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[Three cases of recurrent gastric cancer responding to TS-1 therapy following combination therapy with 5-fluorouracil, mitomycin C and cisplatin].

We report three patients with recurrent gastric cancer responding to TS-1 therapy after combination chemotherapy with 5-fluorouracil, mitomycin C and cisplatin. All 3 cases had undergone total gastrectomy with lymphadenectomy for advanced gastric cancer. Postoperative follow-up computed tomography (CT) showed liver metastases (cases 1 and 3), peritoneal dissemination (case 2) and enlargement of paraaortic lymph nodes (case 1) due to cancer recurrence. After 2 to 4 courses of combined treatment with 5-fluorouracil (500-750 mg/body/day, days 1-5, civ), mitomycin C (6-8 mg/body, day 6) and cisplatin (60-80 mg/body, day 7), CT revealed considerable reduction of the metastatic tumors. Subsequently oral administration of TS-1 (80-100 mg/body/day) for 4 weeks was performed. All 3 patients are well without any signs of increase in tumor size.

Administration, Oral↗

Cumulative effect of risk factors on short-term surgical success of mitomycin augmented trabeculectomy.

CONTEXT: Risk factors for failure of trabeculectomy may have a cumulative effect on the outcome. AIMS: To study the effect of preoperative ocular risk factors on the surgical outcome of trabeculectomy augmented with 2 commonly used doses of Mitomycin C. SETTINGS AND DESIGN: In a prospective cohort study, cases were recruited over an 18 month period. 92 eyes of 83 patients with one to three known risk factors for failure of trabeculectomy underwent Mitomycin-C (MMC) augmented trabeculectomy. METHODS AND MATERIAL: Trabeculectomy was done with a randomly chosen MMC dose of 0.2 mg/ml or 0.4 mg/ml. All cases were followed up for a period of at least 3 months. Surgical success was defined as the lowering of intraocular pressure (IOP) below 21 mmHg during the follow up period. STATISTICAL ANALYSIS USED: Chi square test, paired t test, odds ratio, effect size. RESULTS: Eyes with two or three risk factors (out of aphakic glaucoma, failed trabeculectomy, neovascular glaucoma, post uveitic glaucoma, traumatic glaucoma, adherent leucoma, juvenile glaucoma, prolonged medical therapy, steroid induced glaucoma, post penetrating keratoplasty glaucoma and developmental glaucoma) had a significantly poorer surgical success rate (88% and 78%) than eyes with one risk factor (100%). 0.4 mg/ml MMC used sub-sclerally had a statistically similar effect on lowering the IOP as 0.2 mg/ml in all groups. The rate of complications was significantly higher in the 0.4 mg/ml subgroup. CONCLUSIONS: The presence of more than one preoperative ocular risk factor, affects the surgical success of MMC augmented trabeculectomy in high-risk cases. Because of the significantly higher rate of complications with the higher dose of MMC, this should be used sparingly, only in cases with more than two risk factors.

Adult↗

[Topical treatment with mitomycin C in considerably raised conjunctival intraepithelial neoplasia].

CASE REPORT: We present a case of recurrent conjunctival intraepithelial neoplasia, treated previously on two occasions with excisional biopsy. Although the lesion was considerably raised, topical treatment with mitomycin-C 0.04% was applied, achieving the complete regression of the tumor. DISCUSSION: Topical mitomycin-C acts at the ocular surface. However, successive treatment cycles can achieve complete regression, even in considerably thick tumors.

Administration, Topical↗

[Neoadjuvant intraarterial chemotherapy with nedaplatin, peplomycin and mitomycin C for advanced cervical cancer].

The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case of advanced cervical cancer. Twenty-five cases of advanced cervical cancer (15 cases of stage II with high risks, 10 of stage III, referred to as the 254-S group) treated by NAC using nedaplatin, mitomycin C and peplomycin were compared with 30 cases (22 cases of stage II with high risks, 8 of stage III, referred to as the CDDP group) treated using cisplatin and mitomycin C which is the conventional regimen, in terms of measurable response, pathological response, rate of lymph node metastasis, cumulative survival rate, side effects and relapse style. According to the evaluation by measurable responses, the response rate was 90% (CR 52%) in the 254-S group and 75% (CR 15%) in the CDDP group. For pathological response of the specimen, the CR rate was 16% in the 254-S group and 23% in the CDDP group. The rate of lymph node metastasis extracted surgically was 33% and 41%, respectively. The cumulative survival rate in the 254-S group was about 10% better than in the CDDP group, but no significant difference was found. Leucopenia of both groups was of the same grade. In the 254-S group, although thrombocytopenia was more critical than in the CDDP group, there was a slight tendency to kidney toxicity. The locoregional recurrence rate was 12% in the 254-S group and 30% in the CDDP group. The distant metastasis rate was 16% and 27%, respectively. Although neoadjuvant intraarterial chemotherapy using nedaplatin as a key drug was useful to improve the prognosis of advanced cervical cancer, measures against recurrence outside the pelvis and individualization of medical treatment were considered to lead to a further improvement of the prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

