Evaluation of the role of UGT1A1 genotype testing in colorectal cancer patients administered irinotecan and the occurence of grade 3 and 4 neutropenia.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 412-412 ◽  
Author(s):  
Sushma M. Patel ◽  
Jim Chan ◽  
Rita L. Hui ◽  
Michele M. Spence
Keyword(s):  
Colorectal Cancer ◽  
Cohort Analysis ◽  
Median Number ◽  
Rank Test ◽  
P Value ◽  
Wild Type ◽  
Kaiser Permanente ◽  
Adjusted Risk ◽  
Increased Risk ◽  
Grade 3

412 Background: Irinotecan is metabolized primarily in the liver by the carboxylesterase enzyme to the SN-38 active metabolite and is then inactivated through conjugation by the UGT1A1 enzyme, a polymorphic enzyme. Individuals genotyped with the homozygous allele have an increased risk for grade 3 and 4 neutropenia. Methods: A retrospective cohort analysis was conducted in the Kaiser Permanente California regions. The study period was November 1, 2005 to July 1, 2010 and included patients that were 18 years of age or older, newly initiated on irinotecan for colorectal cancer and had no previous irinotecan therapy within six months of the initiation dose. Patients were excluded if they were enrolled in clinical trials, on granulocyte-colony stimulating factor prophylaxis, and genotype tested for UGT1A1 and subsequently not treated with irinotecan. Patients tested with the UGT1A1 assay were grouped according to their genotype results: wild-type, heterozygous, or homozygous*28. The incidence of grade 3 and 4 neutropenia were compared among patients tested for UGT1A1 variant alleles by their genotype results. Results: A total of 305 (28%) patients were tested with the UGT1A1 assay with a mean age of 62 (+/- 12) years, and 52% of the population female. There were 161 (53%) wild-type, 123 (40%) heterozygous, and 21 (7%) homozygous patients. The median irinotecan dose was 150 mg/m2 (124-180 mg/m2) and median number of irinotecan cycles were 6 (3-12). The wild-type, heterozygous, homozygous*28 population had a 21% (33/161), 24% (29/123), and 48% (10/21) rate of grade 3 and 4 neutropenia. When the homozygous*28 group was compared to the heterozygous and wild-type genotype the adjusted Cox Proportional Hazard was 3.05 (95% CI, 1.55-5.99), p = 0.001. The Kaplan-Meier Log Rank Test yielded a p-value of 0.002. Conclusions: The adjusted risk for homozygous genotyped patients was three times higher compared to the wild-type and heterozygous group for grade 3 and 4 neutropenia. Additional investigational studies examining the benefits of UGT1A1 genotyping as a prognostic test and further effect of dosage adjustments in UGT1A1*28 homozygous initiated on irinotecan therapy are needed.

Phase II study of panitumumab monotherapy in chemotherapy-naïve frail or elderly patients with unresectable, RAS wild-type colorectal cancer: OGSG 1602.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 106-106 ◽  
Author(s):  
Katsuya Ohta ◽  
Takeshi Kato ◽  
Masahiro Goto ◽  
Tetsuji Terazawa ◽  
Shingo Noura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Alternative Hypothesis ◽  
Performance Status ◽  
Single Agent ◽  
P Value ◽  
Intensive Chemotherapy ◽  
Wild Type ◽  
Grade 3

