5-fluorouracil (5FU) pharmacokinetic and hormonal status in female colorectal cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13576-13576
Author(s):  
A. Bononi ◽  
M. Gusella ◽  
G. Crepaldi ◽  
R. Padrini ◽  
E. Ferrazzi
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Elderly Women ◽  
Performance Status ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Hormonal Status ◽  
Significant Difference ◽  
Colorectal Cancer Patients

13576 Background: It is well known that females present a significantly reduced clearance of 5FU compared to males treated with the same doses.We tested the hypothesis that it may depend on the hormonal status, so that pre-menopausal women would have different 5FU pharmacokinetics compared with both postmenopausal women and elderly women. Methods: 48 colorectal cancer patients were prospectively studied: all of them were on adjuvant treatment based on 5FU repeated boluses. On the second day of the first cycle peripheral blood was drawn after drug administration. Plasma level were detected by HPLC analysis and pharmacokinetic parameters were calculated trough a one phase exponential decay model. Results: All patients had 100–90 Karnosky Performance status score. 12 were in pre-menopausal phase (age range : 40–55 years); among the others we distinguished a younger 19 people group (age lower than 70 years old) and an elderly 17 patient group (age equal or higher than 70 years old). They received a 5FU mean dose of 406 ± 15 mg/mq, not significantly different among the three groups. After intravenous bolus injection a high interindividual variability of 5-FU pharmacokinetics was detected: AUC0-∞ (area under the curve of drug plasma levels versus time) ranged between 368 and 1236 mg × min/L and the highest values (>1000) were found in two elderly patients, considered fit; anyway there was no significant difference among AUC of the three groups. 5FU total clearance ranged between 0.53 and 1.9 L/min and means were 1.07 ± 0.3, 1.02 ± 0.3 and 0.98 ± 0.3 L/min in pre-menopausal, postmenopausal and elderly women respectively; again 5FU clearance/ BSA (body surface area), half live elimination times and peak concentration plasma levels were not significantly different among the three groups. Conclusions: It seems that sexual hormonal status do not influence 5FU total body elimination capability, and that pharmacokinetic differences between genders should be related to other factors,as for example Body Composition. Funded by AIRC-Veneto No significant financial relationships to disclose.

Relation between irinotecan-induced cholinergic syndrome and prognosis of colorectal cancer patients.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 859-859 ◽  
Author(s):  
Hiroyuki Fujii ◽  
Taizo Hirata ◽  
Takuya Mura ◽  
Yuko Okada ◽  
Hirotaka Tashiro
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Response Rate ◽  
Performance Status ◽  
Surrogate Marker ◽  
Rank Test ◽  
Chemotherapeutic Regimen ◽  
Significant Difference ◽  
Cholinergic Syndrome ◽  
Colorectal Cancer Patients

859 Background: It is well known that a cetuximab induced rash is strongly associated with improved survival of colorectal cancer patients. Irinotecan Induced Cholinergic Syndrome (IICS), manifesting in such events as early diarrhea and diaphoresis, is a notorious adverse effect of irinotecan. In this study, we reveal the relation between IICS and prognosis of colorectal cancer patients and examine the validity of IICS as a surrogate marker for the efficacy of irinotecan. Methods: We retrospectively reviewed data from 52 colorectal cancer patients who were treated with a chemotherapeutic regimen that included irinotecan at Kure Medical Center between 2012 and 2017. First, to assess the relation between adverse events and efficacy of irinotecan, patients who experienced IICS (n = 11) and did not experience IICS (n = 41) were analyzed from the aspect of overall survival (OS), progression-free survival (PFS), sex, age, dose, performance status (PS) and previous chemotherapy (PC). Kaplan-Meier survival curves were drawn for OS and PFS, and compared by means of a log-rank test. Secondly, to determine the response rate of butylscopolamine for IICS, we injected butylscopolamine 20mg into the irinotecan infusion bag and administered both agents through the intravenous line together to 11 patients who experienced IICS. Results: The presence of IICS was associated with a prolonged median OS (589 vs. 280 days, log-rank p = 0.0282; adjusted hazard ratio (HR) 0.27, 95% confidence interval [CI] 0.06-0.79, p = 0.0140), and prolonged median PFS (317 vs. 154 days, log-rank p = 0.1474; adjusted HR 0.56, 95% CI 0.22-1.25, p = 0.1635). There was no statistically significant difference between the two groups in terms of sex, age, dose, PS and PC. Ten patients of 11 patients who were administered butylscopolamine, experienced complete or partial improvement of IICS. The response rate was nearly 90%. Conclusions: The presence of IICS is associated with an improved OS for colorectal cancer patients and tends to have a positive correlation with PFS. IICS is a viable surrogate biomarker of the antitumor efficacy of irinotecan. As a prophylaxis of IICS, mixing butylscopolamine into the irinotecan infusion bag was remarkably effective.

