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[Experimental study on intraperitoneal sequential MTX/5-FU therapy for peritoneal seeding in comparison with
M Maruyama1, S Takamatsu, N Sugano
1Division of Surgery, Tokyo City Hospital, Ohkubo.
Gan to Kagaku Ryoho. Cancer & Chemotherapy
|December 6, 1997
Summary
Intraperitoneal sequential methotrexate (MTX)/5-fluorouracil (5-FU) chemotherapy is more effective than intravenous administration for treating gastric cancer peritoneal metastases. This method also shows milder side effects in preclinical models.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Advanced gastric carcinoma frequently metastasizes to the peritoneum.
- Intravenous sequential methotrexate (MTX)/5-fluorouracil (5-FU) is a potent chemotherapy regimen.
- Intraperitoneal chemotherapy is proposed for localized peritoneal disease.
Purpose of the Study:
- To experimentally confirm the efficacy of intraperitoneal sequential MTX/5-FU chemotherapy.
- To compare intraperitoneal versus intravenous administration for gastric cancer peritoneal metastases.
- To evaluate the side effects of different administration routes.
Main Methods:
- A peritoneal seeding model was established in nude mice using the human gastric cancer cell line MKN-45.
- Mice were treated with intraperitoneal (i.p.) or intravenous (i.v.) MTX/5-FU on days 7, 14, and 21 post-implantation.
- Tumor burden, nodule counts, and body weight changes were assessed on day 35.
Main Results:
- Intraperitoneal MTX/5-FU significantly reduced peritoneal metastatic nodules compared to i.v. administration (0.41 vs. 5.3 nodules).
- Omental tumor weight was significantly lower in the i.p. group (0.051 g) versus the i.v. group (0.140 g).
- Mice receiving i.p. chemotherapy experienced less body weight decrease, indicating reduced toxicity.
Conclusions:
- Intraperitoneal sequential MTX/5-FU therapy demonstrates superior efficacy over intravenous administration for gastric cancer peritoneal seeding and micrometastases.
- Intraperitoneal administration of MTX/5-FU resulted in milder side effects compared to the intravenous route.
- This study supports the potential of intraperitoneal chemotherapy for managing peritoneal metastases in advanced gastric cancer.