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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2016

01-05-2016 | Original Article

A phase II, open-label trial of bortezomib (VELCADE®) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer

Authors: E. Kontopodis, A. Kotsakis, N. Kentepozidis, K. Syrigos, N. Ziras, M. Moutsos, G. Filippa, A. Mala, L. Vamvakas, D. Mavroudis, V. Georgoulias, S. Agelaki

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2016

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Abstract

Background

Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin.

Methods

Chemotherapy-naïve patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1 mg/m2 i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000 mg/m2, (days 1 and 8), and cisplatin 70 mg/m2 (day 1) in cycles of 21 days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity.

Results

Fifty-three patients [median age 66 years; 79.2 % male; 96.2 % stage IV; performance status (ECOG) 0/1 73.6/26.4 %; adenocarcinoma 45.3 %, squamous cell carcinoma 41.5 %] were enrolled. All patients were evaluable for toxicity and 43 for efficacy. Grade 3–4 hematologic toxicity consisted of neutropenia (22.6 %) and thrombocytopenia (17 %). Grade 2–4 non-hematologic adverse events were fever (9.4 %), fatigue (20.8 %), infection (18.9 %), and dyspnea (15.1 %). There was no >grade 2 neurotoxicity. Febrile neutropenia occurred in two (1.9 %) patients, and there were three possibly treatment-related deaths (5.4 %). In the intention-to-treat population, the objective response rate was 17 % (95 % CI 6.9–27.1 %). No difference in response rate was observed for squamous versus other histology (18.2 vs. 16.1 %, p = 0.845). The median progression-free survival was 2.5 months, the median overall survival 10.6 months and the 1-year survival rate 38.1 %.

Conclusion

The incorporation of bortezomib into the gemcitabine/cisplatin regimen, in the dose and schedule used in this study, could not improve the efficacy of the chemotherapy regimen and has not to be further investigated.
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Metadata
Title
A phase II, open-label trial of bortezomib (VELCADE®) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer
Authors
E. Kontopodis
A. Kotsakis
N. Kentepozidis
K. Syrigos
N. Ziras
M. Moutsos
G. Filippa
A. Mala
L. Vamvakas
D. Mavroudis
V. Georgoulias
S. Agelaki
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-2997-7

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