دورية أكاديمية
A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer
| العنوان: | A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer |
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| المؤلفون: | Boland, Patrick M, Ebos, John M L, Attwood, Kristopher, Mastri, Michalis, Fountzilas, Christos, Iyer, Renuka V, Banker, Christopher, Goey, Andrew K L, Bies, Robert, Ma, Wen Wee, Fakih, Marwan |
| المساهمون: | National Comprehensive Cancer Network, Boehringer Ingelheim |
| المصدر: | JNCI Cancer Spectrum ; volume 8, issue 3 ; ISSN 2515-5091 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2024 |
| الوصف: | Background Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer. Methods Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25. Results Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks. Conclusions The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted. ClinicalTrials.gov identifier NCT02393755 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/jncics/pkae017 |
| الإتاحة: | https://doi.org/10.1093/jncics/pkae017Test https://academic.oup.com/jncics/article-pdf/8/3/pkae017/57369432/pkae017.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.3579EAE3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jncics/pkae017 |
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