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Possibility for Dose Optimization of Pazopanib from Its Plasma Concentration in Japanese Patients with Cancer.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2020 May 01; Vol. 43 (5), pp. 762-766. Date of Electronic Publication: 2020 Feb 29. - Publication Year :
- 2020
-
Abstract
- The currently approved dose of pazopanib (800 mg) is being re-examined owing to its adverse effects. The aim of this study was to evaluate the relationships among starting or maintenance doses of pazopanib, estimated pazopanib C <subscript>min</subscript> , and other clinical factors, including albumin and α-1 acid glycoprotein levels, in soft-tissue sarcoma and renal cell carcinoma. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively. C <subscript>min</subscript> for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. The pazopanib maintenance doses were 200 (n = 4), 400 (n = 34), 600 (n = 4), and 800 mg (n = 1). Most patients (65%) who received a 400 mg dose had an effective pazopanib concentration (≧20 µg/mL), whereas 35% of patients who received the 400 mg dose had ineffective concentrations (<20 µg/mL). Logistic regression analysis revealed that only the albumin level was significantly associated with effective pazopanib concentrations (odds ratio: 1.37, p = 0.0234). In conclusion, a dose of 400 mg had been effective and well tolerated in more than half of patients in this study. However, therapeutic drug monitoring is necessary during pazopanib therapy.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors blood
Angiogenesis Inhibitors pharmacokinetics
Asian People
Carcinoma, Renal Cell drug therapy
Carcinoma, Renal Cell metabolism
Drug Monitoring
Female
Humans
Indazoles
Japan
Kidney Neoplasms drug therapy
Kidney Neoplasms metabolism
Male
Middle Aged
Pyrimidines blood
Pyrimidines pharmacokinetics
Sarcoma drug therapy
Sarcoma metabolism
Sulfonamides blood
Sulfonamides pharmacokinetics
Treatment Outcome
Young Adult
Angiogenesis Inhibitors administration & dosage
Carcinoma, Renal Cell blood
Kidney Neoplasms blood
Pyrimidines administration & dosage
Sarcoma blood
Sulfonamides administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 32115446
- Full Text :
- https://doi.org/10.1248/bpb.b19-00560