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PubMed2002

The association between frequencies of mitomycin C-induced sister chromatid exchange and cancer risk in arseniasis.

In order to examine whether biomarkers of cytogenetic damage and susceptibility, such as spontaneous and mitomycin C-induced sister chromatid exchange (SCE) can predict cancer development, a nested case-control study was performed in a blackfoot endemic area with known high cancer risk. A cohort of 686 residents was recruited from three villages in the arseniasis area. Personal characteristics were collected and venous blood was drawn for lymphocyte culture and stored in a refrigerator. The vital status and cancer development was followed using the National Death Registry, Cancer Registry, and Blackfoot Disease Registry. The follow up period was from August 1991 to July 1997. During this 6-year-period, 55 residents developed various types of cancer. Blood culture samples from 23 of these subjects were unsuitable for spontaneous SCE experiments and 45 of these subjects were unsuitable for mitomycin C-induced SCE experiments due to improper storage. Finally, a total of 32 cancer cases had cytogenetic samples that could be analyzed. About 32 control subjects were selected from those who did not develop cancer in the study period and these subjects were matched to cases by sex, age, smoking habits, and residential area. The results showed that there was no significant difference in the frequencies of spontaneous and mitomycin C-induced SCE between the case and control groups. There was also no significant difference in the net difference of spontaneous and mitomycin C-induced SCE between the case and control groups. These results suggest that SCEs, either spontaneous or mitomycin C-induced, might not be good markers to predict cancer risk.

Arsenic↗
PubMed2001

Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study.

The aim of this study was to investigate the tumour response rate and toxicity of a combination chemotherapy consisting of mitomycin-C and cisplatin in patients with disseminated squamous-cell carcinoma of the uterine cervix. Chemotherapy consisted of mitomycin, 6 mg/m(2) intravenously (i.v.), and cisplatin, 50 mg/m(2) given i.v., both administered on day 1 of each cycle. The regimen was repeated at 4-weekly intervals. Mitomycin-C/cisplatin were used to treat 33 evaluable patients aged 29-67 years (median: 50 years). All patients except 1 had previously been treated with either surgery, radiation or both. At the initiation of chemotherapy, 8 patients had loco-regional and disseminated disease and 25 women had only distant metastases. The overall response rate was 42% (95% confidence interval (CI): 26-61%). Five complete and nine partial responses were observed with a median duration of response of 7.9 months (95% CI: 3.7-23.5 months). 9 patients had stable disease and 10 developed progressive disease during mitomycin-C/cisplatin-treatment. World Health Organization (WHO) grade III/IV side-effects were documented in 15 women, of whom 10 had gastro-intestinal toxicity, 3 had haematological toxicity, 1 had alopecia and 1 developed an allergic reaction to cisplatin. There were neither drug-related deaths nor severe or irreversible renal or hepatic dysfunction or peripheral neuropathy. The median progression-free survival was 5.0 months (95% CI: 3.6-6.2 months) for all patients and 10.5 months (95% CI: 6.2-15.2 months) for the responders. The median overall survival was 11.2 months (95% CI: 6.5-18.4 months).The mitomycin-C/cisplatin combination showed antitumour activity in the treatment of advanced or recurrent squamous-cell carcinoma of the uterine cervix. The regimen was well tolerated and could be administered on an outpatient basis.

Adult↗
PubMed1999

Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type.

BACKGROUND: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). PATIENTS AND METHODS: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. TOXICITY: Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. RESPONSE: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. CONCLUSION: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.

Adult↗
PubMed1997

Mitomycin C reduces scar formation after excimer laser (193 nm) photorefractive keratectomy in rabbits.

