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- Goey, Kaitlyn K. H., et al.
(författare)
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Reporting of patient characteristics and stratification factors in phase 3 trials investigating first-line systemic treatment of metastatic colorectal cancer : A systematic review
- 2018
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 96, s. 115-124
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Forskningsöversikt (refereegranskat)abstract
- Background: Patient characteristics and stratification factors are important factors influencing trial outcomes. Uniform reporting on these parameters would facilitate cross-study comparisons and extrapolation of trial results to clinical practice. In 2007, standardisation on patient characteristics reporting and stratification in metastatic colorectal cancer (mCRC) trials was proposed. We investigated the reporting of prognostic factors and implementation of this proposal in mCRC trials published from 2005 to 2016.Methods: We searched PubMed and Embase (January 2005 – June 2016) for first-line phase 3 mCRC trials. Patient characteristics reporting and use of stratification factors were extracted and analysed for adherence to the proposal from 2007.Results: Sixty-seven trials (35,315 patients) were identified, reporting 48 different patient characteristics (median: 9 [range: 5–18] per study). Age, gender, performance status (PS), primary tumour site and adjuvant chemotherapy were frequently reported (87%–100%), in contrast to laboratory values, such as alkaline phosphatase, lactate dehydrogenase and white blood cell count (10%–25%). We identified 29 different stratification factors (median: 3 [range: 1–9] per study). The most common strata were PS and treatment centre (>60%). A median of 8/12 (range: 4–11) of the proposed parameters was reported. Although the percentage of studies reporting each factor slightly increased over time, there was no significant correlation between publication year and adherence to the proposal from 2007.Conclusions: We observed persistent heterogeneity in the reporting of patient characteristics and use of stratification factors in first-line mCRC trials. The proposal from 2007 has not led to increased uniformity of patient characteristics reporting and use of stratification over time. There is an urgent need to address this issue to improve the interpretation of trial results.
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- Pfeiffer, P, et al.
(författare)
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Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil
- 2006
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 17:2, s. 252-258
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Tidskriftsartikel (refereegranskat)abstract
- Background: The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended. Patients and methods: For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied. Results: From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/ vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results. Conclusion: XELOX30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules. © 2005 European Society for Medical Oncology.
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- Glimelius, Bengt, et al.
(författare)
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Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer
- 2011
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Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 11:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- Irinotecan and 5-fluorouracil (5-FU) are used to treat metastatic colorectal cancer. Irinotecan's active metabolite is inactivated by UDP-glucuronosyltransferase 1A1 (UGT1A1), which is deficient in Gilbert's syndrome. Irinotecan and metabolites are transported by P-glycoprotein, encoded by ABCB1. 5-FU targets folate metabolism through inhibition of thymidylate synthase (TYMS). Methylenetetrahydrofolate reductase (MTHFR) generates active folate necessary for haematopoiesis. We retrospectively genotyped 140 Swedish and Norwegian irinotecan and 5-FU-treated colorectal cancer patients from the Nordic VI clinical trial for selected variants of UGT1A1, ABCB1, TYMS and MTHFR. We found an increased risk of clinically relevant early toxicity in patients carrying the ABCB1 3435 T/T genotype, Odds ratio (OR)=3.79 (95% confidence interval (CI)=1.09-13.2), and in patients carrying the UGT1A1(*)28/(*)28 genotype, OR=4.43 (95% CI=1.30-15.2). Patients with UGT1A1(*)28/(*)28 had an especially high risk of neutropenia, OR=6.87 (95% CI=1.70-27.7). Patients who had reacted with toxicity during the first two cycles were in total treated with fewer cycles (P<0.001), and less often responded to treatment (P<0.001). Genetic variation in ABCB1 was associated with both early toxicity and lower response to treatment. Carriers of the ABCB1 1236T-2677T-3435T haplotype responded to treatment less frequently (43 vs 67%, P=0.027), and survived shorter time, OR=1.56 (95% CI=1.01-2.45).
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- van Lier, LI, et al.
(författare)
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Predictors of Societal Costs of Older Care-Dependent Adults Living in the Community in 11 European Countries
- 2019
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Ingår i: Health services insights. - : SAGE Publications. - 1178-6329. ; 12, s. 1178632918820947-
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to identify predictors of societal costs covering formal and informal care utilization by older home care clients in 11 European countries. Methods: Societal costs of 1907 older clients receiving home care for 12 months from the Aged in Home care (AdHoc) study were estimated using the InterRAI Minimum Data Set for Home Care’s (MDS-HC) resource use items. Predictors (medical, functional, and psychosocial domains) of societal costs were identified by performing univariate and multivariate generalized linear model analyses. Results: Mean societal costs per participant were €36 442, ranging from €14 865 in Denmark to €78 836 in the United Kingdom. In the final multivariate model, country, being married, activities of daily living (ADL) dependency, cognitive impairment, limitations of going out, oral conditions, number of medications, arthritis, and cerebro vascular accident (CVA) were significantly associated with societal costs. Conclusions: Of the predictors, ADL dependency and limitations of going out may be modifiable. Developing interventions targeted at improving these conditions may create opportunities to curtail societal costs.
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