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.

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 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 .

Surgery-induced peritoneal metastasis and its intraoperative treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4092-4092
Author(s):  
Satoshi Murata ◽  
Katsushi Takebayashi ◽  
Masatsugu Kojima ◽  
Hiroshi Yamamoto ◽  
Tsuyoshi Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Cavity ◽  
Peritoneal Metastasis ◽  
Curative Gastrectomy ◽  
Ki 67 ◽  
D2 Gastrectomy ◽  
Gastric Cancer Patients

4092 Background: A large number of advanced gastric cancer patients undergoing curative gastrectomy with D2 lymph node dissection (D2 gastrectomy) show peritoneal metastasis. The source of these metastatic cells and their treatment remain unclear. We examined the mechanism of surgery-induced peritoneal metastasis and determined the appropriate intraoperative treatment. Methods: (1) Curative gastrectomy was performed for 102 gastric cancer patients. Peritoneal lavage fluid was collected before and after gastrectomy. Cytology, RT-PCR, and cell culture were used to determine the presence of cancer cells. Proliferative potential of tumor cells was evaluated using Ki-67 staining. Tumorigenic capacity was assessed by cell injection into the peritoneal cavity of NOD/ShiJic-scid mice. (2) Fifty clinical T3(SE) or T4(SI) advanced gastric cancer patients undergoing curative D2 gastrectomy prospectively received intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in a phase II trial. HIPEC comprised 50 mg CDDP, 10 mg MMC, and 1000 mg 5-FU in 5 L saline maintained at 42–43C° for 30 min. Results: (1) Of 102 peritoneal lavage fluid samples obtained before gastrectomy, 57 from both early and advanced cancer patients did not contain CEA or CK20 mRNA amplification products or cancer cells. Of these 57 samples, CEA or CK20 mRNA was detected in 35 and viable cancer cells were identified in 24 after gastrectomy. Viable cancer cells in all 24 cases showed Ki-67 positivity, indicating proliferative activity. Cultured viable cancer cells developed into peritoneal tumor nodules after spill over into the peritoneal cavity in NOD/ShiJic-scid mice. (2) Fifty patients were eligible for the phase II clinical trial. The overall 5-year survival rate for all patients was 92.4%. This rate in patients with pT2(ss) (n = 12), pT3(se) (n = 35), and pT4(si) (n = 3) disease was 90.0%, 92.3%, and 100%, respectively. Only 2 patients (4%) showed peritoneal relapse. Conclusions: Viable tumorigenic cancer cells spilled over the peritoneal cavity during curative gastrectomy. Intraoperative HIPEC following curative D2 gastrectomy effectively prevented peritoneal metastasis, thereby potentially improving the prognosis of patients with advanced gastric cancer.

Does Neoadjuvant Treatment for Gastric Cancer Patients with Positive Peritoneal Cytology at Staging Laparoscopy Improve Survival?

2008 ◽  
Vol 15 (10) ◽  
pp. 2684-2691 ◽  
Author(s):  
Brian Badgwell ◽  
Janice N. Cormier ◽  
Sunil Krishnan ◽  
James Yao ◽  
Gregg A. Staerkel ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Neoadjuvant Treatment ◽  
Staging Laparoscopy ◽  
Peritoneal Cytology ◽  
Positive Peritoneal Cytology ◽  
Gastric Cancer Patients

Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 139-139
Author(s):  
H. Ishigami ◽  
J. Kitayama ◽  
S. Kaisaki ◽  
H. Yamaguchi ◽  
H. Yamashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Dose Level ◽  
Peritoneal Metastasis ◽  
Phase I Study ◽  
Level 1 ◽  
Grade 3 ◽  
Gastric Cancer Patients ◽  
Experienced Grade

