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5-Fluorouracil Urethral Suppositories for the Eradication of Condyloma Acuminata
0022-5347/78/1202-0174$02. 00/0 Vol. 120, August
THE JOURNAL OF UROLOGY
Printed in U.SA.
Copyright © 1978 by The Williams & Wilkins Co.
5-FLUOROURACIL URETHRAL SUPPOSITORIES FOR THE ERADICATION OF CONDYLOMA ACUMINATA GEORGE W. WEIMAR, LEO A. MILLEMAN, THOMAS L. REILAND
AND
DAVID A. CULP
From the Departments of Urology and Pharmacy, The University of Iowa Hospitals and Clinics, Iowa City, Iowa
ABSTRACT
The formulation of a 5-fluorouracil urethral suppository is described. The suppositories have been found extremely successful in the eradication of intraurethral condylomas. They have provided better patient compliance and dosage monitoring, and have extended patient usefulness to male and female subjects. Condyloma acuminata involving the urethra and urethral meatus are difficult to eradicate. 1• 2 Although podophyllin has remained the mainstay of treatment for non-mucosal lesions it is irritating and cytotoxic to intraurethral mucosal surfaces. Other reported methods of management of intraurethral condylomas have had specific associated complications. 3 Surgical methods of excision and fulguration of intraurethral lesions can result in stricture and increased expense from hospitalization. The report in 1975 by Dretler and Klein on the successful application of 5-fluorouracil (5-FU) cream to intraurethral condylomas has shown that the agent can eradicate these lesions effectively in male subjects. 4 Several adverse factors,
glycol 4,000, polyethylene glycol 400 monosterate and propylene glycol are melted together in 3:1:1 proportions by weight. Fluoracil powder is added to achieve a 5 per cent weight concentration. The mixture is poured into a urethral suppository mold, lubricated with mineral oil and refrigerated until hardened (see figure). The suppositories are of standard length and may be inserted back to back or cut as desired. The patient inserts the suppository into the urethra twice daily for 7 to 10 days.
including the irritative effects to the scrotal and penile skin from spillage, poor patient compliance, lack of dosage monitoring and the inability to use the cream in the short female urethra, prompted us to seek a more standard method to treat deep intraurethral lesions. We report herein a method to form a 5-FU intraurethral suppository that can be inserted into the urethra to a predetermined depth as ascertained by panendoscopy.
to 3 years. No significant complications have occurred. Spillage of the agent has caused superficial scrotal ulcerations but this has not been a problem. No urethral strictures and no evidence of systemic side effects have been noted. Red and white blood cells and platelet counts were monitored during and after therapy and no change was noted.
RESULTS
The 12 male and female patients treated with 5-FU suppositories have had good results. Followup ranges from 4 months
MATERIAL AND METHODS
The suppositories are formulated from fluoracil powder incorporated into a polyethylene glycol base. Polyethylene Accepted for publication December 30, 1977. Read at annual meeting of North Central Section, American Urological Association, San Diego, California, November 6-12, 1977.
174
CASE REPORTS
Case 1. A 22-year-old white man complained of bleeding at the tip of the penis for several days. Physical examination revealed several erythematous 0.5 cm. condylomas at the urethral meatus. Cystoscopy revealed lesions in the meatus extending to the fossa navicularis. Initially, all lesions were fulgurated transurethrally. The patient was seen 2 months later with recurrence of the condylomas in the same location.
