Hopp om förbättring av överlevnad i ovarialcancer

Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival

Principles of chemotherapy

n/aFunding Agencies|Roche</p

Principles of chemotherapy

n/aFunding Agencies|Roche</p

Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer

Background: While recent randomised phase III trials show that trifluridine/tiperacil (TAS-102) may prolong life in patients with refractory metastatic colorectal cancer (rmCRC), palliative aspects on its efficacy and tolerability in real world patients need further elucidation. Methods: A retrospective observational multicentre study was designed, including all patients with rmCRC who received TAS-102 under 2016-2019 in the South East Health Care region of Sweden. 48 patients were identified. Primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), time to ECOG performance status deterioration (PSD), safety and dose reductions, admission to and duration of access to palliative care, and administration of TAS-102 in the last 30 days before death. Results: Median OS, PFS, and time to PSD (a proxy for impaired quality of life) from start of TAS-102 were 6.4 months (95% CI: 4.4-8.4), 2.3 months (95% CI: 1.8-2.7) and 2.5 months (95% CI: 1.9-3.2), respectively. Following uni- and multivariable regression analyses, the number of previous treatment lines (&amp;lt;= 2 vs. &amp;gt;= 3) was statistically independent for OS (median 7.8 vs. 5.3 months, P=0.05), PFS (median 2.4 vs. 1.8 months, P=0.03), and time to PSD (median 2.8 vs. 1.8 months, P=0.03). Thirty-four (71%) of the patients received reduced doses. The most common grade 3-4 toxicity was neutropenia (39%). Forty-three (90%) were admitted to GP or hospital-based home palliative care. Median time for access to any form of palliative care before death was 2.3 (95% CI: 0.5-3.2) months. Few patients (n=3, 7%) received their last dose of TAS-102 in their last 30 days of life. Conclusions: The outcome and tolerability of TAS-102 in rmCRC appear similar in a real-world context and randomised trials. The retrospective design and limited sample size preclude firm conclusions on subgroup analyses, but it appears that the prognosis is slightly better the earlier TAS-102 is introduced. Treatment durations are generally short, and early admission to a palliative care provider is recommended.Funding Agencies|ALF grants Region Ostergotland [LIO-697991, LIO-707011, LIO-697461]; CKOC grants Region Ostergotland; Department of Oncology at Ryhov County Hospital, Jonkoping, Sweden</p

Pattern of endocrine treatment for epithelial ovarian cancer in the Southeast medical region of Sweden : a population-based study

Aim of the study: Endocrine treatment (ET) is an alternative as salvage therapy in epithelial ovarian cancer (EOC) but the usage in routine care is unknown. We evaluated the treatment patterns and outcome of patients receiving ET for EOC in the Southeast medical region in Sweden. Method: Patients were identified through the population-based Southeast Quality Registry for gynaecological cancer. Inclusion criteria were: age ≥18 years, histologically verified EOC diagnosed 2000–2013, ET for ≥4 weeks. Coverage compared with the Swedish National Cancer Registry was 100%. Data extracted from medical records was collected by means of a study-specific Case Report Form. Last date of follow-up was February 1st, 2018. All statistics were descriptive. Results: Altogether 248 (18%) of 1414 patients were treated with ET. Most (49%) had received only one, and 34% two previous lines of chemotherapy. Time from last chemotherapy to ET was 4 months, range 0–55months. The reason for initiating ET was tumor progression (66%), chemotherapy related toxicity (29%) and maintenance (4%). Tamoxifen was prescribed in 94% of cases. Best response was partial (< 5%) and stable disease (50%). No patient had a complete response. 194 (78%) patients received subsequent chemotherapy, of these 27% had 3–7 lines of chemotherapy. Duration of ET was a median 4 months (range 1–80 months). Median time from ET to subsequent chemotherapy was 5 months (range 0–79). The median overall survival was 45 months (range 9–173). Conclusion: In the Southeast region of Sweden, endocrine treatment for EOC was prescribed inconsistently and in various settings, usually initiated by a rising CA-125 level. Poorer documentation and irregular tumor response assessment were observed for endocrine treatment compared to chemotherapy

