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5 FU infusion with mitomycin-C vs. 5 FU infusion with methyl-CCNU in the treatment of advanced upper gastrointestinal cancer: a Southwest Oncology Group Study.

A randomized trial was conducted by the Southwest Oncology Group (SWOG) in advanced carcinoma of the stomach and pancreas. Patients were assigned to receive monthly 5-fluorouracil 96-hour continuous infusions with either bolus mitomycin-C or oral methyl-CCNU. Mitomycin-C and methyl-CCNU were administered every eight weeks. The 5 FU-mitomycin combination produced a 14% and 22% response rate in disseminated stomach and pancreatic carcinoma, respectively. The combination of infusion 5 FU and methyl-CCNU achieved responses in 9% and 5% of stomach and pancreatic tumors, respectively. There was no significant difference in survival between limbs for either tumor. Median survival in gastric carcinoma on the 5 FU-mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU-METHYL-CCNU arm. In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl-CCNU program. Leukopenia was greater for the first course on the mitomycin limb. Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors. Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms.

Antineoplastic Agents↗

Difficulties in evaluating urinary specimens after local mitomycin therapy of bladder cancer.

In order to describe the cytological changes induced by mitomycin in urinary specimens, we re-examined cytological specimens from patients with recurring bladder cancer treated by long-term intravesical mitomycin therapy after transurethral resection. Local mitomycin therapy causes an increase of leukocytes and urothelial cells, especially of the umbrella-cell type, in urinary specimens. During and after the application of mitomycin, the nucleus and the cytoplasm of urothelial cells are enlarged, usually proportionally. Urothelial cells frequently show a giant nucleus, multiple prominent nucleoli, and an enlarged foamy cytoplasm of the umbrella-cell type. Anisokaryosis is also seen. Such cytological changes are more remarkable later in the course of therapy and after the end of therapy, and they often confuse cytological interpretation. However, the nuclei of urothelial cells are usually translucent and not hyperchromatic, and there is rarely a coarse chromatin pattern. On the other hand, in positive specimens during or after local mitomycin therapy, usually a number of tumor cells showing nuclear enlargement, hyperchromatic nuclei, coarse chromatin pattern, and/or increased nuclear-cytoplasmic ratio are found beside the atypical cells changed by mitomycin.

Aged↗

Role of mitomycin in upper digestive tract stricture.

BACKGROUND: Mitomycin C is an anti-fibroblast chemotherapeutic agent that has demonstrated promise in the treatment of head and neck cancer-related cervical stenosis. The present study investigates whether the application of mitomycin C at the time of dilation is both safe and effective in the treatment of head and neck cancer-related upper digestive tract stricture. METHODS: Twelve patients with progressive dysphagia and video-fluoroscopic evidence of upper digestive tract stricture after head and neck cancer treatment were dilated by Maloney or Savory dilators followed by the application of mitomycin C (0.2 mg/0.4 mL saline) to the stenotic segment for 5 minutes. Outcome measures included complication rate, improvement in baseline dietary consistency, and improvement in swallowing-related quality of life as measured by the M. D. Anderson Dysphagia Inventory. RESULTS: All patients experienced improvement in their baseline dietary consistency (p = .002) and M. D. Anderson Dysphagia Inventory composite score (p = .001) after a mean follow-up time of 19 months. No complications from mitomycin use were observed. CONCLUSION: Mitomycin application appears to be a safe and potentially effective treatment for head and neck cancer-related upper digestive tract stricture. Given the small sample size and limited follow-up time, a randomized, controlled trial is needed to determine whether mitomycin application offers additional benefit over standard dilation therapy.

Adenocarcinoma↗

[Hematogenous contact dermatitis after intravesicular instillation of mitomycin C].

