A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer

2005 ◽  
Vol 15 (8) ◽  
pp. 535-546 ◽  
Author(s):  
Stefano Landi ◽  
Federica Gemignani ◽  
Victor Moreno ◽  
Lydie Gioia-Patricola ◽  
Amélie Chabrier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Gene Polymorphisms ◽  
Comprehensive Analysis ◽  
Phase Ii Metabolism ◽  
Metabolism Gene

scholarly journals A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers

2008 ◽  
Vol 29 (6) ◽  
pp. 1164-1169 ◽  
Author(s):  
Shanbeh Zienolddiny ◽  
Daniele Campa ◽  
Helge Lind ◽  
David Ryberg ◽  
Vidar Skaug ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Gene Polymorphisms ◽  
Comprehensive Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Phase Ii Metabolism ◽  
Metabolism Gene

scholarly journals Metabolism of anabolic androgenic steroids

1996 ◽  
Vol 42 (7) ◽  
pp. 1001-1020 ◽  
Author(s):  
W Schänzer
Keyword(s):  
Phase I ◽  
Physical Performance ◽  
Phase Ii ◽  
Anabolic Androgenic Steroids ◽  
Phase Ii Metabolism ◽  
Steroid Molecule ◽  
High Extent ◽  
As Doping ◽  
General Metabolism ◽  
Androgenic Steroids

Abstract Anabolic androgenic steroids (AAS) are misused to a high extent in sports by athletes to improve their physical performance. Sports federations consider the use of these drugs in sports as doping. The misuse of AAS is controlled by detection of the parent AAS (when excreted into urine) and (or) their metabolites in urine of athletes. I present a review of the metabolism of AAS. Testosterone is the principal androgenic steroid and its metabolism is compared with that of AAS. The review is divided into two parts: the general metabolism of AAS, which is separated into phase I and phase II metabolism and includes a systematic discussion of metabolic changes in the steroid molecule according to the regions (A-D rings), and the specific metabolism of AAS, which presents the metabolism of 26 AAS in humans.

Sex hormone-mediated effects on the phase I and phase II metabolism of N-2-fluorenylacetamide

1989 ◽  
Vol 38 (7) ◽  
pp. 1075-1082 ◽  
Author(s):  
Danuta Malejka-Glganti ◽  
Welsonia J. Magat ◽  
Richard W. Decker
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Sex Hormone ◽  
Phase Ii Metabolism ◽  
Mediated Effects

The African hedgehog ( Atelerix albiventris ): Low phase I and phase II metabolism activities

2016 ◽  
Vol 190 ◽  
pp. 38-47 ◽  
Author(s):  
Aksorn Saengtienchai ◽  
Yoshinori Ikenaka ◽  
Nesta Bortey-Sam ◽  
Usuma Jermnark ◽  
Hazuki Mizukawa ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase Ii Metabolism

Phase I/II study of irinotecan, UFT, and leucovorin with hepatic arterial infusion in colorectal cancer patients with unresectable liver metastases: Preliminary results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14549-14549
Author(s):  
T. Yamaguchi ◽  
H. Matsumoto ◽  
K. Takahashi ◽  
M. Yasutome ◽  
T. Mori
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Liver Metastases ◽  
Phase Ii ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Hepatic Arterial Infusion ◽  
Arterial Infusion ◽  
Unresectable Liver Metastases ◽  
Colorectal Cancer Patients

14549 Background: To determine the maximum-tolerated dose (MTD) and to evaluate the efficacy and tolerability of combination chemotherapy of irinotecan (CPT-11), UFT and leucovorin (LV) with hepatic arterial infusion (HAI) in colorectal cancer patients with unresectable liver metastases. Methods: Patients who had unresectable liver metastases from colorectal cancer were treated concurrently with intravenous CPT-11 on day1 of each 14-day treatment cycle with dose escalation, with orally UFT and LV on day 1–7 of each cycle, and with HAI of 5-FU on day 8–14 of each cycle. The primary objective of this phase I study was to determine the MTD of biweekly intravenous CPT-11 and UFT/LV with HAI of 5-FU. In the phase II study, the primary endpoint was to determine the response rate. Results: In the phase I study, the recommended dose of CPT-11 for phase II study was 140 mg/m2 combined with UFT 300 mg/m2/day, LV 75 mg/body/day and 5-FU 2,000 mg/body/week. Sixteen patients were enrolled onto the phase II study. The six patients treated at the recommended dose during the phase I study also included in the phase II analysis (n = 22). Median number of liver metastases was 12 (range, 3 to 35). Median size of maximum diameter was 6.3 cm (range, 2.0 to 12.0 cm). The most common adverse event was neutropenia. The complete and partial response rate totaled 81.8%. Median survival time has not been reached yet. Eleven patients (50.0%) were ultimately able to undergo liver resection. Conclusions: The combination chemotherapy of CPT-11 and UFT/LV with HAI was safe, well tolerate and effective in current population of the patients with unresectable liver metastases from colorectal cancer. Updated toxicity and response data will be available in the spring of 2007. No significant financial relationships to disclose.

