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Retrospective Cohort Study of Intraoperative Administration of Sustained-Release 5-Fluorouracil Implants in Advanced Gastric Cancer Patients.

ABSTRACT: Background: 5-fluorouracil (5-FU) is basically used in the field of postoperative chemotherapy of gastric cancer (GC), the goal of this study was to evaluate improvement of long-term survival rate among GC patients after the 5-FU implants treatment. Methods: The study included 145 patients with gastric cancer who received postoperative chemotherapy with 5-FU implants and had complete follow-up information. According to the sex, age and clinical stage of 5-FU implants group, 74 patients were matched as the control group at the same time. In the study, we compared the 5-year overall survival rate with progression-free survival rate in the two groups, and the drug safety for both groups during the treatment was also compared. Results: The median follow-up time was 85 months (range 60-116 months). 31 patients (21.38%) died of tumor recurrence in 5-FU implants group and 21 (28.38%) in control group. In the control group, metastatic lesions were found in the small intestine, left adrenal gland and peritoneum in three patients. The 5-year progression-free survival (PFS) rate was 79.71% in 5-FU group and 67.12% in control (p = 0.0045). The 5-year overall survival (OS) rate was 77.68% in 5-FU implants group and 64.87% in control (p = 0.0159). Both the 5-years OS and PFS rates in 5-FU group were better than control group without significant side effect. Conclusions: 5-FU implants may improve 5-years OS and PFS rates after surgery in gastric cancer patients, while good safety profile suggests it could be reliable.

SUBMITTER: Ge J

PROVIDER: S-EPMC8076801 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU + DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU + DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU + DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer. Graphical abstract Schematic diagram of sustained co-delivery of 5-Fluorouracil (5-Fu) and cis-platinum (DDP) via biodegradable thermo-sensitive hydrogel, which was used for intraoperative synergistic combination chemotherapy of gastric cancer to inhibit postoperative tumor recurrence and metastasis.Image 1 Highlights • Intraoperative chemotherapy could reduce the recurrence and metastasis after surgical resection of gastroenteric tumors.• 5-FU and DDP co-delivery system based on PLEL was developed for intraoperative combination chemotherapy of gastric cancer.• This dual-drug loaded hydrogel helped to improve synergistic anti-tumor effects and reduce adverse side effects in vivo.• 5-FU+DDP/PLEL could inhibit recurrence of orthotopic tumors and growth of abdominal metastatic tumors in gastric cancer.

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Retrospective Cohort Study of Intraoperative Administration of Sustained-Release 5-Fluorouracil Implants in Advanced Gastric Cancer Patients.

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