Sixteen eyes of eight rabbits were randomised to either mitomycin C or Balanced Salt Solution (BSS) application after photorefractive keratectomy (PRK). Regular examinations of wound healing and haze were performed with the slit lamp. The animals were killed between 1 and 26 weeks after treatment, and the corneas examined by light and electron microscopy. While the grade of haze showed no relevant differences between the two groups, scar tissue was found histologically in the mitomycin group in only 1 of 8 corneas compared with 5 of 8 in the BSS group. A marked reduction in keratocytes in all mitomycin-treated corneas and a normal density of keratocytes in the BSS group was observed. Mitomycin reduced the number of keratocytes in the treated corneas, leading to less scar formation but not to a reduction in haze. Since no morphological correlate has been found, haze remains unexplained in the mitomycin-treated corneas.

Animals↗
PubMed2002

Use of mitomycin C in the treatment of corneal conjunctival intraepithelial neoplasia.

PURPOSE: To evaluate the efficacy of topical mitomycin C as a treatment of corneal conjunctival intraepithelial neoplasia. METHODS: An open prospective analysis of 20 cases of corneal conjunctival intraepithelial neoplasia with recurrent disease (17 patients) or refusing surgery (three patients) were treated with topical mitomycin C. Treatment was with mitomycin C eye drops, either 0.02% or 0.04%, four times daily for 1 week followed by a week off the cycle then repeated for a second week. Patients were examined weekly until the lesions were eradicated. RESULTS: Clinical resolution of disease occurred in 18/20 cases. The mean time to resolution was 4.5 weeks, the mean number of cycles of treatment was two. Average follow up was 13 months with four cases of recurrent disease. These four cases were retreated with complete resolution in two cases. Epithelial toxicity occurred in 10/20 eyes and lid toxicity in two cases. There were no long-term complications on discontinuing mitomycin C. CONCLUSIONS: Mitomycin C is effective in inducing regression of corneal conjunctival intraepithelial neoplasia. Complications are common but self-limiting. An optimal regimen is still to be established.

Administration, Topical↗
PubMed2001

Squamous cell carcinoma of the oesophagus treated with radiation and 5-fluorouracil, with and without mitomycin C.

A retrospective analysis was performed of patients with squamous cell carcinoma of the oesophagus without evidence of distant metastases, who were treated with radical intent. Between 1981 and 1984, and 1989 and 1991, 98 patients were treated with radiation, 5-fluorouracil (5-FU) and mitomycin C; and between 1984 and 1989, 133 patients were treated with radiation and 5-FU without mitomycin C. Actuarial survival and local control were assessed, and prognostic factors were identified for both endpoints. The standard dose of radiation prescribed was 52 Gy to the 95% isodose in 20 fractions over 4 weeks. 5-FU was given by continuous infusion as 1 g/m2 (maximum 1.5 g)/day, for 4 days. Patients who received mitomycin C were given 10 mg/m2 (maximum 18 mg) on day 1. Survival and local relapse-free rates were estimated using the method of Kaplan and Meier, and the Cox proportional hazards model was used to evaluate possible prognostic factors, including the effect of mitomycin C administration. The median survival was 15.4 months (95% confidence interval 12.7-17.2) with 31% 2-year survival (standard error (SE) 3%), and 13% 5-year survival (SE 2%). In the multivariate analysis, lower radiation dose and younger age were the only statistically significant prognostic factors for reduced overall survival and reduced relapse-free rate respectively. There was no difference in survival (chi(2) = 0.07, 1 degree of freedom (df), P=0.79) or local relapse-free rate (chi2 = 0.39, 1 df, P = 0.53) between patients treated with or without mitomycin C. The treatment was well tolerated. Further studies are required to determine the most effective combination of radiation and chemotherapy or other radiation sensitizers for squamous cell carcinoma of the oesophagus.

Aged↗
PubMed2001

Increased efficiency of gamma-irradiated versus mitomycin C-treated feeder cells for the expansion of normal human cells in long-term cultures.

