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PubMed1992

Mode of interaction of 5-fluorouracil, radiation, and mitomycin C: in vitro studies.

An examination of the effects of radiation combined with either 5-fluorouracil, Mitomycin C, or both drugs in vitro has been made using a mouse squamous tumor cell line SCC VIITo and cell viability as an endpoint. Depending on how the survival endpoint was calculated, the interaction of 5-fluorouracil, Mitomycin C, or 5-fluorouracil plus Mitomycin C with radiation was greater than additive (plating efficiency) or only additive (viable cells per flask). These results suggest that the cytostatic effect of these drugs may be an important aspect of their action clinically.

Animals↗
PubMed1993

A toxic interaction between mitomycin C and tamoxifen causing the haemolytic uraemic syndrome.

A comparison of patients receiving combination chemotherapy with mitomycin C, mitozantrone and methotrexate (3M) with and without tamoxifen for treatment of primary breast cancer indicates an increased risk of anaemia (P < 0.0001) and thrombocytopenia (P < 0.001), but not leucopenia for patients receiving tamoxifen with their chemotherapy compared to those receiving the chemotherapy alone. Furthermore, 9 out of 94 patients receiving tamoxifen with 3M developed progressive anaemia, thrombocytopenia and abnormal renal function as early features of microangiopathic haemolytic anaemia, progressing on to various degrees of the haemolytic uraemic syndrome (HUS). This is only rarely seen with patients receiving mitomycin C alone at higher doses than used in the 3M combination and in the presence of active metastatic disease. This syndrome can be fatal and 1 of our 9 patients died. These observations indicate that there may be an interaction between tamoxifen and mitomycin C, causing an increased incidence of anaemia, thrombocytopenia and an increased risk of HUS. The combination of these two drugs should be avoided or carefully monitored.

Adult↗
PubMed1995

Mitomycin C: small, fast and deadly (but very selective).

Mitomycin C, an important antitumor drug and antibiotic, has an extraordinary ability to crosslink DNA with high efficiency and absolute specificity for the sequence CpG. Recent results have shown how mitomycin C crosslinks DNA, and why the sequence specificity is so complete. This new understanding may allow the design of agents that mimic mitomycin C's economy of structure and can crosslink other sequences.

Antibiotics, Antineoplastic↗
PubMed2004

Limbal stem cell deficiency following topical mitomycin C treatment of conjunctival-corneal intraepithelial neoplasia.

PURPOSE: To report a case of conjunctival-corneal intraepithelial neoplasia (CCIN) in an elderly African American patient treated with topical mitomycin C and the subsequent complication of limbal stem cell deficiency. DESIGN: Interventional case report. METHODS: A 92-year-old African American woman was diagnosed with CCIN in the right eye. Following incisional biopsy, the patient received five 1-week courses of 0.04% mitomycin C and was followed over a period of 10 months. RESULTS: The CCIN regressed completely following mitomycin C therapy. Three months later, the patient developed recurrent nonhealing epithelial defects in the right cornea. CONCLUSIONS: Conjunctival-corneal intraepithelial neoplasia may occur in the African American population. Although MMC is effective in eradicating CCIN, a limbal stem cell deficiency may complicate the treatment.

Administration, Topical↗
PubMed2006

Phacotrabeculectomy with mitomycin C in patients with uveitis.

