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PubMed2003

Mitomycin C eliminates the short-term intraocular pressure rise found following Molteno tube implantation.

PURPOSE: Molteno implants remain popular for treating recalcitrant glaucomas. This study aimed to assess the effect of mitomycin C (MMC) use with Molteno tube implantation upon intraocular pressure (IOP) control and complication rates. In particular, the study aimed to assess any change that MMC might have upon the postoperative hypertensive phase. METHODS: A retrospective case record study was conducted of all patients undergoing double plate Molteno implant surgery by one surgeon over 5 years. Eyes with recalcitrant glaucoma unresponsive to previous surgery, or deemed unlikely to succeed with trabeculectomy, underwent double plate Molteno tube implantation. Eyes that had MMC (0.3 mg/mL, 3 min) applied to Tenon's capsule over the secondary plate were compared with eyes that underwent surgery without adjunctive MMC application. RESULTS: Twenty-seven eyes received MMC and were similar to 26 eyes not receiving MMC in terms of glaucoma subtype, age, sex, previous surgery, preoperative IOP and postoperative IOP lowering agents. Those not receiving MMC had raised IOP 31-90 days post implantation compared with MMC treated eyes (P < 0.01) and more often received oral antifibrosis medication (P < 0.05). Complications were no more common with MMC except for initial overdrainage. Significant systemic complications from the use of oral antifibrosis medication were common. CONCLUSIONS: The findings suggest a useful role for MMC. Caution is advised in case selection for MMC use. Mitomycin C treatment over the secondary plate alone permits removal of this plate if MMC-related complications occur without requiring removal of the whole implant.

Adult↗
PubMed2003

[Mitomycin-induced hemolytic-uremic syndrome].

HISTORY AND CLINICAL FINDINGS: A 58-year-old patient suffered from rapidly progressing renal insufficiency and 11 kg weight-loss three months after adjuvant treatment of a carcinoma of the lower bowel (G 2 T 3 N 1 M 0 ) with mitomycine C. At the point of hospitalisation the patient was anuric while suffering from pulmonary oedema, hemolytic anemia and thrombocytopenia. INVESTIGATIONS: Computed tomography and bronchial endoscopy showed pulmonary haemorrhage. Recurrence of carcinoma or metastases were excluded. Renal biopsy revealed mesangiolysis and concentric intimaproliferation (onion skinning). Beside haemolytic anaemia and fragmentocytes toxic damage of the bone marrow was found. TREATMENT AND COURSE: After one week treatment in the intensive care unit because of respiratory insufficiency recovery was observed under plasma separation and high dose corticosteroid therapy. Disease activity involved renal failure, bone marrow insufficiency, microangiopathic anaemia thrombopenia and pulmonary haemorrhage. CONCLUSION: Lung involvement in the course of haemolytic uremic syndrome is rare and carries a high lethality. The case illustrates the need of detailed diagnostic for correct treatment of haemolytic uremic syndrome. If chemotherapy is required in patients with pre-existing or intercurrent renal failure dose adaptation is necessary to avoid dose-dependent toxicity of mitomycine C.

Antibiotics, Antineoplastic↗
PubMed1992

[Local mitomycin C therapy after excision of pterygium].

In order to prevent recurrence of pterygium after excision we treated 21 patients postoperatively with Mitomycin-C-eye drops 0.02%. In a mean follow up of 1 1/2 years, we have not seen any recurrence or side effect. We conclude, Mitomycin-C 0.02% is a safe, simple and effective treatment to prevent recurrence of pterygium and we suggest to continue for a further experience.

Combined Modality Therapy↗
PubMed2002

Impact of irrigation in a new model for in vitro diffusion of mitomycin-C after episcleral application.

