Phase 1 study of paclitaxel, cisplatin, and 5-fluorouracil (TCF) in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14134-14134
Author(s):  
K. Yokoi ◽  
K. Omura ◽  
M. Hirano ◽  
T. Hara ◽  
Y. Munemoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase 1 ◽  
Fixed Dose ◽  
Clinical Effects ◽  
Prior Chemotherapy Regimen ◽  
Disease Stabilization ◽  
Unresectable Gastric Cancer ◽  
Grade 3 ◽  
Anti Tumor Activity

14134 Background: Paclitaxel is effective against gastric cancer with serosal involvement and/or peritoneal dissemination. Combination of cisplatin and 5-fluorouracil is also active against advanced gastric cancer. Therefore, we designed a phase I trial of a combination of paclitaxel, cisplatin and 5-fluorouracil (TCF) to explore potential synergistic effect. Methods: Eligible patients had metastatic or unresectable gastric cancer with up to 1 prior chemotherapy regimen. The fixed dose of cisplatin 25 mg/m2 and paclitaxel 80 mg/m2 with escalation dose of 5-fluorouracil from 300 mg/m2 to a maximum of 600 mg/m2 on days 1, 8 and 15 of a 28 day schedule were administered. MTD and anti-tumor activity were evaluated. Results: No grade 3 or 4 toxicities at least possibly related to the treatments resulting in DLT were observed on every dose level. The clinical effects were determined in 3 patients with measurable lesions out of 7 cases. There were 2 partial responses, and disease stabilization was seen in one patient. Conclusions: Combination of paclitaxel, cisplatin and 5-fluorouracil (TCF) is considered to be feasible, well tolerated and active in patients with advanced gastric cancer and warrants further examination in a phase II trial. No significant financial relationships to disclose.

A phase I study of S-1 administration and a 24-h infusion of cisplatin plus paclitaxel in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4074-4074
Author(s):  
H. Iwase ◽  
M. Shimada ◽  
T. Tsuzuki ◽  
M. Okeya ◽  
K. Kobayashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Advanced Gastric Cancer ◽  
Dose Level ◽  
Combination Chemotherapy ◽  
Single Agent ◽  
Fixed Dose ◽  
Hematological Toxicity ◽  
Level 3 ◽  
Grade 3

4074 Background: S-1 may have a major role in the treatment of gastric cancer as single agent or as a component of combination chemotherapy in Japan. We previously reported a multicentric phase II study of S-1 combined with a 24-h infusion of cisplatin in patients with advanced gastric cancer. This combination was active, safe and had the possibility of being combined with other anticancer drug. Combination chemotherapy with S-1 and cisplatin plus paclitaxel for advanced gastric cancer might yield a stronger antitumor effect. The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD), and the preliminary antitumor activity of S-1 and cisplatin plus paclitaxel for advanced gastric cancer. Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1, and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160, and 180 mg/m2). The DLT was defined as any of the following: grade 3 neutropenia lasting more than 5 days, grade 4 hematological toxicity, grade 3 non-hematological toxicity, or treatment delay of greater than 2 weeks as a result of toxicity. Results: Twenty patients were enrolled. Hematological and non- hematological toxicity of over grade 2 was not observed at dose level 1 and 2. Three patients started at dose level 3. One developed grade 3 neutropenia for 5 days following by grade 2 neutropenia lasted more than 10 days. Five more patients were added at this level. The treatment was delayed over 2 weeks in 1 out of 8 patients. Three patients started at dose level 4. One developed grade 3 neutropenia and needed longer than 14 days to recover. Three patients added this level. In total, at dose level 4 the treatment was delayed over 2 weeks in 3 out of 6 patients as a result of neutropenia. We considered level 4 is the MTD and the RD of paclitaxcel was 160 mg/m2 (dose level 3). The overall response rate was 75%. Conclusions: Triple combination chemotherapy consisting of S-1, cisplatin, and paclitaxel showed a tolerable dose of adverse reactions and favorable antitumor activity for gastric cancer. No significant financial relationships to disclose.

