A randomized phase II factorial design trial of CPT-11 versus PTX versus each combination with S-1 in patients with advanced gastric cancer refractory to S-1: Final results of OGSG0701.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 117-117 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Hiroshi Imamura ◽  
Tomono Kawase ◽  
Masahiro Gotoh ◽  
Yutaka Kimura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
Correct Selection ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B

117 Background: S1 + platinum (SP) is recognized as standard first-line chemotherapy for advanced gastric cancer(AGC), and S1 monotherapy is suggested for frail AGC patients or adjuvant setting in Japan. However, taxane or CPT-11 were often employed as second-line treatment for the patients who were resistant to S1-containing regimen. A retrospective analysis has reported that S1 combination chemotherapy extended overall survival as second-line treatment for AGC. Methods: Patients with AGC who confirmed disease progression by imaging after the first-line therapy with S1 or SP were randomized in four groups; CPT-11 150 mg/m2, day1, q2w (Group A), PTX 80 mg/m2, day1, 8,15, q4w (Group B), CPT-11 80 mg/m2, day1, 15, S-1 80 mg/m2, day1-21, q5w (Group C1), PTX 50 mg/m2,day1, 8, S1 80 mg/m2, day1-14, q3w (Group C2). Primary endpoint was overall survival (OS), and secondary endpoints were progression free survival (PFS), overall response rate (ORR) and safety. Sample size was set at 100 to 120 to achieve 2 months improvement of OS by using CPT-11 or by adding S1 with approximately 80% probability of the correct selection. Results: From July 2008 to March 2012, 127 patients were enrolled. The OS was 11.3/11.3/14.6/10.5 months(M) (Group A/B/C1/C2), 11.8M in Group A+C1 and 11.1M in Group B+C2 (p=0.922, HR: 0.981 [0.679-1.419]), 11.3M in Group A+B and 11.1M in Group C1+C2 (p=0.808, HR: 0.952 [0.643-1.412]), respectively. The PFS was 3.0/4.4/3.8/3.5M (Group A/B/C1/C2), 3.6M in Group A+C1 and 4.1M in Group B+C2 (p=0.035, HR:0.674 [0.468-0.972]) 3.7M in Group A+B and 3.7M in Group C1+C2 (p=0.931, HR: 1.017 [0.643-1.412]). The ORR was 7.1/16.3/4.5/5.0% (Group A/B/C1/C2), 4.7%[1.7-15.2] in Group A+C1 and 12.7%[5.6-23.5] in Group B+C2 (p=0.241), 11.8%[5.8-20.6] in Group A+B and 4.6%[0.6-16.2] in Group C1+C2 (p=0.572).Major Grade 3/4 toxicity (Group A/B/C1/C2, %), was leukopenia (12/7/5/0), neutropenia (29/16/24/24), nausea (7/2/10/5), diarrhea (5/0/10/0), and fatigue (5/2/10/5). Conclusions: From our results, we do not recommend consecutive use of S1 but CPT-11 or PTX monotherapy as second-line treatment in AGC refractory to S1 or SP. Clinical trial information: 000000677.

A randomized phase III trial of second-line chemotherapy comparing CPT-11 alone versus S-1 plus CPT-11 combination therapy in advanced gastric cancer refractory to first-line therapy with S-1 (JACCRO GC-05).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 87-87 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Kazuaki Tanabe ◽  
Masashi Fujii ◽  
Chikara Kunisaki ◽  
Akihito Tsuji ◽  
...  
Keyword(s):  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Group A ◽  
Group B ◽  
Line Chemotherapy

87 Background: In East Asia, S-1 + CDDP (SP) has been employed as first-line therapy for advanced gastric cancer (AGC) from the results of SPIRITS trial. Patients who were resistant to chemotherapy with S-1 in the first-line treatment were widely treated with taxane alone or CPT-11 alone as the second-line treatment. On the other hand, the response rate of combination therapy with S-1 is higher than that of CPT-11 alone. Then, we hypothesized that S-1 + CPT-11 prolongs survival in the second-line treatment comparing with CPT-11 alone after failure in the first-line treatment with S-1. (NCT00639327). Methods: Patients with AGC who confirmed disease progression by imaging after the first-line therapy with SP, S-1 + cocetaxel or S-1 alone except S-1 + CPT-11 were allocated into S-1 plus CPT-11 group (Group A) or CPT-11 alone group (Group B) as second-line chemotherapy. Patients who were relapsed to adjuvant chemotherapy with S-1 were not enrolled. Primary endpoint was overall survival, and secondary endpoints were progression free survival, response rate and adverse events. Results: From March 2008 to June 2011, 304 patients were enrolled, and 294 were eligible for analysis. The overall survival was 8.8 months (M) in the Group A and 9.4M in the Group B. There is no statistically significant difference in both groups (P=0.9156). The progression free survival was 4.8M in the Group A and 4.9M in the Group B (P=0.1568). The response rate was 7.6% in the Group A and 7.4% in the Group B. Grade 3 or higher leukopenia, neutropenia and febrile neutropenia were observed more frequently in the Group A than in the Group B. Conclusions: From our results, we do not recommend consecutive use of S-1 as second-line treatment in patients who are refractory to S-1 in first-line chemotherapy. Clinical trial information: 00639327.

