Phase I trial of fixed-dose rate gemcitabine in combination with bortezomib in advanced solid tumors.
BACKGROUND
Bortezomib demonstrates synergism with gemcitabine via a fixed-dose rate (FDR). The aim of this phase I trial in solid tumors was to establish the maximum tolerated dose (MTD) and safety data for this combination.


METHODS
Twenty-nine patients with a median age of 63 (range 36-84) years and median Karnofsky Performance Status of 90 (range 60-100) were enrolled and treated with bortezomib (1.0 or 1.3 mg/m(2)) on days 1, 4, 8 and 11 and FDR gemcitabine (750, 1,000, or 1,250 mg/m(2)) on days 1 and 8 of each 21-day cycle. Response was evaluated every two cycles.


RESULTS
Dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia and grade 3 liver function test abnormalities. The MTD was bortezomib 1 mg/m2 and FDR gemcitabine 1,250 mg/m(2). The median number of cycles delivered was 3 (range 1-28). There was one partial response and six cases of stable disease. The median duration of response was 8.5 (range 3-20) months.


CONCLUSIONS
FDR gemcitabine and bortezomib combination can be delivered effectively with acceptable toxicity.
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA. tluu@coh.org
Thehang
T
Luu
Warren
W
Chow
Dean
D
Lim
Marianna
M
Koczywas
Paul
P
Frankel
Mihaela
M
Cristea
Kim
K
Margolin
James H
JH
Doroshow
George
G
Somlo
Shikha
S
Gaur
Yun
Y
Yen
Robert J
RJ
Morgan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
D001897:Boronic Acids; D011719:Pyrazines; D003841:Deoxycytidine; D000069286:Bortezomib; D000093542:Gemcitabine