A phase ll study of new combination regimen with trastuzumab, S-1, and CDDP in HER2-positive advanced gastric cancer (HERBIS-1).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4072-4072
Author(s):  
Keisuke Koeda ◽  
Naotoshi Sugimoto ◽  
Junji Tanaka ◽  
Masahiro Tsuda ◽  
Wataru Okamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
New Combination ◽  
Combination Regimen ◽  
Her2 Positive ◽  
Threshold Response ◽  
Grade 3

4072 Background: S-1, a novel oral fluoropyrimidine, plus cisplatin (SP) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. ToGA study demonstrated that trastuzumab (T-mab) combination regimen improved the overall survival of patients with HER2-positive advanced gastric cancer. However, there was no study evaluating the efficacy and the safety of T-mab in combination with S-1 plus cisplatin (SP) regimen. Therefore, we planned this study to examine the efficacy and the safety of the SP plus T-mab. Methods: Patients confirmed to be HER2-positive by IHC and/or FISH (IHC 3+ or IHC 2+ and FISH positive) received S-1 at 80 mg/m2 po, day 1-14, and cisplatin 60 mg/m2 iv, day 1 plus trastuzumab 8 mg/kg iv, day 1 (6 mg/kg iv, d1 from 2nd course), repeated every 3 weeks until disease progression. Primary endpoint was response rate (RR). Secondary endpoints were progression-free survival, overall survival and safety. The threshold response rate was defined as 35%, and the expected rate was set at 50% with a 80% power and a 1-sided alpha value of 0.1 and the calculated sample size was 50 patients. Results: A total of 56 patients (median age 66) were enrolled in this study. The efficacy and the safety analyses were conducted in the full analysis set of 53 patients. (Two patients were excluded for ineligibility and one was for no treatment). The confirmed RR assessed by the independent review committee was 67.9% (95% CI: 53.7 – 80.1), and the disease control rate was 94.3%. The median PFS was 7.1 months (95% CI: 6.0 – 10.1). The median OS was not reached. (The median follow-up time: 9.2 months) The main grade 3/4 adverse events were as follows: neutropenia 34%, leucopenia 8%, anorexia 23%, diarrhea 8%, hypoalbuminemia 4%, vomiting 6%, and increased creatinine 6%. Conclusions: This tri-week regimen with SP plus T-mab showed promising results in patients with HER2-positive advanced gastric cancer. Clinical trial information: UMIN000005739.

Comprehensive analysis of Excision repair complementation group 1, Glutathione S-transferase, Thymidylate synthase, and Uridine diphosphate glucuronosyltransferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15580-e15580
Author(s):  
H. Kim ◽  
B. Seo ◽  
J. Kim ◽  
S. Oh ◽  
S. Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Prospective Trial ◽  
Time To Progression ◽  
Genotype Variation ◽  
High Incidence ◽  
Grade 3 ◽  
Low Expression

e15580 Background: Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens. Oxaliplatin and irinotecan have shown to be effective in the treatment of gastric cancer. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, GST, TS, and UGT1A1predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Methods: Total genomic DNA was extracted from whole blood of patient. The PCR- restriction fragment length polymorphism (RFLP) method was applied to detect the known variant sites of ERCC1, GST, TS, and UGT1A1. Results: Response rate of FOLFOX (N=75) was 24%. Grade 3–4 neutropenia and neurotoxicity were observed 34.7% and 16%, respectively. TTP and OS of 1st line administration of FOLFOX (N=35) was 3.1 months (95% CI, 0.1–6.1 months) and 13.9 months (95% CI, 12.2–15.6 months). Only the GSTM1 positive genotype showed a significantly better time to progression (P=0.023). But significant genotype variation of TS, GST and ERCC1,which assumed to affect to activity of oxaliplatin was not observed to RR, toxicity, and overall survival. Response rate of FOLFIRI (N=74) was 23%. Grade 3–4 neutropenia and diarrhea were observed 55.4% and 9.5%, respectively. TTP and OS of 1st line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5–6.4 months) and 19.0 months (95% CI, 8.5–29.5months). Low expression type (2R/2R, 2R/3C, and 3C/3C) of TS was associated with high incidence of grade ≥3 neutropenia. But significant genotype variation of UGT1A1,which assumed to affect to toxicity of irinotecan was not observed to RR, toxicity, and survival. Conclusions: In this study, GSTM1 positive genotype showed a significantly better time to progression in the advanced gastric cancer treated with FOLFOX. Low expression type (2R/2R, 2R/3C, and 3C/3C) of TS was associated with high incidence of grade ≥3 neutropenia in the advanced gastric cancer treated with FOLFIRI. Well designed prospective trial will be clearly identifying relations between chemotherapy and genetic variations. No significant financial relationships to disclose.