scholarly journals Reduced Plasma Levels of Very-Long-Chain Dicarboxylic Acid 28:4 in Italian and Brazilian Colorectal Cancer Patient Cohorts

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 91 ◽  
Author(s):  
Paul Wood ◽  
Michelle Donohue ◽  
John Cebak ◽  
Taylor Beckmann ◽  
Márcia Messias ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dicarboxylic Acid ◽  
Cancer Patients ◽  
Plasma Levels ◽  
High Resolution Mass Spectrometry ◽  
Sporadic Colorectal Cancer ◽  
Inherited Susceptibility ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients ◽  
Long Chain

Background: There are currently no blood-based biomarkers for early diagnosis of colorectal cancer. Previous research has suggested that very-long-chain dicarboxylic acid (VLCDCA) 28:4 might be such a biomarker. Methods: Using high-resolution mass spectrometry, we analyzed VLCDCA 28:4 in the plasma of colorectal cancer patients in Italian [n = 62] and Brazilian [n = 52] cohorts. Additionally, we investigated individuals diagnosed with familial adenomatous polyposis (FAP; n = 27), one of the most important clinical forms of inherited susceptibility to colorectal cancer. Results: Decrements in plasma levels of VLCDCA 28:4 were monitored in colorectal cancer patients. These decreases were independent of the stage of tumor development and the individual’s age. However, no decrements in VLCDCA 28:4 were monitored in FAP patients. Conclusions: The plasma levels of VLCDCA 28:4 represent a potential biomarker of sporadic colorectal cancer. In addition, it is possible that resupply of this anti-inflammatory lipid may represent a new therapeutic strategy for CRC and inflammatory disorders.

scholarly journals Establishment of prognostic nomogram for elderly colorectal cancer patients: a SEER database analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chaoran Yu ◽  
Yujie Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Area Under The Curve ◽  
Seer Database ◽  
Tumor Node Metastasis ◽  
Database Analysis ◽  
Cancer Specific Survival ◽  
Decision Curve Analysis ◽  
Node Metastasis ◽  
Colorectal Cancer Patients

Abstract Background This study aimed to establish nomogram models of overall survival (OS) and cancer-specific survival (CSS) in elderly colorectal cancer (ECRC) patients (Age ≥ 70). Methods The clinical variables of patients confirmed as ECRC between 2004 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analysis were performed, followed by the construction of nomograms in OS and CSS. Results A total of 44,761 cases were finally included in this study. Both C-index and calibration plots indicated noticeable performance of newly established nomograms. Moreover, nomograms also showed higher outcomes of decision curve analysis (DCA) and the area under the curve (AUC) compared to American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage and SEER stage. Conclusions This study established nomograms of elderly colorectal cancer patients with distinct clinical values compared to AJCC TNM and SEER stages regarding both OS and CSS.

The role of oophorectomy for colon cancer with ovarian metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15113-e15113
Author(s):  
S. Lee ◽  
J. Lee ◽  
H. Ahn ◽  
J. Park ◽  
J. Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Performance Status ◽  
Poor Performance ◽  
Ovarian Metastasis ◽  
Control Group ◽  
Poor Performance Status ◽  
Ovarian Metastases ◽  
Colorectal Cancer Patients