175He received a course of the 5-FU Cystos· the condylomas. copy 3 weeks later revealed no evidence This patient has been followed for 2 years and no recurrences have been noted. Case 2. A zz-·"""""··" white woman with a long history of voiding symptoms had been treated with fulguration 5 times previously for condyloma acuminata surrounding the introitus. Physical examination and panendoscopy showed numerous condylomas of the introitus and urethral mucosa. The woman was treated with 5-FU suppositories twice daily for 10 days. Dysuria was noted during treatment and for 3 days after discontinuing therapy but the voiding pattern then returned to normal. Panendoscopy at 1 and 5 months after therapy revealed no evidence of recurrent condylomas. DISCUSSION
Wearing an athletic support with a small piece of gauze over the meatus and washing the meatus 15 minutes after insertion of the suppository have minimized meatal skin irritation. The suppositories melt within 5 to 10 minutes. The first voiding after insertion cleanses the urethra of suppository remnants. Some patients may have an area of denuded mucosa where the condyloma lesion has sloughed. These erosions may be the source of some initial voiding symptoms during and after therapy but the areas heal spontaneously and no resultant
stricture or voiding have occurred. is not advised until 3 to 4 weeks after treatment to allow for sufficient mucosa! healing. The mechanism of action of 5-FU has been discussed elsewhere. 5 • 6 The action of the compound on rapidly metabolizing cells makes patients with condyloma acuminata ideal candidates for this drug treatment. The use of intraurethral suppositories has effected good patient compliance and more accurate placement and dosage application. It also has extended patient usefulness to male and female subjects. REFERENCES
1. Morrow, R. P., Jr., McDonald, J. R. and Emmett, J. L.:
Condylomata acuminata of the urethra. J. Urol., 68: 909, 1952. 2. Lindner, H.J. and Pasquier, C. M., Jr.: Condylomata acuminata of the urethra. J. Urol., 72: 875, 1954. 3. Kleiman, H. and Lancaster, Y.: Condyloma acuminata of the bladder. J. Urol., 88: 52, 1962. 4. Dretler, S. P. and Klein, L.A.: The eradication ofintraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. J. Urol., 113: 195, 1975. 5. Cohen, S. S., Flaks, J. G., Barner, H. D., Loeb, M. R. and Lichtenstein, J.: The mode of action of 5-fluorouracil and its derivatives. Proc. Nat. Acad. Sci., 44: 1004, 1958. 6. Eaglstein, W. H., Weinstein, G.D. and Frost, P.: Fluorouracil: mechanism of action in human skin and actinic keratoses. I. Effect on DNA synthesis in vivo. Arch. Derm., Hll: 132, 1970.
THE JOURNAL OF UROLOGY
Printed in U.SA.
Copyright © 1978 by The Williams & Wilkins Co.
5-FLUOROURACIL URETHRAL SUPPOSITORIES FOR THE ERADICATION OF CONDYLOMA ACUMINATA GEORGE W. WEIMAR, LEO A. MILLEMAN, THOMAS L. REILAND
AND
DAVID A. CULP
From the Departments of Urology and Pharmacy, The University of Iowa Hospitals and Clinics, Iowa City, Iowa
ABSTRACT
The formulation of a 5-fluorouracil urethral suppository is described. The suppositories have been found extremely successful in the eradication of intraurethral condylomas. They have provided better patient compliance and dosage monitoring, and have extended patient usefulness to male and female subjects. Condyloma acuminata involving the urethra and urethral meatus are difficult to eradicate. 1• 2 Although podophyllin has remained the mainstay of treatment for non-mucosal lesions it is irritating and cytotoxic to intraurethral mucosal surfaces. Other reported methods of management of intraurethral condylomas have had specific associated complications. 3 Surgical methods of excision and fulguration of intraurethral lesions can result in stricture and increased expense from hospitalization. The report in 1975 by Dretler and Klein on the successful application of 5-fluorouracil (5-FU) cream to intraurethral condylomas has shown that the agent can eradicate these lesions effectively in male subjects. 4 Several adverse factors,
glycol 4,000, polyethylene glycol 400 monosterate and propylene glycol are melted together in 3:1:1 proportions by weight. Fluoracil powder is added to achieve a 5 per cent weight concentration. The mixture is poured into a urethral suppository mold, lubricated with mineral oil and refrigerated until hardened (see figure). The suppositories are of standard length and may be inserted back to back or cut as desired. The patient inserts the suppository into the urethra twice daily for 7 to 10 days.
including the irritative effects to the scrotal and penile skin from spillage, poor patient compliance, lack of dosage monitoring and the inability to use the cream in the short female urethra, prompted us to seek a more standard method to treat deep intraurethral lesions. We report herein a method to form a 5-FU intraurethral suppository that can be inserted into the urethra to a predetermined depth as ascertained by panendoscopy.
to 3 years. No significant complications have occurred. Spillage of the agent has caused superficial scrotal ulcerations but this has not been a problem. No urethral strictures and no evidence of systemic side effects have been noted. Red and white blood cells and platelet counts were monitored during and after therapy and no change was noted.
