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PubMed1985

Use of mitomycin as prophylaxis following endoscopic resection of superficial bladder cancer.

A prospective controlled study evaluated the influence of long-term mitomycin instillation therapy on tumor recurrence, tumor progression rate, and patient survival after transurethral resection of superficial bladder tumors. In the mitomycin group, 11.1 per cent had recurrent tumors, and among the controls, 54.8 per cent had recurrent tumors during a mean follow-up of thirty-three and one-half and thirty-four and one-half months, respectively. The control group had 8 recurrent tumors of higher stage and 4 of higher grade, whereas all recurrent tumors in the mitomycin group that occurred in the bladder were either the same grade and the same stage (n = 1) or a lower stage and lower grade (n = 6). Side effects were minimal, with 72 per cent of the patients having no side effects. Chemical cystitis was the most common side effect, followed by generalized rash. No general toxic signs such as myelosuppression were seen.

Administration, Topical↗

PubMed1977

Antitumor effect of combined use of OK-432 and yeast cell wall with mitomycin-C in mice.

Tumor-inhibitory effect of combined use of mitomycin-C and streptococcal preparation (OK-432) or yeast cell wall (YCW) was examined. Twenty-four hours after intraperitoneal inoculation of Ehrlich carcinoma cells, combination therapy was carried out and tumor growth was observed for 40 days. About one-half of mice treated with yeast cell wall at a single dose of 1 mg survived free of tumor. Mitomycin-C at a single dose of 2 microgram was not effective. However, in combination with yeast cell wall, tumor suppression was observed in 70% of the mice. This tumor-inhibitory effect was enhanced by subsequent treatment with OK-432 or yeast cell wall. When these materials were injected separately or in combination with mitomycin-C, the number of peritoneal exudate cells increased about 3 to 6 times after 3 days and these cells exhibited cytotoxic effect on tumor cells. Hemagglutinating antibody to sheep erythrocytes was hardly affected by the combination therapy.

Animals↗

PubMedDate not supplied

Bleomycin alone or combined with mitomycin C in treatment of advanced or recurrent squamous cell carcinoma of the vulva.

Twenty patients with advanced and/or recurrent vulvar carcinoma were treated with bleomycin alone or combined with mitomycin C. Five of 11 patients in the bleomycin-treated group showed objective response (two complete and three partial) and five of nine patients in the bleomycin-mitomycin C-treated group showed objective response (one complete and four partial). No severe side effects were seen. Now that activity against this disease has been demonstrated for bleomycin, alone or combined with mitomycin C, attention should be directed to treating those patients not cured by surgery and radiation therapy alone.

Adult↗

PubMed1984

Mitomycin-induced hemolytic-uremic syndrome.

Four patients who took the antitumor agent mitomycin manifested microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. At autopsy, kidneys from all four patients had a microangiopathy typical of the hemolytic-uremic syndrome (HUS), with thromboses in glomerular capillaries and arterioles, fibrin deposition in mesangium, and prominent cellular intimal proliferation of the interlobular arteries. Development of the HUS was an important factor contributing to death in all four patients. From a review of the literature and our initial results of a randomized chemotherapy protocol for metastatic adenocarcinoma of the colorectum, it appears that mitomycin was the most likely cause for the development of the HUS in these patients. As more patients are being treated with mitomycin, particular care must be taken to monitor them for development of a drug-induced HUS.

Arteries↗

PubMed1981

[Biological characterization including sensitivity to mitomycin C of cultured human ovarian cancers (author's transl)].