PURPOSE: Episcleral application of mitomycin-C (MMC) during glaucoma surgery hinders the post-operative wound healing but may lead to side effects to the ciliary body. We present an experimental model to investigate the influence of irrigation on diffusion of MMC through the sclera and into subscleral compartments. MATERIALS AND METHODS: Scleral quadrants of 10 human donor eyes were mounted on PMMA tubes filled with saline imitating the intraocular fluid. Beneath the sclera a subscleral sponge was fixed to mimic the ciliary body. The episcleral sides of the scleral quadrants were exposed to sponges soaked with 0.2 mg/ml MMC and thereafter irrigated with 0, 40, 100 and 200 ml saline. Mitomycin-C concentrations of the sclera and the subscleral compartments were analyzed by means of high-performance liquid chromatography. In a second experiment, after the application time of one minute, different times of free diffusion until analysis were allowed, to evaluate the time-course of MMC penetration. RESULTS: MMC concentrations declined from the scleral layers (1-13 microg/ml, depending on depth and irrigation) to the subscleral sponge (0.17-0.27 microg/ml) and to the subscleral fluid (0.002-0.05 microg/ml). Irrigation significantly reduced MMC concentrations in the superficial scleral layers and in the subscleral fluid to 10-30% of the no irrigation value. No effect was noted in the deep scleral layers and subscleral sponges. In the second experiment, the subscleral compartments showed higher MMC concentrations with longer diffusion times, whereas no effect on intrascleral MMC concentrations was observed. CONCLUSION: Irrigation reduced MMC concentrations in the superficial scleral layers and in the subscleral fluid by the same amount. The clinical value of irrigation should be reconsidered; a lower dose MMC application without irrigation might be a more rationale approach.

Analysis of Variance↗
PubMed1969

Colicin K. 8. The immunological properties of mitomycin-induced colicin K.

Partially purified colicin K (mCol K) has been obtained from cultures of Escherichia coli K235 induced with mitomycin C. Unlike colicin K (Col K) derived from noninduced cultures of E. coli K235, mitomycin-induced colicin K (mCol K) is not associated with the type O-specific antigen of the colicinogenic bacillus. mCol K elicits in rabbits specific antibodies which precipitate and neutralize the homologous bacteriocin. These colicin-specific antibodies are not precipitated by the colicin-O antigen complex derived from noninduced bacteria. Colicin-neutralizing antibodies can be separated by zone electrophoresis into fractions having different electrophoretic mobilities. The antibodies with lower mobility strongly precipitate the homologous antigen mCol K; those with higher mobility neutralize the bacteriocin and form soluble antigen-antibody complexes.

Animals↗
PubMed1997

Trabeculectomy with multiple applications of mitomycin-C in monkeys with experimental glaucoma.

To inhibit the wound healing process and to achieve a better intraocular pressure lowering effect, we applied mitomycin-C (MMC) topically in trabeculectomy at different time sequences. In this experiment, a model of glaucoma trabeculectomy combined with light microscopic autoradiography study was used to evaluate the clinical and histological effects and the time course of cellular incorporation of tritiated thymidine. This study utilized twelve eyes (divided into three groups) of six monkeys with experimental glaucoma. Group I received 0.08 ml subconjunctival injection of 0.02 mg/ml MMC 24 to 36 hours prior to trabeculectomy. Group II received intraoperative topical application of 0.27 mg/ml MMC for 4 minutes. Group III received the same treatment as group II, along with pre-operative and repeated post-operative conjunctival applications of 0.4 mg/ml MMC for 10 minutes. Surgical success, IOP < 21 mmHg, lasted for a median of 8 days in group I, 56 days in group II and 75 days in group III. Compared with group I, cellular proliferation was significantly inhibited in group II and mostly inhibited in group III. No significant ocular toxicity or profound hypotony was observed. Histological examination of group III on the 90th day after operation showed patent scleral tunnel and hypocellular loose connective tissue in the conjunctival bleb. These results demonstrated that a series of pre-, intra- and repeated postoperative topical applications of mitomycin-C had a prolonged effect in inhibiting wound healing after trabeculectomy in monkeys.

Animals↗
PubMed2003

A phase II study of mitomycin C, cisplatin and protracted infusional 5-fluorouracil in advanced pancreatic carcinoma: efficacy and low toxicity.

