Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MITOMYCIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1988

Assessment of tumor cell sensitivity to mitomycin C by "B23 translocation" assay.

Mouse leukemia cells (p388D1) were grown in medium containing various amounts of mitomycin C for 4 h. Cellular localization of protein B23 was detected using an immunofluorescence technique. Translocation of protein B23 from nucleoli to the nucleoplasm was observed with increasing dose of mitomycin C. To study the correlation of B23 translocation and drug resistance, three human colon carcinoma cell lines, HCT116, HCT116b (a line that is natively or intrinsically resistant to mitomycin C), and HCT116-44 (a line with an acquired resistance to mitomycin C), were employed. These cells were incubated with 1--150 micrograms/ml of mitomycin C. The drug concentration that caused 50% of the cells to have complete translocation (IC50) was determined for each cell line. The IC50 values of HCT116, HCT116b and HCT116-44 were 6, 10 and 50 micrograms/ml, respectively. These IC50 values correlate well with the mitomycin C resistant phenotype of these tumor cells as determined by other in vivo and in vitro assays (Willson, et al. (1985) Cancer Res., 45, 5281-5286). These results identify an inverse relationship between the ease of protein B23 translocation and the degree of mitomycin C resistance in human colon carcinoma cells. This relationship applies to cells that have either acquired mitomycin C resistance or intrinsic resistance to the drug.

Animals↗
PubMed1990

Trimodality therapy (drug/hyperthermia/radiation) with BCNU or mitomycin C.

To develop multimodality treatment combinations with high curative potential in advanced local disease, BCNU (N,N'-bis(2-chloroethyl)-N-nitro-sourea) and mitomycin C were tested with hyperthermia and radiation in the FSaIIC fibrosarcoma system. Growth delay experiments demonstrated that, while neither BCNU nor mitomycin C produced dose modification of the radiation response, and hyperthermia (43 degrees C, 30 min) produced only a moderate dose modification (1.4 +/- 0.2), the combination of BCNU plus hyperthermia resulted in a radiation dose modifying factor (DMF) of 1.9 +/- 0.3, and mitomycin C plus hyperthermia a dose modifying factor of 2.1 +/- 0.4. Tumor cell survival over a range of BCNU doses administered i.p. immediately before hyperthermia resulted in a dose modifying factor of 1.8 +/- 0.2 versus drug alone. With mitomycin C however, giving the drug immediately prior to heating produced a dose modifying factor due to hyperthermia of only 1.2 +/- 0.10. Hoechst 33342 diffusion was used to separate tumor cells into predominately oxic and hypoxic subpopulations. Administration of the single, double and trimodality therapies showed that BCNU was 3.1-fold more toxic to the oxic versus the hypoxic cells whereas mitomycin C was 3.5-fold more toxic to the hypoxic compared to the oxic cells. Hyperthermia was 1.4-fold more toxic to the hypoxic versus the oxic cells whereas 10 Gy of radiation was 2.0-fold more toxic to the oxic compared to the hypoxic cells. The combination of hyperthermia plus radiation increased killing in both Hoechst dye defined subpopulations but relatively more in the hypoxic cells in which killing was 1.8-fold greater than in the oxic cells. When heat was delivered immediately after i.p. administration of the anticancer drugs, hyperthermia increased BCNU killing in the oxic cells by 17.2-fold versus 4.4-fold in the hypoxic cells and increased mitomycin-killing by 2.6-fold in the oxic cells versus 17-fold in the hypoxic cells. Use of the full trimodality treatment, given in the sequence drug (BCNU, 50 mg/kg or mitomycin-C 5 mg/kg)----heat (43 degrees C, 30 min)----radiation (10 Gy) produced a 3 log kill in the oxic cells versus a 2 log kill in the hypoxic cells with BCNU and a 2 log kill in the oxic cells versus a 3 log kill in the hypoxic cells with mitomycin C. These results indicate that the use of selected anticancer drugs with hyperthermia and radiation can produce highly cytotoxic interactions which markedly modify the effect of radiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

The sir locus of Escherichia coli: a gene involved in SOS-independent repair of mitomycin C-induced DNA damage.