106 Background: Single agent of panitumumab (Pmab) is expected to be well tolerated and to improve survival in first-line setting in patients (pts) who are not eligible for intensive chemotherapy, although the efficacy and safety of Pmab for chemotherapy-naïve frail or elderly Japanese pts with wild-type (wt) RAS unresectable colorectal cancer (CRC) have not been yet studied. Methods: We conducted a multi-center phase II study. Pts aged over 76 years, or over 65 who were considered unsuitable for intensive chemotherapy. Pmab 6 mg/kg was administered intravenously every 2 weeks. The primary endpoint was disease control rate (DCR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and the incidence of grade 3 or 4 toxicities. Sample size was set to 36 with exact p-value of 0.05, a power of 0.90, the null of hypothesis of 45% and alternative hypothesis of 70% based on the Clopper-Pearson method. Results: A total 36 pts were enrolled in February 2017 to August 2018. Two pts were excluded; one was a lack of image examination at baseline, and the other was a lack of measurable lesion. The median age was 81 (67-88), with 29 pts (85%) being aged over 76 years. There were 33 (92%) pts with performance status (PS) 0/1, while two (6%) and one (3%) pts were PS 2/3, respectively. Twenty-eight pts (78%) had left-sided CRC, while eight pts had right-sided CRC. The RR was 50.0% (95%CI, 32.4-67.6) including three cases (8.8%) of complete response, and SD was 26.5%, yielding 76.5% of DCR (p < 0.001, 90% confidence interval [CI], 61.5-87.7). The RR with left sided tumor was 65% (95%CI, 44.3-82.8), while that pts with right-sided tumor was 0% (95%CI, 0.0-36.9)(p = 0.003). The major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 17%), hypomagnesemia (n = 4, 11%), fatigue (n = 3, 8%), paronychia (n = 3, 6%), and hyponatremia (n = 3, 6%). The grade 3 hematologic toxicities was neutropenia (n = 1, 3%). Conclusions: Pmab monotherapy showed the favolable efficacy and feasibility in the frail or elderly pts with RAS wt, unresectable CRC. The survival analysis including OS, PFS and TTF is awaiting. Clinical trial information: UMIN000024528.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Quadruplet regimen with capecitabine, irinotecan, oxaliplatin, and bevacizumab in chemo-naive patients with metastatic colorectal cancer: Results from the safety lead-in of QUATTRO-II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 57-57
Author(s):  
Hideaki Bando ◽  
Daisuke Kotani ◽  
Masahito Kotaka ◽  
Akihito Kawazoe ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Braf V600e ◽  
Phase Iii ◽  
Fixed Dose ◽  
Wild Type ◽  
Randomized Phase Ii ◽  
Level 1 ◽  
Grade 3

57 Background: FOLFOXIRI plus bevacizumab (BEV) is regarded as the standard of care for selected patients (pts) with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea. The AXEPT phase III study showed that the modified capecitabine (CAP) + irinotecan (IRI) + BEV (CAPIRI+BEV) [CAP 1600 mg/m2, IRI 200 mg/m2, and BEV 7.5 mg/kg q3wk] treatment was non-inferior to FOLFIRI+BEV, with a lower incidence of hematologic toxicity. We hypothesized that the modified CAPIRI combined with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) would be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: The QUATTRO-II study is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses (RD) of OX and IRI were investigated as a safety lead-in. In Step 2, pts are randomized to either the RD of CAPOXIRI+BEV or FOLFOXIRI+BEV. In Step 1, four dose levels of CAPOXIRI (fixed dose of CAP 1600 mg/m2 and BEV 7.5 mg/kg plus escalated or de-escalated doses of OX and IRI, q3wk) were investigated in a 3+3 manner. A dose level of ≤ 2/6 of dose-limiting toxicity (DLT) cases was expected as the RD. Results: A total of 9 pts (3 at Level 0, 6 at Level 1) were included in Step 1. The baseline characteristics were as follows: the median age was 62 years; 6 were male; 6 presented with a left-sided tumor; 8 had a performance status of 0; all wild type/ RAS mutant/ BRAF V600E mutant were 8/1/0; and UGT1A1 wild type/*6 single hetero/*28 single hetero were 7/0/2. In Level 0 (IRI 200 mg/m2, OX 100 mg/m2), one grade 4 neutropenia and one grade 3 anorexia were observed, but without DLT. In Level 1 (IRI 200 mg/m2, OX 130 mg/m2), two grade 4 neutropenia and one grade 3 colitis were observed, with 1 DLT (febrile neutropenia) case, fully recovered without G-CSF administration. No treatment-related deaths were observed. Although dose modifications were needed in 4 of the 6 pts, no further safety concerns related to treatment continuity were observed in the 2nd or subsequent cycles. Thus, we determined that the dose administered in Level 1 is the RD for Step 2. According to the preliminary efficacy results at 8 weeks after initiating study treatment, 6 pts achieved a partial response (2 in Level 0 and 4 in Level 1). Conclusions: The RD of CAPOXIRI+BEV was 200 mg/m2 IRI, 130 mg/m2 OX, 1600 mg/m2 CAP, and 7.5mg/kg BEV. The randomized phase II Step (Step 2) of QUATTRO-II is ongoing. Clinical trial information: NCT04097444.