A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: OGSG1203 (HERBIS-5).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Daisuke Sakai ◽  
Junji Kawada ◽  
Ryohei Kawabata ◽  
Tomono Kawase ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Disease Control ◽  
Intravenous Infusion ◽  
Response Rate ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Free Survival

128 Background: Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. Continuous administration of trastuzumab beyond first progression is expected to contribute to the benefit of chemotherapy for HER2-positive gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer. Methods: Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m2; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG). Results: From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression free survival and the median overall survival were 3.7 and 7.5 months, respectively. The major grade 3/4 toxic effects were neutropenia (24%); anemia (24%); leucopenia (21%); anorexia (11%); fatigue (14%); hypoalbuminemia (24%); and hypokalemia (14%). One death (NOS) was considered to be related to the study. Conclusions: The results of combination Trastuzumab with irinotecan showed feasible and promising efficacy against advanced HER2-positive chemo-refractory gastric cancer. These findings indicated that trastuzumab continuation use might be beneficial. Clinical trial information: 000008626.

Phase II study of S-1 monotherapy in taxane, cisplatin refractory gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4551-4551
Author(s):  
S. Cho ◽  
S. Lee ◽  
J. Hwang ◽  
W. Bae ◽  
H. Shim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Clinical Benefit ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

4551 Background: S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic protracted continuous infusion of 5-fluorouracil (5-FU). In previous study, S-1 demonstrated promising activity which is comparable to combination chemotherapy in advanced gastric cancer. This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy, in patients with taxane and cisplatin refractory gastric cancer. The primary end point was progression free survival and secondary end points were overall survival, safety and clinical benefit. Methods: Patients were eligible if they had histologically documented gastric adenocarcinoma previously treated with taxane (docetaxel or paclitaxel) and cisplatin; age≥18; Eastern Clinical Oncology Group (ECOG) performance status of 2 or less; adequate organ function; no evidence of gastrointestinal obstruction or passage disturbance. S-1 treatment was performed according to BSA as followed; < BSA 1.25, 80 mg/day, 1.25 ≤ BSA < 1.5, 100 mg/day; BSA ≥ 1.5, 120 mg/day. Every dosage was delivered divided two times and administered for 4 weeks followed by 2 weeks of resting period. Treatment continued until progression of disease or life-threatening adverse events were occurred. Results: Fifty-four patients were enrolled in this study and of the patients, forty-eight patients were evaluable. A total 194 chemotherapy cycles were administered and median number of cycles was three. Four (8.3%) patients had a partial response and 18 (37.5%) patients had stable disease. The median progression free survival and overall survival were 3.8 and 10.2 months, respectively. Grade III/IV hematologic toxicities included neutropenia in 6 patients (12.5%) and there was no febrile neutropenia. Most of nonhematologic toxicities were diarrhea, asthenia, and mucositis, and there was no grade 3 or grade 4 except two patients, who developed grade 3 anorexia and diarrhea, respectively. The clinical benefit response was observed in 16 patients (33.3%). Conclusions: This results showed that S-1 monotherapy was active and safe salvage chemotherapy in patients with advanced gastric cancer previously treated with taxane and cisplatin. No significant financial relationships to disclose.