A Mud1 (lac Apr) insertion has been isolated in a delta (lac)recA+ lexA3(Ind-)rpoB87 gyrA87 mutant of Escherichia coli resulting in a decrease in mitomycin C tolerance and an increase in post-mitomycin C DNA degradation. The mitomycin C sensitivity of the insertion mutant is not further increased by substituting either the rpoB87 or the gyrA mutation by the respective wild-type alleles. However, when both rpoB87 and gyrA87 mutations are replaced by rpoB+ and gyrA+ the strain becomes hypersensitive to mitomycin C. Inactivation of recA in the insertion mutant has no effect on its mitomycin C sensitivity provided both rpoB87 and gyrA87 are present. When either or both of the mutations is/are replaced by the wild-type allele inactivation of recA renders the strain hypersensitive to mitomycin C. The locus of Mud1 (lac Apr) insertion, designated sir (SOS-independent repair), has been mapped between 57 and 61 min on the E. coli linkage map. Expression of the sir gene seems to be constitutive and not enhanced by mitomycin C. These results are discussed in relation to the SOS-independent repair of mitomycin C-induced DNA damage reported earlier.

Bacteriophage lambda↗
PubMed1988

Intravesical thiotepa versus mitomycin C in patients with Ta, T1 and TIS transitional cell carcinoma of the bladder: a phase III prospective randomized study.

A prospective randomized clinical trial was conducted by the National Bladder Cancer Group to compare thiotepa and mitomycin C in ablating residual Ta, T1 and TIS transitional cell carcinoma of the bladder. Eight weekly instillations were given followed by cystoscopy 4 weeks after the treatment was stopped. The over-all complete response rate based on cystoscopy and either biopsy or cytology was 26 per cent for thiotepa versus 39 per cent for mitomycin C (p equals 0.08). The greatest efficacy was seen in the Ta group with mitomycin C demonstrating superiority over thiotepa. Patients with negative cystoscopy and biopsy but who had positive cytology were considered to be partial responders. When partial and complete responders were combined the over-all response rate was 53 per cent for thiotepa and 63 per cent for mitomycin C (p equals 0.23). Patients with TIS appeared to respond equally to thiotepa and mitomycin C. Toxicity included urinary frequency in 22 of the 73 patients in the thiotepa arm and 31 of the 76 patients receiving mitomycin C. A rash was observed in 2 of the thiotepa group versus 14 of the mitomycin C group. Bone marrow depression occurred in 15 patients receiving thiotepa and in 12 receiving mitomycin C.

Administration, Intravesical↗
PubMed1982

Effect of beta-adrenergic stimulants on cytotoxicity of mitomycin C in HeLa cells.

Effects of several autonomic agents on the cytotoxicity of mitomycin C in HeLa cells were studied. When beta-adrenergic stimulants such as isoproterenol, epinephrine, terbutaline and turobuterol were added at concentrations over 10(-14) M 15 to 60 min before mitomycin C, the colony-forming ability of HeLa cells was significantly inhibited more than by mitomycin C alone. The action of isoproterenol and epinephrine on the colony-forming ability of the cells was abolished by propranolol. The intracellular cyclic AMP level of HeLa cells reached the peak of about two-fold the basal level at 30 min after the addition of 10(-8) M isoproterenol. In combination with mitomycin C, the high level of intracellular cyclic AMP induced by isoproterenol was maintained for a significantly longer period in comparison with that by isoproterenol alone, while mitomycin C alone caused essentially no change in the cyclic AMP level. The pretreatment with dibutyryl cyclic AMP also enhanced the effect of mitomycin C. From these findings, it is strongly suggested that the synergistic effect of beta-adrenergic stimulants on the cytotoxicity of mitomycin C is mediated via stimulation of the beta-adrenoceptors of HeLa cells which elevates the intracellular cyclic AMP for a long time in combination with mitomycin C.

Adrenergic beta-Agonists↗
PubMed1985

Mitomycin-C in breast cancer.