Mitomycin C is an alkylating chemotherapeutic agent which is instilled intravesically to prevent recurrence of superficial bladder carcinomas. After several cycles of mitomycin C, our patient developed a pruritic genital dermatitis and palmar desquamation. Following exclusion of a fungal infection, we performed patch tests using the standard series, the major basic ointment ingredients, disinfectants, and mitomycin C in concentrations of 0.001 to 0.1%; the resulting diagnosis was allergic contact dermatitis due to delayed-type hypersensitivity to mitomycin C. The skin rash rapidly resolved with application of topical steroids, and the intravesical chemotherapy was changed to doxorubicin. Eczematous skin reactions are quite common side effects after intravesical instillation of mitomycin C. In the majority of cases, they are caused by delayed-type hypersensitivity reactions, presumably elicited by hematogenous spread of the allergen, and not by irritation. The sensitization most likely occurs via the bladder mucosa. In order to differentiate between allergic and toxic contact dermatitis, patch tests with the above-mentioned mitomycin C concentrations are useful. In cases of mild allergic contact dermatitis the intravesical chemotherapy might be continued with concomitant topical steroids.

Administration, Intravesical↗

Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years' experience.

PURPOSE: To report 12-year follow-up experience with topical mitomycin chemotherapy for diffuse and multifocal primary acquired melanosis (PAM) with atypia and conjunctival melanoma. METHODS: Interventional case series of 16 patients. Mitomycin was a primary treatment for residual epithelial disease in ten patients (eight with PAM with atypia and two with conjunctival melanoma) and as an adjuvant to excision and cryotherapy in six with conjunctival malignant melanoma. Primary treatments consisted of mitomycin 0.04% qid for 28 days (two 14-day cycles) and for 7 consecutive days as adjuvant therapy. Patients were followed for both local recurrence and metastatic disease. RESULTS: Sixteen patients were followed for a mean 81 months (range 13-144 months) after treatment. All tumors responded to chemotherapy. Recurrence was noted in eight (three adjuvant and five primary treatment patients). Three underwent orbital exenteration. The remaining five were treated conservatively. The mean time to recurrence was 36.9 months. The short-term mitomycin-related complications included transient keratoconjunctivitis (n=14), severe keratoconjunctivitis (n=1) and one corneal abrasion with scar formation. The long-term complications included pannus (n=2) and corneal haze (n=1). Visual acuity was maintained within two lines in 14 patients (including measurements just prior to exenteration). Three patients died, one of metastatic conjunctival melanoma. CONCLUSIONS: Conjunctival melanoma and PAM responded to mitomycin 0.04% topical chemotherapy; subepithelial nests appeared resistant to treatment. Treatment-related complications were acceptable. In this series, as primary and adjuvant therapy, topical mitomycin yielded an overall recurrence rate of 50%.

Administration, Topical↗

Postoperative application of mitomycin c improves the complete success rate of primary trabeculectomy: a prospective, randomized trial.

BACKGROUND: The intraoperative application of mitomycin c for primary trabeculectomy is associated with potentially sight-threatening side-effects. This study was performed to evaluate the pressure-lowering effect of postoperative application of mitomycin c for primary trabeculectomy and to evaluate the complications of this new technique. MATERIALS AND METHODS: A randomized, prospective clinical trial with 52 consecutive patients scheduled for glaucoma surgery in one large surgical center was performed. Patients underwent routine trabeculectomy. In group 1, mitomycin c (0.05 mg/ml) was applied topically to the filtering bleb for 5 min on the 3 days after surgery (postoperative application). In group 2, no mitomycin c was applied (controls). The IOP values, visual acuity, number of antiglaucomatous medications and complications were evaluated. RESULTS: Follow-up was evaluated up to 24 months for all patients. The mean intraocular pressure decreased from 31.1 to 15.4 mmHg in group 1 and from 24.8 to 15.6 mmHg in group 2 (P=0.79; t-test). The average number of medications decreased from 2.5 and 2.4 to 0.4 and 0.6 (P=0.53; t-test) in groups 1 and 2, respectively. No cases of hypotony maculopathy occurred. An individual decrease of more than 25% of the IOP was present in 84.6% in group 1 and in 53.8% in group 2 (P<0.017). Survival analysis for eyes with a complete surgical success revealed a better outcome of eyes in group 1 as compared to the eyes in group 2 (P<0.013; log-rank test). CONCLUSIONS: To our knowledge, this is the first prospective, randomized clinical trial to evaluate the efficacy of postoperative mitomycin c application in primary trabeculectomy. The application of mitomycin significantly reduced the IOP while not increasing the rate of complications.