RESULTS
The 12 male and female patients treated with 5-FU suppositories have had good results. Followup ranges from 4 months
MATERIAL AND METHODS
The suppositories are formulated from fluoracil powder incorporated into a polyethylene glycol base. Polyethylene Accepted for publication December 30, 1977. Read at annual meeting of North Central Section, American Urological Association, San Diego, California, November 6-12, 1977.
174
CASE REPORTS
Case 1. A 22-year-old white man complained of bleeding at the tip of the penis for several days. Physical examination revealed several erythematous 0.5 cm. condylomas at the urethral meatus. Cystoscopy revealed lesions in the meatus extending to the fossa navicularis. Initially, all lesions were fulgurated transurethrally. The patient was seen 2 months later with recurrence of the condylomas in the same location.
175He received a course of the 5-FU Cystos· the condylomas. copy 3 weeks later revealed no evidence This patient has been followed for 2 years and no recurrences have been noted. Case 2. A zz-·"""""··" white woman with a long history of voiding symptoms had been treated with fulguration 5 times previously for condyloma acuminata surrounding the introitus. Physical examination and panendoscopy showed numerous condylomas of the introitus and urethral mucosa. The woman was treated with 5-FU suppositories twice daily for 10 days. Dysuria was noted during treatment and for 3 days after discontinuing therapy but the voiding pattern then returned to normal. Panendoscopy at 1 and 5 months after therapy revealed no evidence of recurrent condylomas. DISCUSSION
Wearing an athletic support with a small piece of gauze over the meatus and washing the meatus 15 minutes after insertion of the suppository have minimized meatal skin irritation. The suppositories melt within 5 to 10 minutes. The first voiding after insertion cleanses the urethra of suppository remnants. Some patients may have an area of denuded mucosa where the condyloma lesion has sloughed. These erosions may be the source of some initial voiding symptoms during and after therapy but the areas heal spontaneously and no resultant
stricture or voiding have occurred. is not advised until 3 to 4 weeks after treatment to allow for sufficient mucosa! healing. The mechanism of action of 5-FU has been discussed elsewhere. 5 • 6 The action of the compound on rapidly metabolizing cells makes patients with condyloma acuminata ideal candidates for this drug treatment. The use of intraurethral suppositories has effected good patient compliance and more accurate placement and dosage application. It also has extended patient usefulness to male and female subjects. REFERENCES
1. Morrow, R. P., Jr., McDonald, J. R. and Emmett, J. L.:
Condylomata acuminata of the urethra. J. Urol., 68: 909, 1952. 2. Lindner, H.J. and Pasquier, C. M., Jr.: Condylomata acuminata of the urethra. J. Urol., 72: 875, 1954. 3. Kleiman, H. and Lancaster, Y.: Condyloma acuminata of the bladder. J. Urol., 88: 52, 1962. 4. Dretler, S. P. and Klein, L.A.: The eradication ofintraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. J. Urol., 113: 195, 1975. 5. Cohen, S. S., Flaks, J. G., Barner, H. D., Loeb, M. R. and Lichtenstein, J.: The mode of action of 5-fluorouracil and its derivatives. Proc. Nat. Acad. Sci., 44: 1004, 1958. 6. Eaglstein, W. H., Weinstein, G.D. and Frost, P.: Fluorouracil: mechanism of action in human skin and actinic keratoses. I. Effect on DNA synthesis in vivo. Arch. Derm., Hll: 132, 1970.