A phase I/II study of combination therapy of S-1 and irinotecan in patients with previously untreated metastatic or recurrent colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15023-e15023
Author(s):  
Y. Choi ◽  
T. Kim ◽  
S. Lee ◽  
J. Lee ◽  
H. Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Maximum Tolerated Dose ◽  
Recurrent Colorectal Cancer ◽  
Time To Progression ◽  
Level I ◽  
Grade 3 ◽  
Experienced Grade

e15023 Background: To investigate S-1 and irinotecan (CPT-11) combination as an alternative to infusional 5- fluorouracil/leucovorin plus CPT-11, we performed a phase I/II trial to determine maximum tolerated dose (MTD), efficacy and toxicity in metastatic or recurrent colorectal cancer. In addition, we evaluated the association between genotypes of candidate genes and phenotypes. Methods: S-1 was administered orally at a dose of 70 mg/m2 (level I-III) or 80 (IV and V) from day 1 to 14. CPT-11 was given i.v. on day 1, stepping up to 175 (level I), 200 (II), 225 (III and IV) or 250 (V) mg/m2 . The treatment was repeated every 3 weeks. The association of the UGT1A1 genotypes (*6, *28, and *60) and CYP2A6 genotypes (*4, *7, and *9) with toxicities or efficacy were analyzed in patients who participated in phase II portion. Results: Twenty-three patients entered the phase I and 30 enrolled in phase II study. The MTD of S-1 and CPT-11 was considered to be 80 mg/m2 and 250 mg/m2, respectively. The dose-limiting toxicities (DLTs) were diarrhea and neutropenia. The recommended dose (RD) was determined at a S-1 dose of 80 mg/m2 and a CPT- 11 dose of 225 mg/m2. The overall response rate was 66.7% (95% CI, 48.7–84.6) at the RD level. Median time to progression was 7.6 months (95 % CI, 5.7–9.5). Median survival time was not reached. Grade3–4 neutropenia was observed in 53.4% of the patients. Grade 3–4 nonhematologic toxicities were diarrhea (16.7%) and asthenia (6.7%). The frequencies of UGT1A1*60, *28, and *6 allele were 25.8%, 10.3%, and 15.5%, respectively. Homozygous for *28 or *6 were not observed. All three double heterozygous for *28 and *6 experienced grade 3–4 neutropenia. The allele frequencies of CYP2A6*4, *7, and *9 were 15.5%, 8.6%, and 29.3%, respectively. There were no association between CYP2A6 genotypes and response rates or toxicities. Conclusions: The combination of S-1 and CPT-11 was effective and had manageable toxicities in patients with metastatic or recurrent colorectal cancer. [Table: see text] No significant financial relationships to disclose.

A phase I/II study of biweekly XELIRI plus bevacizumab for patients with metastatic colorectal cancer as second-line chemotherapy (BIXER study): Reports of phase I part and interim analysis of phase II part.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 643-643
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Nobuyuki Mizunuma ◽  
Kiyohiko Hatake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Phase I ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Japanese Patients ◽  
Recommended Dose ◽  
Grade 3 ◽  
Dose Limiting Toxicity

