-
1.
Effects of Goshajinkigan (TJ-107) for oxaliplatin-induced peripheral neurotoxicity using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire in a Phase II, multicenter, randomized, double-blind, placebo-controlled trial.
Aoyama, T, Morita, S, Kono, T, Hata, T, Mishima, H, Sakamoto, J
Journal of cancer research and therapeutics. 2021;(6):1473-1478
-
-
Free full text
-
Abstract
BACKGROUND The aim of the present study was to evaluate the efficacy of TJ-107 for oxaliplatin-induced peripheral neurotoxicity in prospective, multi-institutional, randomized, double-blind, placebo-controlled Phase II trials using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire (FACT-GOG-NTX-12). PATIENTS AND METHODS The patients who were registered to the Goshajinkigan oxaliplatin neurotoxicity evaluation study (UMIN000002211) were analyzed. A NTX-12 from the validated FACT/GOG-NTX-12 was assessed before treatment and at the end of every 2 cycles. RESULTS The comparisons of the median scores for TJ-107 and the placebo at 8 and 26 weeks were as follows: numbness or tingling in the hands (P = 0.5820), numbness or tingling in the feet (P = 0.3236), feeling of discomfort in the hands (P = 0.8219), feeling of discomfort in the feet (P = 0.5361), joint pain or muscle cramps (P = 0.1974), feeling weak all over (P = 0.2771), trouble hearing (P = 0.2832), ringing or buzzing in ears (P = 0.1031), trouble buttoning buttons (P = 0.1653), trouble feeling the shape of small objects when held in hand (P = 0.2919), trouble walking (P = 0.5406), and pain in the hands or feet when exposed to cold temperatures (P = 0.1872). CONCLUSION There might be no clinically significant difference between the use of TJ-107 and the severity and quality of life for patients treated with oxaliplatin.
-
2.
Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.
Mori, N, Keski-Rahkonen, P, Gicquiau, A, Rinaldi, S, Dimou, N, Harlid, S, Harbs, J, Van Guelpen, B, Aune, D, Cross, AJ, et al
JNCI cancer spectrum. 2021;(6)
Abstract
BACKGROUND Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. METHODS We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. RESULTS In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], P trend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. CONCLUSION Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
-
3.
A Phase 2 Randomized Trial of DCL-101, a Novel Pill-Based Colonoscopy Prep, vs 4L Polyethylene Glycol-Electrolyte Solution.
Bachwich, DR, Lewis, JD, Kowal, VO, Jacobson, BC, Calderwood, AH, Kochman, ML
Clinical and translational gastroenterology. 2020;(12):e00264
-
-
Free full text
-
Abstract
INTRODUCTION DCL-101, a novel Pill Prep, is compositionally identical to standard 4L polyethylene glycol-electrolyte solution (PEG-ELS) and delivers the salt encapsulated, with PEG 3350 coadministered as a taste-free oral solution. The aim of this study was to compare the safety, taste, and tolerability of DCL-101 with 4L PEG-ELS in outpatients preparing for colonoscopy, with a secondary objective to assess efficacy. METHODS This was a multicenter, randomized, investigator-blinded, phase 2 clinical trial of 45 adult patients undergoing outpatient colonoscopy. Patients were randomized 2:1 to either DCL-101 (3L in cohort 1; 4L in cohort 2) or 4L PEG-ELS, each administered with split dosing. Safety was assessed over 3 post-treatment clinic visits. Tolerability was measured using the Lawrance Bowel-Preparation Tolerability Questionnaire and the Mayo Clinic Bowel Prep Tolerability Questionnaire. Efficacy was determined by expert central readers, blinded to treatment, using the Ottawa Bowel Preparation Quality Scale, Boston Bowel Preparation Scale, and Aronchick scale. RESULTS Both DCL-101 doses had superior taste and tolerability relative to 4L PEG-ELS. All adverse events were grade 1 with no significant differences in adverse events among the 3 regimens. There were no significant differences in efficacy among the 3 treatments as defined by the centrally read Ottawa Bowel Preparation Quality Scale, Boston Bowel Preparation Scale, or Aronchick scores. There were no inadequate preps as judged by the site endoscopist. DISCUSSION DCL-101 Pill Prep is a novel strategy that vastly improves the taste and tolerability of PEG-ELS solutions with safety and efficacy comparable with split-dose 4L PEG-ELS solutions.