Multicenter randomized phase II study of weekly docetaxel alone versus weekly docetaxel plus oxaliplatin as a second-line chemotherapy in patients with advanced gastric cancer: Preliminary response and safety results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14570-e14570 ◽  
Author(s):  
Jin Young Kim ◽  
Young Rok Do ◽  
Keon Uk Park ◽  
Hun-Mo Ryoo ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Therapy Group ◽  
Progression Free Survival ◽  
Combination Group ◽  
Second Line ◽  
Free Survival ◽  
Weekly Docetaxel ◽  
Line Chemotherapy

e14570 Background: Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990,000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods: The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m2 in docetaxel mono therapy group and docetaxel 36 mg/m2, oxaliplatin 80 mg/m2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results: Fifty two patients were enrolled; median age was 63 years; male (n=42) and female (n=10); docetaxel mono therapy (n=27) and docetaxel/oxalliplatin doublet therapy (n=25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (p=0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (p=0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (p=0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions: Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.

Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4067-4067
Author(s):  
Kohei Shitara ◽  
Keitaro Matsuo ◽  
Kei Muro ◽  
Atsushi Ohtsu
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Rank Correlation ◽  
Progression Free Survival ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Randomized Studies ◽  
Low Correlation ◽  
Line Chemotherapy

4067 Background: The correlation between progression-free survival (PFS) or time to progression (TTP) and overall survival (OS) has been evaluated in patients with advanced gastric cancer (AGC) who received first-line chemotherapy (Shitara, K et al. Invest New Drug 2011; Shitara K and Burzykowski T, et al, ASCO 2011). However, no corresponding analysis had been done in patients who underwent second-line chemotherapy for AGC. Methods: We evaluated the potential of PFS, TTP, response rate (RR), or disease control rate (DCR) to act as surrogates for OS in phase II and III trials of second-line chemotherapy for AGC by comprehensive literature-based analysis. Correlations between each endpoint and OS were evaluated by Spearman rank correlation coefficient (ρ). Subgroup analyses by trial region or type of failure to previous chemotherapy were also conducted. Results: Fifty-six trials, including four randomized studies, were selected for analysis and covered a total of 61 treatment arms and 3,038 patients; 34 studies were conducted in Asia, 20 studies in Non-Asian countries, and two studies in both regions. Median PFS were similar in Asian and Non-Asian trials (3.0 vs. 3.3 months). In contrast, median OS tended to be longer in Asian vs. Non-Asian trials (8.0 vs. 6.0 months; p<0.01). Median PFS/TTP and OS showed a moderate correlation with ρ of 0.51 (95% CI, 0.31-0.73). Correlation tended to be higher in PFS (ρ = 0.62) than TTP (ρ = 0.29) and higher in non-Asian trials (ρ = 0.73) than Asian trials (ρ = 0.32). Correlation between PFS/TTP and OS among the trials in which eligibility required failure to previous fluorouracil and cisplatin also showed low correlation (ρ = 0.48). The RR and DCR also did not show high correlation with OS (ρ = 0.30 for RR; 95% CI 0.04-0.56; ρ = 0.53 for DCR; 95% CI 0.31-0.75). The hazard ratio (HR) of PFS and OS in each arms of the four randomized studies showed a low correlation with ρ of 0.10. Conclusions: Our results indicate that PFS/TTP, RR, and DCR did not correlate sufficiently with OS to be used as surrogate endpoints in patients with AGC who underwent second-line chemotherapy. Further research is needed based on individual patient data from ongoing randomized trials.