The present study first dealt with characterization of two cell lines, Kuramochi and CKS, established from human ovarian cancer. Secondary, the quantitative analyses of sensitivity of the cell lines to Mitomycin C was reported. The two cell lines showed typically epithelial features in vitro. Kuramochi cells, derived from undifferentiated carcinoma, had microvilli on the cell surface, cell continuity with the relative developed junctional complex, but no secretary granules and vesicles. The chromosomal analysis revealed the hyperdiploid modal number of 50. The population doubling time was about 26 hours. CKS cells, derived from serous cystadenocarcinoma, had secretary vesicles, microvilli, but no developed junctional complex. The chromosomal analysis reveals the hypodiploid modal number of 37. The population doubling time was about 34 hours. Biochemical markers of alpha-fetoprotein, human chorionic gonadotropin and carcinoembryonic antigen were not detected in both cell lines. 90% lethal dose of 2-hr-treatment with Mitomycin C was 0.42 microgram/ml in Kuramochi cell line and 1.13 microgram/ml in CKS cell line. These values were higher than the one of the control cell line, KATO-III, derived from signet-ring cell carcinoma of stomach. Ovarian cancers were suggested resistant to Mitomycin C.

Adenocarcinoma, Mucinous↗

PubMed1981

Evaluation of beta-2'-deoxythioguanosine combined with methyl-CCNU or mitomycin in advanced colorectal cancer. A Southwest Oncology Group study.

Two hundred twenty eligible patients with metastatic colorectal carcinoma were treated with a combination of beta-2'-deoxythioguanosine (BTG), plus methyl-CCNU or mitomycin. There was no significant difference in overall response (CR/PR + stable) among fully evaluable patients between the mitomycin plus BTG arm 19/96 (19.7%) and the MeCCNU arm 26/87 (29.8%). Median survival of eligible patients was 19 weeks with mitomycin plus BTG versus 21 weeks with MeCCNU plus BTG: no difference. Median survival of responders (40 weeks) and patients with stable disease (35 weeks) was significantly better than patients with increasing disease (17 weeks): p + 0.001.

Adenocarcinoma↗

PubMed1995

[Progress in laser sclerotomy ab externo] Enlarging the sclerostomy channel and local mitomycin administration].

In a previous study we presented our first results after sclerostomy using a pulsed erbium/holmium: YAG laser. At a fiber diameter of 300 microns a success rate of 20-30% was found after a 1-year follow-up. This study concentrates on the improvement of the parameters for filter survival. METHODS. The fiber diameter and thus the size of the fistula increased to 400 microns. Patients who had undergone fibrosis for a previous fistula were treated intraoperatively with topical mitomycin administration. RESULTS. After a follow-up of 6 months, filter function in the 300 microns group was maintained in 26% of the treated eyes (n = 23), while 400 microns fistulas were successful in 48% (n = 26). In the mitomycin-treated group (n = 6), sclerostomy achieved an IOP regulation in four patients. Postoperative hypotony was more frequent, but did not exceed 2 weeks. CONCLUSION. An increase in fistula diameter improves the long-term results of laser sclerostomy. Mitomycin is useful in maintaining filter function in patients with an unfavorable prognosis.

Antibiotics, Antineoplastic↗

PubMed1994

[Long-term results of intravesical prevention of recurrence with mitomycin C and adriamycin in patients with superficial bladder cancer].

In a prospective multicenter study, four protocols for administration of mitomycin C and Adriamycin by intravesical installation were evaluated for effectiveness in the prevention of recurrent tumours in patients whose superficial bladder tumours (TA and T1) had been removed by transurethral resection. The 3-year and short-term installation protocols were compared with each other and each with a combination of the two. Evaluation after a mean follow up of 62.5 months was possible in 333 patients: the overall recurrence rate was 20.7% and the overall progression rate, 9.3%. No statistically significant differences were found in frequency of tumour recurrence among three mitomycin regimens and an Adriamycin regimen, regardless of the risk groups. However, frequency of recurrence per time unit was much lower in the treatment group with short-term intensive (weekly) mitomycin instillation, which was due mainly to prevention of late recurrence.

Administration, Intravesical↗

PubMed1994

A scleral shield for the application of mitomycin C during trabeculectomy: a rabbit model.

