Sustained release chemotherapeutic microspheres provide superior efficacy over systemic therapy and local bolus infusions.
OBJECTIVE
The present studies evaluated the ability of injectable, biodegradable microspheres releasing carboplatin, doxorubicin, or 5-fluorouracil to suppress the growth of solid tumors implanted subcutaneously or intramuscularly.


METHODS
Seven to 10 days after implantation of MATB-III cells, rats received systemic chemotherapy, intratumoral bolus chemotherapy, or injections of chemotherapeutic microspheres into the tumor center or multiple sites along the outer perimeter of the tumor.


RESULTS
A single treatment with carboplatin, doxorubicin, or 5-fluorouracil microspheres along the perimeter of the tumors produced a significant, dose-related suppression in tumor growth, relative to injections directly into the tumor center. Moreover, five temporally-spaced microsphere treatments along the tumor perimeter (with either doxorubicin or 5-fluorouracil microspheres) completely eradicated 100% of the subcutaneous tumors and 40-53% of the intramuscular tumors. Polypharmacy, accomplished by blending doxorubicin- and 5-fluorouracil-loaded microspheres and injecting them into the tumors was even more efficacious than sustained delivery of either drug alone. Comparable doses of systemic chemotherapy or intratumoral bolus chemotherapy were ineffective.


CONCLUSIONS
Injectable microspheres might be ideal for local, sustained delivery of chemotherapeutic agents to solid tumors. However, attention must be paid to the placement of the microspheres, for injections around the tumor perimeter may be required for efficacy.
Alkermes, Inc, Cambridge, Massachusetts 02139, USA.
Dwaine F
DF
Emerich
Pamela
P
Snodgrass
Denise
D
Lafreniere
Reginald L
RL
Dean
Heather
H
Salzberg
Joanne
J
Marsh
Brigido
B
Perdomo
Mahin
M
Arastu
Shelley R
SR
Winn
Raymond T
RT
Bartus
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007263:Infusions, Parenteral; D015552:Injections, Intralesional; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008863:Microspheres; D009368:Neoplasm Transplantation / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations