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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

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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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Acknowledgments

This work was supported by investigational Grants from the Cretan Association for Biomedical Research (CABR) and Janssen Pharmaceuticals. G. F. and A. M. were recipients of a CABR clinical fellowship.

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Authors and Affiliations

  1. Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece

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

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  1. E. Kontopodis
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Correspondence to V. Georgoulias.

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Conflict of interest

EK has received an honorarium from Janssen-Cilag Pharmaceutical S. A. C. I. All the other authors disclosed no potential conflicts of interest.

Additional information

On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG).

ClinicalTrilas.gov Identifier: NCT01633645.

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Kontopodis, E., Kotsakis, A., Kentepozidis, N. et al. 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. Cancer Chemother Pharmacol 77, 949–956 (2016). https://doi.org/10.1007/s00280-016-2997-7

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