Mitomycin-C, an antitumor antibiotic discovered in 1958, acts as a bifunctional alkylating agent. Initial clinical trials utilized a daily schedule of administration, which led to severe and protracted myelosuppression and inadequate evaluation of the antitumor spectrum of mitomycin-C. In the early 1970s, the intermittent high-dosage schedule of administration was developed: 20 mg/m2 of mitomycin-C intravenously, every 6 to 8 weeks. An overall response rate of 35% was reported by several investigators. Subsequently, other administration schedules were attempted without improvement in therapeutic index. More recently, mitomycin-C was used in combinations with other drugs. Combinations of mitomycin-C and one of the vinca alkaloids have produced response rates of approximately 30% to 40% in patients with extensive previous treatment. In patients not previously exposed to doxorubicin, combinations of mitomycin-C and doxorubicin have offered response rates of approximately 50%. Acute toxicities of mitomycin-C are tolerable and consist of mild nausea, vomiting, and anorexia. Chronic toxicities include cumulative myelosuppression--especially thrombocytopenia--pulmonary toxicity, renal toxicity, and occasionally cardiac toxicity. Mitomycin-C is an effective antitumor agent in breast cancer and should be carefully incorporated in the therapeutic strategy of this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Intra-operative mitomycin C for glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intra-ocular pressure. Mitomycin C is an antimetabolite applied between the sclera and conjunctiva during the initial stages of a trabeculectomy to prevent excessive post-operative scarring and thus reduce the risk of failure. OBJECTIVES: The objective of this review is to assess the effects of intra-operative application of mitomycin C in eyes of people undergoing trabeculectomy. SEARCH STRATEGY: We searched the Cochrane Eyes and Vision Group specialised register, The Cochrane Controlled Trials Register - CENTRAL, MEDLINE, EMBASE and the reference lists of relevant articles. We used the Science Citation Index to search for articles that cited the included studies. We contacted investigators and experts for details of additional relevant trials. SELECTION CRITERIA: We included randomised trials of intra-operative mitomycin C compared to placebo in trabeculectomy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We contacted trial investigators for missing information. Data were summarised using relative risk, odds ratio and weighted mean difference. MAIN RESULTS: This review includes 11 trials involving a total of 698 participants. The trials included three types of participants (those at high risk of failure, those undergoing trabeculectomy combined with cataract surgery, and those with no previous surgical intervention). Mitomycin C appears to be effective in reducing the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean intra-ocular pressure was significantly reduced at 12 months in all three participant groups receiving mitomycin C compared to placebo. No significant increase in permanent sight threatening complications was detected. Some evidence exists that mitomycin C increases the risk of cataract. The quality of trial reporting is poor in eight trials. Repeat analysis with three trials rated as low risk of bias did not yield different results. REVIEWER'S CONCLUSIONS: Intra-operative mitomycin C reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean intra-ocular pressure at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following mitomycin C, no demonstrable significant increase in other side effects was detected.

Antimetabolites↗
PubMed1994

Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer.

The use of mitomycin for metastatic colorectal cancer has been limited by mitomycin's myelosuppressive potential. The objective of this randomized study was to determine whether WR-2721 would decrease the hematologic toxicity of mitomycin in patients with colorectal cancer resistant to fluorouracil-based therapy. Ninety-seven patients with refractory colorectal cancer were randomized to receive either mitomycin 20 mg/m2 only or the same dose of mitomycin after pretreatment with WR-2721, 910 mg/m2. The principal toxicity in both groups was thrombocytopenia. The platelet nadirs were lower in patients receiving single-agent mitomycin (P = 0.026). Surprisingly, no clinical complete or partial responses were noted in either group, and survival was not different between the two groups. Thus, while WR-2721 decreased the thrombocytopenia associated with mitomycin therapy, mitomycin was ineffective in the treatment of refractory colorectal carcinoma.

Adult↗
PubMed1993

Ocular hypotony after trabeculectomy with mitomycin C.

