A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy.
OBJECTIVE
To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies.


METHODS
Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days. Surrogate markers of angiogenesis were evaluated.


RESULTS
Twenty-four patients received 64 courses of therapy. The most common treatment-related adverse events were myelosuppression. Dose-limiting grade 3 and 4 neutropenia and thrombocytopenia were observed when bortezomib was given on days 1, 4, 8, 11. With revised dosing, the maximum tolerated dose (MTD) of bortezomib 0.75 mg/m(2) (days 1, 8), etoposide 75 mg/m(2) (days 1-3), and carboplatin AUC 5 (day 1) was well tolerated, and are the recommended doses for further studies with this combination. No objective responses were observed, however stable disease was noted for greater or equal to four cycles in nine highly refractory patients.
Lieu
Christopher
C
University of Colorado Cancer Center, 1665 North Ursula Street, Aurora, CO, USA.
Chow
Laura
L
Pierson
A Scott
AS
Eckhardt
S Gail
SG
O'Bryant
Cindy L
CL
Morrow
Mark
M
Tran
Zung Vu
ZV
Wright
John J
JJ
Gore
Lia
L
D000328:Adult; D000368:Aged; D000740:Anemia; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced
D014408:Biomarkers, Tumor; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D005047:Etoposide; D016190:Carboplatin