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A multicenter AGEO study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 94-94 ◽  
Author(s):  
Juliette Palle ◽  
David Tougeron ◽  
Astrid Pozet ◽  
Emilie Soularue ◽  
Pascal Artru ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Univariate Analysis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Her2 Positive ◽  
Second Line Chemotherapy ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

94 Background: Trastuzumab in combination with platinum-based chemotherapy is the standard first line regimen in HER2 positive advanced gastric cancer. However, there is no data concerning continuation of trastuzumab beyond first line progression. Methods: This retrospective multicenter study include all consecutive patients with HER2 + advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received after progression of trastuzumab plus platinum-based chemotherapy, a second line chemotherapy with irinotecan, taxane or platinum salt, with or without trastuzumab. The prognostic variables with P values ≤0.10 in univariate analysis were eligible for the Cox multivariable regression model. Results: From August 2007 to March 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; PS 0-1, 71.2%) with advanced (metastatic : 99%) gastric (45.2%) or GEJ (54.8%) cancer. All patients had received first line treatment based on trastuzumab plus fluoropyrimidine and cisplatin (n=54; 51.9%) or oxaliplatin (n=50; 48.1%). As second line chemotherapy, 67 patients (64.4%) received FOLFIRI regimen, including 19 who have continued trastuzumab; 23 patients (22.1%) received a taxane regimen (paclitaxel or docetaxel), including 12 with trastuzumab; and 14 patients (13.5%) received a platinum-based chemotherapy (different from that used in first-line), including 8 with trastuzumab. When considering all regimens of second-line chemotherapy, continuation (n=39) versus discontinuation (n=65) of trastuzumab was significantly associated with an increase on PFS (4.4 vs 2.3 months; p=0.002) and OS (12.6 vs 6.1 months; p=0.001). In multivariate Cox model (including ECOG PS, tumor grade, number of metastatic site, and second-line treatment), continuation of trastuzumab was significantly associated with longer PFS (HR=0.56; 95%CI [0.35-0.89]; p=0.01) and OS (HR=0.47; 95%CI [0.28-0.79]; p=0.004). Conclusions: This study suggests that maintenance of trastuzumab plus second line chemotherapy beyond disease progression has clinical benefit in patients with HER2 positive advanced gastric cancer. These results deserve a prospective randomized validation.

A population-based study evaluating metastatic renal cell cancer (mRCC) patients treated with interferon (IFN) alone, first-line IFN then second-line sunitinib, or sunitinib alone

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15572-15572 ◽  
Author(s):  
C. K. Kollmannsberger ◽  
D. Y. Heng ◽  
N. Murray ◽  
K. N. Chi
Keyword(s):  
Overall Survival ◽  
Standard Treatment ◽  
Population Based ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact

15572 Background: Previously, immunotherapy agents such as IFN were the only treatments available for mRCC. Sunitinib has demonstrated prolonged progression free survival in a phase III trial but overall survival benefit has yet to be determined and few patients (pts) with poor MSKCC prognostic profiles were included. Methods: The province-wide BC Cancer Agency Registry was cross-referenced to the central pharmacy database to identify all pts with the diagnosis of mRCC who were treated with IFN and/or sunitinib. Sunitinib became available after October 2005 under an expanded access program or as standard treatment. Three groups of pts were identified: Group A consisted of pts who received IFN alone between January 2003 to October 2005, Group B was all pts who progressed on first-line IFN after October 2005 and subsequently were treated with second-line sunitinib and Group C was all pts treated with first-line sunitinib. Baseline characteristics and overall survival were collected on all patients. Results: A total of 75 patients were identified with 36 patients in Group A, 23 patients in Group B, and 16 patients in Group C. Data are reported from the initiation of IFN in Group A and the initiation of sunitinib in Groups B and C. Median follow-up was 6.0 months in group A, 7.6 months in group B, and 6.2 months in group C. Median age of treatment initiation (62y vs. 60y vs. 62y), number of metastatic sites (>1 site in 63% vs. 61% vs. 56%), and Karnofsky performance status (79 vs. 86 vs. 81) were similar between groups A, B and C, respectively. The MSKCC prognostic profiles were favorable, intermediate and poor in 26%, 51% and 23% in group A, 17%, 65% and 17% in group B and 31%, 38% and 31% in group C, respectively. The estimated 6-month overall survival in groups A, B and C was 56%, 72% and 100%, respectively (log rank A vs C p=0.009; log rank B vs C p=0.042). Conclusion: With the limitations of retrospective analysis and preliminary follow-up, the introduction of sunitinib as standard treatment into the general population of patients with mRCC appears to be associated with a longer overall survival compared to patients treated with IFN alone. Population-based analysis on the impact of the introduction of sunitinib therapy is ongoing. No significant financial relationships to disclose.

