Faculty Collaboration Database

Synergy between VEGF/VEGFR inhibitors and chemotherapy agents in the phase I clinic. Clin Cancer Res 2014 Dec 01;20(23):5956-63

Date

10/16/2014

Pubmed ID

25316815

DOI

10.1158/1078-0432.CCR-14-1582

Scopus ID

2-s2.0-84918548091 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

PURPOSE: We hypothesized that chemotherapy synergizes with VEGF/VEGFR (VEGF/R) inhibitors in patients with advanced solid malignancies.

EXPERIMENTAL DESIGN: Patients treated on phase I protocols between December 2004 and July 2013 (n = 1,498) were included in this analysis. The primary outcome was clinical benefit, defined as stable disease ≥ 6 months, complete response, or partial response. Two odds ratios (OR) for achieving clinical benefit were calculated: one for patients treated with VEGF/R inhibitors (OR with VEGF/R) and another for patients treated without (OR without VEGF/R). To compare these two ORs, an interaction term was included in the multivariate model: (chemotherapy/factor of interest)×(VEGF/R). We took significant interaction terms (Pinteraction < 0.05) to suggest effect modification (either synergy or antagonism) with VEGF/R inhibitors.

RESULTS: All patients treated with VEGF/R inhibitors exhibited higher OR for clinical benefit than those who were not [OR = 1.9; 95% confidence interval (CI), 1.5-2.4; P < 0.0001]. Use of chemotherapy agents concomitant with VEGF/R inhibitors was associated with significantly higher OR for clinical benefit compared with chemotherapy use without VEGF/R inhibitors [OR with VEGF/R = 1.6 (95% CI, 1.1-2.5) vs. OR without VEGF/R = 0.4 (95% CI, 0.3-0.6), Pinteraction = 0.02]. Specifically, the antimetabolite class was associated with the greatest increase in OR for clinical benefit [OR with VEGF/R = 2.7 (95% CI, 1.5-4.7) vs. OR without VEGF/R = 0.2 (95% CI 0.1-0.3), Pinteraction = 0.004].

CONCLUSIONS: VEGF/R inhibitor was found to synergize with chemotherapeutics. This effect was most pronounced with the antimetabolite class.

Author List

Tang C, Hess K, Jardim DL, Gagliato Dde M, Tsimberidou AM, Falchook G, Fu S, Janku F, Naing A, Piha-Paul S, Subbiah V, Wheler J, Zinner RG, Kurzrock R, Ellis LM, Meric-Berstam F, Hong DS

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Child
Child, Preschool
Drug Synergism
Female
Humans
Male
Middle Aged
Mutation
Neoplasms
Odds Ratio
Protein Kinase Inhibitors
Receptors, Vascular Endothelial Growth Factor
Treatment Outcome
Vascular Endothelial Growth Factor A
Young Adult