PURPOSE: To evaluate the safety and efficacy of combined phacoemulsification, intraocular lens implantation, and trabeculectomy with mitomycin C for the management of uveitic complications. DESIGN: Retrospective case-control study. METHODS: We conducted a retrospective review of the records of 23 consecutive eyes with chronic noninfectious uveitis (uveitic group) and 43 nonuveitic eyes (control group) that had received primary phacotrabeculectomy. Mitomycin C was used in all the uveitic eyes. Considering the high preoperative intraocular pressure (IOP) of the uveitic group, nonuveitic eyes that had a preoperative IOP of >or=20 mm Hg or that had been given two or more medications were included in the control group. All patients were followed for at least one year. The main outcome measures were postoperative vision, IOP control, complications, and acute uveitis relapse rates. RESULTS: Visual outcome of the uveitic group was similar to the control group. In the uveitic group, the success rate of IOP control (91.3% at one year, 84.8% at two years) was favorable but was significantly lower than in the control group (P = .0423). Complications were comparable between the groups. Primary surgical failure in the uveitic group was associated with the postoperative acute uveitis attack. In the uveitic group, the acute uveitis attack rate showed no change after surgery (P = .283). CONCLUSION: With adequate inflammation suppression, phacotrabeculectomy with mitomycin C is an effective and safe therapeutic option for the management of secondary cataract and glaucoma in uveitic eyes. A lower surgical success rate of the uveitic group might be attributable to the postoperative inflammation recurrence.

Acute Disease↗
PubMed2006

XPA versus ERCC1 as chemosensitising agents to cisplatin and mitomycin C in prostate cancer cells: role of ERCC1 in homologous recombination repair.

Nucleotide excision repair is the principal mechanism for the removal of bulky DNA adducts caused by a range of chemotherapeutic drugs, and contributes to cisplatin resistance. In this study, we used synthetic siRNAs targeted to XPA and ERCC1 and compared their effectiveness in sensitising mismatch repair deficient prostate cancer cell lines to cisplatin and mitomycin C. Downregulation of ERCC1 sensitised DU145 and PC3 cells to cisplatin and mitomycin C. In contrast, XPA downregulation did not sensitise either cell line to mitomycin C, and only sensitised DU145 cells to cisplatin. The effects of ERCC1 downregulation may be due to its role in homologous recombination repair. Excision repair of cisplatin adducts in PC3 cells was attenuated to a similar extent by XPA and ERCC1 downregulation. Downregulation of XPA but not ERCC1 caused an increase in the number of cisplatin-induced RAD51 foci in PC3 cells, suggesting that HRR is able to substitute for NER in these cells. We observed co-localisation of ERCC1 and RAD51 in cisplatin treated PC3 cells by immunofluorescence and co-immunoprecipitation, which may represent recruitment of ERCC1/XPF to sites of recombination repair. These results indicate that ERCC1 is a broader therapeutic target than XPA with which to sensitise cancer cells to chemotherapy because of its additional role in recombination repair.

Antineoplastic Agents↗
PubMed2006

The combination of raltitrexed (Tomudex) and mitomycin-C in the treatment of advanced colorectal cancer--a phase II study.

AIMS: To investigate the combination of raltitrexed and mitomycin-C as first-line chemotherapy treatment in patients with advanced colorectal cancer. MATERIALS AND METHODS: A phase II study. RESULTS: In total, 22 patients were treated with a combination of raltitrexed 3 mg/m2 every 3 weeks and mitomycin-C 7 mg/m2 every 6 weeks for up to 24 weeks. The study was closed early for safety reasons as there were three unexpected treatment-related deaths. The overall response rate was 20%, and a further 40% achieved stable disease. The median time to progression was 3.9 months and the median overall survival time was 11.6 months. CONCLUSION: Owing to the potential for increased toxicity, the combination of raltitrexed and mitomycin-C cannot be recommended as first-line treatment in patients with advanced colorectal cancer.

Adult↗
PubMed2005

Crosslinked hyaluronan hydrogels containing mitomycin C reduce postoperative abdominal adhesions.