Several normal human cells, such as hematopoietic stem cells, dendritic cells, and B cells, can be cultured in vitro in defined optimal conditions. Several ex vivo culture systems require the use of feeder cells to support the growth of target cells. In such systems, proliferation of feeder cells has to be stopped, so that they can be used as nonreplicating viable support cells. Because feeder cells need to provide one or few active signals, it is important to maintain them in an metabolically active state, allowing continued expression of specific ligands or cytokines. Mitomycin C and gamma-irradiation treatments are commonly used to prepare nonproliferating feeder cells and are usually considered to be equivalent. Normal human B lymphocytes can be expanded in vitro in the presence of feeder cells expressing the CD40 ligand CD154. Here we compared the ability of gamma-irradiation- and mitomycin C-treated feeder cells to support the expansion of normal human B lymphocytes. The results indicate that expansion of B cells during a long-term culture was 100 times more potent using gamma-irradiated feeder cells compared to mitomycin C-treated cells. This difference could be related to a significant reduction in both cellular metabolism and level of CD154 expression observed in mitomycin C-treated feeder cells, but not in gamma-irradiated cells nor in control untreated cells. These results indicate that mitomycin C-treated feeder cells are metabolically altered, and consequently less efficient at maintaining cell expansion in the long-term cell culture system used.

Animals↗
PubMed1996

Reductase enzyme expression across the National Cancer Institute Tumor cell line panel: correlation with sensitivity to mitomycin C and EO9.

BACKGROUND: Many antitumor drugs require metabolic activation to exert their cytotoxic or cytostatic effects. The so-called bioreductive compounds, whose conversion into active antitumor agents is catalyzed by reductase enzymes, are examples of such drugs. The identification of specific enzymes involved in the activation of these compounds is important in understanding cellular factors that may influence drug antitumor activity. PURPOSE: We measured expression levels of three different reductase enzymes-DT-diaphorase [NAD(P)H (i.e., reduced nicotinamide adenine dinucleotide, with or without phosphate): quinone oxidoreductase]; NADPH:cytochrome P-450 reductase; and NADH (i.e., reduced nicotinamide adenine dinucleotide): cytochrome-b5 reductase- in 69 cell lines (most of the National Cancer Institute [NCI] human tumor cell panel) to see if relationships could be established between the activities of these enzymes and cellular sensitivities to the bioreductive compounds mitomycin C and EO9. METHODS: For all 69 cell lines, the activity of each enzyme was determined using cellular extracts and photometric assays involving the reduction of cytochrome c. Western blot analysis was used to measure the relative amount of DT-diaphorase protein in each extract, and coupled reverse transcription and polymerase chain reactions were employed to assess DT-diaphorase and NADPH:cytochrome P-450 reductase messenger RNA (mRNA) levels in a subset of the cell lines. The cytotoxic and/or cytostatic activities of mitomycin C and EO9 toward the cell lines were determined under aerobic conditions. Relationships between enzyme activity levels and drug sensitivities were assessed by use of the COMPARE program and Pearson correlation coefficients. RESULTS: In general, DT-diaphorase activity levels were higher than those observed for the other two reductases across the entire cell line panel. Measured activities for all three enzymes varied among cell lines derived from the same tissue as well as between lines derived from different tissues; however, tissue-specific patterns of expression could be discerned. Differences in the activity levels of individual enzymes appeared to reflect differences in corresponding enzyme protein and/or mRNA levels. A relationship between enzyme activity and chemosensitivities to mitomycin C and EO9 was observed only for DT-diaphorase (Pearson correlation coefficient = .424 [two-sided P<.0005] for mitomycin C and .446 [two-sided P< or = to .0013] for EO9). CONCLUSIONS: Reductase enzyme expression is heterogeneous across human tumor cell lines, and tissue-specific patterns of expression are apparent. DT-diaphorase activity levels correlate with sensitivities to mitomycin C and EO9, supporting a role for this enzyme in the bioactivation of these anticancer compounds. IMPLICATIONS: Comparison of biochemical, molecular biological, and chemosensitivity data obtained from screening a large number of cell lines (e.g., the NCI tumor cell line panel) may facilitate investigation of factors influencing drug antitumor activity. The knowledge gained may be of value in the development of new anticancer agents or in the selection of patients to receive specific therapies.

