Randomized phase III study of 5-fluorouracil continuous infusion (5FUci) versus methotrexate and 5-FU sequential therapy (MF) in gastric cancer with peritoneal metastasis (JCOG0106)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4545-4545 ◽  
Author(s):  
K. Shirao ◽  
N. Boku ◽  
Y. Yamada ◽  
K. Yamaguchi ◽  
T. Doi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Final Analysis ◽  
Sequential Therapy ◽  
Nutrition Support ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Intestinal Stenosis ◽  
Secondary Endpoints ◽  
Phase Iii Study

4545 Background: Gastric cancer (GC) with peritoneal metastasis (PM) often complicates ascites or intestinal stenosis and the prognosis is still poor. Anti-cancer drugs generally can not be administered for such patients (pts) due to the risk of serious and prolonged adverse events. However, 5FU-based chemotherapy is reportedly relatively safe for PM. We conducted a phase III study to investigate the superiority of MF over 5FUci for GC with PM with a primary endpoint of overall survival (OS) and secondary endpoints of toxicities, ingestion-possible survival (IPS) in pts with initially possible ingestion and proportion of ingestive improvement (%II) in pts requiring nutrition support. Methods: Eligibility criteria included pts with histologically proven gastric adenocarcinoma; inoperable or recurrent GC; PM with radiologically confirmed intestinal stenosis or ascites; 20–75 years old; PS 0–2; no prior treatment except surgery or adjuvant chemotherapy. Treatment with 5FUci (800mg/m2/d, civ, d1–5, q4w) or MF (methotrexate, 100mg/m2, iv, followed 3 h later by 5FU, 600mg/m2, iv, with leucovorin rescue, q1w) were continued until disease progression or unacceptable toxicities. Projected sample size was 236 in total, which had 80% power to detect 40% increase of median OS in MF with 1-sided alpha 0.05. Results: A total of 237 pts were randomized between Oct 2002 and Apr 2007. Final analysis was performed in Dec 2008 when 224 pts (95%) were dead. Results of OS are shown in Table . Median IPS was 8.1M for 5FUci(n=102) and 9.0M for MF(n=103) (p=0.60). %II was 41%(7/17) for 5FUci and 57%(8/14) for MF (p=0.48). Frequencies (%) of grade 4 neutropenia, grade >3 febrile neutropenia, infection with neutropenia, anemia, anorexia, diarrhea, abdominal pain within 6M, and treatment related death (5-FUci/MF) were 0/9, 0/3, 0/5, 10/16, 27/34, 1/10, 5/10 and 2/1, respectively. Conclusions: MF could not become new standard therapy for GC with PM. [Table: see text] 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 study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA4513-LBA4513 ◽  
Author(s):  
N. Boku ◽  
S. Yamamoto ◽  
K. Shirao ◽  
T. Doi ◽  
A. Sawaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Final Analysis ◽  
Phase Iii ◽  
Survival Times ◽  
Time To Treatment Failure ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Significant Superiority

LBA4513 Backgrounds: We conducted a 3-arm phase III study to investigate superiority of CP and non-inferiority of S-1 to 5-FU for advanced gastric cancer in the primary endpoint of overall survival (OS) and secondary endpoints of response rate (RR), time to treatment failure (TTF), non-hospitalized survival (NHS) and toxicities. Methods: Treatments with 5-FU (800mg/m2/d, ci, d1–5, q4w), CP (irinotecan, 70mg/m2, div, d1&15 and cisplatin, 80mg/m2, div, d1, q4w) and S-1 (40mg/m2, b.i.d., d1- 28, q6w) were continued until disease progression or unacceptable toxicities. Tumors were evaluated every two months. With 230 patients (pts) per arm, this study had 80% power to demonstrate 10% superiority of CP and non-inferiority with 5% margin (hazard ratio, HR=1.16) of S-1 and 0.05 study-wise 1-sided alpha. Results: 704 pts having unresectable or recurrent gastric adenocarcinoma with/without target lesions (TL) were randomized between Nov 2000 and Jan 2006. Final analysis was performed in Feb 2007 when 601 pts (85%) were dead. The results of OS are shown in Table . Median TTF/NHS were 2.3M/7.2M for 5-FU, 3.7M/9.5M for CP, and 4.0M/9.2M for S-1. Incidences (%) of grade 4 neutropenia, grade ≥3 febrile neutropenia, infection with neutropenia, anorexia, diarrhea within 6M, and treatment related death (5- FU/CP/S-1) were 0/37/0, 0/9/0, 0/8/0, 13/33/12, 0/9/8, and 0/1.3/0.4. In the subset having TL, RRs of 5-FU/CP/S-1 (n=175/181/175) were 9%/38%/28%, and their median survival times (MST) were 9.0M/12.1M/10.5M and HRs to 5-FU were 0.78 (95%CI, 0.63–0.98) for CP and 0.85 (0.68–1.06) for S-1. In the subset not having TL, the MSTs of 5-FU/CP/S-1 (n=59/55/59) were 13.5M/14.4M/18.1M and HRs were 1.02 (0.68–1.55) for CP and 0.82 (0.55–1.24) for S-1. Conclusions: S-1 showed a significant non-inferiority to 5-FU. Although CP did not show statistically significant superiority to 5-FU in all pts, it may have a benefit for some subgroups such as pts with measurable metastatic diseases. [Table: see text] [Table: see text]