A phase ll study of trastuzumab in combination with triweekly S-1 plus CDDP in HER2-positive advanced gastric cancer (HERBIS-1).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 70-70 ◽  
Author(s):  
Naotoshi Sugimoto ◽  
Junji Tanaka ◽  
Masahiro Tsuda ◽  
Wataru Okamoto ◽  
Hiroyuki Okuda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Rapid Progression ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Threshold Response ◽  
Esophagogastric Junction Adenocarcinoma ◽  
Ecog Ps ◽  
Measurable Lesion

70 Background: S-1, an oral fluoropyrimidine, plus cisplatin (SP) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer (AGC). Although ToGA study demonstrated that trastuzumab (T-mab) in combination with capecitabine plus cisplatin or fluorouracil plus cisplatin improved the overall survival of patients (pts) with HER2-positive AGC, there was no study evaluating the efficacy and the safety of T-mab in combination with SP regimen. Methods: Eligibility criteria included gastric or esophagogastric junction adenocarcinoma; HER2-positive confirmed by IHC and/or FISH (IHC 3+ or IHC 2+ and FISH positive); unresectable or recurrent; measurable lesion; no history of chemotherapy or radiotherapy; age≤75; ECOG PS of 0-1; and adequate organ function. Pts received S-1 at 40–60 mg depending on body surface area, po bid, day 1-14, and cisplatin 60 mg/m2, iv, day 1, plus T-mab 8 mg/ kg, iv, day 1 (6 mg/ kg, iv, d1 from 2nd course), repeated every 3 weeks until disease progression. Primary endpoint was response rate assessed by the RECIST (ver 1.1). The planned sample size was 50 based on the threshold response rate of 35%, the expected rate of 50%, power of 80%, and 1-sided α of 0.1. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible with inadequate renal function and no measurable lesion. Characteristics of 54 eligible pts were as follows: median age of 66 (range 34-75), M/F: 42/12, PS0/1: 42/12, unresectable/recuurent: 51/3, and IHC 2+/3+: 9/45. As one patient did not receive the protocol treatment due to the rapid progression of tumor, the efficacy and the safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate assessed by the independent review committee was 68%, and the disease control rate was 94%. The response rate without interval confirmation was 75%. The grade 3/4 adverse events (>5% of pts) were as follows: neutropenia 30%, leucopenia 8%, anorexia 21%, diarrhea 8%, hypoalbuminemia 8%, vomiting 6%, and increased creatinine 6%. Conclusions: T-mab in combination with triweekly SP regimen showed promising antitumor activity and manageable toxicities in pts with HER2-positiveAGC. Clinical trial information: UMIN000005739.

Updated analysis of HERBIS-1: A phase ll study of trastuzumab (T-mab) in combination with tri-weekly S-1 plus CDDP in HER2-positive advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 98-98
Author(s):  
Makio Gamoh ◽  
Naotoshi Sugimoto ◽  
Hiroto Miwa ◽  
Masahiro Tsuda ◽  
Shinichi Nishina ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Event Analysis ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Esophagogastric Junction Adenocarcinoma

98 Background: The HERBIS study demonstrated the promising antitumor activity and manageable toxicities of S-1 plus cisplatin and T-mab (SPT) regimen in patients (pts) with HER2-positive advanced gastric cancer (AGC) (Sugimoto et al. ASCO GI 2012, Abstract 70). We report the updated time-to event analysis. Methods: Main eligibility criteria were gastric or esophagogastric junction adenocarcinoma, HER2-positive, unresectable or recurrent, measurable lesion, no history of chemotherapy or radiotherapy, ECOG PS of 0-1 and adequate organ function. Pts received S-1(80-120mg / day) on days 1-14, cisplatin 60 mg/m2on day 1 and T-mab 8 mg/ kg on day 1 (6 mg/ kg from 2nd course) repeated every 3 weeks until disease progression. Primary endpoint was response rate (RR) and secondary endpoints were overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and adverse events. The planned sample size was 50 pts. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible and one patient did not receive any treatment. Therefore, the efficacy and safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate was 67.9% (95% CI: 53.7-80.1), and the disease control rate was 94.3% (95% CI: 84.3-98.9). Median OS was 16.0 months (95% CI: 13.3 - NaN), median PFS was 7.8 months (95% CI: 6.0 – 8.8) and median TTF was 5.7 months (95% CI: 4.2 - 7.1), respectively at the median follow-up time of 13.5 months. The main grade 3/4 adverse events were leukopenia 8%, neutropenia 36%, anemia 15%, increased creatinine 6%, hypoalbuminemia 9%, anorexia 23%, diarrhea 8% and vomiting 6%. Conclusions: SPT have promising antitumor activity and manageable toxicities in pts with HER2-positive AGC. Clinical trial information: UMIN000005739.

