A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors
| العنوان: | A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors |
|---|---|
| المؤلفون: | David Cosgrove, Ding Wang, Vassiliki Karantza, Nikita Rudersdorf, Hao Xiong, Todd Busman, Gordana Vlahovic, Mack Mabry, Jianning Yang |
| المصدر: | Investigational New Drugs. 32:976-984 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Paclitaxel, Nausea, Pharmacology, Neutropenia, Carboplatin, chemistry.chemical_compound, Pharmacokinetics, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Aged, Sulfonamides, Aniline Compounds, Navitoclax, business.industry, Middle Aged, medicine.disease, Treatment Outcome, Oncology, chemistry, Toxicity, Vomiting, Female, medicine.symptom, business |
| الوصف: | Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway, controlling the point-of no-return and setting the threshold to engage the death machinery in response to chemical damage. Bcl-2 proteins have emerged as attractive targets for anti-cancer drug development. Navitoclax is a selective, potent, orally bioavailable, small molecule Bcl-2 inhibitor. Primary endpoints assessed the safety and pharmacokinetic (PK) interactions between navitoclax in combination with carboplatin/paclitaxel or paclitaxel alone in patients with solid tumors The study comprised two arms, one a combination of navitoclax with paclitaxel and carboplatin, the second with navitoclax and paclitaxel alone. Nineteen patients were enrolled in this study. The most frequently reported treatment-emergent AEs were alopecia (57.9 %), anemia (52.6 %), nausea (52.6 %), constipation (42.1 %), diarrhea (42.1 %), fatigue (42.1 %), neutropenia (36.8 %), thrombocytopenia (36.8 %), vomiting (31.6 %), decreased appetite (31.6 %), dehydration (26.3 %), and hypomagnesaemia (26.3 %). In the light of significant hematological and non-hematological toxicity the study was ended before de-escalation of navitoclax. Only one partial response was obtained at any dose tested, thus lowering doses could not have increased efficacy. It is the combination of toxicity with modest efficacy that led to discontinuation. No apparent PK interaction was observed between navitoclax and carboplatin or paclitaxel and the combination of navitoclax and paclitaxel had modest anti-tumor activity. |
| تدمد: | 1573-0646 0167-6997 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba8004d0e4e1a1f6ca0e5056722723eb https://doi.org/10.1007/s10637-014-0116-3 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ba8004d0e4e1a1f6ca0e5056722723eb |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15730646 01676997 |
|---|