Mitomycin C radical cation studied by pulse radiolysis.

The formation of the radical cation of mitomycin C (MMC.+) was investigated in aqueous solution by a pulse radiolysis method using SO4.- species as one electron oxidizing agent. The spectroscopic and kinetic characteristics of MMC.+ transients were determined, namely: absorption maxima at 295, 400 and 500 nm, the corresponding molar extinction coefficients are [symbol: see text] 295 = 5.63 x 10(3) dm3 mol-1 cm-1, [symbol: see text] 400 = 2.9 x 10(3) dm3 mol-1 cm-1, [symbol: see text] 500 = 2.32 x 10(3) dm3 mol-1 cm-1; the rate constant for formation of MMC.+ is k = (1.2 +/- 0.2) x 10(10) dm3 mol-1 s-1 and for decay 2k = (4.6 +/- 0.4) x 10(8) dm-3 mol-1 s-1. Based on this fact it can be assumed that not only the well-known mitomycin C radical anion (semiquinone, MMC.-) is efficiently involved in the radiotherapy process, but in a given oxidation environment the MMC.+ species could also play a role in this respect.

Cations↗

[Outcome of surgery for recurrent pterygium using intraoperative application of mitomycin C and amniotic membrane transplantation].

PURPOSE: Preserved human amniotic membrane has been used in reconstruction of the ocular surface. In this paper, we report our method of amniotic membrane transplantation (AMT) for recurrent pterygium. METHODS: Twenty-six eyes of 26 patients with recurrent pterygium are reported. All subjects were operated on with an extensive excision of the subconjunctival fibrous tissues followed by application of mitomycin C (0.04%, 3-5 min) during the operation. Amniotic membrane transplantation was performed with implantation of conjunctival autograft in cases with a large excision. RESULTS: The mean follow up time was 17.3 +/- 9.3 (mean +/- standard deviation) months. Twelve eyes showed severe symblepharon and 14 patients suffered from double vision before the operation. There were only three mild recurrences (12%), 11 patients recovered from double vision, and no major complications such as sclermalasia were noted during the follow-up period. CONCLUSION: AMT with application of mitomycin C is effective in preventing pterygium recurrence and for improved ocular movement. The cosmetic outcome of our methods has also been satisfactory.

Adult↗

[Results of a randomized, double blind prospective study of intravesical chemoprophylaxis with 2 drugs: adriamycin and mitomycin; and 2 ways of initiating the instillations: early and late. Effect on recurrence and progression].

The results of a double blind prospective study comparing the chemoprophylactic effects of adriamycin and mitomycin C and two modes of instillation (early: 6 hours following transurethral resection; late: 7-14 days later) for superficial carcinoma of the bladder are presented herein. Since the minimum follow up is over 5 years, the effects on tumor progression and mortality achieved by each of the 4 arms of the protocol were also evaluated. Concerning tumor recurrence, early instillation of mitomycin and overall early instillation therapy achieved significantly better results (p < 0.01). No differences, however, were observed relative to tumor progression or mortality.

Administration, Intravesical↗

[A case of hepatocellular carcinoma responding to intraarterial infusion of epirubicin and mitomycin C].

A 64-year-old male was admitted for treatment of hepatocellular carcinoma. He was diagnosed as having many tumors in the area of S6 and the AFP level was elevated to 878 ng/ml. Initially, intraarterial infusion of Epirubicin only was not effective. After the first course of treatment, tumors increased in size and the AFP level was elevated. Next, intraarterial infusion of Epirubicin and Mitomycin C was performed. After the second course of treatment, the AFP level decreased from 5,006 ng/ml to 754 ng/ml and the tumors had almost completely disappeared on angiography. The tumors continued to decrease in size and thereafter the AFP level decreased to 10 ng/ml and was not elevated. The tumors almost completely disappeared in this case, and the coadministration of Epirubicin and Mitomycin C provided effective.

