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

• Published in: Cancer chemotherapy and pharmacology 2016-05, Vol.77 (5), p.949-956
• Main Authors: Kontopodis, E., Kotsakis, A., Kentepozidis, N., Syrigos, K., Ziras, N., Moutsos, M., Filippa, G., Mala, A., Vamvakas, L., Mavroudis, D., Georgoulias, V., Agelaki, S.
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib - administration & dosage; Bortezomib - adverse effects; Bortezomib - therapeutic use; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cisplatin - administration & dosage; Cisplatin - adverse effects; Cisplatin - therapeutic use; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Neoplasm Staging; Oncology; Original Article; Pharmacology/Toxicology
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-016-2997-7

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/m 2 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/m 2 , (days 1 and 8), and cisplatin 70 mg/m 2 (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.