The use of mitomycin C during trabeculectomy is associated with a significant degree of persistent hypotony. To address this problem, we designed a scleral shield with a dry sponge glued on it for use in applying mitomycin C that reduces the penetration of the substance through the sclera. The effectiveness of the shield was tested in a rabbit model using regular sponges and sponges with the attached shield. Histopathologic examination of the eyes after 1 month revealed toxic changes in the eyes in which only a regular sponge had been used, but not in those in which the sponges with the attached scleral shield had been used. The scleral shield may help reduce the incidence of hypotony in eyes undergoing trabeculectomy with adjunctive mitomycin C.

Animals↗

PubMed1994

Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis.

Intraperitoneal chemo-hyperthermia with mitomycin C was used to treat 28 patients with far advanced digestive adenocarcinoma and histologically confirmed peritoneal carcinomatosis. Surgical resection of the primary tumor was possible in 17 cases. After closure of the abdominal wall, intraperitoneal chemo-hyperthermia was performed for 90 to 120 minutes under general anesthesia and 32 degrees C hypothermia, through 3 intraperitoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 6 liters of peritoneal dialysate heated to an inflow temperature of 46-49 degrees C. No mortality occurred, and there were 2 post-operative complications, with transitory biological side effects. In 9 out of 10 patients with preoperative malignant ascites, the ascites cleared after treatment. One-year survival rate was 54.2%. These encouraging preliminary results show that intraperitoneal chemohyperthermia with mitomycin C is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive cancers.

Adenocarcinoma↗

PubMed1993

[Mitomycin C in glaucoma surgery].

Glaucoma filtering surgery fails because of scarring of the filtering bleb. Fibroblasts proliferation from the episclera and Tenon capsule play an important role in the scarring process. The use of antimetabolites in glaucoma filtering surgery have a beneficial effect on the lowering of intraocular pressure especially in eye at poor surgery prognosis. They inhibit the fibroblasts proliferation and subsequent scarring of filtering bleb. 5 fluorouracil improves chance of success with filtering surgery but the necessity of multiple subconjunctival injections has many disadvantages including discomfort for the patient and ocular surface problems such as corneal defect and conjunctival wound leak. Mitomycin C with its focal applications limits the toxic effects to tissue directly exposed to the drug. A single intra-operative application leads to a more hypotensive effect with less corneal complications which are two major advantages of this treatment (Kitazawa and al.): Success rate at one year without medical treatment: 88% with MMC-40% with 5 FU. Different tissue culture studies as well as clinical studies demonstrate that the antiproliferative effect of MMC is 100 times more powerful than 5 fluorouracil. Mitomycin C might probably interfere with other steps in the wound healing process. Mitomycin C seems to be a better treatment than 5 fluorouracil. Nevertheless long term randomized prospective human studies are necessary to confirm it.

Adult↗

PubMed1993

A phase I study of the left-shifting agent BW12C79 plus mitomycin C and the effect on the skeletal muscle metabolism using 31P magnetic resonance spectroscopy.

BW12C79 stabilizes the oxyhemoglobin molecule resulting in a reversible left-shift of the oxygen saturation curve. The activity of a number of bioreductive anticancer drugs, such as mitomycin C, may be enhanced under hypoxic conditions. Twenty-four patients with various malignancies received BW12C79 and mitomycin C. BW12C79 was administered i.v. with a loading dose (20-50 mg/kg) over 1 h followed by a maintenance infusion of 4 mg/kg/h for 5 h. Percentage modification of the oxyhemoglobin (degree of left-shift) was dose related with maximum modification of 56% and was maintained for the duration of maintenance infusion of BW12C79. Hemoglobin electrophoresis showed a fast moving band consistent with the BW12C79-oxyhemoglobin complex. Side effects at the top dose level comprised headache, nausea/vomiting, vein irritation, and myocardial ischemia. One other patient suffered from an acute encephalopathy of unknown etiology a few days following BW12C79. 31P magnetic resonance spectroscopy of exercising calf muscles showed increased breakdown of high energy phosphate stores and a greater reduction in pH. Recovery of the high energy phosphate stores after exercise was slow. These results were consistent with reduced oxygen supply due to either a left shift of the oxygen saturation curve and/or reduced muscle blood flow. BW12C79 did not interfere with the pharmacokinetics of mitomycin C. In conclusion, this phase I study demonstrates the feasibility of achieving a significant left shift in the oxygen saturation curve in cancer patients which is maintained for at least 5 h with acceptable toxicity. The maximum tolerated dose of BW12C79 was 50 mg/kg loading infusion followed by a maintenance infusion of 4 mg/kg/h. Magnetic resonance spectroscopy results were consistent with reduced supply of oxygen to exercising skeletal muscle. BW12C79 may be of potential benefit as an adjunct to bioreductive drugs in the treatment of solid tumors.

