A phase I and pharmacologic study of the combination of bortezomib and pegylated liposomal doxorubicin in patients with refractory solid tumors
| العنوان: | A phase I and pharmacologic study of the combination of bortezomib and pegylated liposomal doxorubicin in patients with refractory solid tumors |
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| المؤلفون: | William Riordan, Robert Z. Orlowski, Jason M. Collins, Anastasia Ivanova, Celeste Lindley, E. Claire Dees, Dixie Lee Esseltine, Frances A. Collichio, Lisa A. Carey, Bert H. O'Neil |
| المصدر: | Cancer Chemotherapy and Pharmacology. 63:99-107 |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, Drug, Cancer Research, Maximum Tolerated Dose, Gastrointestinal Diseases, media_common.quotation_subject, Salvage therapy, Pharmacology, Toxicology, Article, Polyethylene Glycols, Bortezomib, Refractory, immune system diseases, Neoplasms, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Combined Modality Therapy, Pharmacology (medical), Doxorubicin, cardiovascular diseases, neoplasms, Fatigue, Aged, media_common, Salvage Therapy, Liposome, Dose-Response Relationship, Drug, business.industry, Middle Aged, Boronic Acids, Hematologic Diseases, Neoplasm Proteins, Treatment Outcome, Oncology, Pyrazines, Liposomes, Proteasome inhibitor, Female, business, Proteasome Inhibitors, medicine.drug |
| الوصف: | Pre-clinical studies combining the proteasome inhibitor bortezomib with anthracyclines have shown enhanced anti-tumor activity. We conducted a phase I trial of bortezomib and pegylated liposomal doxorubicin (PLD) in patients with refractory solid tumors.Patients received bortezomib, 0.9-1.5 mg/m(2), on days 1, 4, 8, and 11 of every 21-day cycle, along with PLD, 30 mg/m(2), on day 4. The goals were to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and to investigate pharmacokinetic and pharmacodynamic interactions of the combination.A total of 37 patients with four median prior therapies were treated. Frequent grade 1-2 toxicities included fatigue, nausea, thrombocytopenia, anemia, neutropenia, constipation, myalgias, and peripheral neuropathy. DLTs included grade 3 nausea and vomiting in 1 of 6 patients receiving bortezomib at 1.2 mg/m(2), and grade 3 nausea, vomiting, and diarrhea in 1 of 6 patients receiving bortezomib at 1.5 mg/m(2). Grade 3 toxicities in later cycles included hand-foot syndrome, thrombocytopenia, anemia, neutropenia, nausea, diarrhea, and abdominal pain. Because of frequent dose-delays, dose-reductions, and gastrointestinal toxicity at the 1.4 and 1.5 mg/m(2) levels, bortezomib at 1.3 mg/m(2) and PLD at 30 mg/m(2) are recommended for further testing. Among 19 patients with breast cancer, four had evidence of a clinical benefit. Pharmacokinetic and pharmacodynamic studies did not show any significant interactions between the two drugs.A regimen of bortezomib, 1.3 mg/m(2) on days 1, 4, 8, and 11 with PLD, 30 mg/m(2), on day 4 of a 21-day cycle, was safe in this study, and merits further investigation. |
| تدمد: | 1432-0843 0344-5704 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::be8c7f1a8847115f803de5c9f5b2ff84Test https://doi.org/10.1007/s00280-008-0716-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....be8c7f1a8847115f803de5c9f5b2ff84 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320843 03445704 |
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