Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer.
OBJECTIVE
Preoperative radiation with combined chemotherapy is effective in shrinking advanced rectal cancer locally and facilitating subsequent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenous administration. This prompted us to evaluate suppository and intravenous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity.


METHODS
Rectal, liver, lymph node, and lung tissue and systemic and portal blood were collected serially from male Sprague Dawley rats to determine drug concentrations following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment groups and received 5-fluorouracil suppositories, mitomycin C suppositories, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 days following this treatment, blood was collected, colonoscopy was performed, and rectal tissue was harvested for histologic examination.


RESULTS
Mitomycin C suppository was significantly less toxic compared with intravenous delivery, and higher rectal tissue concentrations were observed from 10 to 30 minutes (P < 0.05). Compared with intravenous 5-fluorouracil administration and radiation, 5-fluorouracil suppository and radiation resulted in additive myelosuppression at day 6 (P < 0.05) with rapid recovery.


CONCLUSIONS
5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.
Pokorny
R M
RM
Price Institute of Surgical Research and Department of Surgery, University of Louisville School of Medicine, Kentucky 40292, USA.
Wrightson
W R
WR
Lewis
R K
RK
Paris
K J
KJ
Hofmeister
A
A
LaRocca
R
R
Myers
S R
SR
Ackerman
D
D
Galandiuk
S
S
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D000285:Administration, Rectal; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003037:Cobalt Radioisotopes / Q000008:administration & dosage*; D003967:Diarrhea / Q000139:chemically induced; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018714:Radiotherapy, Adjuvant; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012004:Rectal Neoplasms / Q000378:metabolism / Q000628:therapy*; D013488:Suppositories
D000903:Antibiotics, Antineoplastic; D003037:Cobalt Radioisotopes; D013488:Suppositories; D016685:Mitomycin; D005472:Fluorouracil