scholarly journals Motorcycle crashes and upper extremity trauma

SICOT-J ◽  
2021 ◽  
Vol 7 ◽  
pp. 8
Author(s):  
Erin Cravez ◽  
Kelsey A. Rankin ◽  
Nathaniel Ondeck ◽  
Lee Yaari ◽  
Michael Leslie ◽  
...  
Keyword(s):  
Upper Extremity ◽  
Injury Severity ◽  
Cohort Analysis ◽  
Cost Of Care ◽  
Hospital Length Of Stay ◽  
Rank Test ◽  
Severe Injuries ◽  
Increased Risk ◽  
Extremity Injuries ◽  
Motorcycle Crashes

Objectives: Upper extremity injuries following motorcycle crashes (MCC) incur increased healthcare costs and rehabilitation needs. We aim to characterize the epidemiology of MCC upper extremity injuries and identify factors that influence the severity of and cost of care for upper extremity injuries. Methods: We performed a retrospective cohort analysis of 571 patients with upper extremity injuries after MCC at a level 1 trauma center from 2002 to 2013. We collected data pertaining to demographics, helmet use, toxicology, bony injury, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), hospital length of stay (LOS), and cost. Continuous variables were compared using t-test or Wilcoxon rank test, depending on data distribution, and dichotomous variables were compared using Pearson’s chi-squared or Fisher’s exact tests. Regression models were used to evaluate the effect of intoxication or helmets on injury location, severity, cost of care, and LOS. Results: The incidence of MCC upper extremity injury was 47.5%, with hand and forearm fractures the most common injuries (25.5% and 24.7% of total injuries). Intoxicated patients were more likely to have a high cost of care (p = 0.012), extended LOS (p = 0.038), plastic surgery involvement in their care (p = 0.038), but fewer upper extremity bony injuries (p = 0.019). Non-helmeted patients sustained less upper extremity bony injuries (p < 0.001) and upper extremity soft tissue injuries (p = 0.001), yet more severe injuries (ISS ≥ 30, p = 0.006 and GCS < 9, p < 0.01) than helmeted patients. Conclusion: Upper extremity injuries are common in motorcyclists. Despite vital protection for the brain and maxillofacial injury, helmeted MCC patients have an increased incidence of upper extremity injuries compared to non-helmeted patients, but overall have less severe injuries. Intoxicated patients have fewer upper extremity bony injuries, but the higher cost of care, and extended LOS. Therefore, even with the increased risk of injury helmets may expose to the upper extremity, helmets reduced overall morbidity and mortality. In addition to mandatory helmet laws, we advocate for further development of safety equipment focusing specifically on the prevention of upper extremity injuries.

Risk stratification for colorectal cancer in individuals with subtypes of serrated polyps

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324301
Author(s):  
Dan Li ◽  
Amanda R Doherty ◽  
Menaka Raju ◽  
Liyan Liu ◽  
Nan Ye Lei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Control Study ◽  
Community Based ◽  
Kaiser Permanente ◽  
Serrated Polyps ◽  
Increased Risk ◽  
Synchronous Adenoma ◽  
Serrated Lesions ◽  
Serrated Adenomas ◽  
Control Study

ObjectiveThe longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood.DesignThis community-based, case–control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006–2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression.ResultsCompared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8).ConclusionIncreased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.

