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

Abstract

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.

Intraperitoneal Delivery of Cisplatin via a Hyaluronan-Based Nanogel/in Situ Cross-Linkable Hydrogel Hybrid System for Peritoneal Dissemination of Gastric Cancer

“…Clinical trials showed that IP cisplatin administration improved survival of patients with peritoneal dissemination. 11 Such benefits should be further enhanced by use of hydrogels as a matrix for drug loading. Drug-loaded matrix hydrogels in the peritoneal cavity could allow sustained drug release, improving therapeutic outcomes and decreasing side effects.…”

Synopsis of a clinical practice guideline for pancreatic ductal adenocarcinoma with peritoneal dissemination in Japan; Japan Peritoneal Malignancy Study Group

“…Therefore, important goals of treatment would be to control the development of ascites and to improve survival in patients with PDAC with peritoneal dissemination who have poor quality of life and a dismal prognosis. Compared with systemic chemotherapy, intraperitoneal chemotherapy appears to be advantageous for the treatment of peritoneal dissemination due to the high drug concentration achieved in the peritoneal cavity to directly contact tumor nodules 22‐29 . Although hyperthermic intraperitoneal chemotherapy (HIPEC), 30,31 and pressurized intraperitoneal aerosol chemotherapy (PIPAC) 32,33 have also been implemented in patients with PDAC with peritoneal dissemination, the clinical efficacy of these options in patients with PDAC is still under investigation.…”

“…Compared with systemic chemotherapy, intraperitoneal chemotherapy appears to be advantageous for the treatment of peritoneal dissemination due to the high drug concentration achieved in the peritoneal cavity to directly contact tumor nodules. [22][23][24][25][26][27][28][29] Although hyperthermic intraperitoneal chemotherapy (HIPEC), 30,31 and pressurized intraperitoneal aerosol chemotherapy (PIPAC) 32,33 have also been implemented in patients with PDAC with peritoneal dissemination, the clinical efficacy of these options in patients with PDAC is still under investigation. Intraperitoneal chemotherapy with paclitaxel provided a better MST of 14-16 months in a cohort of patients with occult peritoneal dissemination and of 28 months or longer in patients who underwent conversion surgery in phase II studies.…”

Phase 1 trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study)

“…Researchers in Japan have studied repeated cycles of IP paclitaxel in patients with stage-4 gastric cancer with peritoneal involvement. 6,[13][14][15][16] These studies, including the phase-1 dose-finding study by Ishigami et al, 14 were conducted in the Japanese population. In addition, the majority of these studies used S-1 which is not available in some other parts of the world including Australia.…”

“…In addition to the use of S-1 combination chemotherapy regimens which is not routinely used in some countries, many of the published reports on IP chemotherapy have been conducted in particular populations, namely Japanese or Korean patients. 6,[10][11][12][13][14][15][16] We report a phase-1 study which, for the first time, defines a recommended dose of IP paclitaxel in combination with standard systemic chemotherapy in an Australian population.…”