scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer：a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Ugt1a1 Gene ◽  
Geographical Regions ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: UGTlA1 gene polymorphism has different distribution in different ethnicities, geographical regions and ethnic groups, which may lead to different toxicity and efficacy of irinotecan. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled . The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 * 28 and * 6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method.Results: UGT1A1 * 28 wild-type (TA6 / 6), heterozygous mutant (TA6 /7) and homozygous mutant (TA7 / 7) accounted for 69.8%, 30.2% and 0%, respectively. UGT1A1 * 6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7%，20.9% and 2.3%，respectively.UGT1A1 * 28 TA6 / 7 type could increase the risk of grade 3-4 diarrhea (P=0.027), which did not increase the risk of grade 3-4 neutropenia (P=0.092). UGT1A1 * 6 G / A and A / A type could increase the risk of grade 3-4 diarrhea and neutropenia (P=0.001; P=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (P=0.729; P=0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 * 28 and UGT1A1 * 6 (7.0 m vs 7.4 m, P=0.427; 6.9 m vs 7.0m P=0.408).Conclusions: The distribution of UGT1A1*28 and UGT1A1* 6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Ugt1a1 Gene ◽  
Geographical Regions ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: UGTlA1 gene polymorphism has different distribution in different ethnicities, geographical regions and ethnic groups, which may lead to different toxicity and efficacy of irinotecan. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy to develop an individualized irinotecan regimen. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer and 86 patients of this with three generations of Zhuang who were accorded with inclusion and exclusion criteria were enrolled. The distribution of UGT1A1 gene polymorphism was analyzed retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 * 28 and * 6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. Results: UGT1A1 * 28 wild-type (TA6 / 6), heterozygous mutant (TA6 /7) and homozygous mutant (TA7 / 7) accounted for 69.8%, 30.2%and 0%, respectively. UGT1A1 * 6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7% ，20.9%and 2.3%，respectively。UGT1A1 * 28 TA6 / 7 type could increase the risk of grade 3-4 diarrhea (P=0.027), which did not increase the risk of grade 3-4 neutropenia (P=0.092). UGT1A1 * 6 G / A and A / A type could increase the risk of grade 3-4 diarrhea and neutropenia (P=0.001; P=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (P=0.729; P=0.745). The median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 * 28 and UGT1A1 * 6 (7.0m vs 7.4 m, P=0.427; 6.9mvs 7.0m P=0.408). Conclusions: The distribution of UGT1A1*28 and UGT1A1* 6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people,Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer：a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Chinese Han ◽  
Ugt1a1 Gene ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: There are obviously ethnic differences between the UGT1A1 gene polymorphisms.Due to the difference of genetic background and environment,the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients.The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled.The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 *28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. Results: UGT1A1 *28 wild-type (TA6/6), heterozygous mutant (TA6/7) and homozygous mutant (TA7/7) accounted for 69.8%, 30.2% and 0%, respectively. UGT1A1 *6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7%，20.9% and 2.3%，respectively. UGT1A1 *28 TA6 / 7 type could increase the risk of grade 3~4 diarrhea (p=0.027), which did not increase the risk of grade 3~4 neutropenia (p=0.092). UGT1A1 *6 G / A and A / A type could increase the risk of grade 3~4 diarrhea and neutropenia (p=0.001; p=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (p=0.729; p=0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 *28 and UGT1A1 *6 (7.0m vs 7.4m, p=0.427; 6.9m vs 7.0m p=0.408). Conclusions: The distribution of UGT1A1 *28 and UGT1A1 *6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

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 UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer

2009 ◽  
Vol 15 (40) ◽  
pp. 5058 ◽  
Author(s):  
Christoph Schulz ◽  
Volker Heinemann ◽  
Andreas Schalhorn ◽  
Nikolas Moosmann ◽  
Thomas Zwingers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Ugt1a1 Gene

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.

Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer

2003 ◽  
Vol 21 (5) ◽  
pp. 807-814 ◽  
Author(s):  
Charles S. Fuchs ◽  
Melvin R. Moore ◽  
Graydon Harker ◽  
Luis Villa ◽  
David Rinaldi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Significant Difference ◽  
Global Quality Of Life ◽  
Grade 3

Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients. Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m2) or once every 3 weeks (350 mg/m2, or 300 mg/m2 in patients who were ≥ 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation). Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively; P = .43), or median time to progression (4.0 v 3.0 months, respectively; P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups. Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.

scholarly journals Survival Outcomes of Metastatic Colorectal Cancer Patients in Brunei Darussalam and the Impact of KRAS Mutations