A dose-finding study for irinotecan, cisplatin, and S-1 (IPS) in patients with advanced gastric cancer (OGSG 1106).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 144-144
Author(s):  
Hiroki Yukami ◽  
Masahiro Goto ◽  
Takayuki Kii ◽  
Tetsuji Terazawa ◽  
Toshifumi Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Febrile Neutropenia ◽  
Phase I ◽  
Advanced Gastric Cancer ◽  
Phase I Study ◽  
Fixed Dose ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

144 Background: In Japan, S-1 plus cisplatin is regarded as one of the standard first line treatment of advanced gastric cancer (AGC). However, the prognosis of AGC remains dismal. The development of more effective chemotherapeutic regimen is thus warranted. A combination of irinotecan, cisplatin, and S-1 (IPS) can be a promising triplet therapy for advanced gastric cancer. We conducted a phase I study of IPS to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and recommended dose (RD), and to assess its safety and antitumor activity in patients with AGC. Methods: This phase I study was designed and conducted in a 3 + 3 manner to determine the recommended dose (RD) of IPS for the subsequent phase II study. Patients received an escalating dose of intravenous irinotecan (level 1: 100/level 2: 125/level 3: 150 mg/m²) on day 1, a fixed dose of intravenous cisplatin (60 mg/m²) on day 1, a fixed dose of S-1 (80 mg/m² b.i.d.) orally on days 1-14, every 4 weeks. Results: Twelve patients were enrolled between June 2013 and February 2017. During the first cycle, one of the six patients in level 1 and two of six patients in level 2 developed the DLT (grade 4 leucocytopenia and grade 3 febrile neutropenia). The MTD of irinotecan was 125 mg/m 2 (level 2) and the RD of irinotecan was considered to be 100 mg/m² (level 1). The most common grade 3 or 4 adverse events included neutropenia 75 % (9/12), anemia 25% (3/12), anorexia 8% (1/12), and febrile neutropenia 17% (2/12). Among six patients with measurable lesions, the response rate was 66.7% (4/6) [95% CI, 33.3-90.7%]. Two patients were performed R0 resection after IPS, with one patient achieved pathological complete response. The median survival time is under analysis. Conclusions: RD of IPS was determined to be 100 mg/m² of irinotecan, 60 mg/m² of cisplatin, and 80 mg/m² of S-1. Our data showed that this regimen provided acceptable antitumor activity and a favorable toxicity profile. Further evaluation of this regimen is warranted. Clinical trial information: UMIN000006864.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Safety and efficacy of apatinib as third or later line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma: A post-marketing phase IV study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Jin Li ◽  
Shukui Qin ◽  
Lu Wen ◽  
Junsheng Wang ◽  
Wenying Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Line Treatment ◽  
Ecog Performance Status ◽  
Safety And Efficacy ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Grade 3 ◽  
Phase Iv

e16034 Background: Apatinib, a small molecule multi-target tyrosine kinase inhibitor with high selectivity for VEGFR-2, has been approved for the treatment of advanced gastric cancer or gastroesophageal adenocarcinoma in China by significantly improving progression-free survival (PFS) and overall survival (OS). Here, we report safety and efficacy data from an open-label, single-arm, multicenter, phase IV trial of apatinib as a third-line or later line treatment for advanced gastric cancer. Methods: Eligible patients had histologically or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate haematological and hepatic function; and failure of at least two lines of chemotherapy. Patients received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included PFS and OS. Results: The intention-to-treat population (ITT) included 2004 patients. At baseline, the median age was 59 (range, 19-85) years, ECOG performance status of 0/1/2 (%) was 15.4/68.8/15.1, and stage III/IV was 3.5/96.4; 98.8% had metastases, and among which metastatic foci≤2/ > 2 was 64.5/34.2 (%), respectively. 89.6% of the patients were given apatinib 500mg as the initial does and the median treatment duration was 56 days. After a median follow-up of 126.5 days, adverse events (AEs) occurred in 95.1% of the patients and 70.3% were grade ≥3. 87.9% of the patients experienced treatment-related AEs (TRAEs), of which 51% had grade ≥3, 12.3% and 16.8% reduced dose and discontinued the treatment, respectively. 57 (2.9%) TRAEs-related deaths were reported, mainly because of gastrointestinal bleeding (16 cases), upper gastrointestinal haemorrhage (7), cerebral haemorrhage (2), and gastric perforation (1). The incidence of TRAEs of special interest was 74.3%; 38.1% of patients developed grade≥3, mainly including hypertension (26.3%), bleeding (5.1%), proteinuria (4.5%), and hand-foot syndrome (3.1%). In an ITT population, median PFS was 2.7 months (95%CI 2.23-2.79) and median OS was 5.8 months (95% CI 5.42-6.11). Conclusions: This study confirms that apatinib has a well-established and manageable safety profile and survival benefit as third or later line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma. Clinical trial information: NCT02426034.

scholarly journals Clinical effects of preoperative selective arterial chemotherapy in patients with advanced gastric cancer