-
4.
Clinical Impact of Highly Purified, Whey Proteins in Patients Affected With Colorectal Cancer Undergoing Chemotherapy: Preliminary Results of a Placebo-Controlled Study.
Mazzuca, F, Roberto, M, Arrivi, G, Sarfati, E, Schipilliti, FM, Crimini, E, Botticelli, A, Di Girolamo, M, Muscaritoli, M, Marchetti, P
Integrative cancer therapies. 2019;:1534735419866920
Abstract
Background and Aims: Sarcopenia, the loss of both lean body and skeletal muscle mass, may interfere in cancer patients outcome. As investigated, whey proteins could prevent the onset of sarcopenia. We have conducted a study to evaluate the effects of whey protein in colorectal cancer patients, undergoing 5-fluorouracil-based chemotherapy. Methods: After written informed consent, patients were blind randomized 1:1 to whey protein (ProLYOtin; arm A) versus placebo (arm B). The patients were assessed both physically and nutritionally before chemotherapy and after 3 (T2) and 6 months (T3) by body impedance assessment, L3-computed tomography scan, Mini Nutritional Assessment (MNA), and Malnutrition Universal Screening Tool (MUST) tests. Results: Forty-seven patients were included in this preliminary analysis. Baseline characteristics were well balanced between the 2 arms. During chemotherapy, 33 patients were reevaluated: anthropometric parameters (lean body mass from 68.5% to 71.2% vs 68.7% to 66.3%, and sarcopenia from 84% to 54% and 83% to 77% from baseline to T2 evaluation in arms A and B, respectively), nutritional status (MNA >24 = 100% [A] vs 73.7% [B]), and toxicity (no adverse effects in 86% [A] vs 29% [B] and 94% [A] vs 29% [B] for hematological and gastrointestinal toxicities, respectively) resulted to be significantly different. At univariate analysis, a condition of malnutrition risk according to MUST (relative risk [RR] = 7.5, P = .02) or MNA (RR = 1.45, P = .02) and ProLYOtin intake (RR = 0.12, P = .01) were found to be significantly predictive of chemotherapy toxicity. Conclusions: At present, our study shows how whey protein could be an important therapeutic option to improve nutritional status, and particularly to prevent severe toxicity during chemotherapy.
-
5.
Water exchange for screening colonoscopy increases adenoma detection rate: a multicenter, double-blinded, randomized controlled trial.
Cadoni, S, Falt, P, Rondonotti, E, Radaelli, F, Fojtik, P, Gallittu, P, Liggi, M, Amato, A, Paggi, S, Smajstrla, V, et al
Endoscopy. 2017;(5):456-467
Abstract
Background and study aims Single-center studies, which were retrospective and/or involved unblinded colonoscopists, have suggested that water exchange, but not water immersion, compared with air insufflation significantly increases the adenoma detection rate (ADR), particularly in the proximal and right colon. Head-to-head comparison of the three techniques with ADR as primary outcome and blinded colonoscopists has not been reported to date. In a randomized controlled trial with blinded colonoscopists, we aimed to evaluate the impact of the three insertion techniques on ADR. Patients and methods A total of 1224 patients aged 50 - 70 years (672 males) and undergoing screening colonoscopy were randomized 1:1:1 to water exchange, water immersion, or air insufflation. Split-dose bowel preparation was adopted to optimize colon cleansing. After the cecum had been reached, a second colonoscopist who was blinded to the insertion technique performed the withdrawal. The primary outcome was overall ADR according to the three insertion techniques (water exchange, water immersion, and air insufflation). Secondary outcomes were other pertinent overall and right colon procedure-related measures. Results Baseline characteristics of the three groups were comparable. Compared with air insufflation, water exchange achieved a significantly higher overall ADR (49.3 %, 95 % confidence interval [CI] 44.3 % - 54.2 % vs. 40.4 % 95 %CI 35.6 % - 45.3 %; P = 0.03); water exchange showed comparable overall ADR vs. water immersion (43.4 %, 95 %CI 38.5 % - 48.3 %; P = 0.28). In the right colon, water exchange achieved a higher ADR than air insufflation (24.0 %, 95 %CI 20.0 % - 28.5 % vs. 16.9 %, 95 %CI 13.4 % - 20.9 %; P = 0.04) and a higher advanced ADR (6.1 %, 95 %CI 4.0 % - 9.0 % vs. 2.5 %, 95 %CI 1.2 % - 4.6 %; P = 0.03). Compared with air insufflation, the mean number of adenomas per procedure was significantly higher with water exchange (P = 0.04). Water exchange achieved the highest cleanliness scores (overall and in the right colon). These variables were comparable between water immersion and air insufflation. Conclusions The design with blinded observers strengthens the validity of the observation that water exchange, but not water immersion, can achieve significantly higher adenoma detection than air insufflation. Based on this evidence, the use of water exchange should be encouraged.Trial registered at ClinicalTrials.gov (NCT02041507).