e15113 Background: A recent study demonstrated that colorectal cancer with ovarian metastases were less responsive to chemotherapy compared to extraovarian metastases. Hence, the ovary may actually represent a “sanctuary” for metastatic cells from CRC. The aim of the study was to investigate the impact of oophorectomy on survival of colorectal cancer patients with ovarian metastasis. Methods: Between 1996 and 2008, 83 colorectal cancer patients underwent oophorectomy. For the historical control, 47 colorectal cancer patients without oophorectomy were included in the analysis. Survival and its associated factors were analyzed using Kaplan-Meier method, log-rank test and Cox-regression analysis. Results: The median age was younger (48 years) in the oophorectomy group when compared to the historical control (54 years) (P =.012). The proportion of synchronous metastasis was higher in the oophorectomy than the control group (57% vs 30%, respectively; P=.003). After a median follow-up duration of 60.8 months (range, 7.4 - 169.7 months), the median OS was significantly longer in the oophorectomy group (28.1 vs 21.2 months, oophorectomy vs non-oophoreectomy; P=.038). For ovary-specific survival (date of ovarian metastasis diagnosis to death), colorectal cancer patients with oophorectomy showed significantly favorable survival than the control group (20.8 vs 10.9 months, respectively; P<.001). At univariate analyses, no oophorectomy (P=.038), bilaterality of ovarian metastasis (P=0.032), the presence of extraovarian metastasis (P<0.001), elevated CEA (p<0.001), poor performance status (p=0.001), no palliative chemotherapy(p=0.001), no primary disease resection(p=0.005) were identified as significantly poor prognostic factors for overall survival. The no oophorectomy, no chemotherapy, extraovarian metastasis, elevated CEA, poor performance status retained statistical significance at multivariate level. (p=0.003, p=0.004, p=0.005, p=0.015, p=0.029, respectively). Conclusions: Based on this retrospective analysis, the oophorectomy significantly prolonged survival in colorectal cancer patients with ovarian metastases. A potential role of oophorectomy in the management of colorectal cancer should be prospectively studied. No significant financial relationships to disclose.

KRAS mutation profile in colorectal cancer patients in Brazil: A cohort of 989 individuals

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15017-e15017
Author(s):  
M. G. Zalis ◽  
F. M. Vieira ◽  
I. Zalcberg-Renault ◽  
M. H. Bonamino ◽  
C. G. Ferreira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Genetic Background ◽  
Brazilian Population ◽  
Wild Type ◽  
Asian Populations ◽  
Mutation Profile ◽  
Significant Difference ◽  
Colorectal Cancer Patients

e15017 Background: KRAS mutation is common event in colorectal cancer occurring in around 40% of the patients. It is well- known that patients harboring the KRAS mutation do not derive benefit from cetuximab. However data available KRAS mutation profile is limited to Caucasian and Asian individuals and there is a lack of data in the population from Latin America. Brazilian population has a heterogeneous genetic background and this may have pharmacogenetic implications (Suarez-Kurtz, 2006). Methods: Between July and November 2008, we analyzed 989 consecutive patient samples sent to our laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, exons 1 were amplified by PCR and submitted to automatic sequencing. Codons 12 and 13 were analyzed. Results: The median age was 59 years and 53% of the patients were male and 47% female. The percentage of wild-type and mutated KRAS was 62 and 38%, respectively. Among the 375 mutated cases, 87% were in codon 12 versus 13% in codon 13. Mutation Gly12Asp was the most common being detected in 39% of the mutated cases. Due to the sample size a comparison among patients from different regions of Brazil was possible. However, no significant difference was observed in relation to the type or percentage of patients harboring the KRAS mutation. Interestingly, a significant difference in the percentage of mutated KRAS patients was observed between male and female (41 versus 35%, p= 0.05). Conclusions: The profile of KRAS mutation in the Brazilian population is similar to that reported for Caucasian and Asian populations. This is one of the largest cohorts of KRAS genotyping in colorectal cancer patients ever reported. To the best of our knowledge our data is the first to put forward the issue of a potential difference in the mutation rate according to gender. The observed higher incidence of KRAS-mutation in male than female deserves further investigation. No significant financial relationships to disclose.