Because mitomycin C reduces the resistance to aqueous outflow normally provided by postoperative subconjunctival fibrosis, we would expect to see more frequent hypotony after trabeculectomy with mitomycin C than after standard trabeculectomy. To evaluate the incidence of hypotony in trabeculectomy with intraoperative mitomycin C use, we performed a retrospective analysis on 52 eyes of 48 patients who underwent trabeculectomy with mitomycin C. Mitomycin C concentration was 0.4 mg/ml in all eyes, and treatment time ranged from 3 1/2 to seven minutes. We defined hypotony as intraocular pressure lower than 5 mm Hg on two examinations at least four weeks apart and six weeks or more postoperatively. Overall, average intraocular pressure was 22.7 +/- 10.7 mm Hg preoperatively and 10.4 +/- 5.0 mm Hg postoperatively (P < .001), a mean reduction in intraocular pressure of 12.3 +/- 11.5 mm Hg (47.0%). Hypotony occurred in 17 of 52 eyes (32.7%). Seven eyes required trabeculectomy revision for hypotony. Hypotonous eyes received longer treatment with mitomycin C intraoperatively, with a mean application time of 5.3 +/- 1.0 minutes for hypotonous eyes and 4.7 +/- 0.8 minutes for nonhypotonous eyes (P = .03). Sixteen of 43 eyes (37.2%) undergoing primary filtration became hypotonous, as compared to one of nine (11.1%) eyes that had previous filtering procedures (chi 2 = 2.30, P = .13). Nine of 17 hypotonous eyes (52.7%) and five of 35 nonhypotonous eyes (14.3%) had loss of two or more lines of Snellen visual acuity. Hypotony occurred in nearly one third of eyes treated with mitomycin C during trabeculectomy in our study. There was a statistically significant (P = .03) association of hypotony with longer application time of mitomycin C, and a trend toward increased incidence of hypotony in primary filtration.

Adult↗
PubMed1993

Trabeculectomy with mitomycin C for refractory glaucoma in blacks.

The use of one intraoperative application of mitomycin C at the filtration site has been effective in eyes at increased risk for failure of routine trabeculectomy. To study the efficacy and safety of this technique in patients with refractory glaucoma, we prospectively examined 30 eyes of 26 black patients in whom a 0.2-mg/ml solution of mitomycin C was applied between Tenon's capsule and the sclera for five minutes before trabeculectomy. The results were compared to those found in a matched group of 30 eyes of 28 patients who underwent trabeculectomy without mitomycin C. The mean postoperative intraocular pressures were significantly lower in the mitomycin C group than in the control group (P = .001). Of the 30 eyes in the mitomycin C group, 25 (83%) had an intraocular pressure of less than 21 mm Hg without glaucoma medication, compared to 11 of 30 (37%) in the control group (P = .00006). In the mitomycin C group, 19 eyes (63%) developed a cystic avascular thin-walled filtering bleb, four eyes (13%) a late positive Seidel test, and one eye slight scleral thinning over the area where the mitomycin C was applied. Although mitomycin C is effective when used in this manner, further study is required to determine the long-term complications.

Adult↗
PubMed1995

Adjunctive mitomycin C in primary trabeculectomy in phakic eyes.

PURPOSE: The addition of antiproliferative agents, most recently mitomycin C, has improved the outcome of glaucoma filtering surgery in eyes with a high risk of surgical failure. We conducted the present study to determine whether adjunctive mitomycin C would increase the success rate of primary trabeculectomies in phakic eyes. METHODS: Thirty-three eyes of 33 consecutive patients with phakic primary open-angle glaucoma, who were predominantly black (24 black and nine white), who underwent primary trabeculectomy with adjunctive subconjunctival mitomycin C (0.5 mg/ml for three minutes) were compared with a demographically similar historical control group of 30 eyes of 30 consecutive patients (20 black and ten white) with phakic primary open-angle glaucoma, who had undergone primary trabeculectomy without an adjunctive antifibrotic agent. RESULTS: Although the mean preoperative intraocular pressures were similar in both groups (29.0 +/- 6.4 mm Hg in the mitomycin C group and 29.5 +/- 10.0 mm Hg in the control group, P = .61), the mean postoperative intraocular pressure at each follow-up period was significantly lower in the mitomycin C group than in the control group (10.3 +/- 7.1 vs 14.5 +/- 5.1 mm Hg at six months, P = .02; 10.5 +/- 4.9 vs 14.5 +/- 4.4 mm Hg at 12 months, P = .01; and 10.0 +/- 3.1 vs 17.2 +/- 3.0 mm Hg at 18 months, P = .004, respectively). The mean number of postoperative medications was also significantly lower in the mitomycin C group (0.2 +/- 0.4 vs 1.1 +/- 1.4 medications at six months, P = .007; 0.3 +/- 0.4 vs 0.9 +/- 1.1 medications at 12 months, P = .04; and 0.3 +/- 0.5 vs 1.7 +/- 1.2 medications at 18 months, P = .01, respectively). However, the mitomycin C group had a significantly higher incidence of prolonged hypotony (intraocular pressure less than 6 mm Hg) compared with the control group (15% vs 0% at nine months, P = .05). Younger age was associated with a higher incidence of persistent hypotony. CONCLUSIONS: Adjunctive subconjunctival mitomycin C (0.5 mg/ml for a three-minute exposure) in primary trabeculectomies of phakic eyes, while increasing the success rate by decreasing intraocular pressure and postoperative medications, is associated with a higher incidence of prolonged hypotony.

