Phase I Study of Interperitoneal Chenotherapy in Patients With Gastric Adenocarainoma With Peritoneal Seeding
Status:
Completed
Trial end date:
2007-08-01
Target enrollment:
Participant gender:
Summary
Stomach cancer is the most common cancer, and is still leading cause of death in Korea.
Peritoneal seeding is the most common metastases of gastric cancer, and is the most frequent
cause of death from this disease. In addition, there is no standard treatment for peritoneal
dissemination. Even though systemic intravenous chemotherapy is the standard treatment for
metastatic stomach cancer at present, it does not improve the survival of patients with
peritoneal dissemination. Because intraperitoneal(IP) administration results in high
concentration locally with low systemic toxicity, clinical investigators have confirmed the
safety and pharmacokinetic advantage associated with IP delivery of a number of
antineoplastic agents with known activity in cancer. In ovarian cancer, a large randomized
trial demonstrated a small but statistically and clinically significant survival advantage
for women receiving a portion of their therapy intraperitoneally. Drugs such as
5-fluorouracil, cisplatin, mitomycin-C, paclitaxel and docetaxel are used for IP chemotherapy
in patients with gastric cancer. Even the small number of phase III trials reported, some
studies showed improvement in survival for patients randomized to IP therapy compared to
those receiving no postoperative treatment.
Irinotecan(7-ethyl-10-[4-(1-pipperidino)-1-piperidino] carbonyloxy camptothecin; CPT-11),
clinically effective in the treatment of colorectal, lung and gastric cancer, is a carbamate
prodrug metabolized to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In
mouse model, IP administration of CPT-11 was significantly more effective than intravenous
administration for control of both peritoneal seeding and liver metastasis. However,
phamacokinetics of CPT-11 with peritoneal administration in human beings is not well studied.
Although Japanese investigators reported pharmacokinetic data of CPT-11 with few patients,
there is no data about maximum tolerated dose of CPT-11 intraperitoneally.