Adult↗

Combining cisplatin and mitomycin with radiotherapy in anal carcinoma.

PURPOSE: The European Organization for Research and Treatment of Cancer (EORTC) phase II study No. 22953 demonstrated the feasibility of reducing the overall treatment time of chemoradiation, delivering mitomycin C twice rather than once and fluorouracil during the whole treatment. We tested the feasibility of chemoradiation in anal carcinoma with mitomycin and cisplatin in a phase II study. METHODS: Twenty-one patients with locally advanced anal carcinoma (15 women, 6 men) were treated. The first sequence of radiotherapy consisted of 36 Gy over four weeks. After a gap interval of 16 days, a second sequence of radiotherapy was given, delivering 23.4 Gy over 2.5 weeks. Mitomycin C was delivered at 10 mg/m(2) day 1 of each sequence and cisplatin was delivered at 25 mg/m(2)/week of each sequence. RESULTS: The compliance rates for the first sequence with radiation, mitomycinm, and cispaltin (dose and timing) were 100 percent. The median duration gap was 16 days (14-30 days). The compliance rates for the second sequence with radiation, mitomycin, and cisplatin (dose and timing) were 100, 76.2, and 85.7 percent, respectively. Grade > or = 2 acute toxicities of 62, 29, 25, and 5 percent were observed for skin, diarrhea, hematologic, and renal toxicities, respectively. Nineteen patients were in complete response (90.5 percent). CONCLUSIONS: Combining radiation with mitomycin and cisplatin in patients with locally advanced anal cancer is feasible. The results are promising. The EORTC is currently comparing this combination with mitomycin and 5-fluorouracil in a large phase II-III trial.

Adult↗

Increased DT-diaphorase expression and cross-resistance to mitomycin C in a series of cisplatin-resistant human ovarian cancer cell lines.

In a series of ovarian carcinoma cell lines selected in vitro for resistance to cisplatin by continuous exposure to increasing drug concentrations, the level of resistance is proportional to the expression of gamma-glutamylcysteine synthetase (gamma-GCS). To determine if other detoxicating genes are coordinately expressed, we measured the activity of DT-diaphorase and cytochrome P450 reductase. The specific activity of DT-diaphorase, but not that of cytochrome P450 reductase, increased with increasing resistance to cisplatin. Steady-state mRNA levels for DT-diaphorase correlated with enzyme activity and hence with cisplatin resistance. Since the activity of DT-diaphorase has been associated with sensitivity to quinones, we studied the cytotoxicity of mitomycin C under oxic conditions. Unexpectedly, resistance to mitomycin C increased proportionally with that to cisplatin (r = 0.997). Pretreatment with buthionine sulfoximine, which inhibits glutathione (GSH) synthesis, failed to sensitize either the sensitive or the resistant lines to mitomycin C. Thus, the basis for collateral resistance to mitomycin C in the cisplatin-resistant lines under oxic conditions is unrelated to overproduction of GSH. Under hypoxia, the toxicity of mitomycin C to the most sensitive (A2780) cell line was unchanged. However, the most resistant (C200) line was 2-fold more resistant to mitomycin C under hypoxic conditions. The coordinate overexpression of DT-diaphorase and gamma-GCS in the resistant cell lines is thus associated with hypoxic cell resistance, and supports the involvement of shared mechanisms of gene regulation in the observed resistant phenotype.

Antineoplastic Agents↗

Early and late effects of mitomycin C and continuous low-dose-rate irradiation on the mouse skin and soft tissues of the leg.

The early and late effects of combined mitomycin C and continuous low-dose-rate irradiation (CLDRI) on the skin and soft tissues were studied in the C3Hf/SED mice. Localized CLDRI of the hind leg at 0.028 Gy/min with and without mitomycin C was delivered using a 137Cs laboratory irradiator. Mitomycin C at 6 mg/kg was given by continuous infusion through intraperitoneally implanted osmotic mini-pumps during CLDRI. Acute skin reaction was scored from days 13 to 30 and late skin contraction and leg contracture were measured at days 90, 180, 270, and 360 after treatment. Mitomycin C increased the early skin reaction following CLDRI; at a dose of 60 Gy, the dose effect factor was approximately 1.1. However, there was no significant enhancement of late skin contraction or leg contracture by mitomycin C. Our results suggest that mitomycin C can be combined with low-dose-rate brachytherapy without a significant increase in early or late damage to the skin and soft tissues.

