Phase I Trial of Fixed-Dose Rate Gemcitabine in Combination with Bortezomib in Advanced Solid Tumors

• Published in: Anticancer research Vol. 30; no. 1; pp. 167 - 174
• Main Authors: THEHANG LUU, WARREN CHOW, YUNYEN, MORGAN, Robert J, DEAN LIM, KOCZYWAS, Marianna, FRANKEL, Paul, CRISTEA, Mihaela, MARGOLIN, Kim, DOROSHOW, James H, SOMLO, George, GAUR, Shikha
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.01.2010
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Boronic Acids - administration & dosage; Boronic Acids - adverse effects; Bortezomib; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Growth Processes - drug effects; Cell Line, Tumor; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Humans; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Pyrazines - administration & dosage; Pyrazines - adverse effects; Tumors; Antineoplastic agent; fixed-dose rate gemcitabine; Solid tumor; Drug combination; Bortezomib; Gemcitabine; Malignant tumor; Dose rate; solid tumors; Cancerology; Antimetabolic; Analog; Proteasome inhibitor; Dipeptides; Phase I trial; Pyrimidine derivatives; Advanced stage; phase I; Fluorine Organic compounds; Pyrimidine nucleoside; Cancer
• ISSN: 0250-7005; 1791-7530

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. Patients and 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. Conclusion: FDR gemcitabine and bortezomib combination can be delivered effectively with acceptable toxicity.