CP
Belani
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D015331:Cohort Studies; D006801:Humans; D039081:Integrin alpha5beta1 / Q000276:immunology*; D008175:Lung Neoplasms / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D017239:Paclitaxel / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D039081:Integrin alpha5beta1; C516631:volociximab; D016190:Carboplatin; D017239:Paclitaxel