2020 ◽  
Author(s):  
Datul Damit ◽  
Ravi Patnaik ◽  
Liling Chaw ◽  
Shir Kiong Lu ◽  
Telisinghe Pemasiri Upali ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Outcome ◽  
Survival Outcomes ◽  
P Value ◽  
Wild Type ◽  
Kras Gene ◽  
Brunei Darussalam ◽  
Significant Difference ◽  
Chi Squared

Colorectal cancer (CRC) is the third most common cancer, with rising incidence due to lifestyle and diet. 40% of CRC cases are found to have KRAS mutations. In this study, we investigate the survival outcome of metastatic Colorectal cancer mCRC) patients in Brunei Darussalam restrospectively. Chi-squared test was used to compare the survival outcomes of mCRC patients, and Mann-Whitney U test was used to compare the median ages of both groups. Kaplan-Meier survival curves were drawn and logrank test was used to compare the survival outcome between two groups. There was a total of 105 patients with stage IV CRC being treated during the study period. 81.6% (n=62) of mCRC patients were found to have the primary tumours on the left side of the colon. 19 of these 26 (73.1%) mutant KRAS mCRC patients died, while 23 of 50 (46.0%) wild-type KRAS mCRC patients died at the end of the study period, contributing to death rates of 45.2% and 54.8%, correspondingly. 30.3% (n=23) of the study population had a single metastatic site detected (either liver, or lung or any other organs), while 69.7% (n=53) of the 76 mCRC patients had two (double) or more metastatic sites. 69.2% (n=18) and 30.8% (n=8) of the mutant KRAS mCRC patients had mutations within codons 12 and 13, respectively. To our knowledge, this is the first study in Brunei Darussalam to analyse both the survival outcomes of metastatic CRC patients and those of mutant KRAS mCRC patients. Chi-squared analysis showed a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients (p-value = 0.024). There was a significant difference in the survival outcome between the mutant KRAS mCRC patients with RCC and mutant KRAS mCRC with LCC patients. There was no significant difference between the survival outcomes of mutant KRAS patients with mutations in either codon 12 or 13 of the KRAS gene (Table 3). However, there is a significant difference in the median survival periods between the mutant KRAS mCRC patients with mutations in codon 12 and those with mutation in codon 13 of the KRAS gene (p-value = 0.003). In conclusion, we found that mutant KRAS mCRC patients had a significantly poorer OS, which was shown to be worse when the primary tumours were found at the left side of the colon. Mutant KRAS mCRC patients with mutations in codon 12 were found to have shorter survival median periods than those with mutations within codon 13.

scholarly journals Regorafenib-Induced Hand‐Foot Skin Reaction Is More Severe on the Feet Than on the Hands

2019 ◽  
Vol 27 (5) ◽  
pp. 551-556
Author(s):  
Yuma Nonomiya ◽  
Takashi Yokokawa ◽  
Kazuyoshi Kawakami ◽  
Kazuo Kobayashi ◽  
Takeshi Aoyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Metastatic Colorectal Cancer ◽  
Skin Reaction ◽  
Common Side Effect ◽  
Correct Trial ◽  
Significant Difference ◽  
Hand Foot Skin Reaction ◽  
Grade 3 ◽  
Hands And Feet

Regorafenib is a multikinase inhibitor for the treatment of metastatic colorectal cancer. Regorafenib-induced hand‐foot skin reaction (HFSR) is a common side effect during treatment. The reported frequency of HFSR was 80% (grade 3: 28%) in the Japanese subpopulation in the CORRECT trial; however, more detailed data regarding HFSR in terms of onset and sites of susceptibility are unclear. Additionally, the risk factors for regorafenib-induced severe HFSR are unknown. The aim of this study was to compare HFSR between the hands and feet and identify preexisting risk factors for severe HFSR in Japanese patients receiving regorafenib. We retrospectively examined the onset and severity of HFSR on the hands and feet of patients with metastatic colorectal cancer treated with regorafenib from May 2013 to October 2015 in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In addition, we examined the possible association between preexisting clinical factors and severe HFSR. Our results showed that no significant difference in the incidence of HFSR of any grade was observed between the hands (71%) and feet (74%) (p = 0.63). The incidence of grade 3 HFSR was more frequent on the feet (33%) than on the hands (8%) (p < 0.01). The onset of grade 3 HFSR was earlier on the feet than on the hands (p < 0.001). No preexisting risk factor was identified. Our findings indicate that severe HFSR was more prevalent on the feet than on the hands, suggesting the need for appropriate screening for early detection and treatment of regorafenib-induced HSFR.

