Randomized phase III study of S-1 alone versus S-1 + cisplatin in the treatment for advanced gastric cancer (The SPIRITS trial) SPIRITS: S-1 plus cisplatin vs S-1 in RCT in the treatment for stomach cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4514-4514 ◽  
Author(s):  
H. Narahara ◽  
W. Koizumi ◽  
T. Hara ◽  
A. Takagane ◽  
T. Akiya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Primary Endpoint ◽  
Standard Treatment ◽  
High Response Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase Iii Study

4514 Background: S-1 has been widely used against advanced gastric cancer (AGC) not only as monotherapy but also in combination with other cytotoxic compounds. Results of a phase I/II study combining S-1 + cisplatin (CDDP) were very encouraging with a high response rate (RR) of 76%, and the MST (Median Survival Time) of 383 days (Koizumi W et al, Br J Cancer, 2003). Based on these results, a phase III study comparing S-1 alone with S-1 + CDDP has been conducted to further evaluate the efficacy and safety for S-1 + CDDP as a standard treatment for AGC. Methods: This is a randomized, controlled, open-label, parallel, multicenter study. Patients (pts) are randomized to one of two treatment arms. Arm A: Pts receive oral S-1 (40 mg/m2) twice daily 28 days followed by 14 days rest. Arm B: Pts receive oral S-1 (40 mg/m2) twice daily 21 days followed by 14 days rest plus CDDP (60 mg/m2) iv on day 8. Eligibility criteria included unresectable/recurrent AGC, age 20–74, no prior chemotherapy for AGC. Primary endpoint was overall survival (OS). Main secondary endpoints included RR, time to treatment failure (TTF) and toxicity. Based on planned sample size of 284 pts, the trial was designed to have 90% power to detect an improvement in median OS from 8 to 12 months (2-sided log-rank test; significance level 0.05). Results: 305 pts (Arm A/B, 152/153) were randomized between Mar 2002 and Nov 2004. The eligible pts were 299 (Arm A/B, 150/149). Median age was 62.0/61.5 yrs. At a 2 yrs follow-up since last patient in, the MST for Arm A was 335.5 days (95%CI: 292.0 - 402.0) and for Arm B was 396.0 days (95%CI: 342.0 - 471.0). The OS for Arm B was superior to Arm A (log-rank p=0.0366, hazard ratio: 0.774, 95% CI: 0.608 - 0.985). RR was 31.1% for Arm A and 54.0% for Arm B. In Arm A vs Arm B, the most common grade 3/4 toxicities were: leucopenia, 2.0% vs 11.5%; neutropenia, 10.7% vs 39.9%; anemia (decreased Hb), 4.0% vs 25.7%; nausea, 1.3% vs 11.5%; anorexia, 6.0% vs 30.4%. No treatment related death was observed. Conclusions: The combination treatment of S-1 and CDDP met primary endpoint of OS, and was found to be effective and well tolerated in pts with AGC. Accordingly, this regimen can be regarded as one of first-line standard treatment for AGC. No significant financial relationships to disclose.

Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 119-119 ◽  
Author(s):  
Jin Matsuyama ◽  
Yukinori Kurokawa ◽  
Kazuhiro Nishikawa ◽  
Yutaka Kimura ◽  
Atsushi Takeno ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Oral Intake ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Phase Iii Study

119 Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.

Randomized phase III trial of standard D2 versus D2 + para-aortic lymph node (PAN) dissection (D) for clinically M0 advanced gastric cancer: JCOG9501

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA4015-LBA4015 ◽  
Author(s):  
M. Sasako ◽  
T. Sano ◽  
S. Yamamoto ◽  
A. Nashimoto ◽  
A. Kurita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Disease Free Survival ◽  
Operation Time ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Rank Test ◽  
R0 Resection ◽  
Eligibility Criteria ◽  
Curative Intent

LBA4015 Background: The INT-0116 study proved the efficacy of radiochemotherapy after R0 resection for gastric cancer and thus the importance of the local control and the insufficiency of D0/1 surgery. Recently D2 surgery was for the first time proven to improve the survival compared with D1 in a Taiwanese RCT (Lancet Oncol 2006). In our study, D2+PAND was compared with D2 in a RCT. Low operative mortality has been reported (Sano et al. J Clin Oncol 2004) and we now present the survival results. Methods: Eligibility criteria included; histologically proven adenocarcinoma, cT2b-T4, cM0, no macroscopic metastasis to the PAN, negative lavage cytology, adequate organ function, and age <76. Linitis plastica was excluded. Eligible pts were randomly assigned to D2 with or without PAND during surgery. All patients were followed without adjuvant therapy until recurrence. The primary endpoint was overall survival (OS) to be compared by stratified log-rank test. Assuming 256 eligible pts in each arm, the study had 75% power to detect 0.73 hazard ratio for D2+PAND to D2 in OS at 0.05 one-sided alpha. Results: Between 07/1995 and 04/2001, 523 pts were randomized (263 to D2 and 260 to D2+PAND). Baseline characteristics were well balanced between the arms. At the time of the final analysis on 23/03/06, 191 (96 and 95, in D2 and D2+PAND, respectively) had died. The 3- and 5-year OS were 76% and 69% in D2 and 76% and 70% in D2+PAND, respectively (p = 0.57, Hazard ratio was 1.03 (95% CI: 0.77–1.37)). Disease free survival did not show any difference between the groups as well. Median operation time was 63 minutes longer and median blood loss was 230 ml larger in D2+PAND than in D2. There was no difference in the incidence of major surgical complications and hospital mortality (0.8% in both arms). Conclusions: D2 or D2+PAND could be carried out safely and showed excellent survival for advanced gastric cancer treated with curative intent. PAND could not improve the survival achieved by D2. General use of PAND should be avoided. No significant financial relationships to disclose.

