Exploratory study of intraperitoneal paclitaxel plus mFOLFOX6 for gastric cancer patients with peritoneal metastasis and inadequate oral intake.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS222-TPS222
Author(s):  
Shuntaro Yoshida ◽  
Hironori Ishigami ◽  
Kei Muro ◽  
Shigenori Kadowaki ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Metastasis ◽  
Exploratory Study ◽  
Oral Intake ◽  
Phase Iii ◽  
Pelvic Cavity ◽  
Peritoneal Cytology ◽  
Gastric Cancer Patients ◽  
Inadequate Oral Intake

TPS222 Background: Systemic chemotherapy with oral fluoropyrimidine and platinum is recommended for the first-line treatment for unresectable or recurrent gastric cancer in Japan. However, some patients with severe peritoneal metastasis cannot take oral medications because of obstruction or dysfunction of the gastrointestinal tract. FOLFOX is regarded as one of the candidates for the standard of care for gastric cancer, and is now being evaluated in clinical trials. Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown in ovarian and gastric cancer. We developed a regimen combining IP PTX with S-1/PTX, and the phase III trial comparing with S-1/cisplatin suggested efficacy of this regimen. Therefore, we designed a regimen combining IP PTX with mFOLFOX6, and started an exploratory study in gastric cancer patients with peritoneal metastasis and inadequate oral intake. Methods: This is a prospective, multicenter, single-arm phase I/II study. Eligibility criteria include: pathologically proven unresectable or recurrent gastric adenocarcinoma; peritoneal metastasis; inadequate oral intake; adequate bone marrow function; acceptable liver and renal function; ECOG performance status of 0-2 and age between 20-80 years. Patients undergo diagnostic laparoscopy and are implanted with an IP port in the subcutaneous space of the lower abdomen, with a catheter placed in the pelvic cavity. mFOLFOX6 is administered bi-weekly, and IP PTX 20 mg/m2 is administered through an IP port on days 1, 8 and 15. The treatment course is repeated every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint is the 1-year overall survival rate. Secondary endpoints are progression free survival, time to treatment failure, response rate, negative conversion rate on peritoneal cytology and safety. Twenty medical institutions from all over Japan participate in this study, and 34 patients are to be enrolled in two years. Toxicity will be evaluated in the early stage, and the protocol will be reconsidered and revised if all of the first 3 or more than 2 of the first 6 patients develop dose-limiting toxicities. Clinical trial information: UMIN000019206.

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 .

Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4542-4542
Author(s):  
H. Ishigami ◽  
J. Kitayama ◽  
S. Kaisaki ◽  
A. Hidemura ◽  
M. Kato ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Metastasis ◽  
Response Rate ◽  
Peritoneal Dissemination ◽  
Phase Ii Study ◽  
Malignant Ascites ◽  
Peritoneal Cytology ◽  
Grade 3 ◽  
Gastric Cancer Patients

4542 Background: A phase II study to evaluate the efficacy and tolerability of weekly intravenous and intraperitoneal paclitaxel combined with S-1 was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. The primary endpoint was the 1-year overall survival rate. Secondary endpoints were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination confirmed by staging laparoscopy, 13 with peritoneal recurrence, and 6 with positive peritoneal cytology only. The median number of courses administered was 7 (range 1–23). The 1-year overall survival rate was 78% (95% CI, 65–90%). The overall response rate was 56% (95% CI, 32–79%) in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The incidences of grade 3/4 hematological and non- hematological toxicities were 40% and 15%, respectively. The frequent grade 3/4 toxicities included neutropenia (38%), leukopenia (18%), anemia (10%), and nausea (8%). Catheter obstruction observed in one patient was the only complication related to the peritoneal access device or intraperitoneal infusion. There were no treatment-related deaths. Conclusions: Combination chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis. No significant financial relationships to disclose.

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.

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

Phase II study of intraperitoneal paclitaxel plus S-1/paclitaxel for gastric cancer with positive peritoneal cytology: CY-PHOENIX trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 96-96 ◽  
Author(s):  
Masaki Aizawa ◽  
Hironori Ishigami ◽  
Hiroshi Yabusaki ◽  
Atsushi Nashimoto ◽  
Haruhiko Imamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Peritoneal Cavity ◽  
Peritoneal Metastasis ◽  
Phase Ii Study ◽  
Peritoneal Cytology ◽  
Positive Peritoneal Cytology ◽  
Grade 3 ◽  
Gastric Cancer Patients

96 Background: The presence of free cancer cells in the peritoneal cavity has been known as a poor prognostic factor in gastric cancer patients. Intraperitoneal (IP) paclitaxel (PTX) provides powerful local effects in the peritoneal cavity, and we previously reported the efficacy and safety of a regimen combining IP PTX with S-1/PTX in gastric cancer patients with peritoneal metastasis. This multicenter phase II study was conducted to evaluate the efficacy of IP PTX plus S-1/PTX for gastric cancer with positive peritoneal cytology. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, intraperitoneal free cancer cells confirmed by peritoneal washing cytology, and no evidence of overt distant metastasis including macroscopic peritoneal metastasis. Patients were administered IP PTX 20 mg/m2, intravenous PTX 50 mg/m2 on days 1 and 8, and S-1 80 mg/m2/day on days 1-14, q3 weeks. 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: Thirty eight patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 12.5 (range 2-35). The 1-year OS rate was 84.2% (95 % confidence interval, 68.2-92.6%). Of 3 patients with target lesions, partial response and stable disease were obtained in 2 and 1 patient(s), respectively. The peritoneal cytology findings converted from positive to negative in 36 (94.7 %) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 45 % and 26 %, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), leukopenia (7%) and anemia (8%). Regarding adverse events related to IP port, 2 patients developed swelling around the port site. Conclusions: IP PTX with S-1/PTX was suggested to be a promising option for gastric cancer with positive peritoneal cytology through the clearance of cancer cells in the peritoneal cavity. Clinical trial information: UMIN000002850.

scholarly journals Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial

2021 ◽  
Vol 10 (23) ◽  
pp. 5666
Author(s):  
Hironori Ishigami ◽  
Yasushi Tsuji ◽  
Hisashi Shinohara ◽  
Yasuhiro Kodera ◽  
Mitsuro Kanda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Systemic Chemotherapy ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Peritoneal Cytology ◽  
Scirrhous Gastric Cancer ◽  
Peritoneal Lavage Cytology ◽  
Lavage Cytology ◽  
Gastric Cancer Patients

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

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