Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (4) ◽  
pp. 663-667 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Fa-Chyi Lee ◽  
Deepti A. Singh ◽  
Daniel G. Haller ◽  
Heinz-Josef Lenz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Median Number ◽  
Phase Iii ◽  
Highly Active ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastric Cancer Patients

Purpose S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination. Methods Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of ≥ 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed. Results All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death. Conclusion S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

Phase II feasibility study of adjuvant S-1 plus CPT-11 for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0801).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 142-142
Author(s):  
Yutaka Kimura ◽  
Kazumasa Fujitani ◽  
Shugo Ueda ◽  
Hirokazu Taniguchi ◽  
Hiroshi Imamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Performance Status ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
D2 Dissection ◽  
D2 Surgery ◽  
Gastric Cancer Patients

142 Background: An adjuvant chemotherapy with S-1 has become the standard treatment for patients (pts) with stage II/III gastric cancer (GC) in Japan. But, it is assumed that the survival benefit for stage III pts who received S-1 is modest. S-1 plus CPT-11 has not shown the superiority in median overall survival (OS), but shown the well response rate (56%) and tolerability in Phase III trial (TOP-002 study). The aims of this phase II study were to evaluate the feasibility and safety of adjuvant S-1 plus CPT-11 in pts with stage III GC who underwent D2 surgery. Methods: Pts with pathological stage IIIA and IIIB GC who underwent gastrectomy D2 dissection, age 20-75 years, performance status < 1, and informed consent received oral S-1 (80 mg/m2/day) administration for consecutive 3 weeks and intravenous CPT-11 (80 mg/m2) on day 1, 15, repeated every 5 weeks (1 cycle). The treatment was repeated for 4 cycles, followed by S-1 administration until 1 year after surgery. The primary endpoint was feasibility of the 4 cycles administration of S-1 plus CPT-11. Results: We enrolled forty-five pts, 22 males and 23 females with a median age of 61 years, between December 2008 and April 2010. Pathological stages included IIIA in 25 pts and IIIB in 20 pts. The feasibility of planned 4 cycles of treatment was 62.2% (95% CI 46.5-76.2%, p=0.068) with 28 pts out of 45 pts. Non-hematological toxicities of grade 3 or more involved diarrhea in 13%, anorexia in 16%, nausea in 7% and vomiting in 4%. No Grade 4 toxicities were observed. Conclusions: Adjuvant S-1 plus CPT-11 therapy had moderate hematological toxicities, but observed several severe non-hematological toxicities. Therefore, predicted feasibility was not achieved. Although the follow-up period is too short to evaluate OS and feasibility of S-1 administration, it is hoped that this regimen will be a candidate for future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after D2 dissection if OS will be improved.

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 A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

Phase II study of intraperitoneal paclitaxel combined with S-1 plus cisplatin for gastric cancer with peritoneal metastasis: SP + IP PTX trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4529-4529
Author(s):  
Daisuke Kobayashi ◽  
Ryoji Fukushima ◽  
Mitsuhiko Ota ◽  
Sachio Fushida ◽  
Naoyuki Yamashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Peritoneal Metastasis ◽  
Response Rate ◽  
Phase Iii ◽  
Peritoneal Cytology ◽  
Response To Chemotherapy ◽  
Grade 3 ◽  
Gastric Cancer Patients

4529 Background: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of IP paclitaxel (PTX) combined with S-1 and intravenous PTX over S-1/cisplatin (SP), the standard of care as a first-line treatment in Japan, the sensitivity analysis suggested clinical efficacy of the IP PTX. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy have been warranted. After a dose-finding study, we sought to explore efficacy of a new regimen that combined IP PTX with SP. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled in the phase II multi-institutional prospective trial. In addition to the established SP regimen (S-1 administered orally at a dose of 80 mg/m2 bid for 21 days followed by a 14-day rest and cisplatin administered intravenously at a dose of 60 mg/m2 on day 8), IP PTX was administered on days 1, 8 and 22 at a dose of 20 mg/m2. The primary endpoint is overall survival (OS) rate at one year after treatment initiation. Secondary endpoints are progression free survival (PFS), response rate and toxicity. Results: Fifty-three patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 7 (range 1-20). The 1-year OS rate was 74% (95% CI, 60-83%). The median survival time was 19.4 months (95% CI, 16.7 months-). The 1-year PFS rate was 57% (95% CI, 42-69%). The overall response rate was 20% (95% CI, 1-72%) in 5 patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 23 (64%) of 36 patients. Fourteen (26%) patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), anemia (29%), diarrhea (13%) and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in 4 patients. There was 1 treatment-related death. Conclusions: IP PTX combined with SP is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000023000 .

