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 ◽  
...  

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.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4529-4529
Author(s):  
Daisuke Kobayashi ◽  
Ryoji Fukushima ◽  
Mitsuhiko Ota ◽  
Sachio Fushida ◽  
Naoyuki Yamashita ◽  
...  

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 .


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS222-TPS222
Author(s):  
Shuntaro Yoshida ◽  
Hironori Ishigami ◽  
Kei Muro ◽  
Shigenori Kadowaki ◽  
Yasushi Tsuji ◽  
...  

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.


2017 ◽  
Vol 108 (5) ◽  
pp. 978-986 ◽  
Author(s):  
Eiji Higaki ◽  
Shinya Yanagi ◽  
Naoto Gotohda ◽  
Takahiro Kinoshita ◽  
Takeshi Kuwata ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 198-198
Author(s):  
Chikara Kunisaki ◽  
Hirochika Makino ◽  
Jun Kimura ◽  
Ryo Takagawa ◽  
Amane Kanazawa ◽  
...  

198 Background: This study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. Methods: Two cycles of a 3 week regime of the fluoropyrimidine, S-1 (40 mg/m2, orally, twice daily), with cisplatin (60 mg/m2, intravenously, day 8) were administered to patients, separated by a 2 week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n=27). We compared overall survival and prognostic factors in these patients with a non-neoadjuvant group (n=19). Results: For all patients, univariate analysis identified non-curative gastrectomy and positive lavage cytology as adverse prognostic factors; extended lymph node dissection was a positive prognostic factor. Multivariate analysis showed that non-curative resections independently influenced prognosis (hazard ratio=2.902, p=0.011). In the SP group, positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after SP chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. Conclusions: After SP neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 16-16
Author(s):  
Kazuki Kano ◽  
Tsutomu Sato ◽  
Yukio Maezawa ◽  
Kenki Segami ◽  
Tetsushi Nakajima ◽  
...  

16 Background: Treatment strategies for only positive peritoneal lavage cytology findings have not yet been established. The objective of this retrospective study was to clarify the survival and prognosticators in these patients. Methods: Overall survival (OS) rates were examined in 39 patients with gastric cancer who underwent a curative resection and had positive peritoneal cytology in the absence of overt peritoneal metastases between January 2000 and June 2015. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. Results: A total of 39 patients were evaluated. The median overall survival was significantly longer in the 34 patients who received chemotherapy after surgery than that in the 5 who did not (19.1 vs 5.9 months, p < 0.01). Among the patients who received chemotherapy after surgery, univariate and multivariate analyses showed that pN3b was an independent significant prognosticator (hazard ratio of 4.169 with 95% CI: 1.108-15.684, p = 0.035). The median OS was 15.8 months when the patients diagnosed with N3b was 33.1 months when the patients diagnosed with N3a or lower. Conclusions: The prognosis of gastric carcinoma with positive peritoneal lavage cytology without peritoneal metastasis is still poor and need more aggressive treatment. The lymph node metastasis was a significant prognosticator in these patients.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Pengfei Yu ◽  
Zeyao Ye ◽  
Gaiguo Dai ◽  
Yanqiang Zhang ◽  
Ling Huang ◽  
...  

Abstract Background There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. Methods Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1, and S-1 was administered orally(80 mg/m2/day)on days 1–14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). Results A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7–25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3–14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006). Conclusion Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. Trial registration This study has been registered with ClinicalTrials.gov as NCT02549911. Trial registration date: 15/09/2015.


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