دورية أكاديمية
Efficacy and safety of biweekly intravenous administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small cell and non-small cell lung cancer: a multi-tumour, multi-institutional Phase II study
| العنوان: | Efficacy and safety of biweekly intravenous administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small cell and non-small cell lung cancer: a multi-tumour, multi-institutional Phase II study |
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| المؤلفون: | Schöffski, P., Besse, B., Gauler, T., de Jonge, M. J. A., Scambia, G., Santoro, A., Davite, C., Jannuzzo, M. G., Petroccione, A., Delord, J.-P. |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2014 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Original article |
| الوصف: | <$O_ST_ABS>Background<$C_ST_ABS>This multi-center Phase II trial assessed the activity, safety (CTCAE 3.0) and pharmacokinetics (PK) of the pan-Aurora kinase inhibitor danusertib hydrochloride (PHA-739358) in breast (BC), ovarian (OC), pancreatic (PC), colorectal (CRC), small cell (SCLC) and non-small cell lung (NSCLC) cancers <$O_ST_ABS>Methods<$C_ST_ABS>Consenting adult patients with good performance and organ function with advanced/metastatic tumours who had failed systemic therapy were treated in independent, disease-specific cohorts with danusertib 500 mg/m2 given as 24-hour intravenous infusion every 14 days with until progression or unacceptable toxicity. A 2-stage design was applied. Primary endpoint was the progression-free rate (PFR) at 4 months (RECIST1.1). <$O_ST_ABS>Results<$C_ST_ABS>A total of 223 patients were enrolled with 219 actively treated. The median relative dose intensity of danusertib was similar for all tumour types (84.6-99.6 %). The median number of biweekly treatment cycles ranged from 3-4/patient (maximum 5-40 cycles/entity) and the median treatment duration varied between 7.6-10.0 weeks per histotype. Danusertib did not meet pre-specified protocol criteria for clinically relevant activity in any of the treated cancers. The PFR at 4 months was 18.4% in BC, 12.1% in OC, 10.0% in PC, 10.4% in NSCLC (all histotypes), 16.1% in squamous NSCLC and 0% in SCLC and CRC. Some radiological and/or biochemical indication of antitumor activity was seen in BC, OC, PC and NSCLC, including two confirmed partial responses. The most frequent drug-related non-laboratory AEs were fatigue/asthenia, nausea, diarrhoea, anorexia, vomiting, alopecia, constipation and pyrexia. Common laboratory AEs included haematological toxicity, hypalbuminaemia and increases in liver enzymes. Treatment was discontinued due to AEs in only 5.5% of patients. Plasma concentrations of danusertib were in line with results from earlier studies. <$O_ST_ABS>Conclusion<$C_ST_ABS>Single ... |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://annonc.oxfordjournals.org/cgi/content/short/mdu566v1Test; http://dx.doi.org/10.1093/annonc/mdu566Test |
| DOI: | 10.1093/annonc/mdu566 |
| الإتاحة: | https://doi.org/10.1093/annonc/mdu566Test http://annonc.oxfordjournals.org/cgi/content/short/mdu566v1Test |
| حقوق: | Copyright (C) 2014, European Society for Medical Oncology |
| رقم الانضمام: | edsbas.59B01903 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/annonc/mdu566 |
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