A pilot study of low-dose capecitabine plus trastuzumab as first-line treatment for patients older than 75 years with HER2-positive advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 165-165
Author(s):  
Sun Jin Sym ◽  
Young Saing Kim ◽  
Inkeun Park ◽  
Hee Kyung Ahn ◽  
Junshik Hong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Low Dose ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Functional Changes ◽  
Or Gene ◽  
Grade 3 ◽  
Ecog Ps

165 Background: Elderly patients often present with concomitant co-morbidities and age-associated physiologic problems, such as impaired organ function and functional changes that make the selection of optimal treatment difficult. We report the treatment outcome in 13 elderly patients with HER2-positve advanced gastric cancer who treated with low-dose capecitabine plus trastuzumab. Methods: Patients older than 75 years with gastric cancer were eligible for inclusion if their tumors showed overexpression of HER2 protein by immunohistochemistry (IHC) (3+) or gene amplification by FISH and IHC 2+. Capecitabine 1000 mg/m2was given orally twice a day for 14 days followed by a 1-week rest. Trastuzumab was given by intravenous infusion as a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Chemotherapy was given every 3 weeks for eight cycles. Results: Between December 2011 and July 2013, 13 consecutive patients (IHC 3+;7, IHC 2+ and FISH+;6) with a median age of 79 years (range, 75-92 years) were enrolled in this study. ECOG PS was 0/1/2:1/7/5, respectively. A total of 54 cycles of capecitabine plus trastuzumab were administered (median, three cycles; range, 2-8 cycles). Of the 12 patients with measurable lesions, the overall response rate was 41.6% (95% CI, 13.7 to 69.5%). Disease control was achieved in 75.0% of patients. Median progression-free survival was 8.2 months (95% CI, 2.5-13.7 months) and median overall survival was 10.9 months (95% CI, 1.4-20.4 months). Grade 3-4 toxicities were stomatitis (7.6%) and anemia (7.6%). No treatment-related deaths and symptomatic congestive heart failure were observed. Conclusions: Our findings suggest that low-dose capecitabine plus trastuzumab is effective and well tolerated in elderly patients with advanced HER2-positive gastric cancer who are considered ineligible for combination chemotherapy. Prospective trials investigating this regimen in elderly patients with advanced gastric cancer are warranted. Clinical trial information: Gachon University IRB.

A phase Ib study of nivolumab plus trastuzumab with S-1/capecitabine plus oxaliplatin for HER2 positive advanced gastric cancer (Ni-HIGH study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS177-TPS177 ◽  
Author(s):  
Daisuke Takahari ◽  
Takeru Wakatsuki ◽  
Naoki Ishizuka ◽  
Naoki Fukuda ◽  
Hirokazu Shoji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Tumor Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Phase Ib ◽  
Her2 Breast Cancer ◽  
Biomarker Analysis