-
6.
A two-center randomized controlled trial of water-aided colonoscopy versus air insufflation colonoscopy.
Cadoni, S, Gallittu, P, Sanna, S, Fanari, V, Porcedda, ML, Erriu, M, Leung, FW
Endoscopy. 2014;(3):212-8
Abstract
BACKGROUND AND STUDY AIM Water-aided colonoscopy includes water immersion and water exchange. Several small single-center studies have suggested that the use of water rather than air insufflation during colonoscopy reduces pain on insertion. The aim of this study was to investigate whether water-aided colonoscopy is less painful than air insufflation in a large cohort of patients. PATIENTS AND METHODS This was a two-center, randomized controlled trial. Consecutive patients who agreed to start colonoscopy without premedication were included. Sedation was administered on demand. Water-aided colonoscopy was performed using water immersion in the early phase of the study, and subsequently water exchange was used. The primary endpoint was cecal intubation with pain scores of ≤ 2 and sedation with no or ≤ 2 mg midazolam. Secondary outcomes were pain score at discharge, cecal intubation rate and time, and adenoma detection rate (ADR). RESULTS A total of 672 patients were randomized to water exchange (n = 338) or air insufflation (n = 334). The primary endpoint was achieved in more patients in the water exchange group (83.8 % vs. 62 %; P < 0.0005). On-demand sedation was also required less (11.5 % vs. 26.0 %; P < 0.0005) and mean pain score was lower (1.3 vs. 2.3; P < 0.0005) in the water exchange group. The cecal intubation rates were comparable. Water exchange had a significantly higher overall ADR (25.8 % vs. 19.1 %; P = 0.041), proximal ADR (10.1 % vs. 4.8 %; P = 0.014), and proximal < 10 mm ADR (7.7 % vs. 3.9 %; P = 0.046); proximal ADR was also higher in screening-only patients in the water exchange group (18.9 % vs. 7.4 %; P = 0.015). No detailed analysis was possible for the air insufflation vs. water immersion comparison. CONCLUSION The current results confirmed that water exchange minimized the requirement for sedation and increased the ADR.
-
7.
The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial.
Ishikawa, H, Mutoh, M, Suzuki, S, Tokudome, S, Saida, Y, Abe, T, Okamura, S, Tajika, M, Joh, T, Tanaka, S, et al
Gut. 2014;(11):1755-9
Abstract
OBJECTIVE To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. DESIGN A double-blinded, randomised, placebo-controlled multicentre clinical trial was conducted. PARTICIPANTS 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. RESULTS The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints with an adjusted OR of 0.60 (95% CI 0.36 to 0.98) compared with the subjects in the placebo group. Subgroup analysis revealed that subjects who were non-smokers, defined as those who had smoked in the past or who had never smoked, had a marked reduction in the number of recurrent tumours in the aspirin-treated group. The adjusted OR for aspirin treatment in non-smokers was 0.37 (CI 0.21 to 0.68, p<0.05). Interestingly, the use of aspirin in smokers resulted in an increased risk, with an OR of 3.44. In addition, no severe adverse effects were observed in either group. CONCLUSIONS Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. THE CLINICAL TRIAL REGISTRY WEBSITE AND THE CLINICAL TRIAL NUMBER http://www.umin.ac.jp (number UMIN000000697).
