PURPOSE: A phase I study to determine the maximum tolerated dose (MTD) of bortezomib (B) when combined with weekly paclitaxel in patients with advanced solid tumors. PATIENTS AND METHODS: Eligible patients received escalating doses of intravenous (IV) bortezomib (0.6-2 mg/m(2)) on days 2 and 9 and IV paclitaxel at 100 mg/m(2) on days 1 and 8 of a 21-day cycle. Dose escalation was based on two end-points: not exceeding 80% 20S-proteasome inhibition (20-S PI) and the development of dose-limiting toxicity defined as grade 3 or greater non-hematologic or grade 4 hematologic toxicities. RESULTS: Forty-five patients with advanced solid tumors and a median of 3 prior chemotherapy regimens (range 0-9), received 318 doses (median 5, range 1-34) of bortezomib and paclitaxel. Dose-related inhibition of 20-S PI was observed with a maximum inhibition of 70-80% at the MTD of 1.8 mg/m(2) of bortezomib. At the MTD (N = 9) the following toxicities were observed: grade 4 neutropenia without fever (n = 2) and cerebrovascular ischemia (n = 1); grade 3 neutropenia (n = 3), diarrhea (n = 2), nausea (n = 1), and fatigue (n = 1); grade 2 fatigue (n = 5), diarrhea (n = 4), and dyspnea (n = 2). There was one partial response in a patient with an eccrine porocarcinoma. Stabilization of disease was observed in 7 (16%) patients, 3 of whom had advanced pancreatic cancer. CONCLUSION: Sequential paclitaxel and bortezomib in previously treated patients with advanced solid tumors resulted in acceptable toxicity and no evidence of interaction. The recommended phase II dose of bortezomib in combination with weekly paclitaxel was 1.8 mg/m(2).
PURPOSE: A phase I study to determine the maximum tolerated dose (MTD) of bortezomib (B) when combined with weekly paclitaxel in patients with advanced solid tumors. PATIENTS AND METHODS: Eligible patients received escalating doses of intravenous (IV) bortezomib (0.6-2 mg/m(2)) on days 2 and 9 and IV paclitaxel at 100 mg/m(2) on days 1 and 8 of a 21-day cycle. Dose escalation was based on two end-points: not exceeding 80% 20S-proteasome inhibition (20-S PI) and the development of dose-limiting toxicity defined as grade 3 or greater non-hematologic or grade 4 hematologic toxicities. RESULTS: Forty-five patients with advanced solid tumors and a median of 3 prior chemotherapy regimens (range 0-9), received 318 doses (median 5, range 1-34) of bortezomib and paclitaxel. Dose-related inhibition of 20-S PI was observed with a maximum inhibition of 70-80% at the MTD of 1.8 mg/m(2) of bortezomib. At the MTD (N = 9) the following toxicities were observed: grade 4 neutropenia without fever (n = 2) and cerebrovascular ischemia (n = 1); grade 3 neutropenia (n = 3), diarrhea (n = 2), nausea (n = 1), and fatigue (n = 1); grade 2 fatigue (n = 5), diarrhea (n = 4), and dyspnea (n = 2). There was one partial response in a patient with an eccrine porocarcinoma. Stabilization of disease was observed in 7 (16%) patients, 3 of whom had advanced pancreatic cancer. CONCLUSION: Sequential paclitaxel and bortezomib in previously treated patients with advanced solid tumors resulted in acceptable toxicity and no evidence of interaction. The recommended phase II dose of bortezomib in combination with weekly paclitaxel was 1.8 mg/m(2).
Authors: Carol Aghajanian; Steven Soignet; Don S Dizon; Christine S Pien; Julian Adams; Peter J Elliott; Paul Sabbatini; Vincent Miller; Martee L Hensley; Sandra Pezzulli; Christina Canales; Adil Daud; David R Spriggs Journal: Clin Cancer Res Date: 2002-08 Impact factor: 12.531
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Authors: Yi-He Ling; Leonard Liebes; Bruce Ng; Michael Buckley; Peter J Elliott; Julian Adams; Jian-Dong Jiang; Franco M Muggia; Roman Perez-Soler Journal: Mol Cancer Ther Date: 2002-08 Impact factor: 6.261
Authors: Shing M Lee; Daniel Backenroth; Ying Kuen Ken Cheung; Dawn L Hershman; Diana Vulih; Barry Anderson; Percy Ivy; Lori Minasian Journal: J Clin Oncol Date: 2016-02-29 Impact factor: 44.544
Authors: Janice M Mehnert; Antoinette R Tan; Rebecca Moss; Elizabeth Poplin; Mark N Stein; Mika Sovak; Kelly Levinson; Hongxia Lin; Michael Kane; Murugesan Gounder; Yong Lin; Weichung Joe Shih; Eileen White; Eric H Rubin; Vassiliki Karantza Journal: Mol Cancer Ther Date: 2011-06-16 Impact factor: 6.261