Abstract
Background: Preoperative radiotherapy with concomitant intravenous 5-fluorouracil (5-FU-IV) is effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Topical 5-FU application may enhance its radiosensitizing and cytotoxic effects. Suppository and intravenous 5-FU administration were compared with respect to myelosuppression and tissue concentrations.
Methods: Rats received 120 mg/kg 5-FU-IV or via suppository (5-FU-S). White blood cell count, serum albumin, alkaline phosphatase, creatinine, and aspartate aminotransferase (AST) were determined before and serially after 5-FU administration. In a separate experiment, rats received 5-FU-S or 5-FU-IV as already described. Portal and systemic blood, rectal, iliac lymph node, liver, and lung tissue were harvested for high-performance liquid chromatography determination of 5-FU concentrations 30 min, 1, 3, 6, and 12 h after drug administration.
Results: No toxicity was observed in 5-FU-S animals, whereas 63% of 5-FU-IV animals had diarrhea. Weight loss and myelosuppression occurred only in 5-FU-IV animals. Rectal drug concentrations were significantly higher in the 5-FU-S animals compared with 5-FU-IV animals, 0.5–6 h after drug administration. Blood, liver, and lung 5-FU concentrations with 5-FU-S were comparable to those with 5-FU-IV.
Conclusions: 5-FU suppositories are associated with fewer systemic side effects and higher rectal 5-FU concentrations than with 5-FU-IV administration.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Shulka HS, Hughes LE, Davis PW, Whitehead RH, Leach KG. Distribution of 5-fluorouracil to body tissues compared after intraluminal, intravenous, and intramural administration in gastrointestinal cancer.Am J Surg 1977;133:346–50.
Rich TA, Lokich JJ, Chaffey JT. A pilot study of protracted venous infusion of 5-fluorouracil and concomitant radiation therapy.J Clin Oncol 1985;3:402–6.
Byfield JE, Frankel SS, Sharp TR, Hoenback CL, Callipari FB. Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation.Int J Radiat Oncol Biol Phys 1985;11:791–800.
Takahashi T, Kohno K, Yamaguchi T, Narisawa T. Preoperative use of 5-fluorouracil suppository for carcinoma of the rectum.Am J Surg 1982;143:183–5.
Takahashi T, Mizusawa H, Kato T, Yamaguchi T. Preoperative irradiation and 5-fluorouracil suppository for carcinoma of the rectum.Am J Surg 1988;156:58–62.
Barbieri-Heyob M, Merlin JL, Weber B. Determination of 5-fluorouracil and its main metabolite in plasma by high-performance liquid chromatography.J Chromatography 1992;573:247–52.
O'Connell MJ, Martenson JA, Wieand HS, Krook JE, MacDonald JS, Haller DG, Mayer RJ, et al. Improving adjuvant therapy for rectal cancer by combining protracted infusion fluorouracil with radiation therapy after curative surgery.N Engl J Med 1994;331:502–7.
Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, et al. Effective surgical adjuvant therapy for high risk rectal carcinoma.N Engl J Med 1991;324:709–15.
Percarpio B, Bitterman J, Sabbath K, Alfano F, Ruszkowski R, Bowen J. Combined modality preoperative therapy for unresectable rectal cancer.Conn Med 1992;56:7–9.
Shumate CR, Rich TA, Skibber JM, Ajani JA, Ota DM. Preoperative chemotherapy and radiation therapy for locally advanced primary and recurrent rectal carcinoma.Cancer 1993;71:3690–6.
Papillon J. Surgical adjuvant therapy for rectal cancer: present options.Dis Col Rectum 1994;37:144–8.
Minsky BD, Cohen AM, Kemeny N, Enker WE, Kelsen DP, Schwartz G, Saltz L, et al. Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer.J Radiat Oncol 1993;25:821–7.
Chan A, Wong A, Langevin J, Khoo R. Preoperative concurrent 5-fluorouracil infusion, mitomycin C and pelvic radiation therapy in tethered and fixed rectal carcinoma.Int J Radiat Biol Phys 1993;25:791–9.
Landry JC, Koretz MJ, Wood WC, Bahri S, Smith RG, Costa M, Daneker GW, et al. Preoperative irradiation and fluorouracil chemotherapy for locally advanced rectosigmoid carcinoma: Phase I–II study.Radiology 1993;188:423–6.
Anderson JH, Kerr DJ, Setanoians A, Cooke TG, McArdle CS. A pharmacokinetic comparison of intravenous versus intra-arterial folinic acid.Br J Cancer 1992;65:133–5.
Mossa MA, Osman AM, El-Sayed M, El-Asser AA, Ismael N, El-Merzabani MM. Distribution and toxicity of 5-fluorouracil after intraperitoneal and anal submucosal administration.J Pharm Belg 1992;47:129–34.
Rousselot LM, Cole DR, Grossi CE, Conte AJ, Gonzalez EM, Pasternak BS. A five year progress report on the effectiveness of intraluminal chemotherapy (5-fluorouracil) adjuvant to surgery for colorectal cancer.Am J Surg 1968;115:140–7.
Rougler P, Nordlinger B. Large scale trial for adjuvant treatment in high risk resected colorectal cancers.Ann Oncol 1993;4:821–8.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galandiuk, S., Wrightson, W., Marr, L. et al. Suppository delivery of 5-fluorouracil in rectal cancer. Annals of Surgical Oncology 3, 270–276 (1996). https://doi.org/10.1007/BF02306282
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02306282