Possibility for Dose Optimization of Pazopanib from Its Plasma Concentration in Japanese Patients with Cancer

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 Cmin, and other clinical factors, including albumin and α-1 acid glycopro...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2020/05/01, Vol.43(5), pp.762-766
Main Authors: Tanaka, Hiroyuki, Hiraga, Hiroaki, Takekuma, Yoh, Harabayashi, Toru, Nagamori, Satoshi, Endo, Masayuki, Sugawara, Mitsuru
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Albumin
Angiogenesis Inhibitors - administration & dosage
Angiogenesis Inhibitors - blood
Angiogenesis Inhibitors - pharmacokinetics
Asian Continental Ancestry Group
Cancer
Carcinoma, Renal Cell - blood
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - metabolism
Drug dosages
Drug Monitoring
Female
Humans
Japan
Kidney cancer
Kidney Neoplasms - blood
Kidney Neoplasms - drug therapy
Kidney Neoplasms - metabolism
low dose
Male
Middle Aged
Patients
pazopanib
Pyrimidines - administration & dosage
Pyrimidines - blood
Pyrimidines - pharmacokinetics
Renal cell carcinoma
Sarcoma
Sarcoma - blood
Sarcoma - drug therapy
Sarcoma - metabolism
Side effects
Sulfonamides - administration & dosage
Sulfonamides - blood
Sulfonamides - pharmacokinetics
Targeted cancer therapy
therapeutic drug monitoring
Treatment Outcome
Young Adult
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Summary: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 Cmin, 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. Cmin 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 (
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b19-00560