Adult↗

PubMed1993

Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtration surgery.

Intraoperative mitomycin C has been shown to be highly effective in increasing the success rate of glaucoma filtration surgery. Between October 1991 and June 1992, 169 eyes of 156 patients underwent filtration procedures with intraoperative mitomycin C. In the postoperative period, five eyes (2.9%) developed hypotony maculopathy, characterized by disc edema, vascular tortuosity, and chorioretinal folds in the macular area. Cryotherapy was applied to three eyes, and was effective in reversing the hypotony in two of them. However, the visual prognosis was poor: after a mean follow up of 5.3 months (range, 3.5 to 8 months), visual acuity returned to preoperative levels in one case. Hypotony maculopathy may develop after glaucoma filtration surgery with intraoperative mitomycin C. We suggest restricting the indication of its adjunctive use to eyes with poor surgical prognosis or those in which a very low intraocular pressure is desired. The use of extra sutures (which can be sectioned by laser) or releasable sutures to prevent excessive filtration in the postoperative period also is advisable.

Administration, Topical↗

PubMed1977

Immunity to lymphoid tumors in syngeneic mice by immunization with mitomycin C-treated cells.

Immunization of mice with syngeneic mitomycin C-treated lymphoid tumor cells (EL-4 and S49A) conferred a high degree of immunity to transplantation with viable tumor cells in syngeneic animals. The development of this immunity was paralleled by the development of specific cell-mediated cytotoxicity; no anti-tumor antibodies could be detected in the immunized animals. In contrast to the high immunoprophylactic capacity of mitomycin C-treated cells, attempts to utilize these cells for immunotherapy were unsuccessful. Preliminary experiments did not reveal antigenic differences between mitomycin C-treated and untreated tumor cells.

Animals↗

PubMed1993

A phase II trial of mitomycin C, 5-fluorouracil and radiation therapy in the treatment of unresectable non-small cell lung cancer.

We conducted a study evaluating the efficacy of simultaneous administration of 5-fluorouracil, mitomycin C, and X-irradiation in unresectable Stage III non-small cell lung cancer. Radiation was delivered in a split course to a total of 55 Gy. In the first course, radiation was administered daily in 250 cGy fractions for 12 treatments. Following a two week rest, an additional 10 treatments of 200 cGy fractions were delivered. Chemotherapy consisted of 10 mg/M2 of mitomycin C on day 1, and 1000 mg/M2 per day of 5-fluorouracil by continuous infusion on days 1 through 5 and 29 through 33. Twenty-one enrolled patients were evaluable. The overall response rate was 52% (95% confidence intervals 31-73%), with a median duration of response of 42 weeks. There were 5 complete responders (24%) and four of these patients remain disease-free with follow-up between 24-54 months. The median survival time for all patients was 59 weeks. For the complete responders the median survival time has not yet been reached, but is in excess of 42 months. Toxicity consisted of moderate stomatitis and myelosuppression. The sustained remissions obtained by 4 of 21 patients (18%) treated with concurrent mitomycin C, 5-fluorouracil and x-irradiation are encouraging and deserve further study.