BACKGROUND: The effective treatment of unresectable pancreatic carcinoma represents a formidable challenge. There is a need to develop systemic therapies which combine efficacy with acceptable toxicity. The current 'gold standard' gemcitabine gives an objective response rate of the order of 20% and median survival up to 6 months. Here we have evaluated the efficacy and toxicity of mitomycin C, cisplatin and protracted infusional 5-fluorouracil (MCF). PATIENTS AND METHODS: Forty-five patients with locally advanced (13 patients) or metastatic (32 patients) pancreatic carcinoma were treated with mitomycin C 7 mg/m(2) 6 weekly, cisplatin 60 mg/m(2) 3 weekly and protracted venous infusion 5-FU 300 mg/m(2)/day. Patients were evaluated for response after three cycles and received six cycles in total in the absence of progressive disease or poor tolerance. Median age was 62 (45-75) years; 41 patients were World Health Organization performance status 0-1. RESULTS: Treatment was well tolerated with 36 (84%) patients completing three or more cycles. Grade 3 or 4 toxicities were uncommon: anaemia in three patients (7%), mucositis in two (5%), nausea and vomiting in three (7%) and diarrhoea in one (1%). An objective response was seen in 21 (46%) patients. There was one complete response. The median survival overall was 7.1 months and 10.5 months in responders. The median duration of response was 4.3 months. One-year survival was 29%, 2-year survival was 18%. CONCLUSIONS: MCF combines efficacy with low toxicity in the treatment of advanced pancreatic carcinoma. The efficacy is at least comparable and may be superior to single-agent gemcitabine and MCF may therefore provide a cost-effective alternative.

Aged↗
PubMed2004

Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial.

BACKGROUND: Patients with advanced biliary tract carcinoma face a particularly dismal prognosis, and no standard palliative chemotherapy has yet been defined. Among several different single agents, mitomycin C and, more recently, the oral fluoropyrimidine capecitabine and the nucleoside analogue gemcitabine, have been reported to exert antitumour activity. In view of a potential drug synergy, the present randomised phase II trial was initiated. The aim was to investigate the therapeutic efficacy and tolerance of mitomycin C (MMC) in combination with gemcitabine (GEM) or capecitabine (CAPE) in previously untreated patients with advanced biliary tract cancer. PATIENTS AND METHODS: A total of 51 patients were entered in this study and randomly allocated to treatment with MMC 8 mg/m2 on day 1 in combination with GEM 2000 mg/m2 on days 1 and 15 every 4 weeks, or MMC 8 mg/m2 on day 1 plus CAPE 2000 mg/m2/day on days 1-14, every 4 weeks. In both arms, chemotherapy was administered for a total of 6 months unless progressive disease occurred earlier. RESULTS: Pretreatment characteristics were well balanced between the two treatment arms. The overall independent review committee-confirmed response rate among those treated with MMC + GEM was 20% (five of 25) compared with 31% (eight of 26) among those treated with MMC + CAPE. Similarly, median progression-free survival (PFS; 4.2 versus 5.3 months) and median overall survival (OS; 6.7 versus 9.25 months) tended to be superior in the latter combination arm. Chemotherapy was fairly well tolerated in both arms, with a comparably low rate of only grade 1 and 2 non-haematological adverse reactions. Also, only four (17%) patients in both treatment arms experienced grade 3 leukocytopenia, and three (13%) and four (17%) had grade 3 thrombocytopenia in the MMC + GEM and MMC + CAPE arm, respectively. CONCLUSIONS: The results of this study indicate that both combination regimens are feasible, tolerable and clinically active. The MMC + CAPE arm, however, seems to be superior in terms of response rate, PFS and OS, and should therefore be selected for further clinical investigation in advanced biliary tract cancer.

Adolescent↗
PubMed1973

Somatic crossing over in Glycine max (L.) Merrill: mutagenicity of sodium azide and lack of synergistic effect with caffeine and mitomycin C.

