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

B. Besse, L. C. Tsao, D. T. Chao, Y. Fang, J. C. Soria, Salah Almokadem, Chandra Belani

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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). Patients and methods: Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in comb nation 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 antivolociximab 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.

Original languageEnglish (US)
Article numbermds281
Pages (from-to)92-96
Number of pages5
JournalAnnals of Oncology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2013

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Carboplatin
Paclitaxel
Integrins
Non-Small Cell Lung Carcinoma
Pharmacokinetics
Safety
Antibodies
Comb and Wattles
Maximum Tolerated Dose
Hyponatremia
Poisons
Neutropenia
Disease-Free Survival
Fatigue
Biomarkers
volociximab
Confidence Intervals
Hemorrhage
Neoplasm Metastasis
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

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title = "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",
abstract = "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). Patients and methods: Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in comb nation 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 antivolociximab 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.",
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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. / Besse, B.; Tsao, L. C.; Chao, D. T.; Fang, Y.; Soria, J. C.; Almokadem, Salah; Belani, Chandra.

In: Annals of Oncology, Vol. 24, No. 1, mds281, 01.01.2013, p. 92-96.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Besse, B.

AU - Tsao, L. C.

AU - Chao, D. T.

AU - Fang, Y.

AU - Soria, J. C.

AU - Almokadem, Salah

AU - Belani, Chandra

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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). Patients and methods: Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in comb nation 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 antivolociximab 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.

AB - 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). Patients and methods: Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in comb nation 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 antivolociximab 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.

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