EORTC 10968: a phase I clinical and pharmacokinetic study of polyethylene glycol liposomal doxorubicin (Caelyx, Doxil) at a 6-week interval in patients with metastatic breast cancer. European Organization for Research and Treatment of Cancer.
BACKGROUND
We performed a phase I study of polyethylene glycol (pegylated, Stealth) liposomal doxorubicin (Caelyx, Doxil) using a prolonged (6-week) dose interval to reduce the incidence of skin toxicity that was dose-limiting at more conventional dose intervals, and which appeared to be schedule dependent.


METHODS
Eligible for the study were metastatic breast cancer patients who had received a maximum of one prior therapy for metastatic disease. The defined dose levels were 60, 70, 80 and 90 mg/m2.


RESULTS
Twenty patients were assessed at starting doses of 60 mg/m2 (n = 9) or 70 mg/m2 (n = 11). The dose-limiting toxicity was mucositis. Severe skin toxicity was not observed at the 60 mg/m2 dose level, and occurred in only one patient treated at 70 mg/m2. Significant neutropenia, alopecia, and nausea and vomiting were rare events. No clinical cardiac events occurred, despite a median cumulative doxorubicin dose of 323 mg/m2 (range 5-630 mg/m2). Partial responses were documented in five patients. Pharmacokinetics were assessed in 15 patients, and confirmed the long terminal half-life of the agent (median 77 h) demonstrated in earlier studies.


CONCLUSIONS
The recommended dose of Caelyx/Doxil using this schedule is 60 mg/m2 every 6 weeks. This is a safe and effective regimen that permits prolonged administration of anthracycline to patients with metastatic breast cancer.
Hamilton
A
A
IDBBC, Brussels, Belgium.
Biganzoli
L
L
Coleman
R
R
Mauriac
L
L
Hennebert
P
P
Awada
A
A
Nooij
M
M
Beex
L
L
Piccart
M
M
Van Hoorebeeck
I
I
Bruning
P
P
de Valeriola
D
D
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009426:Netherlands; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D008081:Liposomes; D004317:Doxorubicin