Impact of CYP3A5(*)3 and CYP2C8-HapC on Paclitaxel/Carboplatin-Induced Myelosuppression in Patients with Ovarian Cancer

The influence of genetic variants on paclitaxel-induced toxicity is of considerable interest for reducing adverse drug reactions. Recently, the genetic variants CYP2C8(*)3, CYP2C8-HapC, and CYP3A5(*)3 were associated with paclitaxel-induced neurotoxicity. We, therefore, investigated the impact of CYP2C8-HapC and CYP3A5(*)3 on paclitaxel/carboplatin-induced myelosuppression and neurotoxicity. Thirty-three patients from a prospective pharmacokinetics study were genotyped using pyrosequencing. Patients with variant alleles of CYP2C8-HapC were found to have significantly lower nadir values of both leukocytes and neutrophils (p andlt; 0.05) than patients with the wild-type genotype. CYP3A5(*)3/(*)1 patients were shown to have borderline, significantly lower nadir values of leukocytes (p = 0.07) than (*)3/(*)3 patients. Combining the two genotypes resulted in a significant correlation with both leukopenia and neutropenia (p = 0.01). No effect of these genetic variants on neurotoxicity could be shown in this rather small study, but their importance for paclitaxel-induced toxicity could be confirmed.Funding Agencies|Swedish Cancer Society||Swedish Research Council||European Commission|CHEMORES LSHC-CT-2007-037665|Ostergotland County Council||</p

Impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors : a population-based cross-sectional study

Background We explored the impact of persistent sensory and motor taxane-induced peripheral neuropathy (TIPN) symptoms on health-related quality of life (HRQL) among early-stage breast cancer survivors (ESBCS). Methods A population-based cohort of 884 residual-free ESBCS received a postal questionnaire, including the EORTC chemotherapy-induced PN (CIPN20) and the EORTC QLQ-C30 instruments. Mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated and adjusted for confounding factors (age, lifestyle factors, co-morbidities; linear regression analyses). Interpretation of QLQ-C30 results were based on guidelines. Results Response rate was 79%, and 646 survivors were included in the analysis. In median, 3.6 (1.5-7.3) years had elapsed post-taxane treatment. All TIPN symptoms had a significant impact on global QoL, which worsened with increased severity of TIPN. Between 29.5% and 93.3% of ESBCS with moderate-severe TIPN reported a clinical important impairment of functioning and personal finances, 64.3-85.7% reporting "difficulty walking because of foot drop," and 53.1-81.3% reporting "problems standing/walking because of difficulty feeling ground under feet" had impaired functioning/finances. The difference in mean scores between affected and non-affected survivors was highest for "numbness in toes/feet" and "difficulty walking because of foot drop." Moderate-severe "difficulty climbing stairs or getting out of chair because of weakness of legs" and "problems standing/walking because of difficulty feeling ground under feet" were associated with the largest clinically important differences on all scales. Conclusion Persistent sensory and motor TIPN is associated with clinically relevant impairment of global QoL, functioning, and personal finances among ESBCS, which increased with level of TIPN severity.Funding Agencies|Linkoping University; Swedish Cancer Society [190224]; Medical Research Council of Southeast Sweden [FORSS-932359]; FuturumThe Academy for Health and Care, Jonkoping County Council [575361]; Forsknings-ALF [LIO-901261]</p

Patterns of recurrence and survival in vulvar cancer : A nationwide population-based study