scholarly journals Renin–angiotensin system blocker use and the risk of acute kidney injury after colorectal cancer surgery: a population-based cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e032964
Author(s):  
Charlotte Slagelse ◽  
H Gammelager ◽  
Lene Hjerrild Iversen ◽  
Kathleen D Liu ◽  
Henrik T Toft Sørensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Acute Kidney Injury ◽  
Cohort Study ◽  
Angiotensin Receptor Blockers ◽  
Kidney Injury ◽  
Population Based ◽  
Adjusted Risk ◽  
Increased Risk ◽  
The Impact ◽  
Postoperative Aki

ObjectivesIt is unknown whether preoperative use of ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) affects the risk of acute kidney injury (AKI) after colorectal cancer (CRC) surgery. We assessed the impact of preoperative ACE-I/ARB use on risk of AKI after CRC surgery.DesignObservational cohort study. Patients were divided into three exposure groups—current, former and non-users—through reimbursed prescriptions within 365 days before the surgery. AKI within 7 days after surgery was defined according to the current Kidney Disease Improving Global Outcome consensus criteria.SettingPopulation-based Danish medical databases.ParticipantsA total of 9932 patients undergoing incident CRC surgery during 2005–2014 in northern Denmark were included through the Danish Colorectal Cancer Group Database.Outcome measureWe computed cumulative incidence proportions (risk) of AKI with 95% CIs for current, former and non-users of ACE-I/ARB, including death as a competing risk. We compared current and former users with non-users by computing adjusted risk ratios (aRRs) using log-binomial regression adjusted for demographics, comorbidities and CRC-related characteristics. We stratified the analyses of ACE-I/ARB users to address any difference in impact within relevant subgroups.ResultsTwenty-one per cent were ACE-I/ARB current users, 6.4% former users and 72.3% non-users. The 7-day postoperative AKI risk for current, former and non-users was 26.4% (95% CI 24.6% to 28.3%), 25.2% (21.9% to 28.6%) and 17.8% (17.0% to 18.7%), respectively. The aRRs of AKI were 1.20 (1.09 to 1.32) and 1.16 (1.01 to 1.34) for current and former users, compared with non-users. The relative risk of AKI in current compared with non-users was consistent in all subgroups, except for higher aRR in patients with a history of hypertension.ConclusionsBeing a current or former user of ACE-I/ARBs is associated with an increased risk of postoperative AKI compared with non-users. Although it may not be a drug effect, users of ACE-I/ARBs should be considered a risk group for postoperative AKI.

Relationship between Genetic Polymorphism of CYP1A1 at Codon 462 (Ile462Val) in Colorectal Cancer

2008 ◽  
Vol 23 (1) ◽  
pp. 18-23 ◽  
Author(s):  
P.V. Pereira Serafim ◽  
I.D. Cotrim Guerreiro da Silva ◽  
N. Manoukian Forones
Keyword(s):  
Colorectal Cancer ◽  
Group Versus ◽  
Positive Association ◽  
Control Group ◽  
Case Group ◽  
Wild Type ◽  
Cancer Group ◽  
Increased Risk ◽  
Colorectal Cancer Patients ◽  
Alcohol Users

Aims and background The enzyme cytochrome P450 plays an important role in the metabolization and detoxification of various compounds. CYP1A1 is a polymorphic enzyme and some of its alleles have been correlated with an increased risk of developing various types of cancer. The aim of this study was to investigate the incidence of the polymorphism A→G (Ile462Val, exon 7) in colorectal cancer patients and the correlation of this polymorphism with others risk factors. Patients and methods 114 Brazilian patients with colorectal cancer were matched by age and sex to 114 healthy individuals. DNA was extracted from peripheral blood and the genotypes of the polymorphisms were assessed by PCR-restriction fragment length polymorphism. Results In the case group 64 subjects were male, 53 were alcohol users and 68 were smokers. In the control group 61 were male, 67 were alcohol users and 53 smokers. There were 14 subjects with wild-type homozygous A/A, 97 with heterozygous A/G, and 3 with homozygous mutated G/G in the cancer group versus 81 subjects with wild-type homozygous A/A and 33 with heterozygous A/G in the control group. The presence of the G allele (OR 5.14, 95%CI 3.15–10.80) was associated with an increased risk of colorectal cancer (p=0.001). The prevalence of smokers was higher in the cancer group (p=0.047, OR 1.71, 95%CI 1.03–3.11). Conclusion These results suggest a positive association between the A→G polymorphism and the risk of colorectal cancer. In addition, smoking was also a colorectal cancer risk. We did not find any correlation between this polymorphism and sex, grade of differentiation, stage, or evolution of the disease.