Combined analysis of three randomized phase III trials comparing S-1 monotherapy and S-1 combination therapy for first-line treatment of advanced gastric cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 49-49
Author(s):  
Madoka Takeuchi ◽  
Wataru Ichikawa ◽  
Kohei Shitara ◽  
Yu Sunakawa ◽  
Koji Oba ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Phase Iii Trials

49 Background: S-1 is the gold standard for first line therapy of advanced gastric cancer in Asia. There have been multiple meta-analyses published researching and comparing the efficacy and safety of S-1 monotherapy versus combination1,2. However there has been no analysis using actual trial data. Methods: Actual data from three randomized Phase III trials were combined to compare the efficacy of S-1 Monotherapy and S-1 combination therapy. The START trial, comparing S-1 and combination S-1 with docetaxel, SPIRITS, comparing S-1 and combination S-1 with cisplatin and TOP-002, comparing S-1 and S-1 combination with irinotecan, were merged and combined. For this analysis, the three S-1 arms were combined (n = 642) and the different S-1 combination therapy were combined (n = 617) creating two new treatment arms. The primary efficacy outcome of overall survival, progression free survival and subset analysis of overall survival stratified by baseline characteristics were performed. Results: A total of 1248 patients, including 210 Korean patients from the START were used in the analysis. The median overall survival days for S-1 combination and monotherapy was 382 [209, 648] and 321 [177, 597] and median progression free survival days for S-1 combination and monotherapy was 153 [81, 267] and 122 [61, 204]. Both overall survival (p = 0.0088 HR = 0.85 (0.76,0.96)) and progression free survival ( p = < 0.001 HR = 0.75 (0.67,0.85)) was significantly longer in the combination therapy arm compared to the monotherapy arm. Conclusions:Although there are limitations, the analysis re-confirms that S-1 combination therapy shows to be more efficacious compared to S-1 monotherapy for advanced gastric cancer patients. It must be noted that heterogeneity of the S-1 arm was not carefully considered when combining the S-1 data for the trials. In addition, the results are limited to the Asian (Japanese and Korean) population.

scholarly journals Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mashiro Okunaka ◽  
Daisuke Kotani ◽  
Ken Demachi ◽  
Akihito Kawazoe ◽  
Takayuki Yoshino ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Hazard Ratio ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Abstract Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9 months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P = 0.573). Median overall survival (OS) was 10.9 months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3 months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P = 0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC.

scholarly journals The relationship between peripheral neuropathy and efficacy in second-line chemotherapy for unresectable advanced gastric cancer: a prospective observational multicenter study protocol (IVY)

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hiroaki Tanioka ◽  
Takeshi Nagasaka ◽  
Futoshi Uno ◽  
Masafumi Inoue ◽  
Hiroyuki Okita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Neuropathy ◽  
Advanced Gastric Cancer ◽  
Primary Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Oncology Group ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

Abstract Background Paclitaxel is used in second-line conventional chemotherapies to manage patients with unresectable advanced gastric cancer (GC). Paclitaxel-induced peripheral neuropathy is a known adverse event leading to treatment discontinuation. Additionally, oxaliplatin which causes irreversible peripheral neuropathy is now commonly used in first-line chemotherapy for advanced GC in Japan. Thus, examining the incidence of peripheral neuropathy with paclitaxel after oxaliplatin is necessary to improve the quality of life and outcomes of patients with advanced GC in the second-line treatment setting. Methods This prospective observational multicenter study, (which we named IVY study), will evaluate the degree of chemotherapy-induced peripheral neuropathy (CIPN) and the efficacy of second-line chemotherapy for unresectable advanced GC. A patient neurotoxicity questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) will be used to assess CIPN during the second-line treatment. The key eligibility criteria are as follows: 1) unresectable or recurrent GC histologically confirmed to be primary adenocarcinoma of the stomach, 2) age over 20 years, 3) Eastern Cooperative Oncology Group performance status score of 0–2, 4) written informed consent following full study information is provided to the patient, 5) progression or intolerance for first-line chemotherapy comprising fluorinated pyrimidine and platinum anticancer drugs (cisplatin or oxaliplatin) for advanced GC. 6) presence of evaluable lesions as confirmed using a computed tomography (CT) or magnetic resonance imaging. A total of 200 patients is considered to be appropriate for inclusion in this study. Discussion The results of this study will provide some information on CIPN with the sequential usage of oxaliplatin as first-line chemotherapy to paclitaxel as second-line chemotherapy in clinical practice. Trial registration This trial is registered in the University Hospital Medical Information Network’s Clinical Trials Registry with the registration number UMIN000033376 (Registered 11 July 2018).

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