Phase I trial of pegylated liposomal doxorubicin and docetaxel in advanced breast cancer.
OBJECTIVE
To develop a combination of pegylated liposomal doxorubicin (Doxil; Alza Pharmaceuticals, Palo Alto, CA) and docetaxel (Taxotere; Aventis Pharmaceutical, Parsipanny, NJ) that can be safely used for the treatment of advanced breast cancer.


METHODS
Forty-one patients with locally advanced (n = 10) or metastatic (n = 31) breast cancer received Doxil (30-, 40-, or 45-mg/m(2) intravenous [IV] infusion over 30 to 60 minutes), followed 1 hour later by docetaxel (60 or 75 mg/m(2) by IV infusion over 1 hour) in cohorts of three to six patients. Dose-limiting toxicity (DLT) was defined as febrile neutropenia, prolonged neutropenia, or grade 3 to 4 nonhematologic toxicity that occurred during cycle 1.


RESULTS
In conjunction with docetaxel 75 mg/m(2) every 4 weeks, the MTD of Doxil was 30 mg/m(2) and required granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. Without G-CSF, the MTD was docetaxel 60 mg/m(2) and Doxil 30 mg/m(2) every 3 weeks; only 1 (7%) out of 15 patients treated at this dose level had cycle 1 DLT. Infusion reactions were common with Doxil with the recommended infusion schedule during the first cycle (55%) but were reduced with a modified schedule (7%). There was no clinically significant cardiac toxicity. Objective response occurred in eight of nine assessable patients with stage III disease and in 16 (52%) of 31 patients (95% confidence interval, 34% to 70%) with stage IV disease.


CONCLUSIONS
The recommended dose and schedule of this combination for further evaluation is Doxil 30 mg/m(2) and docetaxel 60 mg/m(2) given every 3 weeks without G-CSF. When used with G-CSF, it is Doxil 30 mg/m(2) and docetaxel 75 mg/m(2) every 4 weeks.
Sparano
J A
JA
Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Bronx, NY 10461-2373, USA.
Malik
U
U
Rajdev
L
L
Sarta
C
C
Hopkins
U
U
Wolff
A C
AC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000506:poisoning* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000506:poisoning; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous / Q000009:adverse effects; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate; D043823:Taxoids
D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel