1.
Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study.
Ko, YJ, Canil, CM, Mukherjee, SD, Winquist, E, Elser, C, Eisen, A, Reaume, MN, Zhang, L, Sridhar, SS
The Lancet. Oncology. 2013;(8):769-76
Abstract
BACKGROUND No standard treatment exists for patients with platinum-refractory urothelial cancer. Taxanes and vinflunine are commonly used, but response is less than 20% with no survival benefit. In this phase 2 study, we assessed efficacy and tolerability of nanoparticle albumin-bound (nab) paclitaxel in platinum-refractory urothelial cancer. METHODS We did an open-label, single-group, two-stage study at five centres in Canada. We enrolled patients aged at least 18 years with histologically confirmed, locally advanced, or metastatic measurable urothelial cancer, with documented progression on or within 12 months of treatment with one previous platinum-containing regimen. Patients received nab-paclitaxel at 260 mg/m(2) intravenously every 3 weeks. Treatment continued until disease progression or occurrence of unacceptable toxic effects. The primary endpoint was objective tumour response, defined by a complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (version 1.0) criteria. Tumour response and safety were assessed in all patients who received at least one cycle of nab-paclitaxel. This study is registered with ClinicalTrials.gov, number NCT00683059. FINDINGS We enrolled 48 patients between Oct 16, 2008, and June 23, 2010. Patients received a median of six cycles (range one to 15). 47 patients were evaluable; one (2·1%) had a CR and 12 (25·5%) had PRs, resulting in an overall response of 27·7% (95% CI 17·3-44·4). The most frequently recorded adverse events of any grade were fatigue (38 of 48; 79%), pain (37 of 48; 77%), alopecia (34 of 48; 71%), and neuropathy (30 of 48; 77%). The most frequently recorded adverse events of grade 3 or higher were pain (11 of 48; 23%), fatigue (five of 48; 23%), hypertension (three of 48; 6%), neuropathy (three of 48, 6%), and joint stiffness or pain (two of 48; 4%). INTERPRETATION Nab-paclitaxel was well tolerated in this population of patients with pretreated advanced urothelial cancer with an encouraging tumour response. These results warrant further study of nab-paclitaxel in second-line treatment of urothelial cancer. FUNDING Abraxis Bioscience, Celgene.
2.
Tolerability and patient acceptance of sodium phosphate tablets compared with 4-L PEG solution in colon cleansing: combined results of 2 identically designed, randomized, controlled, parallel group, multicenter phase 3 trials.
Kastenberg, D, Barish, C, Burack, H, Dalke, DD, Duckor, S, Putnam, W, Valenzuela, G, ,
Journal of clinical gastroenterology. 2007;(1):54-61
Abstract
GOALS Evaluate patient tolerance and acceptance of a sodium phosphate (NaP) tablet purgative compared with a 4-L polyethylene glycol (PEG) solution. BACKGROUND Characteristics and side effects of bowel purgatives deter patients from undergoing screening colonoscopy. Published data demonstrated comparable bowel cleansing with NaP tablets and a 4-L PEG solution in 2 phase for 3 studies. This report presents data on patient tolerability and acceptance. STUDY Two identically designed, randomized, investigator-blinded, and multicenter trials were performed. Tolerability and patient acceptance were based on purgative regimen compliance, incidence of gastrointestinal adverse events, and patient responses to questionnaires. RESULTS Eight hundred forty-five patients were assessed (420 and 425 in the tablet and PEG solution groups, respectively). Patient compliance with the tablet regimen was greater: 94% of patients took all the tablets compared with 57% completing the PEG solution regimen (P<0.0001). Nausea, vomiting, and bloating occurred significantly less often in patients taking NaP tablets (P<0.0001). Among patients taking tablets, 88.4% rated them "easy" or "slightly difficult" to take, compared with 60.6% of patients taking the PEG solution. The preparation's taste was rated "barely tolerable" or "not tolerable" by 1% of patients treated with NaP tablets and 23.6% treated with PEG solution. Drinking the required volume of clear liquid for the tablet or PEG preparation was rated "easy" or "slightly difficult" by 92.2% and 66.9% of patients, respectively. Almost all (90.7%) patients taking the tablets indicated they would take the same preparation in the future, compared with 67.1% of patients taking the PEG solution (P<0.0001 for each comparison). CONCLUSIONS Tolerability and patient acceptance of a NaP tablet purgative were superior to 4-L PEG solution.
3.
Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion.
Glassman, SD, Dimar, JR, Carreon, LY, Campbell, MJ, Puno, RM, Johnson, JR
Spine. 2005;(15):1694-8
Abstract
STUDY DESIGN Prospective, randomized, unblinded study of iliac crest bone graft (ICBG) versus recombinant human bone morphogenetic protein-2/compression resistant matrix (rhBMP-2/CRM)in a posterolateral instrumented fusion procedure. OBJECTIVES Document initial radiographic characteristics, based on computed tomography, with rhBMP-2/CRM for posterolateral fusion at 6 and 12-month intervals. SUMMARY OF BACKGROUND DATA As the acceptance of INFUSE bone graft as an ICBG replacement becomes more widespread, surgeons have begun to study applications for rhBMP-2 in posterior spinal fusion. Preclinical studies have examined variables including carrier composition, rhBMP-2 concentration, and rhBMP-2 dose. Pilot studies have been performed with encouraging initial results. METHODS Patients with single level lumbar degenerative disease were enrolled in a randomized study of ICBG versus rhBMP-2/CRM in a posterolateral instrumented fusion procedure. Computed tomography scans at 6 and 12 months were graded as demonstrating no fusion (grade 1), partial or limited unilateral fusion (grade 2), partial or limited bilateral fusion (grade 3), solid unilateral fusion (grade 4), or solid bilateral fusion (grade 5). RESULTS At our institution, 74 patients (38 rhBMP-2/CRM, 36 ICBG) reached minimum 1-year follow-up and were included in this analysis. Mean fusion grade (scale1-5) at 6 months after surgery was 4.35 in the rhBMP-2/CRM group versus 3.09 in the ICBG group (P < 0.0001). At 1 year after surgery mean fusion grade was 4.62 in the rhBMP-2/CRM group versus 3.77 in the ICBG group (P < 0.0023). CONCLUSIONS These early results are encouraging and suggest a more rapid incorporation and development of the fusion mass with rhBMP-2/CRM than iliac crest autograft in a single level posterior instrumented fusion.