-
8.
A clear liquid diet is not mandatory for polyethylene glycol-based bowel preparation for afternoon colonoscopy in healthy outpatients.
Jung, YS, Seok, HS, Park, DI, Song, CS, Kim, SE, Lee, SH, Eun, CS, Han, DS, Kim, YS, Lee, CK
Gut and liver. 2013;(6):681-7
Abstract
BACKGROUND/AIMS: A dietary regimen consisting of a clear liquid diet (CLD) for at least 24 hours is recommended for colonoscopy preparation. However, this requirement results in problems in patient compliance with bowel preparation. The aim of this study was to evaluate the efficacy of a CLD compared with a regular diet (RD) for colonoscopy preparation using a polyethylene glycol (PEG) solution. METHODS This was a multicenter, randomized, investigator-blind prospective study. A total of 801 healthy outpatients undergoing afternoon colonoscopy were randomized to either a CLD or RD in addition to a 4 L PEG regimen. RESULTS The quality of bowel cleansing was not different between the CLD and RD groups in terms of the proportion with excellent or good preparation. In addition, no significant differences were observed between the two groups for polyp and adenoma detection rates and overall adverse events. Good compliance with bowel preparation was higher in the RD group than in the CLD group. CONCLUSIONS A CLD for a full day prior to colonoscopy should not be mandatory for PEG-based bowel preparation. Dietary education concerning the avoidance of high-fiber foods for 3 days before colonoscopy is sufficient, at least for healthy outpatients.
-
9.
Cost-effectiveness of adjuvant FOLFOX therapy for stage III colon cancer in Japan based on the MOSAIC trial.
Shiroiwa, T, Takeuchi, T, Fukuda, T, Shimozuma, K, Ohashi, Y
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2012;(2):255-60
Abstract
OBJECTIVE To evaluate the cost-effectiveness of adjuvant FOLFOX therapy versus 5-fluorouracil/leucovorin (FU/LV) for patients with stage III colorectal cancer. METHODS We performed the cost-effectiveness of FOLFOX compared with standard FU/LV treatment by the retrospective analysis of patient-level data from the randomized controlled Multicenter International Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) trial. Predicted mean time spent in each disease state was calculated by our statistical model, which takes into account the cure rate and treats death from causes other than colon cancer as a competing risk. We performed this analysis from the perspective of the health-care payer. Using a time horizon of 30 years, both cost and effectiveness were discounted by 3% per year. RESULTS Estimated cure rates for colon cancer were 0.715 (FOLFOX) and 0.622 (FU/LV). Estimated medical costs of FOLFOX were JPY 3.1 million (USD 34,000) compared with JPY 1.9 million (USD 22,000) of FU/LV. The mean estimated quality-adjusted life-year was 9.83 with FOLFOX and 9.07 with that of FU/LV. The incremental cost-effectiveness ratio of FOLFOX was JPY 1.5 million (USD 17,000) per quality-adjusted life-year compared with FU/LV, which was supported by sensitivity analysis. Even if we assume that Japanese outcomes were better than those reported by the MOSAIC trial, which would reduce the difference between cure rates for each treatment to 5%, the incremental cost-effectiveness ratio remained below 5.0 million (USD 56,000) per quality-adjusted life-year. CONCLUSIONS Adjuvant FOLFOX is a cost-effective treatment for stage III colon cancer in Japan compared with FU/LV therapy. Even when parameters were changed to reflect smaller improvements with FOLFOX, the conclusion is the same.
-
10.
A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802).
Ychou, M, Raoul, JL, Douillard, JY, Gourgou-Bourgade, S, Bugat, R, Mineur, L, Viret, F, Becouarn, Y, Bouché, O, Gamelin, E, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2009;(4):674-80
-
-
Free full text
-
Abstract
BACKGROUND This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. PATIENTS AND METHODS A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS). RESULTS Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53% to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively. CONCLUSION Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.