Antineoplastic Agents↗
PubMed1998

Caffeine effect on the mitotic delay induced by G2 treatment with UVC or mitomycin C.

It is well established that DNA lesions trigger cell cycle check-points causing a mitotic delay that is required for their repair before cells enter the mitotic phase. Caffeine, in some cases, can remove this delay and consequently potentiates the yield of induced chromosome aberrations. The objective of this study was to test the effect of a G2 treatment with S-dependent agents (UV light and mitomycin C) on the cell kinetics of a G2 cell population and evaluate whether post-treatments with caffeine could modulate removal of the expected cell cycle delay. Cell kinetics were monitored by analysing the mitotic index (MI) values in combination with the 5-bromo-2'-deoxyuridine (BrdUrd) labelling technique. Chinese hamster fibroblast cultures (AA8) were treated in G2 phase of the cell cycle with 8 and 15 J/m2 UV light or 0.1 and 0.6 microgram/ml mitomycin C for 1.5 h. Post-treatments with caffeine were performed at dose levels and recovery times where the mitotic indices were substantially reduced. The results obtained showed that both UV light and mitomycin C induced a G2 arrest, as indicated by MI values and the absence of BrdUrd-labelled metaphases. For UV light the G2 block was observed at lower and higher dose levels after 1.5 h, while for mitomycin C it was observed only at the higher dose level after 1 h. However, in both cases the block lasted approximately 1 h, after which, even though slowed down, the cell population entered mitosis, as indicated by increased MI values. This block was not removed by caffeine post-treatment. In contrast, caffeine G2 post-treatment was able to remove G2 arrest induced by G1-S treatments. Accordingly, our results suggest that both UV light- and mitomycin C-induced damage must be processed during S phase to allow caffeine to remove induced G2 blocks.

Animals↗
PubMed1985

Hematologic toxicity of cisplatin and mitomycin in combination for squamous cell carcinoma of esophagus.

Seventy-six patients with squamous cell carcinoma of the esophagus (SCE) were treated with either cisplatin and mitomycin in combination or as single agents on ECOG protocol 2278. Sixty-six patients were evaluated for toxicity. Of 13 evaluable mitomycin and cisplatin treated patients, six (46%) experienced ECOG grade 4 thrombocytopenia and/or leukopenia. Of 28 evaluable patients treated with mitomycin alone, two (7%) experienced such toxicity; and of 25 evaluable patients treated with cisplatin alone, none experienced this toxicity. The average total dose prior to toxicity for those receiving mitomycin and cisplatin in combination was 51 mg and 131 mg, respectively, with average time to toxicity 3.6 weeks. For those two patients who received mitomycin alone, the average total dose was 68 mg and average time to toxicity 6.5 weeks. For those patients receiving cisplatin alone, the average total dose was 220 mg. The reasons for the enhanced hematologic toxicity of the agents together are not apparent, but it would be prudent to caution investigators using these agents in combination with potentially myelosuppressive drugs.

Aged↗
PubMed1991

Etoposide and mitomycin in the treatment of non-small-cell lung cancer. A phase I-II evaluation.

Sixty-five patients (20 patients who had had prior radiotherapy and 45 patients who had not had prior radiotherapy) were entered into a study evaluating escalating doses of etoposide and mitomycin in the treatment of non-small-cell lung cancer (NSCLC). Twenty-two percent of patients who had not received prior radiotherapy responded to the chemotherapy, compared with 5% of patients who had received prior radiotherapy. The best response rate and median survival time was 30% and 31.9 weeks, respectively, seen in three of 10 patients receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3. The major toxicity was hematologic--mainly leukopenia, in 59% of patients who had had no prior radiation therapy and were receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 150 mg/M2 i.v. days 1-3 (grade 3 and 4 hematologic toxicity). The mitomycin-etoposide drug combination has some activity in patients with NSCLC who have not received prior radiotherapy. The recommended starting dose is mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3, administered every 4 weeks.