Glycine max (soybean) is one angiosperm which lends itself to the study of somatic crossing over. This is made possible because some varieties have gene combinations Y(11)Y(11), Y(11)y(11) and y(11)y(11) in the segregating populations from Y(11)y(11) plants. The gene in question is responsible for chlorophyll synthesis. The Y(11)Y(11) plants have dark green leaves, Y(11)y(11) are light green and y(11)y(11) plants are golden yellow. The heterozygous plants have dark green, yellow and dark green-yellow (double) spots on the leaves of the untreated control material, whereas the two homozygotes are almost always devoid of somatic sectoring. Application of caffeine, or mitomycin C, to the seeds increased the frequency of double, dark green and yellow spots on the Y(11)y(11) background. Possibly, some dark green or yellow spots originate by failure of one of the two components of what might start as a double spot due to somatic crossing over. The application of NaN(3) increases the frequency of dark green or yellow spots, almost exclusively. The two spots increase in equal frequency. The y(11)y(11) plants so treated do not have any light green sectors, but dark green, Y(11)Y(11), plants do develop a few light green or very dark green spots. The data indicate that NaN(3) is capable of inducing nondisjunction, but does not cause mutations (at this locus), chromosome fragmentations (segmental losses) or somatic crossing over to an appreciable degree. It has previously been shown that caffeine-induced chromosome rejoining in Vicia faba can be inhibited by treating the roots with NaN(3). In the present experiments NaN(3) did not affect the processes of somatic crossing over as induced by caffeine or mitomycin C. The effect was additive. This system offers advantages for studying chemical mutagens in that somatic crossing over, point mutations, segmental losses through chromosome breakage and nondisjunction can all be studied in a single treatment to the seeds.

Azides↗
PubMed1992

A randomized prospective study of cisplatin and vinblastine versus cisplatin, vinblastine and mitomycin in advanced non-small cell lung cancer.

From June 1986 to February 1989, 103 patients with advanced non-small cell lung cancer, with no previous chemotherapy, were randomized to receive either a combination of cisplatin and vinblastine (group A) or the same combination with the addition of mitomycin (group B). In group A, 15/48 evaluable patients had objective responses, as did 8/45 in group B. The median survivals were 35 and 32 weeks, respectively. The median survival of patients with response or stable disease was 43 weeks. Response and survival did not differ significantly between treatment groups. The addition of mitomycin to the two-drug combination showed no major therapeutic benefit, while bone marrow toxicity was increased. Three patients in group B died of sepsis. Among the different patient characteristics, disease stage, performance status and response had influence on survival.

Adult↗
PubMed1992

Mitoxantrone and mitomycin C as second-line treatment for advanced breast cancer.

Forty-three evaluable patients with advanced breast cancer were treated with a combination of mitoxantrone 10 mg/sqm and mitomycin C 10 mg/sqm every 3 weeks. Two patients (4%) achieved objective responses lasting 3 and 16 months. The median duration of survival after protocol entry was 6 months (range 1-22) and the median progression-free survival was 3.5 (range 1-20). Only mild toxicities were observed. We concluded that the mitoxantrone and mitomycin C combination has limited toxicity but low activity and only brief disease palliation in advanced breast cancer.

Adult↗
PubMed1979

The mechanism of the riboflavin sensitized photodestruction of mitomycin C.

A detailed in vitro study was made of the riboflavin sensitized photodestruction of mitomycin C. The dependences of the quantum yield in the system were examined on the introduction of various amounts of quenchers, such as halogen ion, paramagnetic ion, 1,4-diazabicyclo[2,2,2]octane, 2,6-di-tert-butyl-p-cresol, and p-hydroquinone. The results are consistent with a mechanism involving oxygen molecule in the excited singlet state as the photochemically reactive species. The rate constant of the reaction between the excited singlet oxygen and mitomycin C was calculated to be 8.9 x 10(9) M-1.S-1.

Cations, Divalent↗
PubMedDate not supplied

Sensitivity of rat testes to inhibitors of nucleic acid synthesis. III. The inheritance of mitomycin C-induced structural rearrangements of chromosomes.