Antineoplastic Combined Chemotherapy Protocols↗

[Portal blood levels of mitomycin C after intraperitoneal administration].

Portal blood levels of mitomycin C (MMC) were measured after intraperitoneal administration of 10 or 20 mg of mitomycin C following pancreatoduodenectomy. The portal concentration of MMC increased rapidly to the maximum concentration of 826 +/- 364 ng/ml at 5 minutes after administration, when the dosage was 20 mg (four cases). The peripheral blood levels followed the portal levels and the maximum concentration was 397 +/- 123 ng/ml at 15 minutes. Then the MMC levels of both portal and peripheral blood decreased gradually, but concentration higher than 100 ng/ml was maintained for 90 minutes after administration. In four patients given 10 mg of MMC, the patterns of the blood levels were similar, but the concentration was lower than in the group given 20 mg. In both groups, the AUC values were higher in portal than in peripheral blood. MMC administered intraperitoneally was absorbed rapidly through portal circulation and a high MMC level of portal blood was obtained. Therefore, it would prevent the dissemination of cancer cells into the liver which may well occur during operation for pancreatic carcinoma.

Humans↗

TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer.

PURPOSE: Recent studies have found an association between certain TP53 mutations and resistance to anthracycline-based primary medical therapy in breast cancer. The purpose of this study was to investigate whether TP53 mutational status also might influence the response to a non-anthracycline-containing regimen in primary breast cancer. EXPERIMENTAL DESIGN: Thirty-five patients with locally advanced breast cancer were investigated for TP53 mutations before receiving combination chemotherapy with 5-fluorouracil (1000 mg/m(2) on days 1 and 2) and mitomycin (6 mg/m(2) on day 2), administered every 3 weeks for 2-10 cycles in the neoadjuvant setting. RESULTS: Mutations in the TP53 gene, in particular those affecting loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (i.e., increase in the diameter product of tumor lesion by >/=25%; P = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains, respectively). No statistically significant correlation between TP53 LOH and response to therapy was seen. CONCLUSION: This study revealed a significant association between lack of response to 5-fluorouracil and mitomycin and mutations affecting the L2/L3 domains of the p53 protein. Together with our previous finding that such mutations predict resistance to weekly doxorubicin, our data suggest that mutations affecting this particular domain of the p53 protein may cause resistance to several different cytotoxic compounds applied in breast cancer treatment.

Adult↗

[Effect of low-intensity microwave of on mitomycin C-induced genotoxicity in vitro].

OBJECTIVE: To study that low-intensity microwave whether or not enhances the genotoxic effects of mitomycin C(MMC) on human lymphocytes. METHODS: Single strand DNA breaks and chromosomal aberrations were measured by comet assay and cytokinesis-blocked micronucleus(CBMN) test in vitro when human lymphocytes were exposed to 2,450-MHz microwave (5.0 mW/cm2) alone and in combination with mitomycin C. RESULTS: In the comet assay, the average comet lengths of microwave group[(29.1 +/- 8.1) micron in male and (25.9 +/- 7.5) micron in female] were not significantly different from those of control groups [(26.3 +/- 6.6) and (24.1 +/- 4.3) micron respectively] (P > 0.05). The average comet lengths of MMC group(0.0125, 0.0250, 0.0500, 0.1000 microgram/ml) were significantly longer than those of control groups (P < 0.01) and were increased with the dose of MMC. The average comet lengths of microwave combined with MMC (MW + MMC) also were increased with the doses of MMC and were significantly longer than those of control groups (P < 0.01). When MMC was > or = 0.0250 microgram/ml, microwave and MMC synergistically increased the single strand DNA breaks. In the micronucleus test, the average micronucleus rates of microwave groups were not higher than those of control groups (P > 0.05). The average micronucleus rates of MMC groups and MW + MMC groups were significantly higher than those of control groups (P < 0.01) when MMC was > or = 0.0500 microgram/ml. The average micronucleus rates of MW + MMC groups seemed higher than those of corresponding MMC groups, however the difference was not significant (P > 0.05). CONCLUSION: Low-intensity(2,450-MHz) microwave did not induce DNA and chromosome damages on human lymphocytes, but enhanced the effects of DNA breaks induced by MMC.

