Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced nonsquamous non-small-cell lung cancers Journal Article
| Authors: | Hellmann, M. D.; Sturm, I.; Trnkova, Z. J.; Lettieri, J.; Diefenbach, K.; Rizvi, N. A.; Gettinger, S. N. |
| Article Title: | Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced nonsquamous non-small-cell lung cancers |
| Abstract: | Background The combination of bevacizumab, an antiangiogenesis agent, with cytotoxic chemotherapy improves survival in patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. In this phase I trial we evaluated the safety, pharmacokinetics (PK), and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Patients and Methods Chemotherapy-naive patients with advanced nsNSCLCs were treated with regorafenib 60 mg/d continuously and cisplatin 75 mg/m2 with pemetrexed 500 mg/m2 once every 21 days for up to 6 cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Results Nine patients enrolled before premature termination of the study because of slow recruitment and a change in the development strategy of regorafenib by the study sponsor. Five patients experienced at least 1 treatment-related Grade 3 adverse event. No Grade 4 or 5 toxicity occurred. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Minor PK interactions between regorafenib and chemotherapy were observed. Conclusion Regorafenib had acceptable tolerability and minor PK interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. Encouraging activity was appreciated in chemotherapy-naive patients with advanced nsNSCLCs. However, the small number of patients treated limits conclusions that can be drawn from these results. © 2015 Elsevier Inc. All rights reserved. |
| Keywords: | adult; clinical article; controlled study; treatment response; aged; clinical trial; constipation; drug tolerability; cisplatin; advanced cancer; area under the curve; cancer combination chemotherapy; cancer growth; diarrhea; drug efficacy; drug safety; hypertension; side effect; treatment duration; chemotherapy; cancer staging; outcome assessment; anorexia; progression free survival; controlled clinical trial; drug eruption; multiple cycle treatment; neutrophil count; sensory neuropathy; esophagitis; mucosa inflammation; tinnitus; epidermal growth factor receptor; maintenance therapy; creatinine; hemoglobin; creatinine blood level; hemoglobin blood level; angiogenesis; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; backache; coughing; dizziness; dyspnea; alanine aminotransferase; aspartate aminotransferase; albumin; thorax pain; multicenter study; thrombosis; muscle weakness; peripheral edema; cancer fatigue; glucose blood level; tandem mass spectrometry; open study; glucose; heartburn; headache; maximum plasma concentration; time to maximum plasma concentration; drug blood level; high performance liquid chromatography; maximum tolerated dose; phase 1 clinical trial; embolism; hiccup; amylase blood level; hand foot syndrome; triacylglycerol lipase blood level; liquid chromatography; sodium; sodium blood level; alopecia; epistaxis; pemetrexed; amylase; potassium; triacylglycerol lipase; motor neuropathy; hemoptysis; non small cell lung cancer; nsclc; epiphora; albumin blood level; stomach pain; potassium blood level; chemotherapy induced nausea and vomiting; regorafenib; human; male; female; article |
| Journal Title: | Clinical Lung Cancer |
| Volume: | 16 |
| Issue: | 6 |
| ISSN: | 1525-7304 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2015-11-01 |
| Start Page: | 514 |
| End Page: | 522 |
| Language: | English |
| DOI: | 10.1016/j.cllc.2015.04.003 |
| PROVIDER: | scopus |
| PUBMED: | 26003007 |
| PMCID: | PMC4750397 |
| DOI/URL: | |
| Notes: | Export Date: 2 November 2015 -- Source: Scopus |
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