OBJECTIVE: To evaluate the efficacy of crosslinked hyaluronan (HA) hydrogels that contained covalently-bound mitomycin C (MMC) in reducing postoperative adhesions in a rat uterine horn model. DESIGN: Two independent parameters were investigated: [1] the quantity of MMC in preformed crosslinked hydrogel films and [2] the efficacy of intraperitoneal injection of in situ crosslinkable solutions. SETTING: University animal research facility. ANIMAL(S): Female Wistar rats. INTERVENTION(S): Injuries (3 x 10 mm) were made to contacting serosal surfaces of the medial uterine wall musculature in female rats. Two treatment protocols were used. In the first, sterile crosslinked HA films that contained different MMC loadings (0, 0.5%, and 2%) were applied to two injured uterine horns; control animals received no films. In the second protocol, MMC-loaded crosslinked HA gels that contained different MMC loadings (0.31%, 0.625%, and 1.25%) were spread on the site of uterine horn injury (1 mL); then, an additional 4 mL of the same formulation was injected into the peritoneal cavity after abdominal closure. Control animals were injected with 5 mL of buffer only. MAIN OUTCOME MEASURE(S): Extent of postoperative adhesions between uterine horns and with surrounding tissues and organs. RESULT(S): Mitomycin C-loaded crosslinked HA films and in situ crosslinked gels were more effective in reducing postoperative adhesion formation than were buffer controls or crosslinked HA films without MMC. CONCLUSION(S): Mitomycin C-loaded crosslinked HA films and gels reduced formation of postoperative intraperitoneal adhesions.

Abdomen↗
PubMed2006

Cutaneous complications of intravesical treatments for bladder cancer: granulomatous inflammation of the penis following BCG therapy and penile gangrene following mitomycin therapy.

Transitional cell carcinoma of the bladder is frequently treated with intravesical injection of immunotherapeutic (eg, BCG) or chemotherapeutic (eg, mitomycin C) agents. The aim of this study was to report cutaneous complications of intravesical therapy in 2 patients with transitional cell carcinoma of the bladder. A 69-year-old man had an ulceration at the base of the penis and papules involving the glans penis 1 month after injection of intravesical BCG. Biopsy findings showed granulomatous inflammation with foci of dermal necrosis suggestive of a BCG-related granulomatous reaction. The second patient was a 73-year-old man with penile gangrene. Erythema involving his penis and perineum had developed within 24 hours after intravesical administration of mitomycin C, which spilled onto his perineum during catheter removal. The resulting penile gangrene required penectomy 3 months after the injection. Mitomycin C patch testing showed a clear allergic contact reaction. Dermatologists should be aware of these potential cutaneous complications.

Administration, Intravesical↗
PubMed2005

Transepithelial phototherapeutic keratectomy/photorefractive keratectomy with adjunctive mitomycin-C for complicated LASIK flaps.

PURPOSE: To evaluate the efficacy of transepithelial phototherapeutic keratectomy/photorefractive keratectomy (PTK/PRK) with prophylactic mitomycin-C for the treatment of refractive errors and maintenance of corneal clarity following flap complications in laser in situ keratomileusis (LASIK). SETTING: Outpatient tertiary care center, Chicago, Illinois, USA. METHODS: Ten eyes of 10 patients with LASIK flap complications had transepithelial PTK/PRK for correction of ametropia. Mitomycin-C 0.02% was applied to the stroma for 2 minutes following laser ablation. Postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refractions, and slitlamp examinations were obtained. RESULTS: Preoperatively, the mean UCVA was 20/400 (range 20/40 to counting fingers), the mean BSCVA was 20/28.5, and the spherical equivalent refractive errors ranged from +4.00 to -10.75 diopters (D). After the procedure, the mean UCVA was 20/28, the mean BSCVA was 20/21, and the spherical equivalent refractive errors ranged from +0.37 to -1.00 D. The mean follow-up ranged from 8 to 28 months. No patient experienced delayed reepithelialization, haze, or other signs of toxicity. CONCLUSION: Mitomycin-C can be a useful adjunctive therapy for the prevention of haze when applying surface excimer laser therapy to a cornea following LASIK flap complications.

Adult↗
PubMed2006

Presence of mitomycin-C in the anterior chamber after photorefractive keratectomy.

