Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma
| العنوان: | Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma |
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| المؤلفون: | Carlos Cordon-Cardo, P Lyn, Robert J. Motzer, P Lianes, J P O'Brien, Patricia Fischer, R L Ngo |
| المصدر: | Journal of Clinical Oncology. 13:1958-1965 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Urology, Vinblastine, Asymptomatic, Pharmacokinetics, Renal cell carcinoma, Bradycardia, Tumor Cells, Cultured, medicine, Carcinoma, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Carcinoma, Renal Cell, Dexamethasone, Aged, Chemotherapy, business.industry, Stereoisomerism, Middle Aged, medicine.disease, Immunohistochemistry, Drug Resistance, Multiple, Kidney Neoplasms, Surgery, Verapamil, Oncology, Drug Therapy, Combination, Female, Hypotension, medicine.symptom, business, medicine.drug |
| الوصف: | PURPOSE The reduced cardiac toxicity of the dextro-(d-) stereoisomer of verapamil (dexverapamil; Knoll Pharmaceuticals, Whippany, NJ) warrants its study as a potential multidrug-resistance (MDR) reversal agent. PATIENTS AND METHODS Twenty-three patients with advanced renal cell carcinoma (RCC) were treated with vinblastine at a dose of 0.11 mg/kg intravenous (IV) bolus injection on days 1 and 2 every 21 days. Dexverapamil was added to subsequent cycles after resistance had been demonstrated. Dexverapamil treatment was begun 18 hours before day 1 of vinblastine administration and was given orally every 6 hours for 12 doses. Patients in group A were treated with a dose of 120 mg/m2, and those in group B were treated with 180 mg/m2 plus dexamethasone; plasma concentrations achieved in patients were correlated with in vitro effects. RESULTS Toxicities included hypotension, asymptomatic bradycardia, and mild atrioventricular conduction delays, although one patient had dexverapamil discontinued for grade IV congestive heart failure. There were no partial or complete responses. The mean day-1 serum dexverapamil plus norverapamil plasma concentrations were 2,575 ng/mL (range, 697 to 6,015 ng/mL) for group A and 1,654 ng/mL (range, 710 to 4,132 ng/mL) for group B at the time of vinblastine administration. These concentrations were in the range of those that reversed vinblastine resistance in vitro. CONCLUSION The advantage of dexverapamil as an MDR reversal agent is its potential for achieving desired blood levels with substantially less toxicity than the racemic mixture of verapamil. Based on tolerability, it is a suitable drug for further study in clinical trials of malignancies other than RCC that attempt to achieve MDR reversal. The dose of 120 mg/m2 given orally every 6 hours, with dose escalation based on individual tolerance, represents a feasible schedule to be considered for such studies. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb6b1e27ed9444c2805c4b0f7d808024Test https://doi.org/10.1200/jco.1995.13.8.1958Test |
| رقم الانضمام: | edsair.doi.dedup.....bb6b1e27ed9444c2805c4b0f7d808024 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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