TPS177 Background: Trastuzumab (Tmab) with cisplatin and fluoropyrimidines improved the overall survival (OS) of patients (pts) with HER2 (+) advanced gastric cancer (AGC). Nivolumab (Nivo) is an anti-programmed cell death-1 (PD-1) antibody that demonstrated a survival benefit as third line or later of AGC. To date, most trials investigating anti-PD-1 antibody for 1st line treatment focus on HER2 (-) AGC. In HER2(+) breast cancer mouse model, combining Tmab with anti-PD-1 antibody was reported to enhance ADCC activity of Tmab, and show greater tumor regression. In our data, the PD-L1 expression was observed in 44% of tumor cells and 70% of immune cells in human HER2(+) AGC. Based on these data, we have plannedthis phase Ib investigator-initiated trial to investigate the safety and tolerabirity of Nivo plus Tmab and either S-1 or capecitabine (Cape) plus Oxaliplatin (Ox) for pts with HER2(+) AGC. Methods: Histopathologically confirmed HER2(+) AGC with mesurable lesions, aged > 20 years, chemo-naïve pts are enrolled in this study. Pts receive Nivo (360 mg/body; day 1) plus Tmab (course1, 8 mg/kg; course 2 onward, 6 mg/kg; day 1) and either S-1 (40 mg/m2 bid d1-14; cohort 1) or Cape (1000 mg/m2 bid d1-14; cohort 2) plus Ox (130 mg/m2; day 1) every three weeks until desease progression or unacceptable toxicity. In the primary part, six pts for each cohort will be assessed for tolerability.To estimate the objective response rate (ORR) in the analysis-set, on our hypothesis that a true response rate is 80%, 20 pts are required for the 90% C.I. to be ± 20%. Therefore the expansion part for each cohort will be 12-15 pts. Primary endpoint is safety. Secondary endpoint is tolerability and exploratory endpoints include ORR, disease control rate, progression free survival and OS. Collaborative biomarker analysis includes whole exome sequences, RNA sequences, gut microbiome, and IHC using biopsy specimens. In addition, T-cell repartry, circulating tumor DNA and exomes will be also analyzed using blood obtained during treatment. This study just has been initiated at four sites in Japan. Clinical trial information: UMIN000034222.

The efficacy and toxicity of 3-weekly TS-1 containing chemotherapy in patients with unresectable advanced gastric cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14580-e14580
Author(s):  
Tae Yong Kim ◽  
Byeong IL Lee ◽  
Gyu IM Kim ◽  
Ju Young Kim ◽  
Jin Seok Ahn ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Weekly Basis ◽  
Free Survival ◽  
Good Efficacy ◽  
Grade 3 ◽  
Good Treatment Option ◽  
Robust Evidence

e14580 Background: TS-1 has shown good efficacy against unresectable advanced gastric cancer (AGC). Conventionally TS-1 containing chemotherapy (CTx) is performed on 5-weekly or 6-weekly basis. We lack robust evidence for the efficacy and safety of 3-weekly TS-1 containing CTx. In Korea, 3-weekly TS-1 containing CTx can be used as off-label under permission of Health Insurance Review and Assessment service (HIRA). We and HIRA conducted this study to confirm the efficacy and tolerability of 3-weekly TS-1 containing CTx in unresectable AGC. Methods: We retrospectively analyzed patients with unresectable AGC who received 3-weekly TS-1 containing CTx between June 2007 and January 2011. In 3-weekly TS-1 monotherapy, TS-1 40-60mg depending on patient’s body surface area was administered orally twice a day for 14 days followed by a 1-week rest every 3 weeks. In 3-weekly TS-1/cisplatin combination CTx, TS-1 40mg/m2 was given orally twice a day for 14 days followed by 1-week rest and cisplatin 60 mg/m2 on day 1 was given by intravenous infusion every 3 weeks. Results: A total of 1372 patients (TS-1 monotherapy: 265 (19.3%), TS-1/cisplatin : 1107 (80.7%)) were enrolled from 31 institutions. Response rate of 3-weekly TS-1 monotherapy was 18.1%. Progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% C.I., 4.5-5.9) and 14.3 months (95% C.I., 10.6-17.9), respectively. Response rate of 3-weekly TS-1/cisplatin was 29.4%. PFS and OS of 3-weekly TS-1/cisplatin were 6.8 months (95% C.I., 6.3-7.4) and 16.1 months (95% C.I., 14.4-17.9) respectively. Common toxicities of TS-1 monotherapy included nausea/vomiting (N/V) (13.6%), anemia (13.2%) and neutropenia (10.2%). However, the incidences of more grade 3/4 toxicities were less than 3.0%. All grades of neutropenia, N/V and anemia occurred in 35.4%, 21.1% and 13.3% of patients receiving 3-weekly TS-1/cisplatin. However, grade 3/4 toxicities including neutropenia, N/V and anemia occurred in only 17.8%, 3.0% and 2.9%. Conclusions: Three-weekly TS-1 monotherapy or TS-1/cisplatin CTx showed good efficacy and well tolerability. Our study suggests that 3-weekly scheduled regimens may be a good treatment option for unresectable AGC patients.