PURPOSE: To assess the presence of mitomycin-C (MMC) in hen aqueous humor after photorefractive keratectomy (PRK). SETTING: Instituto Universitario de Oftalmobiología Aplicada, Faculty of Medicine, University of Valladolid, and Department of Analytical Chemistry, Faculty of Sciences, University of Valladolid, Valladolid, Spain. METHODS: Mitomycin-C 0.02% was applied topically for 2 minutes to a right hen's eye after PRK (Group A) and to the left eye with intact epithelium (Group B). At different time points (10, 30, 60, 360, and 720 minutes), aqueous humor was extracted and high-performance liquid chromatography was performed to detect and quantify MMC levels. RESULTS: The mean maximum drug concentration of MMC measured in the aqueous humor was 187.250 microg/L +/- 4.349 (SD) in Group A and 93.000 +/- 4.899 microg/L in Group B, both detected 10 minutes after topical application. Statistically significant differences were found between Groups A and B at 10, 30, and 60 minutes, with decreasing MMC levels in both groups but a higher concentration in Group A. After 360 minutes, MMC levels were undetectable in Group B and after 720 minutes in Group A. CONCLUSIONS: Mitomycin-C was detectable in the aqueous humor of the hen eye after topical application in PRK-treated eyes and in eyes with intact epithelium. The presence of MMC is of concern as it may lead to ocular toxicity in the long term.

Administration, Topical↗
PubMed2004

Long-term effects of mitomycin C in pterygium surgery on scleral thickness and the conjunctival epithelium.

PURPOSE: To evaluate the long-term effects of intraoperative application of mitomycin C on the scleral thickness and the conjunctival epithelium at the surgical site of pterygium excision. DESIGN: Prospective observational case series. PARTICIPANTS: Twenty-four patients who underwent excision of primary pterygium with intraoperative mitomycin C in our department during the year 1996. METHODS: Patients were evaluated by slit-lamp biomicroscopy, impression cytology, and high-frequency ultrasonography. Impression cytology was performed by applying a small nitrocellulose filter paper for a few seconds at the excision area and for a few seconds at the opposite perilimbal area, and subjecting the specimens to the periodic acid-Schiff-Gill modified Papanicolaou staining protocol. The morphology of the conjunctival epithelium and goblet cell density (GCD) were recorded. High-frequency ultrasound was performed at the same sites, and the scleral thickness was measured at a distance of 1 mm from the limbus. MAIN OUTCOME MEASURES: Goblet cell density, conjunctival epithelial morphology, and the scleral thickness at the operated and nonoperated sites. RESULTS: All patients had successful pterygium removal with no corneal recurrence after a mean follow-up of 77.2+/-3.9 months (range, 72-84). Impression cytology revealed normal nongoblet conjunctival epithelial cells at the excision area, with a 4-fold decrease in the GCD at the excision area when compared with the contralateral nonoperated site (296+/-120 cells/mm(2) and 1183+/-310 cells/mm(2), respectively; P = 0.0036). No differences were noted between the scleral thicknesses at the operated site (750+/-70 microm) and the opposite site (740+/-80 microm) (P = 0.84). CONCLUSIONS: A single application of mitomycin C after pterygium excision is not associated with reduction in scleral thickness more than 6 years postoperatively. The conjunctival epithelium retains its normal phenotype, with a marked reduction of the GCD.

Adult↗
PubMed2005

Intraoperative mitomycin C and amniotic membrane transplantation for fornix reconstruction in severe cicatricial ocular surface diseases.