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer

2016 ◽  
Vol 34 (22) ◽  
pp. 2636-2643 ◽  
Author(s):  
Cora Sternberg ◽  
Andrew Armstrong ◽  
Roberto Pili ◽  
Siobhan Ng ◽  
Robert Huddart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Point ◽  
Castration Resistant ◽  
Phase Iii Study

Purpose Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Randomized phase II trial comparing folfirinox (5FU/leucovorin [LV], irinotecan [I] and oxaliplatin [O]) vs gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA). First results of the ACCORD 11 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4516-4516 ◽  
Author(s):  
M. Ychou ◽  
F. Desseigne ◽  
R. Guimbaud ◽  
M. Ducreux ◽  
O. Bouché ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Safety Data ◽  
Median Number ◽  
Tumor Location ◽  
Phase Iii ◽  
Expert Review ◽  
First Results

4516 Background: In a phase II trial of Folfirinox (F) in 35 MPA patients (pts), we reported a 26% response rate and median survival of 9.5 months (mo) with quality of life improvement (Conroy, JCO 2005). The aim of this phase II trial was to compare the response rate and safety of F vs G in pts with MPA. Methods: Chemotherapy-naïve pts aged 18–75 years with histologically or cytologically confirmed measurable MPA were randomized to receive G (1,000 mg/m2 IV weekly x 7 for 8 weeks [wks] then weekly x 3 out of 4 wks) or F (O 85mg/m2 d1 + I 180mg/m2 d1 + LV 400mg/m2 d1 followed by 5FU 400mg/m2 bolus d1 and 2,400 mg/m2 46h continuous infusion biweekly). Patients were stratified by centre, performance status (ECOG 0 versus 1), and primary tumor location (head vs other). Primary endpoint was response rate. Results: From 01/05 to 11/06, all planned 88 pts (44 per arm) were enrolled. Median age was 56 yrs [35–76]. Currently, safety data for 81 pts (41F/40G) and efficacy data for 65 pts (31F/34G) are available (17 too early). One pt was ineligible in arm F. Two pts, one in each arm, did not receive protocol therapy. Median number of wks on treatment was 18 (F) and 7 (G). No toxic death occurred. Main grade 3–4 toxicities (arm F vs G) were G3 neutropenia (32%/17.5), G4 neutropenia (19.5%/0), G3–4 thrombocytopenia (12%/0), G3 vomiting (17%/2.5), G3 transaminases (0%/15) and G3–4 fatigue (27%/15).Confirmed partial responses (PR) rates (F/G) were 38.7% (12/31) and 11.7 % (4/34) according to the investigators and median duration of response was 6,3 and 4,6 mo. PR and stable disease (SD) were documented for 21/31 evaluable pts in arm F and expert review confirmed 13 PR (41.9 %) and 6 SD (19.3%). Conclusions: Folfirinox induces a response rate > 30% with manageable toxicity in ECOG 0–1 pts with MPA. According to these interim results, this trial will continue as a phase III study. Updated results will be presented at the meeting. Supported by a PHRC 2004 grant from the French Ministry of Health. [Table: see text]

A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and GEJ cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4563-4563
Author(s):  
B. F. El-Rayes ◽  
B. Patel ◽  
M. Zalupski ◽  
N. Hammad ◽  
A. Shields ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Phase Ii ◽  
Primary Tumor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Median Number ◽  
Acute Neuropathy ◽  
Number Of Cycles

4563 Background: VEGF (vascular endothelial growth factor) has a central role in angiogenesis, tumor growth and metastasis of gastric cancer. Bevacizumab, an anti-VEGF monoclonal antibody, has demonstrated anti-tumor activity in multiple diseases. This phase II study was undertaken to determine the effects of adding bevacizumab to a regimen of docetaxel and oxaliplatin. Methods: The primary endpoint was time to progression (TTP) in patients with locally advanced or metastatic adenocarcinoma of the gastric or gastroesophageal junction treated with docetaxel, oxaliplatin and bevacizumab. Previously untreated patients with a performance status (PS) of 0–1 were eligible for this study. Patients received bevacizumab 7.5 mg/kg, docetaxel 70 mg/m2 and oxaliplatin 75 mg/m2 administered on day 1 of a 21 day cycle. Results: A total of 23 patients (median age 57, males 70%, gastric 52%) were enrolled on the study. Median PS was 1. The median number of cycles was 5. Ten patients are still receiving treatment on study. Partial responses were documented in 10 (59%) patients and stable disease in 7 (41%). No treatment related deaths were observed. The most commonly reported grade 3–4 toxicities were neutropenia (13%), leukopenia (4%), fever (4%), acute neuropathy (4%), and hypertension (4%). Gastrointestinal (GI) perforation occurred in 3 patients. Perforation was not found at the tumor site in the patient who required surgery. The site of perforation could not be ascertained in the second patient who was managed medically. Both patients had had no prior surgical resection of the primary tumor. The third perforation presented as a tracho-bronchial fistula. The patient had previously undergone surgical resection of his primary tumor after receiving chemoradiotherapy to the thoracic area. Conclusions: The regimen of docetaxel, oxaliplatin and bevacizumab appears to be very active. The development of GI perforations in 3 patients is of concern. At this time, bevacizumab should not be used in gastric or gastroesophageal junction cancers outside of a clinical trial until its safety is well established. [Table: see text]