2014 ◽  
Vol 22 (21) ◽  
pp. 3118
Author(s):  
Xue-Hua Xing ◽  
Lin Wang ◽  
Li Sheng ◽  
Da-Tong Sun ◽  
Chun Qiu
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Clinical Effects

scholarly journals Regional hyperthermia combined with chemotherapy in advanced gastric cancer

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 85-90
Author(s):  
Hongming Fang ◽  
Yaping Zhang ◽  
Zhibing Wu ◽  
Xiaoyan Wang ◽  
Hui Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Prognostic Score ◽  
Glasgow Prognostic Score ◽  
Disease Stage ◽  
Regional Hyperthermia ◽  
Clinicopathologic Characteristics ◽  
Treatment Plans ◽  
Grade 3 ◽  
Clinical Potential

AbstractIntroductionThis study aims to investigate the potential effects of regional hyperthermia combined with chemotherapy (RHCT) as a treatment strategy for advanced gastric cancer (AGC).Method118 AGC patients were randomly divided into treatment plans with chemotherapy (CT) alone or with RHCT. The prognostic value of clinicopathologic characteristics was assessed in terms of overall survival of AGC patients.ResultsThe disease control rate was determined to be 70.9% and 46.0% for the RHCT and CT group, respectively (P = 0.006). The median survival was determined to be 23.5 months for the RHCT group and 14.0 months for the CT group (P = 0.010). The 3-year survival rate for the RHCT group was 11.4% and 0% for the CT group (P = 0.018). No difference in grade 3 or 4 adverse events was observed between the two groups (P > 0.05). Multivariate analysis showed that hyperthermia, disease stage, Glasgow prognostic score, and abdominal metastasis were closely associated with the prognosis of these AGC patients.ConclusionThe study suggests that combination treatment with RHCT for AGC has clinical potential for both short- and long-term curative effects without compromising toxicity.

scholarly journals Hemostatic radiotherapy for inoperable gastric cancer: a pilot study

2020 ◽  
Vol 93 (1111) ◽  
pp. 20190958
Author(s):  
Osamu Tanaka ◽  
Akihiko Sugiyama ◽  
Tatsushi Omatsu ◽  
Masahiro Tawada ◽  
Chiyoko Makita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prospective Study ◽  
Response Rate ◽  
Disease Free Survival ◽  
Fixed Dose ◽  
Free Survival ◽  
Entire Cohort ◽  
Randomized Controlled Studies ◽  
Low Toxicity ◽  
Grade 3

Objective: Standard treatment for progressive gastric cancer with bleeding includes hemostatic radiotherapy (RT); however, the only prospective study using a fixed dose with fractions during hemostatic RT did not introduce re-irradiation. Therefore, we determined the utility of RT including re-irradiation for gastric cancer. Methods: In this study, 31 patients with gastric cancer and bleeding were treated with an initial dose of 20 Gy/5 fractions for the whole stomach and a salvage dose of 15 Gy/5 fractions for the partial stomach. Patients achieving hemostasis, defined as a stable hemoglobin level within 30 days following irradiation, were considered responders, whereas those with no cessation of bleeding and those with re-bleeding within 30 days of irradiation were considered non-responders. We evaluated response rate, disease-free survival, overall survival (OS), re-irradiation, and adverse events (AEs). Results: The response rate of initial RT was 80% (25/31). 6 of the 25 patients underwent re-irradiation, and all 6 were responders (100%). The median OS was significantly different among the entire cohort and one-time irradiation and re-irradiation groups (91, 76, and 112 days, respectively). No AEs of grade ≥3 were observed. Initial low-dose RT followed by reirradiation was effective in reducing AEs and did not cause any further AEs. Conclusion: Hemostatic RT was an effective approach with low toxicity, and re-irradiation was effective and tolerable, with no patients developing severe AEs. Further, randomized controlled studies are warranted to determine the ideal dose and number of fractions for initial RT in patients with gastric cancer and bleeding. Advances in knowledge: In this prospective study on hemostatic radiotherapy for gastric cancer, the response rate was 80% using a fixed dose of 20 Gy/5 fractions and the salvage dose of 15 Gy for re-bleeding was effective. Future comparative studies should include other doses with 20 Gy as a control.