The inheritance of mitomycin C-induced aberrations was studied. Examination of spermatogonia showed statistically significant differences between the progeny of the untreated and treated rats in terms of total aberrant cells and chromosomal structural rearrangements. With the exception of gaps, breaks and fragments, which showed no significant differences between the progeny of the two treatment groups, the rest of the aberrations scored revealed significant increases in their frequencies with an increase in daily doses of mitomycin C (MC). The profile of the aberrations demonstrated a high incidence of X and Y chromosome dissociations, multiple autosomal associations, hypodiploidy, and translocation. Translocations consisted of autosome-autoome, autosome-X chromosome, autosome-X-Y chromosome, and autosome-Y chromosome. It is suggested that the reduced number of offspring per female in the F1 was the consequence of inherited MC-induced chromosomal errors.

Animals↗
PubMed1990

Mitomycin is active against refractory germ-cell tumors. A phase II study.

Mitomycin was used as single-agent therapy in seven male patients with nonseminomatous germ-cell tumors resistant to platinum analogues. The toxicity was high, especially hematological and pulmonary, in this heavily pretreated group. Mitomycin was active in this situation and one complete and one partial response of 18 and 20 weeks' duration, respectively, were seen.

Adult↗
PubMed1992

Phase II study of combination therapy with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small-cell lung cancer.

Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.

Adult↗
PubMed1995

A randomized study of bolus fluorouracil plus folinic acid versus 21-day fluorouracil infusion alone or in association with cyclophosphamide and mitomycin C in advanced colorectal carcinoma.

From May 1988 to June 1992, 129 eligible patients suffering from measurable advanced colorectal cancer were enrolled in a randomized study comparing bolus fluorouracil plus leucovorin (FU-FA); continuous fluorouracil infusion (FU-cont); FUcont plus cyclophosphamide and mitomycin C (FUMIC). FU-FA consisted of weekly fluorouracil (FUra) bolus (600 mg/m2) 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of leucovorin, for 6 weeks every 8 weeks. FUcont patients were planned to receive 400 mg/m2/day FUra infusion, for 21 days every 28 days. In FUMIC patients, FUcont was associated with weekly cyclophosphamide bolus (300 mg/m2) and monthly mitomycin C bolus (10 mg/m2). Quality of life was evaluated using six linear analogue scales, completed by the patient. Accrual in the FUMIC arm was stopped after the 25th patient because of toxicity. The response rates were 22 of 48 (45.8%) with FUcont and 13 of 52 (25%) with FU-FA (P = .048). Progression-free survival (median: 8 v 4.4 months; P = .0026) and overall survival (median: 12.9 v 9.6 months; P = .028) were significantly greater for the FUcont arm compared with the FU-FA arm. Toxicity was observed in 62% of the FUcont patients (grade 3-4: 10%), mainly hand-foot syndrome, diarrhea, mucositis, and mainly gastrointestinal in 69% of the FU-FA patients (grade 3-4: 11.6%). Linear analogue scales exploring quality of life, available for the first 6 months, gave similar scores in FU-FA and FUcont patients. We conclude that this FUcont schedule, achieving high FUra dose-intensity, offers significant advantages, in terms of response and survival, over weekly FUra plus leucovorin.

Adenocarcinoma↗
PubMed2000

Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial.

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.

Adult↗
PubMed2001

Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study.

The prognosis of malignant pleural mesothelioma is poor, with a median survival time from diagnosis of 7 to 17 months. At present there is no standardized treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with malignant pleural mesothelioma were enrolled in our study. The characteristics of patients were: 16 men and 6 women; median age 61 years (range, 49-77 years); stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and 2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases. The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7, 9, 14, and 19 months of duration) were achieved; the overall response rate (ORR) was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment (31.8%). According to the pathologic type, ORR for the only epithelial type was 39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1-22). The overall median survival time was 13.5 months (range, 1-50); the median survival time of responders significantly differed from that of nonresponders (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19 patients (78.9%) with pleural effusion at the time of diagnosis showed an important reduction in pleural fluid during chemotherapy. Hematologic toxicity was the main side effect; World Health Organization grade III to IV of neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and 22.7% of patients, respectively. From the data presented here, this regimen can be considered active in the treatment of malignant pleural mesothelioma.

Aged↗