Paclitaxel pharmacokinetics and response to chemotherapy in patients with advanced cancer treated with a weekly regimen.
BACKGROUND
Paclitaxel pharmacokinetics were shown to be related to toxicity and survival.


METHODS
We evaluated the effects of time above paclitaxel concentrations of 0.05 micromol/l (T(>0.05) and systemic exposures (AUC) to total and unbound paclitaxel (tPAC, uPAC) on response in patients with advanced cancer treated with weekly 1-h or 3-h infusions.


RESULTS
After 6 weeks of therapy (WOT), 13 out of 21 assessable patients showed either partial response (PR) or stable disease (SD), while 8 had progressive disease (PD). As compared to patients with PD, those with PR or SD showed similar AUCs to uPAC and tPAC but higher (p < 0.05) T (>0.05). Patients with T(>0.05) > or = 20.7 hours had lower probability (p < 0.05) to progress within 12 WOT.


CONCLUSIONS
Taking the heterogeneity of the studied tumor types into account, we found T(>0.05) to be associated with response to treatment. This emphasizes the value of threshold models for the investigation of paclitaxel pharmacodynamics.
Mielke
Stephan
S
Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg i. Br., Germany. mielkes@nhlbi.nih.gov
Sparreboom
Alex
A
Behringer
Dirk
D
Mross
Klaus
K
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011446:Prospective Studies
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel