PURPOSE: To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC). PATIENTS AND METHODS: Patients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m(2) (arm A) or bortezomib 1.3 mg/m(2) plus irinotecan 125 mg/m(2) (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability. RESULTS: A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade >or= 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B. CONCLUSION:Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC.
RCT Entities:
PURPOSE: To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC). PATIENTS AND METHODS: Patients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m(2) (arm A) or bortezomib 1.3 mg/m(2) plus irinotecan 125 mg/m(2) (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability. RESULTS: A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade >or= 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B. CONCLUSION:Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC.
Authors: Dan T Vogl; Edward A Stadtmauer; Kay-See Tan; Daniel F Heitjan; Lisa E Davis; Laura Pontiggia; Reshma Rangwala; Shengfu Piao; Yunyoung C Chang; Emma C Scott; Thomas M Paul; Charles W Nichols; David L Porter; Janeen Kaplan; Gayle Mallon; James E Bradner; Ravi K Amaravadi Journal: Autophagy Date: 2014-05-20 Impact factor: 16.016
Authors: George P Kim; Michelle R Mahoney; Daniel Szydlo; Tony S K Mok; Robert Marshke; Kyle Holen; Joel Picus; Michael Boyer; Henry C Pitot; Joseph Rubin; Philip A Philip; Anna Nowak; John J Wright; Charles Erlichman Journal: Invest New Drugs Date: 2010-09-14 Impact factor: 3.850
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
Authors: Allyson J Ocean; Paul Christos; Joseph A Sparano; Manish A Shah; Rhonda K Yantiss; Jonathan Cheng; Juan Lin; Michael Papetti; Dan Matulich; Felice Schnoll-Sussman; Christen Besanceney-Webler; Jenny Xiang; Maureen Ward; Kaili Temple Dilts; Roger Keresztes; Shannon Holloway; Eric X Chen; John J Wright; Maureen E Lane Journal: Invest New Drugs Date: 2014-02-15 Impact factor: 3.850