Pharmacogenetic Assessment of Toxicity and Outcome in Patients With Metastatic Colorectal Cancer Treated With LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05

2010 ◽  
Vol 28 (15) ◽  
pp. 2556-2564 ◽  
Author(s):  
Valérie Boige ◽  
Jean Mendiboure ◽  
Jean-Pierre Pignon ◽  
Marie-Anne Loriot ◽  
Marine Castaing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
First Line ◽  
Free Survival ◽  
Increased Risk ◽  
Grade 3 ◽  
Cancérologie Digestive

Purpose The aim was to investigate whether germline polymorphisms within candidate genes known or suspected to be involved in fluorouracil (FU), oxaliplatin, and irinotecan pathways were associated with toxicity and clinical outcome in patients with metastatic colorectal cancer (mCRC). Patients and Methods Blood samples from 349 patients included in the Fédération Francophone de Cancérologie Digestive 2000-05 randomized trial, which compared FU plus leucovorin (LV5FU2) followed by FU, leucovorin, and oxaliplatin (FOLFOX) followed by FU, leucovorin, and irinotecan (FOLFIRI; sequential arm) with FOLFOX followed by FOLFIRI (combination arm) in terms of progression-free survival (PFS) and overall survival, were collected. Twenty polymorphisms within the DPD, TS, MTHFR, ERCC1, ERCC2, GSTP1, GSTM1, GSTT1, and UGT1A1 genes were genotyped. Results The ERCC2-K751QC allele was independently associated with an increased risk of FOLFOX-induced grade 3 or 4 hematologic toxicity (P = .01). In the sequential arm, TS-5′UTR3RG and GSTT1 alleles were independently associated with response to LV5FU2 (P = .009) and FOLFOX (P = .01), respectively. The effect of oxaliplatin on tumor response increased with the number of MTHFR-1298C alleles (test for trend, P = .008). The PFS benefit from first-line FOLFOX was restricted to patients with 2R/2R (hazard ratio [HR] = 0.39; 95% CI, 0.23 to 0.68) or 2R/3R (HR = 0.59; 95% CI, 0.42 to 0.82) TS-5′UTR genotypes, respectively. Conversely, patients with the TS-5′UTR 3R/3R genotype did not seem to benefit from the adjunction of oxaliplatin (HR = 0.96; 95% CI, 0.66 to 1.40; trend between the three HRs, P = .006). Conclusion A pharmacogenetic approach may be a useful strategy for personalizing and optimizing chemotherapy in mCRC patients and deserves confirmation in additional prospective studies.

Randomized multicenter phase III trial of oxaliplatin plus raltitrexed compared to oxaliplatin plus fluorouracil and leucovorin treatment in recurrent and metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4102-4102
Author(s):  
J. Wang ◽  
J. Li ◽  
S. Qin ◽  
T. Liu ◽  
Z. Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Median Number ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Progression Of Disease ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