Efficacy analyses of a randomized phase III clinical trial of combined therapy with CPT-11/CDDP versus CPT-11 alone in patients with advanced or recurrent gastric cancer refractory to prior S-1 chemotherapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 69-69
Author(s):  
Hitoshi Inagaki ◽  
Kazuhiro Nishikawa ◽  
Kazumasa Fujitani ◽  
Naotoshi Sugimoto ◽  
Tadashi Shigematsu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Combined Therapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Second Line ◽  
Eligibility Criteria ◽  
Recurrent Gastric Cancer ◽  
Secondary Endpoints

69 Background: There has been no established regimen as the second-line treatment for advanced gastric cancer (AGC), though CPT-11 showed survival benefit over BSC. Combination of CPT-11 with CDDP is one of the promising regimens as the second-line chemotherapy after S-1 mono-therapy. Methods: This is a prospective, multicenter randomized phase III study comparing CPT-11+CDDP (Arm A) vs. CPT-11 alone (Arm B) in patients with advanced or recurrent gastric cancer resistant to S-1 mono-therapy or prior adjuvant chemotherapy using S-1. Eligibility criteria include histologically confirmed gastric adenocarcinoma, age over 20 years old, PS: 0-2, adequate organ functions and written informed consent. Arm A: patients received CPT 11 60mg/m2 and CDDP 30mg/m2 on day 1, q2w. Arm B: patients received CPT-11 150mg/m2on day 1, q2w. Stratification was made according to PS, advanced or recurrence cases, institution and presence or absence of measurable target lesions. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), time to treatment failure (TTF), response rate (RR), and safety. Results: 168 patients were registered between 2007 and 2011. Arm A (n=84) and Arm B (n=84) were well balanced for baseline factors. Median age was 67 vs 68 years old, number of advanced/recurrence after resection was 36/48 vs 35/49, and median number of treatment course was 5 vs. 6 (range:0-31, 0-39). Common grade 3/4 toxicities in Arm A vs. Arm B were neutropenia; 35.4% vs. 27.2% (p=0.259), anemia; 15.9% vs. 3.7% (p=0.009), diarrhea; 0% vs. 2.5% (p=0.152), nausea; 3.7% vs. 4.9% (p=0.687), vomiting; 1.2% vs. 3.7% (p=0.305), anorexia 6.1% vs. 8.6% (p=0.534). The rate of patients who were required dose modification for these toxicities was 22.9% vs 21.4%. The pooled OS, PFS and RR for both Arms were as follows; 13.8 months (95% CI, 10.7 to 17.5), 4.5 months (95% CI, 3.7 to 5.1), and 13.7%. Conclusions: There was no significantly difference in the incidence and severity of adverse events in both Arms except for anemia. Updated efficacy data of secondary endpoints will be presented. Clinical trial information: UMIN000002571.

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.

A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
Yoshikazu Kotani ◽  
Miyako Satouchi ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
Nobuyuki Yamamoto ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Severe Diarrhea ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
To Receive

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.

Phase III study of intraperitoneal paclitaxel plus s-1/paclitaxel compared with s-1/cisplatin in gastric cancer patients with peritoneal metastasis: PHOENIX-GC trial.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 4014-4014 ◽  
Author(s):  
Hironori Ishigami ◽  
Yoshiyuki Fujiwara ◽  
Ryoji Fukushima ◽  
Atsushi Nashimoto ◽  
Hiroshi Yabusaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Metastasis ◽  
Phase Iii ◽  
Phase Iii Study ◽  
Gastric Cancer Patients

Primary results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Masanori Terashima ◽  
Yuichiro Doki ◽  
Yukinori Kurokawa ◽  
Junki Mizusawa ◽  
Hitoshi Katai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Operation Time ◽  
Final Analysis ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Hospital Death ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Grade 3

5 Background: The role of bursectomy dissecting the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon for preventing peritoneal metastasis had long been controversial. We conducted a phase III trial evaluating the role of bursectomy in patients with subserosal (SS) / serosal (SE) gastric cancer. Patient accrual had been completed on Mar. 2015. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival. A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: Between Jun 2010 and Mar 2015, 1,204 patients were accrued from 57 institutions (non-bursectomy 602, bursectomy 602). Patients’ background and operative procedures were well balanced between the arms. After completion of patient enrollment, the second interim analysis was performed on Sep 2016, with 54% (196/363) of the expected events observed. The 3y-survival were 86.0% (95%CI, 82.7 to 88.7) in non-bursectomy arm and 83.3% (95%CI, 79.6 to 86.3) in bursectomy arm. Hazard ratio for bursectomy was 1.075 (98.5%CI: 0.760 to 1.520) with predictive probability in favor of bursectomy at the final analysis of 12.7%. These results led to early study termination based on the recommendation of the Data and Safety Monitoring Committee. Operation time was longer (median 222 min vs 254 min) and blood loss was larger (230 ml vs 330 ml) in bursectomy arm; however, the incidence of patients received blood transfusion was not different between the arms (4.8% vs 4.5%). Although the incidence of pancreatic fistula was a bit higher in bursectomy arm (2.5% vs 4.8%), the incidence of Grade 3 or higher complications was not different between the arms (11.6% vs 13.3%). Five patients in non-bursectomy arm and one patient in bursectomy showed in-hospital death. Conclusions: Although bursectomy can be safely performed without increasing morbidity and mortality, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.

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