643 Background: Capecitabine is an oral fluoropyrimidine prodrug, which is converted to fluorouracil (5-FU) predominantly in the tumor cells. In Japan, capecitabine is mainly used in combination with oxaliplatin (XELOX) in treatment for metastatic colorectal cancer (mCRC) since its approval in 2009. The results of capecitabine plus Irinotecan (CPT) (XELIRI) with or without bevacizumab (BV) in EU or US patients were previously reported, but not in Japanese. Thus, we conducted this study to assess the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC. Methods: Patients with prior chemotherapy including oxaliplatin and BV for mCRC, wild or hetero type of UGT1A1 *6*28 were eligible for this study. This was a phase I study composed of two steps, and dose limiting toxicity (DLT) was assessed during the first treatment cycle. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous CPT 180 mg/m2 on day 1, and BV 5mg/kg on day 1 every two weeks. To evaluate the initial safety, 3-6 patients received XELIRI+BV (CPT 150mg/m2) in step 1, and 6 patients received XELIRI+BV (CPT 180mg/m2) in step 2. If DLT occurred in 1 patient in step1, 3 patients would be newly added to step 1, and if in none of 3 or 1-2 of 6 patients, the step 2 would be started. If DLT occurred in less than or equal to 2 of 6 patients in step 2, phase II study would be proceeded, and if In more than 2 of 6 patients, phase II would be conducted at the recommended dose of step 1. Results: In step 1 and 2 of phase I, initial safety of 9 patients was confirmed without occurrence of DLT. Adverse events observed in step 1 and 2 were: neutropenia in 2 and 1; anorexia in 1 and 1; diarrhea in 1 and 1; stomatitis in 1 and 1; alanine or aspartate aminotransferase increased in 1 and 3, respectively. There was no grade 3 or greater adverse events. Conclusions: In mCRC patients with wild or hetero of UGT1A1*6*28 genotype, safety of biweekly XELIRI+BV was confirmed and recommended dose of CPT-11 was determined as 180mg/m2. Interim analysis of safety of phase II part will be reported at the meeting.

Colorectal cancer: Improving screening in rural clinic.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19215-e19215
Author(s):  
Thuy Thanh Thi Le ◽  
Lorraine Fleckenstein ◽  
Zhaozhi Jiang ◽  
Shellian Davis ◽  
Lakshmi Yarlagadda
Keyword(s):  
Colorectal Cancer ◽  
Mortality Rate ◽  
Phase I ◽  
Phase Ii ◽  
Late Stage ◽  
Chart Review ◽  
Flexible Sigmoidoscopy ◽  
Study Patient ◽  
Screening Rate ◽  
Robeson County

e19215 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. From 2010 to 2014, CRC was also the second leading cause of cancer deaths in North Carolina (NC). Between 2012-2016, the age adjusted mortality rate was 18-25 per 100,000 persons in Robeson County, NC. During this timeframe, it is estimated that if all people aged 50 and older in NC were routinely screened, 40 out of 100 deaths from late stage CRC can be prevented. A chart review in a rural primary care clinic identified patients not being appropriately screened for targeted intervention. Methods: Retrospective chart review at Lumberton Medical Clinic, a rural outpatient Internal Medicine Clinic, reviewed 1622 records from adults 50-75 years old during the timeframe September 2017 - August 2018 for phase I and 1588 records from September 2018-August 2019 for phase II. Patients with history of CRC or status-post colectomy for other reasons were excluded from this study. Patient records were assessed for compliance with USPTF CRC screening guidelines – adults aged 50 to 75 years receive screening as follows: 1) Fecal occult blood testing (FOBT) annually 2) Flexible sigmoidoscopy every 5 years 3) Colonoscopy every 10 years OR 4) Combined FOBT (every 3 years) + flexible sigmoidoscopy (every 5 years). Following data analysis in phase I, interventions to increase screening rates were initiated – provider education, posters hung in exam rooms, and individualized letters mailed to patients found deficient. The success of this effort was measured in phase II. Results: For phase I, the review showed 56% of patients received appropriate screening and 44% were found with no documentation of screening. Following interventions, 76% received appropriate screening and 24% with no documentation. Thus, there is ~35% improvement in screening rate. Conclusions: The mortality rate from CRC is higher in Robeson County compared to the NC state rate. Additionally, 40% of deaths from late-stage CRC may be prevented by doing a routine screening. It is the responsibility of providers to emphasize the importance of proper screening. This retrospective review showed ~ 35% improvement in screening rates following interventions. The result might not be as high as expected due to several factors: 1) new resident physicians and faculty 2) few posters were taking down due to disagreement with the guidelines by one of the 3 main providers 3) patients might not receive the letters. To further increase the screening rate, we are implementing the “Preventive Maintenance” tab in our electronic medical record system at the end of clinic visits.

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