Phase I and pharmacologic study of weekly doxorubicin and 1 h infusional paclitaxel in patients with advanced breast cancer.
Doxorubicin and paclitaxel both display strong antitumor activity in the treatment of breast cancer. The optimal schedule of this combination, however, remains undefined. In this phase I and pharmacologic study, we administered weekly 12 mg/m2 doxorubicin as a bolus infusion immediately followed by a 1 h 80 mg/m2 paclitaxel infusion to patients with metastatic breast cancer. A total of 119 weekly courses were delivered to seven patients. Grade IV neutropenia was observed in two patients at the first dose level, thus already defining the maximum tolerated dose. Pronounced non-hematologic toxicities were mild neuropathy (grade I: 39%) and stomatitis (grade I: 19%, grade II: 8%). No signs of cardiac toxicity were observed with this dose schedule. Three partial responses were achieved in this group of heavily pretreated patients. The pharmacokinetics of paclitaxel, doxorubicin and Cremophor EL with this schedule were analyzed. Overall, the schedule was well tolerated and combined with its preliminary response rate justifies further evaluation in phase II studies.
Panday
V R
VR
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
ten Bokkel Huinink
W W
WW
Rosing
H
H
Koopman
F J
FJ
Hillebrand
M J
MJ
Dubbelman
R C
RC
van Tellingen
O
O
Schellens
J H
JH
Beijnen
J H
JH
D000328:Adult; D000505:Alopecia / Q000139:chemically induced / Q000150:complications; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity
D000970:Antineoplastic Agents; C000515:cremophor EL; D004317:Doxorubicin; D017239:Paclitaxel; D005990:Glycerol