PURPOSE: To investigate whether intraoperative application of mitomycin C may enhance the success of amniotic membrane transplantation in symblepharon lysis and fornix reconstruction in severe cicatricial ocular surface diseases. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Sixteen patients (8 female, 8 male; 18 eyes) with a mean age of 41+/-23.4 years (range, 3-79) and suffering from severe chemical/thermal burns (7 eyes), multiple recurrent pterygia and pseudopterygia (5 eyes), Stevens-Johnson syndrome (4 eyes), and ocular cicatricial pemphigoid (2 eyes) were consecutively enrolled. All except for 2 eyes had had prior surgical attempts of surgical reconstruction, including 6 eyes with a mucous membrane graft (MMG), but still presented with symblepharon and persistent ocular surface inflammation. INTERVENTION: After excision of subconjunctival fibrovascular tissues, 0.04% mitomycin C was applied for 5 minutes in the deep fornix before amniotic membrane transplantation. MAIN OUTCOME MEASURES: Deeper fornix, noninflamed ocular surface, and full motility. RESULTS: The mean epithelial healing time was 4.2+/-1.9 weeks. During the follow-up of 14.16+/-5.2 months, all eyes showed a marked reduction of conjunctival inflammation, a deep fornix, and a continuous tear meniscus. Of 12 eyes with motility restriction, 2 eyes with multiple recurrent pterygia and 1 eye with severe thermal burn showed recurrence of partial motility restriction 2 months after surgery. The vision of 9 eyes was successfully restored by an additional keratolimbal allograft with subsequent penetrating keratoplasty (6 eyes). CONCLUSION: Intraoperative application of mitomycin C is an effective means to reduce chronic and deep-seated conjunctival inflammation, and helps amniotic membrane restore a deep fornix after symblepharon lysis, even in eyes that had a failed MMG. Restoration of deep fornix and tear meniscus is an important prerequisite to achieve successful reconstruction by subsequent limbal stem cell transplantation.

Adolescent↗
PubMed2005

Limbal allograft, amniotic membrane transplantation, and intraoperative mitomycin C for recurrent pterygium.

OBJECTIVE: To conduct a pilot study evaluating the efficacy and safety of limbal allograft, preserved amniotic membrane transplantation, and intraoperative mitomycin C treatment for recurrent pterygium. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 11 patients with recurrent pterygium. The mean number of previous surgeries for pterygium was 1.9+/-1.4 (range, 1-6). INTERVENTION: All subjects received limbal allograft, preserved amniotic membrane transplantation, and intraoperative mitomycin C. MAIN OUTCOME MEASURES: Pterygium recurrence and complications. RESULTS: The mean follow-up period was 21.6+/-5.6 months (range, 16-36 months). There was no pterygium recurrence in any of the eyes. Symblepharon reappeared in 3 eyes and diplopia recurred in 2 eyes. There were no other surgical complications and there was no graft rejection. CONCLUSIONS: Limbal allograft, preserved amniotic membrane transplantation, and intraoperative mitomycin C may be a safe and effective procedure for recurrent pterygium.

Aged↗
PubMed2004

Contact diode laser myringotomy and mitomycin C in children.

OBJECTIVE: To investigate the use of contact diode laser myringotomy (C-LAM), combined with topical mitomycin C, as an alternative method for prolonged middle ear ventilation in children with otitis media with effusion. STUDY DESIGN AND SETTING: Prospective study at a tertiary care pediatric institution. METHODS: Fifteen children enrolled in the study. Mitomycin C was applied to the intact tympanic membrane in the right ears, whereas saline on the left side was used for controls. C-LAM was then performed in all ears. Outcome measures included healing rate and scarring, ear infection, and long-term audiometric follow-up. RESULTS: There was no significant difference in median healing rate. In each group, the median was between the third and fourth month. Normal hearing thresholds were obtained in all children at 2-year follow-up. CONCLUSION: C-LAM proved to be an effective method for medium-term ventilation, but topical mitomycin C before C-LAM did not prolong patency rate in our patients. No significant complication was encountered at 2-year follow-up.

Alkylating Agents↗
PubMed2005

Total nasopharyngeal stenosis: treatment with laser excision, nasopharyngeal obturators, and topical mitomycin-c.