The correlation of thrombin-activated fibrinolysis inhibitor (TAFI) levels and clinicopathologic factors in advanced colorectal cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22217-e22217
Author(s):  
T. Salman ◽  
A. Bilici ◽  
B. O. Ustaalioglu ◽  
M. Seker ◽  
B. Sonmez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Large Scale ◽  
Performance Status ◽  
Blood Levels ◽  
Thromboembolic Events ◽  
Fibrinolysis Inhibitor ◽  
Clinicopathologic Factors ◽  
Colorectal Cancer Patients

e22217 Background: There are many ongoing researchs for novel prognostic factors in colorectal cancers. Increased thromboembolic events were associated with poor prognosis and survival in cancer patients. Thrombin-activated fibrinolysis inhibitor (TAFI), which has inhibitory effects on fibrinolysis, was proven to play a major role in hypercoagulopathy and was reported to reach high blood levels in cancer patients compared to those in the general population. Methods: TAFI levels were measured. The correlation between those levels and clinicopathologic features were analyzed in 82 patients with advanced stage colorectal cancer receiving treatment in our clinic. Results: Eighty-two patients were evaluated. Patients characteristics included 54 males (65.9%), 28 females (34.1%); median age 56.4 (range:24–76). The mean TAFI levels was 198,36±70,01 Ğer yazali and TAFI levels were found to be high in 70% of patients. High levels of TAFI were more common in rectum cancer patients compared with colon cancer patients. There was no significant correlation between TAFI levels and clinicopathologic factors, such as age, sex, body mass index, performance status, number of metastases, grade, vascular invasion, perineural invasion and CEA levels. The TAFI levels of patients receiving bevacizumab (202.1±66.6) were more higher than those no receiving (191,83±76,21), but this association was not statistically significant (p>0.05). Conclusions: Although the statistical analysis proved insignificant in our study, the effect of thromboembolic events on prognosis and survival is well established. Thus, large scale prospective studies are required to determine prognostic factors. No significant financial relationships to disclose.

Defining mild, moderate, and severe fatigue in cancer patients and survivors: E2Z02, a trial of the Eastern Cooperative Oncology Group.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9099-9099
Author(s):  
Xin Shelley Wang ◽  
Fengmin Zhao ◽  
Michael Fisch ◽  
Tito R. Mendoza ◽  
Ann M. O'Mara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Survivors ◽  
Cancer Patients ◽  
Rating Scale ◽  
Performance Status ◽  
Fatigue Management ◽  
Severe Fatigue ◽  
Patient Reported ◽  
Fatigue Severity ◽  
Colorectal Cancer Patients

9099 Background: Although mild, moderate and severe categories have been used in clinical guidelines for fatigue management in cancer patients, the optimal cutpoints on a 0-10 scale for delineating these categories have not been replicated. Methods: A multicenter ECOG study (E2Z02) enrolled breast, lung, prostate, or colorectal cancer patients with any treatment status. Fatigue and symptom interference were measured on the 0-10 numerical rating scale of the M. D. Anderson Symptom Inventory (MDASI). The optimal boundaries for categorizing fatigue severity were determined by the largest F ratios from MANOVA (Serlin’s criteria, 1995). Logistic regression with robust standard errors was used to identify risk factors for moderate/severe fatigue for cancer survivors (defined as patients with no evidence of disease and receiving no cancer treatment). Results: The optimal cutpoints that identified 3 distinct levels of fatigue severity for the 2341 patients were: ratings of 1-3 as mild, 4-6 as moderate, and 7-10 as severe. Known-group validity for these cutpoints was established by significant differences of fatigue severity by ECOG performance status and patient-reported quality of life (all P<0.001). Using these cutpoints, 45% (983/2177) of patients undergoing active therapy had moderate/severe fatigue, with significant more mild fatigue in breast and colorectal cancer patients, while more severe fatigue in lung cancer patients (p<.001). Among cancer survivors, 29% (150/515) had moderate/severe fatigue (breast 31%, colorectal 27%, prostate 22%, lung 33%). Younger age (OR=0.97, 95% CI=0.95-0.99) and poor performance status (OR=4.21, 95% CI=2.36-7.51) were associated with more moderate/severe fatigue in cancer survivors. Survivor time was also associated with moderate/severe fatigue in breast and colorectal cancer survivors (>=5yrs vs. <5yrs: OR=0.23, P<0.01 for breast, OR=9.3, P=0.03 for colorectal). Conclusions: This multicenter study confirmed the standard cutpoints for fatigue severity used in NCCN fatigue management guidelines. It also provides a profile of moderate to severe fatigue prevalence for actively treated cancer patients and for cancer survivors.

