An experimental study of regional chemotherapy using CDDP-loaded microspheres for esophageal cancer.
OBJECTIVE
The purpose of this study was to assess the antitumor effects of cisplatin-loaded microspheres (CDDP-MS) and the efficacy of the administration of CDDP-MS into the mediastinum.


METHODS
To evaluate the antitumor effect, we first performed a paratumoral injection of CDDP-MS to FF6 tumor-bearing DA rats to compare its effect with that of the intraperitoneal injection of a CDDP solution at different doses.


RESULTS
In the CDDP-MS groups the tumor growth was effectively delayed in proportion to the dosage of CDDP-MS. All rats treated with the CDDP solution at a dose of 10 mg/kg died within 1 week, while no rats treated with CDDP-MS even at a CDDP dose of 20 mg/kg were lost. In the second experiment, which was designed to determine the delivery of the microspheres-released CDDP to various organs, CDDP-MS was injected directly into the mediastinum via the diaphragm in male Wistar rats. In the CDDP-MS group, the plasma CDDP concentration stayed significantly lower than that in the CDDP solution (intravenous) group while the tissue CDDP concentration in the paratracheal lymph nodes was higher. Moreover, the lymph node-to-kidney platinum ratio was eight times higher in the rats given CDDP-MS intramediastinally than in those given the CDDP solution intravenously.


CONCLUSIONS
These results demonstrate that a high dose of CDDP can be administered with less systemic side effects by means of encapsulation in the microspheres, and that the administration of CDDP-MS into the mediastinum is more effective for delivering CDDP to the paratracheal lymph nodes. As a regional chemotherapy after esophageal cancer operation, the injection of CDDP-MS into the mediastinum for targeting of the lymph nodes thus promises to be an effective treatment.
Nakamura
Yoshiki
Y
Department of Surgery, Kobe University School of Medicine, Hyogo, Japan.
Hamabe
Yutaka
Y
Ikuta
Hajime
H
Hyon
Suong-Hyu
SH
Kuroda
Yoshikazu
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007267:Injections; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008482:Mediastinum; D008863:Microspheres; D009368:Neoplasm Transplantation; D011098:Polyglactin 910; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D011098:Polyglactin 910; D002945:Cisplatin