139 Background: Intraperitoneal (IP) chemotherapy is promising for the treatment of gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous (IV) PTX in phase I and phase II studies (Oncology. 2009; Ann Oncol. 2010). Secondly, we developed a new IP-containing chemotherapy regimen, IV PTX plus IP cisplatin (CDDP) and PTX, for patients who have failed S-1-based chemotherapy. We performed a phase I study to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Methods: A total of 9 gastric cancer patients were enrolled who had shown progression of peritoneal metastasis after S-1-based chemotherapy. PTX was administered intravenously at a dose of 100 mg/m2 and intraperitoneally over 1 hour with an initial dose of 20 mg/m2 (level 1), stepped up to 30 or 40 mg/m2 depending on observed toxicity. CDDP was subsequently administered intraperitoneally at a dose of 30 mg/m2 over 24 hours after PTX infusion. PTX and CDDP were administered on days 1 and 15 in 4-week cycles. Results: At dose level 1, dose-limiting toxicities (DLTs) were observed in 2 of 3 patients. One patient experienced grade 4 leukopenia, and the other grade 3 vomiting. Because of higher toxicities than anticipated, the initial dose-escalation schedule was abandoned, and the doses of IV PTX and IP CDDP were reduced to 80 mg/m2 and 25 mg/m2, respectively, while keeping the dose of IP PTX at 20 mg/m2 (level 0). At dose level 0, one of the first 3 patients experienced grade 3 nausea, and an additional 3 patients experienced no DLTs. Consequently, the MTD and RD were determined to be dose level 1 and dose level 0, respectively. No patients experienced complications related to the peritoneal access device or IP infusion. Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials. No significant financial relationships to disclose.

Analysis Of Risk Factors Of Positive Peritoneal Cytology In Patients Treated For Gastric Cancer – Preliminary Report*

2015 ◽  
Vol 87 (10) ◽  
Author(s):  
Radosław Lisiecki ◽  
Arkadiusz Spychała ◽  
Katarzyna Pater ◽  
Dawid Murawa
Keyword(s):  
Gastric Cancer ◽  
Surgical Treatment ◽  
Cancer Cells ◽  
Peritoneal Cavity ◽  
Peritoneal Metastases ◽  
Histological Type ◽  
Gastric Body ◽  
Peritoneal Cytology ◽  
Positive Cytology ◽  
Positive Peritoneal Cytology

AbstractPresence of free gastric cancer cells in the peritoneal cavity of patients who underwent surgical treatment for gastric cancer is a negative prognostic factor and caused rapid disease recurrence, manifested as peritoneal metastases.Positive peritoneal cytology despite lack of visible peritoneal metastases was regarded as M1 class in the TNM classification (7was to analyze factors associated with positive peritoneal cytology and identify groups of patients in whom diagnostic laparoscopy plus peritoneal lavage in the diagnostic process could affect therapeutic decisions.The study enrolled patients with gastric cancer who underwent surgical treatment at the Department of Surgery, Wielkopolskie Oncology Center in Poznań. During the laparotomy, after opening of the peritoneal cavity, 200 ml of physiological saline at 37°C was administered in the tumor region. After this fluid was mixed, 100 ml of lavage fluid was collected. This fluid was subsequently spun many times to obtain sediment for cytology and immunohistochemistry investigation using anti-BerEp-4, CK 7/20, and B72.3.Results of peritoneal cytology were analyzed jointly with clinical factors – patient’s age, sex and pathology factors – tumor invasion, involvement of lymph nodes, histological grade, histological type according to Lauren and localization of the cancer in the stomach.Analysis of the peritoneal fluid for presence of free cancer cells was done in 51 patients. Positive peritoneal cytology was found in 12 (23.5%) patients. In the group of patients with positive cytology, all patients had T3/T4 tumors and all were found to have lymph node metastases, while G3 cancer was found in 83.3% of patients. In patients with positive cytology, diffuse gastric cancer according to Lauren predominated (9 of 12 patients, 75%), while in patients with negative cytology – intestinal type (20 of 39 patients, 51.2%). In the group of patients with positive histology, the whole stomach was involved by the cancer process in 7 of 12 patients (58.3%), while in the group with negative histology, in 29 of 39 patients the tumor was located in the gastric body and prepyloric part (74.4%).Based on this study we can conclude that determinants of positive peritoneal cytology include: tumor stage T3/T4, N+, G3, cancer located in the whole stomach, diffuse histological type according to Lauren.

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