Adenocarcinoma↗

PubMed1995

[Primary trabeculectomy for open-angle glaucoma with mitomycin C].

We examined the results of postoperative intraocular pressure (IOP) control and complications of trabeculectomy with mitomycin C in open angle glaucoma patients who had not undergone any other ocular surgery. The subjects were 80 eyes of 70 patients who underwent surgery with 0.04% mitomycin C as an adjunct for 3 minutes and were followed for 7-24 months (mean +/- standard deviation: 13 +/- 3.4). The preoperative IOP was 21-32 mmHg (mean +/- standard deviation: 24.6 +/- 4.3) in maximum tolerable medications. IOP control ratio, which was analysed with the Kaplan-Meier method at 24 months after surgery was 81.6% without any antiglaucoma medications, vs 92.0% with medications. These values were significantly higher (p < 0.05) than the results of trabeculectomy with 5-fluorouracil or without antimetabolic agents previously performed in our clinic. Shallow chamber in 18 eyes (23%), choroidal detachment in 14 eyes (18%), hypotonus maculopathy in 7 eyes (9%), and cataract progression in 5 eyes (7%) were recognised as complications. Although there are some complications to be conquered, trabeculectomy with mitomycin C seems to be effective in treating primary open angle glaucoma patients.

Adult↗

PubMed1996

[Mitomycin C-DNA adduct detection in rat organs and human liver].

Mitomycin C-DNA adduct formation was detected in rat organs and also in human tissues by 32P-postlabeling assay. The adduct levels were 1-4 adduct/ 10(8) nucleotides in the human liver after 20 mg of mitomycin C by intra-artery administration and which level was higher comparing with the levels in the rat liver after 10 times more dosages of mitomycin C administration by intra-venous injection. The levels in the human liver were maintained at least 56 days after administration. Organ-specific differences of adduct levels were observed in rat experiments: the adduct levels of liver, lung and kidney were stable but rapidly decreased in stomach and colon. These results, which were obtained from the experiments using the normal parts of each organs may indicate that the drug effectivity for adduct formation was sufficient with smaller dose in the stomach and colon, but disappeared quickly, mean while, the drug effectivity was undergoing in relatively high levels for longer periods in the liver lung and kidney. The analysis of human liver samples may suggest that the selective intra-artery injection induced stronger drug effectivity for adduct formation in human organs.

Adult↗

PubMed1996

Epithelial barrier function of the filtering bleb conjunctiva and the cornea after trabeculectomy with mitomycin C.

PURPOSE: To evaluate epithelial barrier function of the filtering bleb conjunctiva and the cornea after trabeculectomy with adjunct, intraoperative mitomycin C, by using a newly developed slit-lamp fluorophotometer. SUBJECTS AND METHODS: Thirteen patients with normal-tension glaucoma with a cystic filtering bleb who had undergone unilateral trabeculectomy with mitomycin C only once at least 1 year previously were subjected to the study. Epithelial barrier function of the bleb conjunctiva and the cornea in the operated eye was evaluated using an Anterior Fluorometer FL-500 to measure the uptake of topically applied fluorescein. RESULTS: Fluorescein uptake (nanograms per milliliter, mean +/- standard error) by the bleb conjunctiva (1,857 +/- 380) was not significantly different from either the uptake by the superior bulbar conjunctiva in the operated eyes, located approximately 90 degrees C away from the filtering bleb (1,974 +/- 258), or the uptake by the conjunctiva in the intact eyes, located symmetrically against the bleb (1,913 +/- 248). The corneal uptake in the operated eye (56.1 +/- 10.2) was not significantly different from that in the intact eye (53.5 +/- 8.3). CONCLUSIONS: Epithelial barrier function of the cystic filtering bleb conjunctiva and the cornea long after trabeculectomy with mitomycin C was demonstrated to be almost identical to that of the control.

Aged↗