Adenocarcinoma↗
PubMed1995

Syndrome of acute dyspnea related to combined mitomycin plus vinca alkaloid chemotherapy.

We report the incidence, clinical features, and course of acute dyspnea following combination chemotherapy using mitomycin and vindesine or vinblastine. The courses of 387 patients with advanced non-small cell lung cancer receiving combined mitomycin and vinca alkaloid chemotherapy were analyzed. Of these patients, 25 experienced acute respiratory distress. Factors contributing to the dyspnea are reported. The syndrome is characterized by the sudden onset of dyspnea without other respiratory symptoms. Acute shortness of breath always occurred on a day when a vinca alkaloid was administered. The median number of previous doses of vinca alkaloid at the time of the event was 10 and the median number of prior mitomycin doses was 3. Rechallenge with the drug in two cases led to recurrence. The incidence was 4% in a group of 378 patients on four protocols for non-small cell lung cancer. Radiographs of 87% of patients showed new focal or diffuse interstitial infiltrates. Arterial blood gases demonstrated low PO2 and increase in A-a gradient. Pulmonary function tests revealed severely impaired diffusing capacity. Substantial improvement occurred over 24 hours. Approximately 60% of the patients experienced chronic respiratory impairment that only partially responded to corticosteroid therapy. No other causes for this syndrome were identified. A syndrome of acute dyspnea occurred in 4% of patients treated with mitomycin and vinca alkaloid therapy. The syndrome has a distinctive presentation, which can lead to chronic pulmonary insufficiency. Clinicians caring for patients receiving combined therapy with mitomycin and a vinca alkaloid should be aware of this type of acute pulmonary toxicity. Further studies are necessary to clarify its etiology.

Acute Disease↗
PubMed2002

The intraoperative use of mitomycin-C in excision of ocular surface neoplasia with or without limbal autograft transplantation.

PURPOSE: To evaluate the efficacy of intraoperative mitomycin-C in excision of ocular surface neoplasia for prevention of recurrence. METHODS: Seven patients (eight eyes), three men and four women, aged 56 to 87 years (mean, 73.8 years), with lesions suspicious for corneal or conjunctival neoplasia, were operated on between October 1998 and March 2000. During excision of the lesion, mitomycin-C 0.02% was applied intraoperatively for 5 minutes. In two cases, excision was combined with conjunctival limbal autograft transplantation. All excised lesions were sent for histopathologic evaluation. RESULTS: During the follow-up period ranging from 6 to 28 months (mean, 16 months) one patient (one eye) died of an unrelated cause. Histopathologic study showed four cases of squamous cell carcinoma, one case of carcinoma in situ, two cases of dysplasia, and one case of actinic keratosis. Of the eight eyes, no clinical recurrence of the lesion occurred in seven eyes, whereas one eye with squamous cell carcinoma showed mild recurrence 5 months after surgery and was successfully treated with topical mitomycin-C. Up to the last follow-up of this case 10 months later, the lesion did not recur. CONCLUSION: The excision of conjunctival and corneal epithelial neoplasia combined with the intraoperative use of mitomycin-C seems to reduce the recurrence rate. The combined use of mitomycin-C and conjunctival limbal autograft transplantation in two cases did not alter the surgical outcome. More cases and a longer follow-up are needed to establish the efficacy of such an approach.

Aged↗
PubMed1999

Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: the final results of a European Organization for Research in Cancer Therapy Genitourinary Group Trial.