Adult↗
PubMed1997

Adjuvant mitomycin C following endoscopic treatment of upper tract transitional cell carcinoma.

PURPOSE: A variety of topical agents have been used for transitional cell carcinoma of the upper tract. Mitomycin C has limited systemic absorption when given intravesically because of its high molecular weight. We reviewed our experience with mitomycin C following endoscopic treatment of upper tract transitional cell carcinoma. MATERIALS AND METHODS: Since 1991, 19 patients (21 renal units) have undergone a total of 28 treatments with mitomycin C for high volume, recurrent or multifocal transitional cell carcinoma. Of the 19 patients 12 had an absolute indication for nephron sparing treatment. Following ureteroscopic biopsy and treatment of upper tract transitional cell carcinoma, 40 mg. mitomycin C in 3 divided doses was instilled via a ureteral catheter, which was clamped between doses to give an exposure time of 30 minutes. Eighteen patients have undergone ureteroscopic surveillance following a total of 26 treatments. RESULTS: No systemic side effects occurred during or after treatment with mitomycin C. One patient had a prominent local inflammatory reaction following neodymium:YAG ablation and mitomycin C treatment of a renal pelvic tumor. The average size of the treated tumors was 17 mm. (range 5 to 30). The grade of the tumors (when known) was 1 in 5 patients, 1 to 2 in 2, 2 in 8 and 3 in 4. Most tumors were treated with either neodymium:YAG (6 cases) or holmium:YAG laser (8) or a combination of both (8). Following 1 to 4 treatments with mitomycin C 11 of 19 evaluable renal units (58%) were rendered free of disease. Six of those 11 renal units (54%) had an ipsilateral recurrence after a mean of 30 months of followup, 4 of which were treated endoscopically, and 7 (64%) are now disease-free without extirpative surgery. Four patients have undergone nephroureterectomy for persistent or recurrent disease. No patient has suffered local or distant progression of disease. CONCLUSIONS: Instillation of mitomycin C for upper tract transitional cell carcinoma appears to be safe and can be considered for adjuvant treatment in select cases. More data are necessary to determine its efficacy.

Aged↗
PubMed1998

Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in Chinese hamster ovary cells overexpressing NADPH:cytochrome C (P-450) reductase and DT-diaphorase.

We have directly demonstrated the involvement of human NADPH: cytochrome c (P-450) reductase in the aerobic/hypoxic differential toxicity of mitomycin C and porfiromycin in living cells by varying only this enzyme in a transfected cell line. In the same manner, we have implicated rat DT-diaphorase in the aerobic and hypoxic activation of mitomycin C, but found only a minor role for this enzyme in the aerobic activation of porfiromycin. DT-Diaphorase does not cause the production of an aerobic/hypoxic differential toxicity by mitomycin C, but rather activates this agent through an oxygen insensitive pathway. The evidence suggests that DT-diaphorase activates mitomycin C more effectively than porfiromycin, with porfiromycin being preferentially activated through a one-electron reductive pathway. The therapeutic potential of mitomycin antibiotics in the treatment of cancer can be envisioned to be enhanced for those tumors containing elevated levels of the bioreductive enzymes. However, cytogenetic heterogeneity within the tumor cell population and the various environmental factors which impact on bioreductive enzyme function, including pH and oxygen tension, may subvert this approach. Moreover, if high tumor levels of a drug activating enzyme reflect high levels in the normal tissues of the patient, normal tissue damage may also be enhanced with possibly no improvement in the therapeutic ratio. Approaches utilizing gene therapy, whereby a specific bioreductive catalyst is introduced into the tumor cell population via a targeting vehicle to activate a particular prodrug, may be more effective in that not only will the prodrug of choice be specifically activated in the tumor, but the source of the catalyst, be it bacterial, rodent, or human, will not be important. In fact, in the case of DT-diaphorase and mitomycin C, the rat form of the enzyme could be advantageous because it is more effective in activating mitomycin C than is the human form of this enzyme. Assuming targeted gene delivery to malignant cells, a non-host enzyme which is more effective at activating mitomycin C than the analogous host enzyme might also result in less drug activation in normal tissue and, hence, less normal tissue toxicity.

