Taxanes in metastatic breast cancer patients with impaired liver function

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609 Taxanes are eliminated through the hepatobiliary route, and published guidelines for administration in patients (pts) with liver dysfunction (LD) have not been clinically useful. We prospectively assessed a method for safe administration of the taxanes in metastatic breast cancer (MBC) pts with differing degrees of LD as measured by standard liver function tests and attempted to correlate this dosing strategy with toxicities and standard pharmacokinetic (PK) measures of the two available taxanes, paclitaxel (pac) and docetaxel (doc). METHODS: Eligible pts were those with hepatic metastases from MBC who were candidates for pac or doc and who met the following criteria: Group I) total bilirubin (TBili) normal and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) 1.5–2.5 x upper limit of normal (ULN) and alkaline phosphatase (Alk Ph) ≥ 2.5 x ULN; Group II) TBili normal and ALT/AST 2.5–5 x ULN and/or Alk Ph ≥ 2.5 x ULN in the absence of bone metastases; Group III) TBili 1.5–3 x ULN and ALT/AST 1.5–2.5 x ULN and/or Alk Ph ≥ 2.5 x ULN; Group IV) TBili 1.5–3 x ULN and ALT/AST 2.5–5 x ULN and/or Alk Ph ≥ 2.5 x ULN; Group V) TBili > 3 x ULN and any ALT/AST/Alk Ph or ALT/AST > 5 x ULN and any TBili or Alk Ph. All other causes for LD were ruled out, and bile duct obstruction was surgically or endoscopically corrected, if possible, prior to study entry. Chemotherapy doses were as outlined in the table below. All pts signed informed consent for participation. RESULTS: 35 pts were enrolled (12 on pac, 23 on doc). Grade 3/4 toxicity per patient included fatigue (pac=42%, doc=57%), myalgias (pac=33%, doc=22%), infection w/neutropenia (pac=25%, doc=22%), infection w/o neutropenia (pac=25%, doc=4%), diarrhea (pac=17%, doc=4%), mucositis (pac=8%, doc=4%), and peripheral neuropathy (pac=0%, doc=4%). Initial analyses indicate that PK data did not correlate with toxicity. CONCLUSIONS: The taxanes can be administered to pts with MBC and LD following dose attenuation as utilized in this study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Bristol-Myers Squibb Aventis, Bristol-Myers Squibb, sanofi-aventis Aventis, Bristol-Myers Squibb