Lapatinib Plus Paclitaxel Versus Paclitaxel Alone in the Second-Line Treatment ofHER2-Amplified Advanced Gastric Cancer in Asian Populations: TyTAN—A Randomized, Phase III Study

2014 ◽  
Vol 32 (19) ◽  
pp. 2039-2049 ◽  
Author(s):  
Taroh Satoh ◽  
Rui-Hua Xu ◽  
Hyun Cheol Chung ◽  
Guo-Ping Sun ◽  
Toshihiko Doi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Iii ◽  
Similar Proportion ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Open Label ◽  
Significant Difference ◽  
Phase Iii Study

PurposeIn Asian countries, paclitaxel once per week is used as second-line treatment in advanced gastric cancer, including human epidermal growth factor receptor 2 (HER2) –positive tumors. The role of anti-HER2 agents, including lapatinib, in this setting and population is unclear.Patients and MethodsTyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m2or paclitaxel alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), time to progression (TTP), overall response rate (ORR), time to response, response duration, and safety. Analyses were based on immunohistochemistry (IHC) and gastrectomy status, prior trastuzumab therapy, and regional subpopulations.ResultsMedian OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044), with no significant difference in median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001). Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%).ConclusionLapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population.

scholarly journals Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer

2015 ◽  
Vol 26 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Y. Yamada ◽  
K. Higuchi ◽  
K. Nishikawa ◽  
M. Gotoh ◽  
N. Fuse ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Iii ◽  
Phase Iii Study

Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: A randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4540-4540 ◽  
Author(s):  
P. C. Thuss-Patience ◽  
A. Kretzschmar ◽  
T. Deist ◽  
A. Hinke ◽  
D. Bichev ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Phase Iii ◽  
Open Label ◽  
Logrank Test ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
Line Chemotherapy

4540 Background: Up to now the value of 2nd-line therapy for metastatic gastric cancer is unclear. So far there are no randomized phase III data comparing 2nd-line chemotherapy to BSC. Irinotecan has proven activity in 1st-line therapy. In this randomized phase III study we compared irinotecan to BSC to evaluate the value of 2nd- line chemotherapy for gastric cancer. Methods: Prospective multicenter randomized phase III study, open label. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma. Objective tumor progession (PD) within 6 months after 1st- line chemotherapy. ECOG PS 0–2. Statistics: Primary endpoint: Overall survival (OS). Hypothesis: H1: OS(Irinotecan)>OS(BSC). Calculated number of pts needed (power 80%, alpha error 5%): 60 pts per arm. Stratification for a) PD less versus (vs) more than 3 months after 1st line chemotherapy, b) ECOG PS 0/1 vs 2. Treatment: Arm A: Irinotecan 250mg/m2 q3w (1st cycle) to be increased to 350 mg/m2, depending on toxicity. Arm B: BSC Results: Between Oct 2002 and Dec 2006 40 pts were randomized. The study was closed prematurely due to poor accrual. Arm A:21 pts, arm B 19 pts. Median age A: 58 yrs (43–73), B: 55 yrs (35–72); PD less vs more than 3 months after 1st-line chemotherapy: A: 18 / 3, B: 17 / 2pts. ECOG PS 0/1 vs 2: A: 17/ 4, B: 14/ 5pts. Pre-treatment with cisplatin: A: 21, B:19 pts. Arm A: 68 cycles administered in 21 pts. Toxicity: (main CTC grade 3/ 4): Nausea 1 pt, vomiting 1 pt, diarrhoea: 5 pts, neutropenic fever: 2 pts, data incomplete 6 pts. In 37% of 19 evaluable pts irinotecan dose was escalated to 350mg/m2. Response (19 pts evaluable): No objective responses, SD 58%, PD 42%. Improvement of tumor related symptoms: 44% of pts in arm A, 5% in arm B. Survival: (evaluable pts arm A 21, arm B 18): median survival arm A: 123 days (95%CI 95–216), arm B 72.5 days (95%CI 41–106); OS: HR=2.85 (95%CI 1.41–5.79), Logrank test (two-sided): p=0.0027. Conclusions: To our knowledge this is the first randomized phase III study investigating 2nd- line chemotherapy in gastric cancer. Irinotecan as 2nd-line chemotherapy significantly prolongs overall survival compared to BSC. 2nd-line chemotherapy can now be considered as a proven option in gastric cancer. [Table: see text]

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