A UGT1A1 genotype-directed phase II toxicity and efficacy-finding study of irinotecan combined with S-1 as first-line treatment in advanced gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4154-TPS4154
Author(s):  
Xiaofeng He ◽  
Zedong Du ◽  
Feng Wen ◽  
Pengfei Zhang ◽  
Ruilei Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
The Body ◽  
Chinese Patients ◽  
Severe Neutropenia ◽  
High Dose ◽  
Wild Type ◽  
First Line ◽  
Different Doses ◽  
Ugt1a1 Genotype

TPS4154 Background: The best chemotherapy regimen for advanced gastric cancer (AGC) is uncertain, but promising findings have been reported with Irinotecan (IRI) plus S-1. However, IRI can induce severe neutropenia or diarrhea associated with homozygosity of the UGT1A1*28 or UGT1A1*6 alleles. This trial was designed to compare the toxicity and efficacy on different doses of IRI combined with S-1 according to UGT1A1 genotype as first-line chemotherapy in AGC in Chinese patients. Methods: Previously untreated patients with histologically proven gastric or gastroesophageal junction adenocarcinoma, aged between 18 and 75 years with ECOG performance status 0-2 were classified according to UGT1A1 genotype: wild-type (none of *28 or *6 allele); heterozygous (only one of *28 or *6 allele); or homozygous (*28/*28, *6/*6, or double heterozygous for *28 and *6). Patients were randomized (1:1) to receive either low or high dose of IRI given i.v. (90 min) on day 1 in each genotype group. The low and high dose of IRI were 80mg/m2 and 200 mg/m2 in the wild-type group, 80 mg/m2 and 150 mg/m2 in the heterozygous group, 40 mg/m2 and 80 mg/m2 in the homozygous group. S-1 was administered orally at a dose level set on the basis of the body surface area (BSA): 40 (BSA<1.25 m2), 50 (BSA≥1.25 to<1.5 m2 ) or 60 mg (BSA≥1.5 m2) twice a day on day1-7. Courses were repeated every 2 weeks, unless disease progression, unacceptable toxicity or patient refusal. The primary endpoint was to explore the safety and efficacy on different doses of IRI combined with S-1 according to UGT1A1 polymorphism. Based on the frequency of UGT1A1*28 and UGT1A1*6 gene polymorphism in Asian gastrointestinal cancer patients, the chi-square test and fisher exact test were used to evaluate the planned sample size which is 100 in total: 40 for the wild-type, 40 for the heterozygous and 20 for the homozygous group. Until now, 8 patients have been enrolled. Clinical trial information: ChiCTR-OCH-12002472.

Combining cetuximab with FOLFOX regimen as the first-line therapy of KRAS wild-type advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 157-157
Author(s):  
Yung-Sung Yeh
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Large Scale ◽  
Direct Sequencing ◽  
Radical Resection ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

157 Background: Gastric cancer is one of the most common cancers worldwide with a high incidence in Asian countries, including Taiwan. For patients with recurrent or non-resectable advanced gastric cancer (AGC), chemotherapy or the combination of target and chemotherapy was chosen for therapy in AGC patients. We prospectively analyzed the safety and efficacy of cetuximab combined with FOLFOX4 as the first-line setting in patients with AGC. Methods: From January 2010 to January 2013, a total of 20 patients with histologically confirmed unresectable advanced/recurrent gastric cancer were enrolled into this study. Direct sequencing of KRAS mutation status was performed before the treatment. All patients received cetuximab 500 mg/m2every 2 weeks, and chemotherapy was administered with FOLFOX regimen of oxaliplatin at 85 mg/m2 plus leucovorin 200 mg/m2 on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 24-hour continuous infusion of 1000 mg/ m2 5-FU on days 1-2 biweekly. Therapy was continued until disease progression or intolerable adverse events or receiving surgical resection. Results: All tumor tissues of 20 AGC patients were KRAS wild-type. With the median therapy of 6 cycles (4-8 cycles), clinical efficacy, according to RECIST criteria, showed an overall response rate of 55% (11/20), and 20% (4/20) of patients exhibited stable disease as well as 25% (5/20) who had progressive disease. Radical resection could be obtained in 30% (3/10) of unresectable patients as the neoadjuvant therapy. The median time to progress (TTP) was 8.3 months and the median overall survival (OS) was 12.2 months. The grade III-IV adverse events was observed in 4 of 20 (20%) patients, including 15% of neutropenia (3/20), 5% of skin rash (1/20), 10% of nausea and vomiting (2/20) as well as 15% of asthenia (3/20). Conclusions: Cetuximab combined with FOLFOX as the first-line therapy for KRAS wild-type AGC patients appears to have favorable efficacy and safety, and the possibility of conversion to radical resection. Grade 3-4 adverse events were relatively uncommon. Despite this preliminary favorable outcome; however, a long-term result and large scale clinical trial is mandatory to verify it.