Animals↗
PubMed1988

Mitomycin eye drops as treatment for pterygium.

The authors used an antineoplastic-antibiotic agent, mitomycin, in the form of eye drops as adjunctive treatment for primary and recurrent pterygia after surgical excision. Sixteen primary and four recurrent pterygia were treated with 1.0 mg/ml mitomycin eye drops, 14 primary and 10 recurrent pterygia were treated with 0.4 mg/ml mitomycin eye drops, and 18 primary pterygia were treated with placebo eye drops. Postoperative follow-up for the eyes treated with mitomycin eye drops ranged from 3 to 34 weeks (mean, 23 weeks). One of 44 pterygia treated with mitomycin recurred after 5 months (recurrence rate, 2.3%), whereas 16 of 18 primary pterygia treated with placebo eye drops developed postoperative granulomas and recurrent pterygia with a mean postoperative period of 6 weeks (recurrence rate, 88.9%). Topical mitomycin (1.0 mg/ml) caused conjunctival irritation, excessive lacrimation, and mild superficial punctate keratitis. These topical side effects were minimized with the 0.4 mg/ml mitomycin dosage. No systemic toxicity was noted with either dosage. The authors believe that mitomycin eye drops is a safe and effective adjunct to surgical excision in the treatment of primary or recurrent pterygia, or both.

Adolescent↗
PubMed1997

Intraoperative mitomycin in primary pterygium excision. A prospective, randomized trial.

PURPOSE: Conjunctival autograft transplantation and postoperative mitomycin therapy are two adjuvant treatment methods shown to lessen the high pterygium recurrence rate seen with simple excision alone. The authors conducted a prospective, randomized study comparing these two techniques with a relatively new treatment method using intraoperative mitomycin application. METHODS: Fifty patients with 56 primary pterygia were randomized to 1 of 3 treatment groups: conjunctival autograft (group 1), postoperative mitomycin 0.2 mg/ml four times a day x 7 days (group 2), and intraoperative mitomycin 0.4 mg/ml x 3 minutes (group 3). The mean follow-up time was 16 months (range, 6 to 28 months). RESULTS: Recurrences developed in 4 (22.2%) of 18 eyes in group 1, 4 (21.1%) of 19 eyes in group 2, and 2 (10.5%) of 19 eyes in group 3. Complications developed in two, patients from group 2, scleral thinning managed successfully with a scleral patch graft, and epithelial toxicity that resolved on discontinuation of mitomycin on postoperative day 6. There were no complications in the other two groups. CONCLUSIONS: Intraoperative mitomycin is a simple and effective alternative to postoperative mitomycin therapy, showing the lowest recurrence rate in their series with no toxicity during the study period. If the decision is made to use adjunctive mitomycin, the authors recommend intraoperative application over postoperative administration.

Administration, Topical↗
PubMed1997

Dacryocystorhinostomy with intraoperative mitomycin C.