Use of the intensity of membranous EGFR staining by immunohistochemistry to predict the efficacy of chemotherapy containing cetuximab in KRAS wild-type patients with metastatic colorectal cancer: A retrospective analysis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 516-516
Author(s):  
Naoki Takahashi ◽  
Yasuhide Yamada ◽  
Hirokazu Taniguchi ◽  
Kohei Akiyoshi ◽  
Yoshitaka Honma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Objective Response ◽  
Endoscopic Biopsy ◽  
Rank Test ◽  
Wild Type ◽  
Mutation Status ◽  
Significant Difference ◽  
Kras Mutation Status

516 Background: KRAS mutation status is a strong predictive factor for anti-EGFR monoclonal antibody therapy efficacy in metastatic colorectal cancer (mCRC). In the BOND trial, objective response rates to cetuximab in irinotecan-refractory mCRC were not significantly different based on the intensity of EGFR staining by immunohistrochemistry (IHC). However, this result was not evaluated by KRAS mutation status, so we retrospectively evaluated the relationship between the efficacy of chemotherapy containing cetuximab and the intensity of membranous EGFR staining in KRAS wild type (KRAS-WT) patients. Methods: Between August 2008 and July 2011, specimens of 391 CRC patients were collected by endoscopic biopsy or surgical resection. EGFR staining by IHC and genetic screening for KRAS status were performed and intensity of EGFR staining was scored by the Guidelines for Interpreting EGFR pharmDx, DAKO. We analyzed 94 KRAS-WT patients who received combination chemotherapy with an irinotecan-regimen plus cetuximab or cetuximab monotherapy and met the following criteria: histologically proven mCRC adenocarcinoma , at least 1 previous regimen of standard fluoropyrimidine - containing chemotherapy , ECOG PS score 0-2, and adequate hepatic and renal function. Patients were classified into 2 groups by intensity of EGFR staining: (A) absence of staining and weakly to moderately positive (IHC 1+ and IHC 2+), (B) strongly positive (IHC 3+). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared in Groups A and B by the log-rank test. Results: There was no significant difference in patient characteristics between the 2 groups except for primary site. The median PFS of Groups A (n=76) and B (n=18) were 5.4 months and 9.1 months (p= 0.029), the median OS was 8.1 months and 13.2 months (p=0.054) and response rate was 20.1% and 33.3%, respectively. Conclusions: In KRAS-WT patients with fluoropyrimidine-containing chemotherapy-refractory mCRC, strong intensity of EGFR staining by IHC might be predictive for efficacy of chemotherapy containing cetuximab.

Retrospective cohort study on the safety and efficacy of panitumumab for patients with metastatic colorectal cancer: The HGCSG1002 study—Analysis of after cetuximab refractory.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 541-541
Author(s):  
Yoshimitsu Kobayashi ◽  
Hiraku Fukushima ◽  
Takahide Sasaki ◽  
Satoshi Yuki ◽  
Hiroyuki Okuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Daily Practice ◽  
Free Survival ◽  
Naive Group ◽  
Significant Difference ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Egfr Antibody

541 Background: In the previous studies, panitumumab (Pmab) has been demonstrated the efficacy for patients with metastatic colorectal cancer (mCRC) in all treatment lines. It is still controversial about the efficacy of Pmab for patients that had progressed on prior cetuximab (Cmab), though there had been a few reports (from Metges et al. and Wadlow et al.) regarding the efficacy of Pmab after Cmab refractory or intolerance. To evaluate the efficacy and safety of Pmab in patients with cetuximab-refractory mCRC, in comparison with anti-EGFR antibody naïve patients (Cmab-naïve) and Cmab-refractory or intolerance patients (prior-Cmab). Methods: Two hundred patients with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG 1002 study). Of these, the patients that were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin, and were administered Pmab monotherapy were included in this analysis. Results: Of 93 patients (44 prior-Cmab and 49 Cmab-naïve) were evaluated. There were no significant differences in the baseline characteristics of the patients in each group. The incidence of Grade 3 or higher any skin toxicities were higher in the Cmab-naïve (26.5.%) than in the prior-Cmab (11.4%). The overall response rate (RR) was not significantly difference (prior-Cmab/ Cmab-naïve, 9.1%/ 10.2%), but the disease control rate (DCR) was slightly higher in Cmab-naïve group (38.6%/ 55.1%, p=0.15). Progression free survival (PFS) and overall survival (OS) were follows: prior-Cmab/ Cmab-naïve, 2.8m/ 3.1m, 6.8m / 9.5m. There was a significant difference between the two groups in OS curve (p=0.04). Conclusions: Pmab was safely administered to heavily pretreated mCRC patients in daily practice. Although there were no significant differences in RR, DCS and PFS between prior-Cmab and Cmab-naïve, but the median OS was longer for the Cmab-naïve group compared with the prior-Cmab group. Therapeutic efficacies of Pmab for prior-Cmab patients did not comparable to those for Cmab-naïve patients. We are now performing a phase II trial on the efficacy of Pmab for Cmab-refractory mCRC patients.

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