A phase I/II study of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines.
BACKGROUND
Proteasome inhibitors are a novel class of compounds entering clinical trials as a method to increase tumour sensitivity to standard chemotherapy. This phase I/II trial was carried out to evaluate the combination of capecitabine and the proteasome inhibitor bortezomib in anthracycline and/or taxane-pretreated patients with metastatic breast cancer.


METHODS
A total of 35 patients were treated with bortezomib (1.0-1.3 mg/m(2) on days 1, 4, 8 and 11) and capecitabine (1500-2500 mg/m(2) on days 1-14) in 3-week intervals for up to eight cycles.


RESULTS
The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m(2) and capecitabine 2500 mg/m(2). The treatment was generally well tolerated and associated with toxic effects that were consistent with the known side-effects of the individual agents. The intent-to-treat overall response rate was 15% and an additional 27% of patients had stable disease (SD). In the 20 patients treated at the MTD, the response rate was 15% and 40% had SD. Median time to progression and overall survival were 3.5 months [95% confidence interval (CI) 1.9-4.4] and 7.5 months (95% CI 5.6-14.6), respectively. Median duration of response was 4.4 months.


CONCLUSIONS
The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated patients.
Schmid
P
P
Medical Oncology, Imperial College London, Charing Cross Hospital, London, UK. p.schmid@imperial.ac.uk
Kühnhardt
D
D
Kiewe
P
P
Lehenbauer-Dehm
S
S
Schippinger
W
W
Greil
R
R
Lange
W
W
Preiss
J
J
Niederle
N
N
Brossart
P
P
Freier
W
W
Kümmel
S
S
Van de Velde
H
H
Regierer
A
A
Possinger
K
K
D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D020714:Maximum Tolerated Dose; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D018943:Anthracyclines; D001897:Boronic Acids; D011719:Pyrazines; D043823:Taxoids; D003841:Deoxycytidine; D000069287:Capecitabine; D000069286:Bortezomib; D005472:Fluorouracil