Objective. To examine the patterns of recurrence and how these patterns are associated with survival in vulvar squamous cell carcinoma. We also explored the survival impact of surgical groin staging (SGS). Methods. Nationwide population-based study including women diagnosed with vulvar squamous cell carcinoma between 2012 and 2015 and registered in the Swedish Quality Registry for Gynecologic Cancer. Cumulative incidence rates (CIR), recurrence-free (RFS) and overall survival (OS) were calculated by Kaplan Meier estimates. The impact of SGS on RFS and OS was analyzed by proportional hazards models. Results. 489 eligible women were included. Median follow-up time was 64 months. The overall recurrence rate was 22.3%. Site of recurrence: local in 61.0%, groin in 30.0%, distant in 9.0%. The CIR for local recurrences increased with time (5.9% at 2-years, 14.7% at 5-years) while the rate of groin and distant recurrences was nearly steady (5.5% to 6.3% and 1.5% to 1.7%, respectively). Median 2-year and 4-year OS post-recurrence was 57.8% and 37.4% for local, 17.2%, 10.3% for groin and 0% for distant recurrences, respectively. SGS was omitted in 23.7% of surgically treated women with FIGO stages IB-II and significantly associated with worse RFS (Hazard ratio, HR, 1.9; 95%CI, 1.0-3.5; p = 0.04) and OS (HR 2.0; 95%CI, 1.1-3.8; p = 0.04) after adjustment for age, FIGO stage, tumor size, resection margins and performance status. Conclusion. The cumulative incidence of isolated vulvar recurrence was low but for those affected the prognosis was poor. Surgical groin staging is a crucial part of primary treatment and should not be omitted. (c) 2021 Published by Elsevier Inc.Funding Agencies|Swedish Society for Gynecologic Cancer</p

Real World Evidence on Second-Line Palliative Chemotherapy in Advanced Pancreatic Cancer

Background: The outcome and tolerability of palliative second line chemotherapy for advanced pancreatic cancer (APC) in real life patients are largely unknown. Prognostic parameters for risk stratification and treatment guidance are lacking. Materials and Methods: A population based multicenter retrospective cohort study was conducted, covering all APC patients who received palliative second-line chemotherapy between 2011 and 2018 at any cancer center in the South East Region of Sweden. Primary outcome was overall survival after second-line therapy (OS2). Time to treatment failure after second-line therapy (TTF2), hematological toxicity, and unplanned hospitalizations were key secondary outcomes. A number of baseline potentially prognostic parameters were assessed. Results: A total of 509 patients received first-line palliative chemotherapy, and of these 167 (33%) received at least one dose of second-line therapy and formed the final study population. Median OS2 was 5.2 months (95% CI = 4.7–5.7) and median TTF2 was 1.9 months (1.5–2.2). OS2 and TTF2 were similar regardless regimen, including comparison of the two most common regimens (fluoropyrimidine monotherapy vs. fluoropyrimidine/oxaliplatin doublet). Multivariate analysis revealed that normal plasma albumin (≥35) and serum CA-19-9 above median (&gt;1,550) were independent predictors for OS2 (HR = 0.21, p &lt; 0.001 and HR = 2.03, p = 0.009) and TTF2 (HR = 0.22, p &lt; 0.001 and HR = 2.03, p = 0.01), while ECOG performance status &gt;1 was predictive for TTF2 (HR = 2.05, p = 0.032). Grade 3–4 hematological toxicity was registered in 17 patients (10%). 50 (30%) had at least one event of hospitalization. Conclusion: The real world outcome of second line palliative chemotherapy for refractory APC remains dismal. Baseline plasma albumin, serum CA-19-9, and performance status emerge as key prognostic factors, and should be further studied as tools for individualized treatment decisions.Funding Agencies|Futurum, Academy for Health and Care Jonkoping County Council [695491]; Medical Research Council of Southeast Sweden [FORSS-751541]; ALF grants Region Ostergotland [LIO-697991, LIO-707011, LIO-697461]; Sveriges Gastro-Onkologiska Forening (GOF); CKOC grants Region Ostergotland</p

Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer

The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty-eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performed in vivo with quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activity in vivo affected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.This is the authors’ version of the following article: Henrik Green, Peter Söderkvist, Per Rosenberg, Rajaa A Mirghani, Per Rymark, Elisabeth Avall Lundqvist and Curt Peterson, Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer, 2009, Basic and clinical pharmacology and toxicology, (104), 2, 130-137. which has been published in final form at: http://dx.doi.org/10.1111/j.1742-7843.2008.00351.x Copyright: Blackwell Publishing http://eu.wiley.com/WileyCDA/Brand/id-35.html</p