Acute-Phase Reaction↗

The effect of low pH and hypoxia on the cytotoxic effects of SR4233 and mitomycin C in vitro.

PURPOSE: We examined the effect of acidic pH and hypoxia on the cytotoxicity of SR4233 and mitomycin C in vitro. METHODS AND MATERIALS: The importance of tumor microenvironment to the response of solid tumors to cytotoxic treatment is well established. The bioreductive drug SR4233 has a very substantial selective toxicity for hypoxic cells. We have used both Chinese hamster and human tumor cells to investigate the influence of low pH and hypoxia on the response of cultured cells to treatment with SR4233 or mitomycin C. RESULTS: We found that low pH (6.6) had little effect on the hypoxic toxicity of SR4233; under aerobic conditions, however, low pH substantially increased the cytotoxic effects of 1 h exposure to SR4233, with drug dose enhancement ratios (ER) of 3.9 and 2.5 in V79 and HT-29 cells, respectively. In similar studies with mitomycin C, hypoxia had little effect on the cytotoxicity of mitomycin C in V79 cells, though a low pH of 6.6 enhanced the cytotoxicity under both aerobic and hypoxic conditions (ER approximately 2). In HT-29 cells, neither low pH nor hypoxia had any significant effect on mitomycin C toxicity. CONCLUSION: Low pH, like hypoxia, is a common feature of solid tumors and can be an important determinant of the cytotoxic effect of bioreductive drugs such as SR4233 and mitomycin C.

Animals↗

Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.

PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes. DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia. METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH. RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively). CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.

Administration, Topical↗

Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia.

PURPOSE: To evaluate the efficacy of topical mitomycin C in treating conjunctival and corneal epithelial dysplasia and neoplasia. METHODS: Seven eyes of seven patients with conjunctival and corneal epithelial dysplasia and neoplasia were treated with one drop of topical mitomycin C 0.04% four times a day for 7 days in alternate weeks. The patients' charts were reviewed retrospectively. Patients with either multiple recurrences or extensive ocular surface involvement were treated. In all eyes, the diagnosis of epithelial dysplasia or neoplasia was confirmed by histopathology before the onset of therapy. Patients were examined at least every 14 days during treatment and examined at intervals after completion of treatment. RESULTS: With topical mitomycin C, six eyes of seven patients had complete clinical regression of their conjunctival and corneal epithelial dysplasia and neoplasia. One eye of one patient had partial clinical regression of conjunctival and corneal epithelial dysplasia. Follow-up after completion of topical mitomycin C therapy and excision of residual disease ranged from 2 to 16 months (mean, 9 months; SD, 4.3 months) and was without clinical sign of recurrence. Topical mitomycin C therapy was associated with transitory ocular discomfort, conjunctival injection, tearing, photophobia, and punctate epithelial keratopathy. CONCLUSION: In this small series of eyes, topical mitomycin C was effective as a treatment for conjunctival and corneal epithelial dysplasia and neoplasia.

Adult↗

Comparative toxicity of mitomycin C and 5-fluorouracil in vitro.

The adjunctive use of antimetabolites has revolutionized surgical procedures to correct glaucoma in the past decade. Although much is known about the in vitro and in vivo actions of 5-fluorouracil and mitomycin C, their use in the eye has raised new questions about cellular toxicity. For example, filtering blebs after a surgical procedure supplemented with mitomycin C are relatively avascular in comparison with those seen with 5-fluorouracil supplementation. We investigated the effect of 5-fluorouracil and mitomycin C on cultured capillary endothelial cells and fibroblasts. The viability and morphologic characteristics of 3T3 fibroblasts and capillary endothelial cells were studied in light of increasing doses of 5-fluorouracil and mitomycin. Both cell types showed similar sensitivity to mitomycin C. However, fibroblasts were far more sensitive to 5-fluorouracil than were the cultured microvascular endothelial cells. Thus 5-fluorouracil appears to be toxic to fibroblasts while sparing vascular endothelial cells, whereas mitomycin C is cytotoxic for both cell types.