PURPOSE: To observe the effect of intraoperative mitomycin C on the size of the osteotomy site after dacryocystorhinostomy.: METHODS: A total of 15 eyes of 14 patients diagnosed with primary acquired nasolacrimal duct obstruction were assigned randomly to either a mitomycin C group or a control group. The surgical procedures in both groups were exactly the same, except that in the patients in the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the osteotomy site and then after 30 minutes was removed transnasally. Nasoendoscopic findings were recorded at the completion of the surgery and at 1 month, 3 months, and 6 months after surgery for the two groups. A computer-aided digitizer was used to calculate the surface area of the osteotomy site, and a Student's t test was used to compare the difference between the two groups. RESULTS: All patients in the mitomycin C group remained symptom free after removal of their silicone tube (100% success), and there was one patient in the control group who had recurrent epiphora (87.5% success). Septo-osteotomy adhesion was found in two patients in the control group (25%), but there was no such adhesion found in the patients in the mitomycin C group. In the mitomycin C group, the average final surface area of the osteotomy at the end of the sixth postoperative month was 27.10 +/- 5.78 mm2, whereas that of the control group was only 10.83 +/- 3.37 mm2. Although the immediate postoperative surface area of the osteotomy showed no significant difference between the two groups, a statistically significant difference was noted at 6 months. CONCLUSION: Intraoperative mitomycin C is effective in maintaining a larger osteotomy size. This modification may possibly improve success rates over the traditional dacryocystorhinostomy procedure.

Chemotherapy, Adjuvant↗
PubMed1997

FR900482, a close cousin of mitomycin C that exploits mitosene-based DNA cross-linking.

BACKGROUND: The class of antitumor antibiotics that includes FR900482 has a very close structural analogy to the mitomycins, one of which, mitomycin C, has been in widespread clinical use for more than 20 years. Like mitomycin C, these antitumor antibiotics are reductively activated in vivo and covalently cross-link DNA as a result of activity of the mitosene moiety generated on reduction. Owing to differences in structure and the attendant mechanistic differences in bioreductive activation between the mitomycins and FR900482, FR900482 does not produce an adventitious superoxide radical anion during reductive activation and thus does not exhibit oxidative strand scission of DNA. It is postulated that the low clinical toxicity of FR900482 relative to mitomycin C is a direct manifestation of the mechanistic differences of bioreductive activation leading to the highly reactive DNA cross-linking mitosenes. RESULTS: Using Fe(II)-EDTA footprinting, we showed that the two natural products FR900482 (1) and dihydro, FR66979 (3), and the semi-synthetically derived triacetate FK973 (2), display remarkable selectivity for 5' deoxy-CG sequences of DNA, and that this selectivity is abolished upon deletion of the exocyclic N2 amine of either participating guanosine residue. In addition, we investigated the mono alkylation abilities of FR66979 with respect to a number of inosine-substituted oligonucleotides and observed that the FR900482 class of compounds were able to give rise to easily separable orientation isomers of their respective cross-links. CONCLUSIONS: The FR900482 class of antitumor antibiotics cross-link DNA in a fashion analogous to the mitomycins. The cross-linking reaction yields two orientation isomers which are of vastly different electrophoretic mobility and which also exhibit radically different DNA-protein recognition properties upon reaction with AluI restriction endonuclease. In addition, mono-alkylation of DNA by FR66979 shows little, if any, dependence upon pre-covalent interactions deemed necessary for the mitomycins. These insights support the proposal that the FR900482 class of compounds represents a compelling clinical replacement for mitomycin C, given its greatly reduced host toxicity and superior DNA interstrand cross-linking efficacy.

Alkylation↗
PubMed2006

Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial.

BACKGROUND: The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer. METHODS: After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website . FINDINGS: Median follow-up was 88 months (IQR 63-110). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (69 months [95% CI 55-86] vs 21 months [15-54]; difference between groups 48 months [42-54], log-rank p=0.0012). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (41.9% [32.7-51.5] vs 57.9% [48.7-67.5]; difference between groups 16.0% [2.7-29.3], log-rank p=0.0012); progression (9.3% [3.8-14.8] vs 21.9% [17.9-25.9]; difference between groups 12.6% [3.0-22.2], log-rank p=0.004); overall mortality (21.5% [13.5-29.5] vs 32.4% [23.4-41.4], difference between groups 10.9% [0.6-21.2], log-rank p=0.045); and disease-specific mortality (5.6% [1.2-10.0] vs 16.2% [6.1-23.3], difference between groups 10.6% [2.5-18.7], log-rank p=0.01). Side-effects were mainly localised to the bladder. INTERPRETATION: BCG-induced inflammation might increase the permeability of the bladder mucosa such that mitomycin can reach the target tissue more easily and exert its anticancer effect.

Aged↗