Phase II study of cetuximab plus weekly cisplatin and 24-hour infusion of high-dose 5-fluorouracil and leucovorin for the first-line treatment of advanced gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4567-4567 ◽  
Author(s):  
K. Yeh ◽  
C. Hsu ◽  
C. Hsu ◽  
C. Lin ◽  
Y. Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Serum Triglyceride ◽  
High Dose ◽  
Serum Triglyceride Level ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

4567 Background: Cisplatin-HDFL regimen, using weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil (5-FU) and leucovorin, is commonly used in Taiwan for patients with advanced gastric cancer (GC), showing an overall response rate of approximately 60% (95% CI: 45%-76%) [J Clin Oncol (Suppl) 2006; 24(18S): A14063 ]. We have demonstrated that cetuximab is cytotoxic to human GC cells, and has a chemosensitizing effect for cisplatin and 5-FU in GC cells [Proc AACR 2006; 47: A1233]. Methods: All patients had pathologically confirmed metastatic/ recurrent chemonaive GC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, WHO PS 0/1/2, adequate hepatic, renal, and bone marrow functions. Cetuximab 400 mg/m2 was given as 2h infusion, initially (i.e., D1 of cycle 1); and followed by weekly 1h infusion of 250 mg/m2 (i.e., D8, D15, D22 of cycle 1, and D1, D8, D15, D22 of cycle 2). Cisplatin 35 mg/m2 was given as a 24h infusion, admixing with 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 (HDFL), D1, D8. A 24h infusion of HDFL was given on D15. Cycles were repeated every 28 days, and response evaluation was performed every 2 cycles & at the end of protocol treatment. The primary end-point was confirmed objective response rate (RR) by RECIST. Results: Between Dec. 2005 and Nov. 2008, 35 patients (M:19, F:16) with a median age of 56 (40–74) were enrolled and evaluable for response assessment. The overall RR was 68.6% (51–83%, 95% C.I.) with 1 CR and 23 PRs. Among a total of 269 cycles (median: 7, range: 2 to 22+ cycles) given, Gr3/4 neutropenia, infection, and hepatic toxicity developed in 6.0%, 4.8%, and 0.74% of 269 cycles, respectively. Two patients have developed acute hepatitis B flare-up among seven HBsAg (+) carriers, and were well controlled by lamivudine. Gr1, Gr2, and Gr3 acne- like rashes have developed in 57.1%, 31.4%, 5.7%; and Gr1, Gr2, Gr3 paronychia have developed in 40.0%, 8.6%, and 2.9% of 35 patients, respectively. Median PFS (range: 3 to 22+ months) and median OS (range: 3 to 35+ months) was11.0 and 14.5 months, respectively. Conclusions: Cetuximab plus infusional cisplatin-HDFL is a highly effective regimen with low toxicity and favourable survival in the first-line treatment of advanced GC. No significant financial relationships to disclose.

Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin as First-Line Therapy for Advanced Gastric Cancer

Chemotherapy ◽  
2016 ◽  
Vol 61 (4) ◽  
pp. 197-203 ◽  
Author(s):  
Wenna Wang ◽  
Jing Huang ◽  
Yunxia Tao ◽  
Xiao Lyu ◽  
Lin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Significant Difference ◽  
Grade 3

Background: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. Methods: Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. Results: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. Conclusions: The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation.

Sign in / Sign up

Export Citation Format

Share Document