PURPOSE: The outcome of patients with symptomatic metastatic prostate cancer is poor and improved treatment regimens are urgently needed. Theoretically, the combination of orchiectomy and chemotherapy could reduce androgen sensitive and insensitive cells in the prostate. This European Organization for Research in Cancer Therapy Genitourinary Group randomized, multicenter phase III trial demonstrates the outcome of orchiectomy alone versus orchiectomy followed by intravenous mitomycin C. MATERIALS AND METHODS: A total of 189 patients with metastatic prostate cancer and poor prognostic factors were randomized in this trial by 42 institutions. Of these patients 184 (97%) were eligible for study, including 90 treated with orchiectomy alone (orchiectomy only arm) and 94 treated with orchiectomy followed by 15 mg./m.2 mitomycin C in 1 week (combined treatment arm). Mitomycin C was administered every 6 weeks and treatment was continued as long as tolerance and patient compliance allowed, and no progression was observed. Objective and subjective criteria for progression were clearly defined in the protocol. RESULTS: Patient and tumor characteristics were well balanced between the 2 treatment arms. At a median followup of 4.2 years 144 patients had died, including 112 of prostate cancer. No significant differences for time to overall (p = 0.17), subjective (p = 0.25) and objective (p = 0.08) progression were found between the 2 treatment groups. For progression-free survival no difference was noted (p = 0.67) between the 2 treatment groups but a trend in favor of orchiectomy alone was observed for overall survival (p = 0.04). Mitomycin C induced considerable hematological, gastrointestinal, renal and pulmonary toxicity leading to discontinuation in 31% of patients with pulmonary toxicity and 7% with renal deterioration. In addition, the quality of life evaluation revealed significant reduction in the combined treatment arm. CONCLUSIONS: Based on the results of this randomized phase III study orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognostic factors cannot be recommended due to failure of improvement in survival and reduced quality of life parameters.

Antibiotics, Antineoplastic↗
PubMed2002

Topical mitomycin C and cephalosporin in endolymphatic sac surgery.

OBJECTIVE: To determine whether intraoperative topical application of the drug mitomycin C to the endolymphatic sac area in conjunction with endolymphatic sac ballooning surgery (ESBS) can safely achieve longer-lasting relief from incapacitating, medically intractable Meniere symptom-complex than ESBS alone. STUDY DESIGN/METHOD: A retrospective study is presented of 142 cases of ESBS performed by the author between May 1998 and November 1999, in which a solution of mitomycin C diluted to 1 mg/mL of physiological saline was applied to the sac area for 5 minutes followed by irrigation with a cephalosporin antibiotic solution. The results of the 103 of 142 cases diagnosed as classic Meniere's disease or endolymphatic hydrops are given special attention, comparing them with the results of an earlier-reported series of 109 cases of ESBS sharing the same diagnostic and result evaluation criteria but not using mitomycin C. RESULTS: In terms of vertigo control, the comparative short-term rates (<3 y) of complete/substantial control for the aforementioned 103-case series and earlier 109-case series are similar: respectively, 90.3% (after 1.5--3 years' follow-up) versus 91.7% (after 2.5-3 years' follow-up). In the 103-case series, to date, there has been no recurrence of incapacitating vertiginous symptoms necessitating revision surgery, whereas in the 109-case series, although there were likewise no cases necessitating revision surgery during the reported 2.5-to 3-year follow-up period, at least 8 patients in that series are known to have undergone revision surgery at later dates. Hearing results were significantly better (P =.004) in the 103-case series than the 109-case series: respectively, 30.0% versus 12.8% hearing improvement. CONCLUSIONS: Preliminarily, the superior hearing results in the present series indicate that possible adverse effects of mitomycin C on the inner ear and endolymphatic system have been averted; and no recurrence of incapacitating symptoms to date offers hope that longer-term efficacy of endolymphatic sac surgery using mitomycin C can be maintained.

Administration, Topical↗
PubMed1994

Late effects of locally delivered mitomycin C on formation of neointima and on vasomotor response to acetylcholine.