Multivariate analysis of factors affecting overall survival in minority-based population of young colorectal cancer patients: A single-institution experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14186-e14186
Author(s):  
Shivi Jain ◽  
Kireet Agrawal ◽  
Shinoj Pattali ◽  
Abhijai Singh ◽  
Kamal Agrawal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Family History ◽  
Cancer Patients ◽  
Stage Iv ◽  
Female Ratio ◽  
Stage Iv Colorectal Cancer ◽  
Significant Difference ◽  
Colorectal Cancer Patients

e14186 Background: Overall survival in colorectal cancer is influenced by obesity, age, gender and stage at diagnosis. However, in minority based populations, effect of the above factors on overall survival has not been studied in any detail. Hence, we undertook this retrospective study to evaluate effect of above factors on overall survival in young colorectal cancer patients. Methods: 1,195 subjects with colorectal cancer treated at John H. Stroger Hospital of Cook County between 2000 and 2008 were retrospectively analyzed. 179 subjects with age 50 years and younger were identified. 146 of 179 subjects with available Body Mass Index (BMI) in kg/m2 were included in the study. Effect of BMI, age, sex, race, LDH and CEA levels, stage, site of tumor, smoking and family history on overall survival was evaluated using standard statistical multivariate analysis. Results: In our population, 22 of 146(15%) were underweight (BMI<20), 56 of 146(38.4%) were normal weight (BMI 20-24.9), 46 of 146(31.5%) were overweight (BMI 25-29.9) and 22 of 146(15%) were obese (BMI >30). Male: female ratio was 1.4:1. 75 of 146(51.7%) were African American, 23 of 146(15.9%) were Caucasians. 50 of 146(34.2%) were stage IV colorectal cancer at diagnosis. On univariate analysis, BMI<20(p=0.031, HR 2.1, 95% CI 1.15-3.82), CEA >4ng/ml (p=0.005, HR 1.93, 95% CI 1.21-3.08) and stage IV colorectal cancer (p<0.001, HR 6.1, 95% CI 2.42-15.53) were significantly associated with decreased overall survival. LDH<200 U/L was significantly associated with improved overall survival (p 0.029, HR 0.6, 95% CI 0.391-0.950). On multivariate analysis, stage IV colorectal cancer was a single significant independent predictor of overall survival (p=0.001, 95% CI 2.47-27.78). CEA>4ng/ml was marginally significant for decreased overall survival (p=0.06, 95% CI 0.978-3.015). On the contrary, no statistically significant difference was found on overall survival with age, BMI>20, gender, race, tumor location, smoking and family history. Conclusions: Advanced stage and CEA >4ng/ml are independent prognostic variables for decreased overall survival in minority based population of young colorectal cancer.

Clinical and pathological characteristics of elderly colorectal cancer patients over 70 years old and comparison with patients under 50 years old.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14174-e14174
Author(s):  
Betul Erismis ◽  
Nadire Kucukoztas ◽  
Samed Rahatli ◽  
Selim Yalcin ◽  
Omer Dizdar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Systemic Disease ◽  
Performance Status ◽  
The Elderly ◽  
University Hospital ◽  
Individual Treatment ◽  
Pathological Characteristics ◽  
Colorectal Cancer Patients

e14174 Background: Incidence of colon cancer increases with age and generally is diagnosed at the age of between 60-75. Because of comorbidities in elderly patients who are older 70 years of age, lower doses of adjuvant or metastatic therapy is given them or the other option can be the chemotherapeutics which had less side effects. Methods: We aim to identify clinical and pathological characteristics of elderly colorectal cancer patients over 70 years of age who were followed at Baskent University Hospital and compare with CRC patients under the 50 years of age. Results: 182 CRC patients were assigned to the study who were followed between 1998-2011. We classified the patients into two categories according to the age. 91 participants were over 70 years of age and 91 participants were under 50 years of age. There were no significant differences between two groups for gender and percentage of patients having surgery (p=0.65/0.732). History of having systemic disease was significantly higher in the elderly group (p<0.001). Adjvuvant chemotherapy was given to the 38 (53.5%) patients aged over 70 and 66 (91.7%) patients aged under 50 (p<0.001). We compared the both groups for progression free and overall survival time for all stages. However, there were no statistically significant differences between two groups. Conclusions: Our study confirms that elderly CRC patients get benefit from the adjuvant chemotherapy treatment as the same as patients under 50 years of age. Therefore, physcians should consider about performance status and systemic disease in elderly patients and give an individual treatment to them.

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