3T3 Cells↗

Clinical and histopathologic observations concerning hypotony after trabeculectomy with adjunctive mitomycin C.

Prolonged hypotony-induced maculopathy is a serious complication of trabeculectomy with adjunctive mitomycin C. We performed trabeculectomies with intraoperative mitomycin C on 59 eyes of 52 consecutive patients. Exposure time to mitomycin C was five minutes in the first seven patients, two of whom had prolonged hypotony-induced maculopathy. One of these required surgical revision of the filtering procedure. Light and electron microscopic study of the excised, avascular bleb disclosed an irregular epithelium and largely acellular subepithelium of loosely arranged connective tissue. In the remaining 52 eyes, the exposure time to mitomycin C was titrated between two and five minutes according to each patient's risk for failure of filtration from excessive fibrosis. Four additional cases of prolonged hypotony-induced maculopathy occurred among these 52 cases (7.7%), all of which were in the lower risk groups that received two- or three-minute exposure to mitomycin C. Four procedures failed, requiring further glaucoma surgery, and all of the patients were in the higher risk groups, receiving three- to five-minute exposures. Our titration of the exposure time to mitomycin C may have reduced, but did not eliminate, the risk fo prolonged hypotony-induced maculopathy, and further study is needed to establish the optimum protocol for the use of this drug as an adjunct to trabeculectomy.

Adolescent↗

Randomized trial of intraoperative mitomycin C in surgery for pterygium.

PURPOSE: To report the efficacy and safety of intraoperative application of mitomycin C in surgery for pterygium. METHODS: In a prospective randomized and double-blind study done within a span of 2.5 years in 50 eyes (50 patients) with primary progressive pterygium, mitomycin C in a concentration of 0.02 mg/ml soaked in a sterile 5 x 5-mm sponge was applied over the bare sclera intraoperatively as an adjuvant therapy in 25 eyes after pterygium excision. These cases were compared with another 25 similar eyes that underwent the same procedure but in which gentamicin solution 0.3% was used instead of mitomycin C solution. RESULTS: Three eyes (12%) in the mitomycin C group showed recurrence within 7 months of surgery compared with eight eyes (32%) of the gentamicin control group within 3 to 5 months. Mild side effects, such as pain, photophobia, and delayed wound healing, were observed within the first 1 to 2 weeks postoperative in both groups. In the mitomycin C-treated group, corneal changes in the form of superficial punctate keratitis (three eyes) and limbal avascularity (two eyes) subsided within 2 weeks postoperatively. Follow-up time for these cases ranged from 18 to 21 months. CONCLUSIONS: A diluted solution of mitomycin C, 0.02 mg/ml, with an accurate size of sterile sponge applied to bare sclera after primary pterygium excision decreases the rate of recurrence to a greater extent than does gentamicin solution and is not associated with severe complications.

Adult↗

A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma.

PURPOSE: We compared the efficacy and toxicity of long-term mitomycin C versus bacillus Calmette-Guerin (BCG) instillation in patients at high risk for recurrence and progression of superficial bladder carcinoma. MATERIALS AND METHODS: Our randomized comparison study included 261 patients with primary dysplasia, or stage Tis, stage T1, grade 3 and multiple recurrent stage Ta/T1, grade 1 or 2 disease. Mitomycin C (40 mg.) or Pasteur strain BCG (120 mg.) was instilled weekly for 6 weeks, then monthly for up to 1 year and every 3 months during year 2. RESULTS: After a median followup of 39 months 49% of the patients given BCG and 34% given mitomycin C were disease-free (p < 0.03), compared to 48 and 35%, respectively, of those with stage Ta or T1 disease, and 54 and 33%, respectively, of those with dysplasia or stage Tis tumor. Tumor progressed in 13% of patients, with no statistically significant difference observed regarding progression between the mitomycin C and BCG groups. Side effects were more common after BCG instillation, with 5 cases of severe side effects compared to 1 in the mitomycin C group. Treatment was stopped due to toxicity in 10% of the patients. CONCLUSIONS: The majority of patients tolerated long-term intravesical therapy well. BCG instillation was hampered by more frequent side effects. BCG was superior regarding recurrence prophylaxis, since patients given BCG had fewer recurrences and a significantly longer time to treatment failure compared to those treated with mitomycin C. No statistically significant difference was observed regarding progression.

