PURPOSE: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. PATIENTS AND 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.
PURPOSE: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. PATIENTS AND 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.
Authors: Ivana Zavrski; Christian Jakob; Peter Schmid; Holger Krebbel; Martin Kaiser; Claudia Fleissner; Marleen Rosche; Kurt Possinger; Orhan Sezer Journal: Anticancer Drugs Date: 2005-06 Impact factor: 2.248
Authors: Robert G Maki; Andrew S Kraft; Kelly Scheu; Jennifer Yamada; Scott Wadler; Cristina R Antonescu; John J Wright; Gary K Schwartz Journal: Cancer Date: 2005-04-01 Impact factor: 6.860
Authors: J Adams; M Behnke; S Chen; A A Cruickshank; L R Dick; L Grenier; J M Klunder; Y T Ma; L Plamondon; R L Stein Journal: Bioorg Med Chem Lett Date: 1998-02-17 Impact factor: 2.823
Authors: B C Potts; M X Albitar; K C Anderson; S Baritaki; C Berkers; B Bonavida; J Chandra; D Chauhan; J C Cusack; W Fenical; I M Ghobrial; M Groll; P R Jensen; K S Lam; G K Lloyd; W McBride; D J McConkey; C P Miller; S T C Neuteboom; Y Oki; H Ovaa; F Pajonk; P G Richardson; A M Roccaro; C M Sloss; M A Spear; E Valashi; A Younes; M A Palladino Journal: Curr Cancer Drug Targets Date: 2011-03 Impact factor: 3.428