Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group
العنوان: | Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group |
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المؤلفون: | Ippokratis Messaritakis, Ioannis Varthalitis, Sophia Agelaki, E Samantas, E Hartabilas, P. Katsaounis, F. Koinis, Athanasios Kotsakis, G. Fountzilas, V. Georgoulias, V Karavassilis, S Peroukidis, Nikolaos K. Kentepozidis |
المصدر: | British Journal of Cancer |
بيانات النشر: | Springer Science and Business Media LLC, 2017. |
سنة النشر: | 2017 |
مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, Phases of clinical research, Angiogenesis Inhibitors, Carboplatin, angiogenesis, chemistry.chemical_compound, 0302 clinical medicine, pazopanib, Clinical endpoint, Aged, 80 and over, Sulfonamides, SCLC, Middle Aged, Neoplastic Cells, Circulating, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, second line, medicine.drug, Adult, medicine.medical_specialty, Indazoles, Antineoplastic Agents, Disease-Free Survival, Pazopanib, 03 medical and health sciences, Refractory, Internal medicine, medicine, Humans, Survival rate, Aged, business.industry, medicine.disease, Small Cell Lung Carcinoma, CTC, Pyrimidines, 030104 developmental biology, chemistry, Drug Resistance, Neoplasm, Clinical Study, Cisplatin, Neoplasm Recurrence, Local, business, Progressive disease |
الوصف: | Background: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. Patients and methods: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800 mg per day per os) was administered until progressive disease (PD). Circulating tumour cells (CTCs) were enumerated using the Cellsearch assay. Results: All patients were evaluable for response and toxicity. In the intention-to-treat analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence interval (CI): 5.0–22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD. Accrual in cohort B was halted because the hard-stop rule was met; in cohort A, the PFS-R was 59% (95% CI: 43.5–74.4; PR=7, SD=16). Nine (23.1%) patients received pazopanib for >6 months and 3 of them for >12 months. One pazopanib cycle resulted to a significant decrease to the number of patients with ⩾5 CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS for all patients was 2.5 months (95% CI: 1.9–3.1 months) and 6.0 months (95% CI: 3.8–8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No unexpected toxicity was observed. Conclusions: Second-line treatment with pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising objective responses and disease control; CTC enumeration might serve as a reliable surrogate biomarker of response. |
تدمد: | 1532-1827 0007-0920 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c0e5805410b31b5b372b6efffb3367b https://doi.org/10.1038/bjc.2017.137 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....9c0e5805410b31b5b372b6efffb3367b |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15321827 00070920 |
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