scholarly journals Phase II Prospective Study of Trastuzumab in Combination with S-1 and Oxaliplatin (SOX100) Therapy for HER2-Positive Advanced Gastric Cancer

2021 ◽  
Author(s):  
Yoshinori Mori ◽  
Hiromi Kataoka ◽  
Masahide Ebi ◽  
Kazunori Adachi ◽  
Yoshiharu Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Grade 3 ◽  
Peripheral Sensory

Abstract Purpose The standard first-line treatment for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) is trastuzumab in combination with cisplatin and fluoropyrimidines. We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC.Methods In this single-arm, multicenter phase II study, patients with HER2-positive AGC received S-1 (80–120 mg per day) orally on days 1–14, oxaliplatin (100 mg/m2) intravenously on day 1, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. Results A total of 25 patients from six centers were enrolled from December 2015 to March 2020. In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5%–86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5–22.9) months, 7.6 (95% CI 5.0–10.9) months, and 75.0 (95% CI 53.3–90.2) %, respectively. Major grade 3/4 adverse events included anorexia (20%), anemia (16%), peripheral sensory neuropathy (16%), and diarrhea (15%). Conclusion SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.

Trastuzumab (T-mab) in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: Feasibility and preliminary efficacy.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 124-124
Author(s):  
Yasushi Sato ◽  
Tetsuji Takayama ◽  
Hiroyuki Ohnuma ◽  
Masahiro Hirakawa ◽  
Takahiro Osuga ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Gastric Cancer ◽  
R0 Resection ◽  
Combination Regimen ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Unresectable Gastric Cancer ◽  
Grade 3

124 Background: Recently the efficacy of trastuzumab (T-mab) for HER2-positive gastric cancer has been reported. We have developed a triplet-drug combination regimen consisting of docetaxel, CDDP, and S-1 (DCS) and reported that the regimen provides very high response rates (BJC 2007; CCP 2009 and 2013). To increase the efficacy of DCS in patients (pts) with HER2-positive unresectable gastric cancer, we carried out a feasibility study for the DCS-T-mab (DCS-T) regimen. Methods: Eligibility criteria included the following: age between 20 and 80 years; unresectable HER2-positive metastatic gastric cancer; normal cardiac function. Pts received oral S-1 (40 mg/m2 b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m2), docetaxel (50 mg/m2) and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks. Results: This study included 16 pts: median age, 60 years (34 – 76 years), 11 males and 5 females. PS 0/1/2, 10/4/2; differentiated/undifferentiated-type histology, 11/5; U/M/L, 7/8/1; HER2 3+, 13; HER2 2+/FISH+, 3; T3/T4a/T4b, 11/4/1; N0/N1/N2/N3, 2/0/4/10; and distant lymph nodes/liver/peritoneum/lungs/bone/ovaries, 11/7/4/2/1/1. The completion rate until the third cycle was 100%. According to the RECIST criteria, the objective response rate was 93.3%, and the median cycle to response was 1 (1–3 cycles). Adverse events of grade 3 or greater severity were: leukopenia/neutropenia, 68.8/81.3%; FN, 12.5%; anorexia, 25%; and diarrhea, 25%. All of these side effects were well controlled. Non-curative factors disappeared in 7 of 16 cases and R0 resection was carried out in 6 cases (37.5%) including 2 pts with liver metastases. A pathological response was found in 83 % of 6 resected cases. At a median follow-up of 9.8 months (2.3 – 23 months), median PFS was 12.8 months and median OS was not yet reached. Conclusions: T-mab in combination with DCS is a feasible regimen in pts with unresectable HER2-positive gastric cancer. The observed response rate is very promising and warrants further investigation. Clinical trial information: UMIN000005603.

Sign in / Sign up

Export Citation Format

Share Document