Irinotecan plus S-1 (IRIS) versus S-1 alone as first line treatment for advanced gastric cancer: Preliminary results of a randomized phase III study (GC0301/TOP-002)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
K. Chin ◽  
H. Iishi ◽  
H. Imamura ◽  
O. Kobayashi ◽  
H. Imamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Survival ◽  
Single Agent ◽  
Rest Period ◽  
Phase Iii ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
Gastric Cancer Patients

4525 Background: Irinotecan has single agent activity and combination activity with S-1 reportedly in phase I/II studies with advanced gastric cancer patients (pts). S-1, oral fluoropyrimidine, also has activity on gastric cancer. A multicenter, randomized phase III trial comparing IRIS to S-1 alone in advanced gastric cancer was conducted. Methods: Pts with previously untreated gastric cancer were randomized to Arm A (oral S-1 80 mg/m2/day from day 1 to 28 followed by a 14-day rest period), or Arm B (oral S-1 80 mg/m2/day from day 1 to 21 and intravenous irinotecan 80 mg/m2 on days 1 and 15 followed by a 14-day rest). Treatment was continued unless disease progression was observed. Inclusion criteria: PS (ECOG) of 0 to 2; adequate major organ functions. Primary endpoint was overall survival. Results: From June 2004 to November 2005, 326 pts were randomized to arm A (162 pts) and arm B (164 pts). Pts characteristics (arm A vs. arm B) were as follows: median age: 63 vs. 63 years, PS 0–1: 97% vs. 97%, and distribution of subtype of intestinal/diffuse/others: 44%/55%/1% vs. 41%/58%/1%. Among 187 RECIST-evaluable pts (93 vs 94) reviewed by independent review panel, best response rates were 26.9% for arm A and 41.5% for arm B(p=0.035). Among 319 toxicity-evaluable patients (161 vs 158), grade 3 or 4 toxicities for arm A vs arm B (% of pts) were as follows: neutropenia 9.3% vs 26.6%, diarrhea 5.6% vs 15.8%, anorexia 9.9% vs 15.8%, nausea 3.7% vs 7.0%, vomiting 0.6% vs 2.5%. Conclusions: IRIS is effective, and well tolerated in pts with advanced gastric cancer. Survival analysis is underway. No significant financial relationships to disclose.

Pharmacogenetics of peripheral neuropathy in elderly patients (>65 years) with advanced gastric cancer receiving oxaliplatin-based chemotherapy within a randomized phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14515-e14515
Author(s):  
E. Goekkurt ◽  
S. Al-Batran ◽  
L. Obermann ◽  
C. Pauligk ◽  
N. Homann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Neuropathy ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Cox Regression ◽  
Phase Ii Study ◽  
High Grade ◽  
Significant Difference ◽  
Grade 3

e14515 Background: Peripheral neuropathy (PNP) is a dose-limiting side effect of oxaliplatin based chemotherapy. High grade PNP may compromise quality of life especially in elderly patients (pts). A randomized multicenter phase II study was conducted to compare fluorouracil, leucovorin, oxaliplatin with or without docetaxel (FLO vs. FLOT, respectively) in elderly pts with advanced gastric cancer (AGC). Our purpose was to identify pharmacogenetic markers as predictors of high grade PNP within this study. Methods: 143 pts were enrolled in this study. Pts. were numerically >65 years or numerically >59 years but classified biologically >65 years as defined by an Instrumental Activities of Daily Living score of <8. PNP was classified according to an oxaliplatin specific scale. Genotyping was performed using PCR-based RFLP or TaqMan®-based allelic discrimination. 20 polymorphisms in 13 genes being part of the metabolism of the applied drugs or DNA repair were analyzed. Statistical analyses were based on stepwise multivariate cox regression models and included genotypes and clinical parameters. Results: Median age was 71 years (range 60–83). Pts received in median 6 cycles of treatment (range 1–12). 130 pts were evaluable for PN at time of analyses. Of these, 68 received FLO and 62 received FLOT. Cumulative grade 3 PNP occurred in 49% of pts without a significant difference between FLO and FLOT receiving pts (44% and 53%, respectively, p=0.4). Genotypes of TS and MTHFR could be identified as independent risk factors for grade 3 PNP by multivariate analyses. Pts carrying a TS promoter genotype known to be associated with low TS expression (2R/2R, 2R/3RC, 3RC/3RC) were at higher risk for developing grade 3 PNP compared to pts without one of these genotypes (OR 3.0 [95%CI 1.27; 7.06], p=0.01). Pts carrying MTHFR1298AC or CC genotypes were also at higher risk for experiencing grade 3 PNP compared to pts with the wildtype MTHFR-1298AA genotype (OR 3.1 [95%CI 1.26; 7.60], p=0.01). In fact, 89% of pts that experienced grade 3 PNP were carriers of at least one of these risk genotypes. Conclusions: Polymorphisms of TS and MTHFR might be associated with grade 3 PNP in AGC pts receiving oxaliplatin based chemotherapy. No significant financial relationships to disclose.

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