Abstract
Purpose: To identify the optimal schedule for intraperitoneal (i.p.) infusion of floxuridine (FUDR) against peritoneal micrometastases from gastric cancer. Methods: The efficacy of continuous i.p. infusion of FUDR was compared with that of bolus i.p. administration in peritoneal gastric cancer (MKN45) xenografts. The FUDR continuous delivery system in this study was in the form of injectable poly(lactic-coglycolic) acid (PLGA) microspheres intended for i.p. injection. Animals were treated by continuous i.p. infusion using FUDR-loaded microspheres or bolus i.p. administration of FUDR. Results: In vitro testing demonstrated that FUDR was released slowly from the microspheres at a rate of approximately 5% of the total encapsulated drug per day. In in vivo studies, the peritoneal level was found to persist and was approximately 5- to 50-fold higher than that of plasma for more than 2 weeks following a single injection of the microspheres. An in vitro MTT assay showed that exposure time clearly influenced the cytotoxic potency of FUDR. In vivo, continuous infusion was more effective against peritoneal tumor than bolus administration at equivalent doses. However, compared with bolus administration, toxicity was increased, resulting in a reduced maximum tolerated dose (MTD) with continuous infusion. When the treatment was carried out at each MTD (continuous 1 mg/kg, bolus 600 mg/kg), continuous infusion had no advantage in inhibiting tumor growth. Conclusions: Owing to the higher toxicity and the equal efficacy of continuous infusion compared with bolus administration, continuous infusion is not recommended in i.p. FUDR treatment.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 415-422 |
| Number of pages | 8 |
| Journal | Cancer Chemotherapy and Pharmacology |
| Volume | 53 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2004 |
| Externally published | Yes |
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Keywords
- Adjuvant chemotherapy
- Drug delivery system
- FUDR
- Microsphere
- PLGA
ASJC Scopus subject areas
- Cancer Research
- Pharmacology
- Oncology
Cite this
Comparison of intraperitoneal continuous infusion of floxuridine and bolus administration in a peritoneal gastric cancer xenograft model. / Inoue, Kentaro; Onishi, Hiraku; Kato, Yoshinori; Michiura, Taku; Nakai, Koji; Sato, Mutsuya; Yamamichi, Keigo; Machida, Yoshiharu; Nakane, Yasushi.
In: Cancer Chemotherapy and Pharmacology, Vol. 53, No. 5, 05.2004, p. 415-422.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparison of intraperitoneal continuous infusion of floxuridine and bolus administration in a peritoneal gastric cancer xenograft model
AU - Inoue, Kentaro
AU - Onishi, Hiraku
AU - Kato, Yoshinori
AU - Michiura, Taku
AU - Nakai, Koji
AU - Sato, Mutsuya
AU - Yamamichi, Keigo
AU - Machida, Yoshiharu
AU - Nakane, Yasushi
PY - 2004/5
Y1 - 2004/5
N2 - Purpose: To identify the optimal schedule for intraperitoneal (i.p.) infusion of floxuridine (FUDR) against peritoneal micrometastases from gastric cancer. Methods: The efficacy of continuous i.p. infusion of FUDR was compared with that of bolus i.p. administration in peritoneal gastric cancer (MKN45) xenografts. The FUDR continuous delivery system in this study was in the form of injectable poly(lactic-coglycolic) acid (PLGA) microspheres intended for i.p. injection. Animals were treated by continuous i.p. infusion using FUDR-loaded microspheres or bolus i.p. administration of FUDR. Results: In vitro testing demonstrated that FUDR was released slowly from the microspheres at a rate of approximately 5% of the total encapsulated drug per day. In in vivo studies, the peritoneal level was found to persist and was approximately 5- to 50-fold higher than that of plasma for more than 2 weeks following a single injection of the microspheres. An in vitro MTT assay showed that exposure time clearly influenced the cytotoxic potency of FUDR. In vivo, continuous infusion was more effective against peritoneal tumor than bolus administration at equivalent doses. However, compared with bolus administration, toxicity was increased, resulting in a reduced maximum tolerated dose (MTD) with continuous infusion. When the treatment was carried out at each MTD (continuous 1 mg/kg, bolus 600 mg/kg), continuous infusion had no advantage in inhibiting tumor growth. Conclusions: Owing to the higher toxicity and the equal efficacy of continuous infusion compared with bolus administration, continuous infusion is not recommended in i.p. FUDR treatment.
AB - Purpose: To identify the optimal schedule for intraperitoneal (i.p.) infusion of floxuridine (FUDR) against peritoneal micrometastases from gastric cancer. Methods: The efficacy of continuous i.p. infusion of FUDR was compared with that of bolus i.p. administration in peritoneal gastric cancer (MKN45) xenografts. The FUDR continuous delivery system in this study was in the form of injectable poly(lactic-coglycolic) acid (PLGA) microspheres intended for i.p. injection. Animals were treated by continuous i.p. infusion using FUDR-loaded microspheres or bolus i.p. administration of FUDR. Results: In vitro testing demonstrated that FUDR was released slowly from the microspheres at a rate of approximately 5% of the total encapsulated drug per day. In in vivo studies, the peritoneal level was found to persist and was approximately 5- to 50-fold higher than that of plasma for more than 2 weeks following a single injection of the microspheres. An in vitro MTT assay showed that exposure time clearly influenced the cytotoxic potency of FUDR. In vivo, continuous infusion was more effective against peritoneal tumor than bolus administration at equivalent doses. However, compared with bolus administration, toxicity was increased, resulting in a reduced maximum tolerated dose (MTD) with continuous infusion. When the treatment was carried out at each MTD (continuous 1 mg/kg, bolus 600 mg/kg), continuous infusion had no advantage in inhibiting tumor growth. Conclusions: Owing to the higher toxicity and the equal efficacy of continuous infusion compared with bolus administration, continuous infusion is not recommended in i.p. FUDR treatment.
KW - Adjuvant chemotherapy
KW - Drug delivery system
KW - FUDR
KW - Microsphere
KW - PLGA
UR - http://www.scopus.com/inward/record.url?scp=2142642244&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2142642244&partnerID=8YFLogxK
U2 - 10.1007/s00280-003-0748-z
DO - 10.1007/s00280-003-0748-z
M3 - Article
C2 - 15132129
AN - SCOPUS:2142642244
VL - 53
SP - 415
EP - 422
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 5
ER -