Chromosome Aberrations↗

Pterygium excision using 193-nm excimer laser smoothing and topical mitomycin C.

A total of 31 eyes with primary pterygium and 24 eyes with recurrent pterygium underwent surgical treatment and were followed for at least 1 year. The surgery involved a conventional bare-sclera technique combined with excimer laser smoothing of the wound bed. Postoperatively, the eyes were medically treated with topical mitomycin C (0.02%) for 4 days and with steroids for several weeks. No recurrence was noted within the 1st year in the primary pterygium group, whereas recurrence was observed in 3/24 eyes that had been treated for recurrent pterygium, equivalent to a recurrence rate of 12.5% in this subgroup. Nine eyes (16.4%) had gained 2 lines or more in visual acuity by 1 year after surgery. Granuloma developed in 3 eyes, and dellen formation was detected in 1 eye after surgery. The combination of surgical management with local mitomycin therapy may be considered to be a safe and effective technique for the removal of pterygium. Although the visual results were good, the role of excimer laser smoothing in the treatment of this disorder needs further investigation.

Female↗

High dose mitomycin C for treatment of advanced gastric cancer.

Thirty five patients (26 males and 9 females) with advanced gastric cancer confirmed by pathology were treated by high-dose mitomycin C. According to the following dose and schedules: Mitomycin C 20 mg intravenously per week and a total of 60 mg. Three weeks later, all the patients received FT-207 600 mg daily and a total of 20-40 g. The ages ranged from 24 to 75 years, 11 had cancer of cardia, 6 had cancer of gastric body, and 18 had cancer of gastric antrum. Eleven patients could not have an operation. Seventeen patients were recurrence of post operation. Eighteen of 35 patients received CR (7/35) and PR (11/35), the response rate was 51.43% of the responders, the median duration of remission and survival were 7.3 (range, 2-16) and 12.2 (range, 3-30) months, respectively. Common doses were instilled. The main side effects were leukopenia (10/35) and thrombocytopenia (7/35). None of these patients had liver and kidney function damage.

Adult↗

[Activity of toremifene plus mitomycin, vindesin and cisplatin regimen in unresectable non-small cell lung cancer].

OBJECTIVE: To investigate the activity and clinical efficacy of toremifene plus mitomycin, vindesin and cisplatin regimen (MVP) in non-small cell lung cancer (NSCLC). METHODS: A549 cells were seeded into 96 wells at the concentration of 10 x 10(4)cells/well and exposed to different agents. Seventy-two hours later, the cytotoxicity of the agents were evaluated with the method of MTT. The clinical trial included 63 patients with chemtherapy-naive NSCLC and 30 patients who had received chemotherapy (Pre-treatment arm). The chemotherapy-naive patients were randomly divided into the toremifene-treatment arm and the control arm. Each patient was given MVP chemotherapy. Five days before the chemotherapy, those in the toremifene-treatment group and pre-treatment arm started toremifene 420 mg daily orally for 7 days. The response was evaluated after two cycles of chemotherapy and toxic side effects and the survival of the patients were followed up. RESULTS: Toremifene decreased the IC(50) of chemotherapeutic agents and increased their cytotoxicity. In the clinical trial, the response rate and median survival were 47% and 11 months in the toremifene-treatment arm and 32% and 9 months in the control arm, respectively. The difference between the two arms was not significant. The response rate and median survival were 17% and 7 months in the pre-treatment arm, respectively. The toxicity among the three groups was not significantly different. CONCLUSIONS: Toremifene can improve the cytotoxicity of cisplatin, mitomycin and vindesin. Toremifene plus MVP regimen is safe and effective in the treatment of NSCLC.

Aged↗

[Efficacy of hepatic arterial infusion therapy for advanced hepatocellular carcinoma using 5-fluorouracil, epirubicin and mitomycin-C].