4102 Purpose: To compare oxaliplatin (L-OHP) plus raltitrexed (RTX) with L-OHP plus fluorouracil and leucovorin (LV/5FU) for patients (pts) with recurrent and metastatic colorectal cancer(CRC). Methods: Eligible pts had to have histologically proven recurrent or metastatic CRC,not having previously received oxaliplatin as palliative chemotherapy,ECOG PS = 2,age:18∼70,and adequate hematological,renal and hepatic function.After written informed consent,pts were randomized to L-OHP:130 mg/m2 d1 + RTX: 3 mg/m2 d1 (Arm A) or + LV: 200 mg/m2 + 5FU:375 mg/m2 d1–5 (Arm B). Results: Between Jan 2005 and July 2006, 216 pts were enrolled at 15 centers in China.112 pts (mean age: 55.0 (19∼70), M/F: 57/46, PS 0/1/2: 46/53/13) were randomly assigned to A and 102 (mean age: 54.2(22∼70), M/F: 54/46, PS 0/1/2: 44/59/9) to B. 203 pts were eligible for response evaluation (A:103, B:100).The median number of cycles was 4 (1∼6) in A and 3 (1∼6) in B (P=0.1431).The RR was 29.1% (CR:2, PR:28, SD:50 , PD:23) in A and 17.0% (CR:2, PR:15, SD:46 , PD:37) in B (P=0.0437).The disease-control rate was 77.7% in A and 63.0% in B (P=0.0237). After a median follow-up of 10 months (4–16.5),92 pts had had progression of disease (40 in A and 52 in B); 73 deaths had occurred (35 in A and 38 in B), median time to progression was not reached. Following-up is ongoing.The median QoL scores for the two arms were comparable. 214 were included in the safety analyses (A:112, B:102). There was a higher incidence of neutropenia (48.2% verse 29.4%, P=0.005) and transaminase increase (49.1% verse 35.3%, P=0.041) among A. Grade 3 or 4 neutropenia was much common in pts in A than those in B (20.5% verse 4.9% , P=0.001), but was complicated by fever in only 3.6% of cases (4 pts) in A and in 2.9% of cases (3 pts) in B. No pts were dead or infectious due to neutropenia. There were similar rates of grade 3 or 4 transaminase elevation in the two groups. Vomitting and anorexia were much commoner with B. Conclusions: The L-OHP+RTX seems beneficial in recurrent and metastatic CRC, demonstrating better response rate and higher disease control rate with acceptable tolerability, maintenance of QoL and convenient administration schedule. No significant financial relationships to disclose.

Safety report of a phase II trial of irinotecan plus S-1 (IRIS) with cetuximab in patients with KRAS wild type of metastatic colorectal cancer: HGCSG0902.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14062-e14062
Author(s):  
Yoshito Komatsu ◽  
Satoshi Yuki ◽  
Takashi Kato ◽  
Ayumu Hosokawa ◽  
Ichiro Iwanaga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Safety Analysis ◽  
Wild Type ◽  
Safety Report ◽  
Multicenter Phase ◽  
Secondary Endpoints ◽  
Grade 3

e14062 Background: IRIS is one of the standard regimens as second line treatment in metastatic colorectal cancer since IRIS demonstrated the non-inferiority to FOLFIRI (FIRIS study) in Japan. We previously presented IRIS plus bevacizumab (ESMO 2010), however; there is still lack of combination data of IRIS plus molecular target drugs. Thus we conduct the study of IRIS plus cetuximab (HGCSG0902) and this is the planned safety analysis for first 20 patients. Methods: HGSCG0902 is a multicenter phase ll study. Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS wild type. Patients (pts) received S-1 80-120 mg/m2/day p.o. on days 1-14 and irinotecan 100mg/m2 on days 1 and 15 repeated 28 days. Cetuximab administrated 400mg/m2 loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was response rate and the secondary endpoints were disease control rate, PFS, OS and safety. Results: Demographics of the 20 enrolled pts were male/female: 13/7, median age: 64.5, colon/rectal: 13/7, PS0/1: 12/8, prior bevacizumab +/-: 15/4 pts. Cetixumab were administrated weelkly/bi-weekly: 9/11 pts. 70% of pts had adverse events (AE). The most common non-hematological AE were diarrhea (85%), acne-like rash (80%), fatigue (75%) and anorexia (60%) and hematological AE were anemia (90%), AST increase (75%) and ALT increase (70%). The main grade 3-4 AE were diarrhea (45%), acne-like rash (20%), anorexia (20%) and stomatitis (20%). These AE were as expected. Nineteen pts stopped the treatment due to progression (52.6%) and AE (36.8%). Conclusions: This safety analysis suggests that IRIS plus cetuximab is well-tolerated and easy to administer.

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