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- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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- Kjersem, J B, et al.
(författare)
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AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin.
- 2016
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Ingår i: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 16:3, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54.
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- Bahadoer, Renu R., et al.
(författare)
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One-year excess mortality and treatment in surgically treated patients with colorectal cancer : A EURECCA European comparison
- 2021
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 47:7, s. 1651-1660
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mortality in the first postoperative year represents an accurate reflection of the perioperative risk after colorectal cancer surgery. This research compares one-year mortality after surgery divided into three age-categories (18-64, 65-74, ≥75 years), focusing on time trends and comparing treatment strategies.Material: Population-based data of all patients diagnosed and treated surgically for stage I-III primary colorectal cancer from 2007 to 2016, were collected from Belgium, the Netherlands, Norway, and Sweden. Stratified for age-category and stage, treatment was evaluated, and 30-day, one-year and one-year excess mortality were calculated for colon and rectal cancer separately. Results were evaluated over two-year time periods.Results: Data of 206,024 patients were analysed. Postoperative 30-day and one-year mortality reduced significantly over time in all countries and age-categories. Within the oldest age category, in 2015–2016, one-year excess mortality varied from 9% in Belgium to 4% in Sweden for colon cancer and, from 9% in Belgium to 3% in the other countries for rectal cancer. With increasing age, patients were less likely to receive additional therapy besides surgery. In Belgium, colon cancer patients were more often treated with adjuvant chemotherapy (p < 0.001). For neoadjuvant treatment of rectal cancer, patients in Belgium and Norway were mostly treated with chemoradiotherapy. In the Netherlands and Sweden, radiotherapy alone was preferred (p < 0.001).Conclusions: Despite improvement over time in all countries and age-categories, substantial variation exists in one-year postoperative mortality. Differences in one-year excess postoperative mortality could be due to differences in treatment strategies, highlighting the consequences of under- and over-treatment on cancer survival.
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- Bahadoer, Renu R., et al.
(författare)
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The survival gap between young and older patients after surgical resection for colorectal cancer remains largely based on early mortality : A EURECCA comparison of four European countries
- 2022
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Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 13:6, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- Background: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements - especially in perioperative care - have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries.Methods: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (<65, 65–75, ≥75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated.Results: Data of 206,024 patients were analyzed. In general, compared to patients <65 years, patients ≥75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3–2.8] and RER rectal cancer 2.6 [95% CI 2.3–2.9]). After surviving the first year, CS was mostly not statistically different between patients <65 years and patients ≥75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients ≥75 years with stage III colon or rectal cancer (except for rectal cancer in Norway).Conclusions: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year.
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- Carlsson, Göran, 1951, et al.
(författare)
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A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer
- 2022
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: 5-fluorouracil (5-FU) combined with a folate remains an essential treatment component for metastatic colorectal cancer (mCRC). Leucovorin is the folate most often used, but requires intracellular conversion to a reduced folate, and has high pharmacokinetic variability and limited bioavailability in patients with low folate pathway gene expression. Arfolitixorin is an immediately active form of folate, [6R]-5,10-methylenetetrahydrofolate ([6R]-MTHF), and may improve outcomes.Patients and methods: This open-label, multicenter, phase I/II study in patients with mCRC (NCT02244632) assessed the tolerability and efficacy of first-or second-line arfolitixorin (30, 60, 120, or 240 mg/m2 intravenous) with 5-FU alone, or in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan, every 14 days. Safety, efficacy, and pharmacokinetics were assessed before and after four cycles (8 weeks) of treatment.Results: In 105 treated patients, investigators reported 583 adverse events (AEs) in 86 patients (81.9%), and 256 AEs (43.9%) were potentially related to arfolitixorin and 5-FU. Dose adjustments were required in 16 patients (15.2%). At 8 weeks, 9 out of 57 patients assessed for efficacy achieved an objective response (15.8%), and all 9 achieved a partial response. Six of these nine patients had received arfolitixorin as a first-line treatment. A further 33 patients (57.9%) achieved stable disease. Pharmacokinetics were assessed in 35 patients. The average tmax was 10 min, and area under the plasma concentrationetime curve from time 0 to 1 h increased linearly between 30 and 240 mg/m2. No accumulation was observed for [6R]-MTHF following repeated administration, and there were no major pharmacokinetic differences between cycle 1 and cycle 4 at any dose.Conclusions: Arfolitixorin is a well-tolerated moderator of 5-FU activity. It is suitable for further investigation in mCRC and has the potential to improve treatment outcomes in patients with low folate pathway gene expression. Arfolitixorin can easily be incorporated into current standard of care, requiring minimal changes to chemotherapy regimens.
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