Intraosseous delivery of paclitaxel-loaded hydroxyapatitealginate composite beads delaying paralysis caused by metastatic spine cancer in rats.
OBJECTIVE
Bone is frequently the first site and the only site of breast cancer at recurrence. Local control is important especially for metastatic spine cancer, because epidural spinal cord compression is significantly associated with the quality of life and survival of these patients. The authors have developed a local delivery system of paclitaxel in the form of hydroxyapatite-alginate composite beads. This study was conducted to clarify the therapeutic effect in a rat model of metastatic spine cancer.


METHODS
Twenty-one rats with metastatic spine cancer were divided into 3 groups: a local treatment group (6 rats), a systemic treatment group (9 rats), and a control group (6 rats). The hind-limb motor function of the animals was monitored daily by using the Basso-Beattie-Bresnahan scale. The authors monitored the disease-free time and survival times. The log-rank test was used to define statistically significant differences between the 3 groups.


RESULTS
The animals in the control group developed hind-limb paralysis at a mean of 10.8 days and died at a mean of 16.0 days. The animals treated with 2.4 wt% of paclitaxel-loaded hydroxyapatite-alginate composite beads (the local treatment group) showed a 140-150% increase in the disease-free time and survival time compared with that of the control group. Although an approximately 30-fold higher dosage of paclitaxel was administered, the therapeutic effect was not evident in the systemic treatment group.


CONCLUSIONS
Intraosseous delivery of paclitaxel-loaded hydroxyapatite-alginate composite beads delayed paralysis caused by metastatic spine cancer in rats. The results indicate that intraosseous chemotherapy may provide an effective local treatment of metastatic spine cancer.
Abe
Tetsuya
T
Department of Orthopedic Surgery, and Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Sakane
Masataka
M
Ikoma
Toshiyuki
T
Kobayashi
Mihoko
M
Nakamura
Satoshi
S
Ochiai
Naoyuki
N
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000464:Alginates; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004337:Drug Carriers; D017886:Durapatite; D005260:Female; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D008863:Microspheres; D017239:Paclitaxel / Q000008:administration & dosage*; D010243:Paralysis / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013125:Spinal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D000464:Alginates; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D017886:Durapatite; D017239:Paclitaxel