Adjuvants, Immunologic↗

Intraoperative episcleral versus postoperative topical application of mitomycin-C for trabeculectomies.

OBJECTIVE: To assess the efficacy of a new application technique of mitomycin-C to enhance the outcome of filtering surgery in cases of complicated glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Fifty consecutive patients scheduled for glaucoma surgery in one large surgical center. INTERVENTION: Patients underwent routine trabeculectomy. In group 1, mitomycin-C (0.05 mg/ml) was applied topically to the filtering bleb on days 1, 2, and 3 after surgery (postoperative application). In group 2, mitomycin-C (0.2 mg/ml) was applied by means of to a sponge during surgery (intraoperative application). MAIN OUTCOME MEASURES: Preoperative and postoperative intraocular pressure (IOP) values, visual acuity, the need for antiglaucoma medication, previous surgical procedures, and the need for further surgical interventions were monitored. RESULTS: Sufficient follow-up data were available from 24 of 25 patients in each of the two groups. The follow-up ranged from 12 to 28 months and was evaluated at 12 months for all patients. The mean IOP decreased from 27.3 to 15.5 mmHg in group 1 and from 29.0 to 17.5 mmHg in group 2. The average number of medications decreased from 2.3 and 2.4 to 0.9 and 0.8 (P = 0.68; t test) in groups 1 and 2, respectively, at the 12-month visit. Hypotony was more frequent in group 2, in which the only case of hypotony maculopathy occurred. There was a tendency of more eyes with lower IOP values in this group. The rate of loss of visual acuity of more than 2 lines was higher in group 2. Failures were more frequent in group 2 (7 of 24) compared with group 1 (1 of 24) (P = 0.04, chi-square test). CONCLUSIONS: To our knowledge, this is the first prospective, randomized clinical study to evaluate the efficacy of this different technique of mitomycin-C application. The postoperative application of mitomycin-C was effective, having few failures. This application of mitomycin-C may be associated with a lower rate of complications when used in eyes with complicated forms of glaucoma.

Administration, Topical↗

Aqueous and vitreous concentration of mitomycin C by topical administration after glaucoma filtration surgery in rabbits.

PURPOSE: The authors investigated the aqueous and vitreous pharmacokinetics of mitomycin after postoperative topical administration in rabbits. METHODS: Filtration surgery was performed in one eye of each rabbit. On the first postoperative day, mitomycin solution (0.4 mg/ml) was administered by either topical drop or cellulose sponge in both eyes of each rabbit. Aqueous and vitreous paracenteses were performed at 0.25, 0.5, 1, 2, 3, and 4 hours thereafter. Three rabbits were tested at each time interval for each type of administration. RESULTS: After topical drop administration, the peak aqueous concentration was 0.03 +/- 0.02 microgram/ml (mean +/- standard error) in surgical eyes and 0.06 +/- 0.03 microgram/ml in control eyes. After sponge administration, the peak aqueous concentration was 0.10 +/- 0.03 microgram/ml in surgical eyes and 0.08 +/- 0.04 microgram/ml in control eyes. Peak aqueous concentrations from drop and sponge applications were achieved at 1 to 2 hours after administration. Vitreous levels were well below the concentration known to cause retinal toxicity at all time intervals tested. CONCLUSION: Postoperative topical administration of mitomycin was successful in delivering mitomycin into the aqueous humor of rabbit eyes. Alternative methods of mitomycin application from the currently popular intraoperative administration may be beneficial in situations in which mitomycin delivery across intact conjunctiva may be desirable.

Administration, Topical↗