OBJECTIVE: Severe nasopharyngeal stenosis after uvulopalatopharyngoplasty (UPPP) is a dreaded complication. Very little has been written about successful treatment because attempts at correction frequently fail. Severe stenosis of the nasopharynx drastically worsens speech, swallowing, and obstructive sleep apnea (OSA). We present our successful experience with severe stenosis focusing on a simple functional repair using topical mitomycin-c as well as differing daytime and nighttime palatal obturators. METHODS: Three adults with total or near-total nasopharyngeal stenosis secondary to UPPP were referred to our institution after multiple failed attempts at repair. Each presented with significant OSA on polysomnogram (PSG), with excessive daytime somnolence and voice and swallowing complaints. Under general anesthesia, a CO2 laser is used to create an opening in the nasopharynx. Removable and adjustable palatal obturators are fashioned to keep the nasopharynx open with a daytime insert piece with a small obturator hole for diminished velopharyngeal insufficiency and a nighttime piece without an insert to maximize recumbent airflow. Obturators are removed 6 months later with topical application of mitomycin-c as a fibroblast inhibitor. All patients were followed clinically for at least 1 year and received posttreatment PSG. RESULTS: All patients experienced resolution of their stenoses. Swallowing and voice complaints resolved. Either OSA was eliminated or any residual OSA was successfully treated with nasal continuous positive airway pressure. Serial videoendoscopic images throughout the treatment phase demonstrate the effectiveness of this new technique. CONCLUSIONS: Severe nasopharyngeal stenosis is a rare but devastating complication of UPPP. We introduce a simple technique that uses functional palatal obturators and topical mitomycin-c and describe our success with this treatment algorithm.

Adult↗
PubMed2005

O(6)-methylguanine DNA-methyltransferase (MGMT) overexpression in melanoma cells induces resistance to nitrosoureas and temozolomide but sensitizes to mitomycin C.

Alkylating agents play an important role in the chemotherapy of malignant melanomas. The activity of alkylating agents depends on their capacity to form alkyl adducts with DNA, in some cases causing cross-linking of DNA strands. However, the use of these agents is limited by cellular resistance induced by the DNA repair enzyme O(6)-methylguanine DNA-methyltransferase (MGMT) which removes alkyl groups from alkylated DNA strands. To determine to what extent the expression of MGMT in melanoma cells induces resistance to alkylating agents, the human cell line CAL77 Mer- (i.e., MGMT deficient) were transfected with pcMGMT vector containing human MGMT cDNA. Several clones expressing MGMT at a high level were selected to determine their sensitivity to chemotherapeutic drugs. Melanoma-transfected cells were found to be significantly less sensitive to nitrosoureas (carmustine, fotemustine, streptozotocin) and temozolomide with an increase of IC(50) values between 3 and 14 when compared to parent cells. No difference in cell survival rates between MGMT-proficient and -deficient cells was observed for melphalan, chlorambucil, busulphan, thiotepa and cisplatin which preferentially induce N(7) guanine lesions. Surprisingly, MGMT overexpression increased the sensitivity of CAL77 cells to mitomycin C by approximately 10-fold. Treatment of clonal cell lines with buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase which depletes cellular glutathione, completely reversed this unexpected increase in sensitivity to mitomycin C. This observation suggests that glutathione is involved in the sensitivity of MGMT-transfected cells to mitomycin C and may act synergistically with MGMT via an unknown mechanism.

Antineoplastic Agents↗
PubMed2003

Punctal-canalicular stenosis associated with mitomycin-C for corneal epithelial dysplasia.

PURPOSE: To report a case of punctal-canalicular stenosis after topical mitomycin C use for corneal dysplasia. To the authors' knowledge, this association has not previously been described. DESIGN: Observational case report. METHOD: A 62-year-old woman was noted to have a right inferotemporal corneal dysplastic lesion. She received a topical course of mitomycin-C 0.04% four times a day, which subsequently invoked a toxoallergic reaction. One month later, the patient developed right-sided epiphora. RESULTS: Probing demonstrated complete stenosis of the right lower canaliculus, 5 mm from the punctum. CONCLUSION: Mitomycin-C use may lead to lacrimal apparatus fibrosis and symptomatic epiphora when inciting a toxoallergic reaction.

Administration, Topical↗