TOPGEAR: An international randomized phase III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer (AGITG/TROG/EORTC/NCIC CTG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4141-TPS4141 ◽  
Author(s):  
Trevor Leong ◽  
Mark Smithers ◽  
Michael Michael ◽  
Val Gebski ◽  
Alex Boussioutas ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Therapy ◽  
Phase Ii ◽  
Preoperative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Phase Iii ◽  
Standards Of Care ◽  
Current Status ◽  
Quality Assurance Program ◽  
Resectable Gastric Cancer

TPS4141 Background: Optimal management of patients with resectable gastric cancer remains unknown. Since the INT0116 and MAGIC trials, there are 2 standards of care for adjuvant therapy: postoperative chemoradiotherapy (CRT) and perioperative ECF chemotherapy. The important question arising from these studies is whether CRT is superior to chemotherapy alone as adjuvant therapy. This randomized phase II/III trial will compare CRT to chemotherapy alone in the preoperative setting. Methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either preoperative chemotherapy alone (ECFx3 as per MAGIC regimen) or preoperative CRT (ECFx2 followed by 45Gy of radiation with concurrent 5-FU). Following surgery, both groups will receive 3 further cycles of ECF. The trial is being conducted in two Parts; Part I (phase II component) will recruit 120 patients with the aim of demonstrating sufficient efficacy and safety of preoperative CRT, as well as trial feasibility. Part II (phase III component) will recruit a further 632 patients to provide a total of 752. The primary endpoint for Part I is pathological complete response rate, and for Part 2 it is overall survival. The trial includes formal quality of life and biological sub-studies. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. Current status: This study is an international, intergroup trial led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. To date, 36 patients have been recruited from 20 sites in Australia and New Zealand; European and Canadian sites will commence recruitment in 2012.

Phase II study of intraperitoneal docetaxel plus capecitabine/cisplatin for gastric cancer with peritoneal metastasis: XP+IP DOC trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4039-4039 ◽  
Author(s):  
Ryoji Fukushima ◽  
Hironori Ishigami ◽  
Hiroto Miwa ◽  
Motohiro Imano ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Peritoneal Metastasis ◽  
Phase Ii Study ◽  
Median Number ◽  
Peritoneal Cytology ◽  
Response To Chemotherapy ◽  
Grade 3 ◽  
Gastric Cancer Patients

4039 Background: Intraperitoneal (IP) chemotherapy with taxanes provides sustained high local concentrations, and the efficacy of IP paclitaxel (PTX) has been shown in ovarian cancer. We previously reported the safety and efficacy of IP PTX plus systemic chemotherapy in clinical trials. Capecitabine/cisplatin (XP) is one of the standard regimens for the first-line treatment of advanced gastric cancer worldwide. We designed a new regimen combining IP docetaxel (DOC) with XP, and the recommended dose of IP DOC was determined to be 10 mg/m2 in a phase I study. A phase II study of XP plus IP DOC was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled. DOC was administered intraperitoneally at 10 mg/m2 on days 1 and 8. Cisplatin was administered intravenously at 80 mg/m2 on day 1, and capecitabine was administered at 1000 mg/m2 bid for 14 consecutive days, repeated every 21 days. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Out of 50 patients enrolled, 48 patients received protocol treatment, and were evaluated for OS and toxicity. The median number of courses was 6 (range 1-15). The 1-year OS rate was 75% (95% confidence interval, 60-85%). The best overall response was stable disease in all the three patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 28 (76%) of 37 patients. Nineteen patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 42% and 48%, respectively. The frequent grade 3/4 toxicities included neutropenia (21%), leukopenia (8%), anemia (29%), anorexia (25%) and nausea (17%). Infection of the intraperitoneal port was observed in one patient. There were no treatment-related deaths. Conclusions: Combination chemotherapy of XP plus IP DOC regimen is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000016469.

Multicenter Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (33) ◽  
pp. 5201-5206 ◽  
Author(s):  
Manish A. Shah ◽  
Ramesh K. Ramanathan ◽  
David H. Ilson ◽  
Alissa Levnor ◽  
David D'Adamo ◽  
...  
Keyword(s):  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Patient Characteristics ◽  
Time To Progression ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Upper Gastrointestinal Bleed ◽  
Grade 3

Purpose Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Results Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Conclusion Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

Sign in / Sign up

Export Citation Format

Share Document