BACKGROUND: Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure. METHODS: In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography. RESULTS: No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17 +/- 0.03 versus 0.27 +/- 0.03 mm2, P < 0.03) and lower intima: media area ratio (0.60 +/- 0.31 versus 1.09 +/- 0.42, P < 0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P < 0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries. CONCLUSIONS: Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.

Acetylcholine↗
PubMed2002

Long-term effects of simultaneous subconjunctival and subscleral mitomycin C application in repeat trabeculectomy.

PURPOSE: To assess the efficacy and safety of simultaneous mitomycin C application under conjunctival and scleral flaps in patients with repeat trabeculectomy. METHODS: A total of 44 patients (44 eyes) with previous failed filtering surgery were randomized to one of two groups. The both-flaps group comprised 22 patients (22 eyes) with trabeculectomy and intraoperative mitomycin C application under conjunctival and scleral flaps, whereas the subconjunctival group comprised 22 patients (22 eyes) with subconjunctival application of mitomycin C. Particular attention was paid to intraocular pressure, postoperative medications, visual acuity, filtering bleb appearance, and complications. The mean follow-up time was 38.18 +/- 12.48 months. RESULTS: The mean preoperative intraocular pressure decreased from 39.1 +/- 7.3 mm Hg to the postoperative level of 15.6 +/- 4.8 mm Hg in the both-flaps group (P = 0.014), and from 39.4 +/- 8.4 to 18.7 +/- 5.8 mm Hg in the subconjunctival group (P = 0.018). There was a statistically significant difference in intraocular pressure at all follow-up times, except at 1 week and 1 month postoperatively. Kaplan-Meier survival analysis showed there was no significant difference in total success rate (complete plus qualified success) between the two groups (P = 0.622, log-rank test). However, the two survival curves for the complete success subgroups (without additional medications) confirmed that mitomycin C applications under both flaps had a higher success rate than subconjunctival application (P = 0.043, log-rank test). No statistically significant difference in medications was present between the two groups, and no severe complications developed in either group. CONCLUSIONS: Trabeculectomy augmented with mitomycin C application at both sites could produce a greater lowering of intraocular pressure with low incidence of postoperative complications, and could provide an increased chance of long-term success. The procedure is effective and safe in patients with repeat trabeculectomy.

Adult↗
PubMed2006

Prospective evaluation of preoperative factors associated with successful mitomycin C needling of failed filtration blebs.

PURPOSE: To study the long-term effectiveness and factors involved in successful needling of failed filtration blebs with mitomycin C (MMC). MATERIALS AND METHODS: We conducted a prospective, nonrandomized comparative trial that included 34 consecutive patients (34 eyes) who underwent mitomycin C needling of a failed filtering bleb after trabeculectomy followed by a 0.01 mL injection of mitomycin C (0.2 mg/ml). The success of the needling revision was defined as absolute if the intraocular pressure (IOP) was < 21 mm Hg without antiglaucoma medications and qualified if the IOP was < 21 mm Hg with antiglaucoma medications. Preoperative and perioperative factors were evaluated for an association with postoperative success using Kaplan-Meier survival analysis. RESULTS: The mean follow-up was 14.2 +/- 9.8 months. The mean preoperative IOP was 25.5 +/- 4.4 mm Hg, which decreased to 11.1, 13.4, 15.8, 16.7, 14.9, 14.1, 13.9, and 13 on postoperative day 1, postoperative week 1, and after 1, 3, 6, 9, 12, and 24 months, respectively (P = 0.001 for each comparison). At the final visit, success was absolute in 15 eyes (44.1%) and qualified in 14 eyes (41.2%). The success rates were 90% and 75% at 1 and 2 years, respectively. The success of the needling procedure was highly correlated with glaucoma filtration surgery performed less than 4 months previously (Kaplan-Meier analysis, log-rank test P = 0.006). CONCLUSIONS: Mitomycin C needling revision appears to have a high long-term success rate. Surgery performed less than 4 months previously contributes to the success of the initial mitomycin C needling procedure.

Adult↗