TY - JOUR
T1 - Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases
AU - Eckmann, Karen
AU - Michaud, Laura B.
AU - Rivera, Edgardo
AU - Madden, Timothy L.
AU - Esparza-Guerra, Laura
AU - Kawedia, Jitesh
AU - Booser, Daniel J.
AU - Green, Marjorie C.
AU - Hortobagyi, Gabriel N.
AU - Valero, Vicente
N1 - Funding Information:
This work was supported by grants from Bristol-Myers Squibb and Sanofi-Aventis, and the National Cancer Institute Cancer Center Support (grant CA016672).
PY - 2014/4
Y1 - 2014/4
N2 - Background: Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction. Methods: Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patients level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression. Results: Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy. Conclusions: Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.
AB - Background: Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction. Methods: Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patients level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression. Results: Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy. Conclusions: Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.
KW - Docetaxel
KW - chemotherapy
KW - hepatic dysfunction
KW - liver impairment
KW - metastatic breast cancer
KW - taxanes
UR - http://www.scopus.com/inward/record.url?scp=84898948465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898948465&partnerID=8YFLogxK
U2 - 10.1177/1078155213480536
DO - 10.1177/1078155213480536
M3 - Article
C2 - 23676510
AN - SCOPUS:84898948465
SN - 1078-1552
VL - 20
SP - 120
EP - 129
JO - Journal of Oncology Pharmacy Practice
JF - Journal of Oncology Pharmacy Practice
IS - 2
ER -