BACKGROUND/AIM: Prognosis of advanced hepatocellular carcinoma (HCC) treated by conventional therapies has been considered to be poor. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using FEM (5-fluorouracil, epirubicin, mitomycin-C) regimen for advanced HCC. METHODS: Eighteen patients received repeated HAIT using an implanted drug delivery system. Of the 18 patients, 8 patients had HCC with portal vein tumor thrombosis, 9 patients had recurrent HCC after transarterial chemoembolization (TACE) and 1 patient after surgical resection. The patients received 5-fluorouracil (330 mg/m(2), every week), epirubicin (30 mg/m(2), every 4 weeks) and mitomycin-C (2.7 mg/m(2), every 2 weeks). RESULTS: Mean age was 51 years. The response rate (complete response+partial response) by tumor size on abdominal CT was 38.9%. Survival ranged from 2 to 24 months and the median survival time was 8 months. The cumulative survival rate of responders group was significantly higher than non-responders group (p=0.0385). The mean levels of serum alpha-FP and PIVKA-II in responders group decreased after HAIT (3,179 ng/mL and 2,850 ng/mL) than before (11,218 ng/mL and 4,396 ng/mL), but not significantly. Chemotherapy-related side effects were nausea, vomiting and alopecia. Three patients had catheter-related complications. One patient developed gastric ulcer. CONCLUSIONS: HAIT using FEM regimen is a useful therapeutic option for patients with advanced HCC with portal vein tumor thrombosis or ineffective response to other therapies.

Adult↗

Inoperable oropharyngeal carcinoma treated with concomitant irradiation, mitomycin C and bleomycin - long term results.

Patients with inoperable head and neck tumors were treated concomitantly with radiochemotherapy with mitomycin C and bleomycin in our prospective randomized clinical trial (1991- 1993). For the subgroup of patients with oropharyngeal carcinoma the results with radiochemotherapy were significantly superior to irradiation alone. Such scheme of treatment was then adopted as standard method. Here we present the long-term results and dose- response relationships in patients with inoperable oropharyngeal carcinoma treated by the same radiochemotherapy scheme till 1997. Ninety-five patients with stage III and IV inoperable oropharyngeal squamous cell carcinoma were treated with curative intent, concomitantly with supra-voltage irradiation 2 Gy/day 5 times weekly to 60-73 Gy, bleomycin 5 mg 2 times weekly and. one application of mitomycin C 15 mg/m(2) after 10 Gy. Logistic dose- response curve was calculated. Median follow-up was 85 months. The loco-regional control, disease- free survival and overall survival at 5 years were 55%, 51% and 32% (95% CI: 44-67%, 41-62%, 22-42%), respectively. The probability of new primary malignancy at 5 years was 23%. In multivariate analysis performance status, biological equivalent dose, dose of bleomycin, and stage were identified as independent prognostic factors for loco-regional control, disease-free, and overall survival. Th gamma-value of dose response curve was 2.86. The outcome of the disease was directly proportional to intensity of irradiation and chemotherapy. It appears that in our concomitant radiochemotherapy MiC increased radioresponsiveness of the tumor by its effect on hypoxic fraction.

Adult↗

[Simultaneous determination of 7-methylguanosine and mitomycin C by capillary electrophoresis with amperometric detection].

A method based on capillary electrophoresis with amperometric detection (CE-AD) has been developed for the simultaneous determination of 7-methylguanosine and mitomycin C. The detection electrode was a 0.3 mm carbon disc electrode at a working potential of 950 mV (versus Ag/AgCl electrode). A suitable electrolyte consists of 20 mmol/L phosphate buffer (pH 9.4), with the separation voltage of 18 kV, the injection time of 10 s, and the injection voltage of 18 kV. Under optimum conditions, the two analytes could be well separated within 10 min in a 60 cm length capillary. The current responses were linear over about two orders of magnitude (0.50 - 50 mg/L) with detection limits (S/N = 3) of 0. 050 and 0.025 mg/L for 7-methylguanosine and mitomycin C, respectively. The proposed method was successfully applied to determine the synthetic urine and serum samples. The recoveries were found in the range of 93.0% - 97.2%.

Alkylating Agents↗

[The multiple character of mutation of resistance to mitomycin C in Erwinia carotovora subsp. carotovora].

It has been shown that mutants of Erwinia carotovora subsp. carotovora (ECA) resistant to mitomycin C could be characterized by the change of colonies morphology, sensitivity to bacteriocins, and by the change of pathogeneity. It is supposed that mutations responsible for the stability to mitomycin C touch the synthesis of cell membranes components. In some cases MCr-mutations caused cardinal changes--the loss of prototrophy and synthesis of carotinoid pigment. The mutants obtained in this work can be used to study the pathogenic process in Erwinia carotovora. Some of MCr- mutants are the handy indicators of carotovoricins.

Bacteriocins↗