A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer.
OBJECTIVE
Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer.


METHODS
Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1-14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety.


RESULTS
Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4-7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin > or = 560 mg/m2.


CONCLUSIONS
The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1-14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.
Rocca
Andrea
A
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Via P. Maroncelli 40, 47014 Meldola, FC, Italy. a.rocca@irst.emr.it
Maltoni
Roberta
R
Passardi
Alessandro
A
Massa
Ilaria
I
Aquilina
Michele
M
Ridolfi
Ruggero
R
Ibrahim
Toni
T
Cecconetto
Lorenzo
L
Sarti
Samanta
S
Pietri
Elisabetta
E
Nanni
Oriana
O
Amadori
Dino
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D020714:Maximum Tolerated Dose; D055118:Medication Adherence; D008875:Middle Aged; D009362:Neoplasm Metastasis
D003841:Deoxycytidine; D000069287:Capecitabine; D004317:Doxorubicin; D005472:Fluorouracil