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At least 991 records · Page 55Linked to original sources
PubMed1998

Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology.

PURPOSE: Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles (M-CH) in preventing intraabdominal recurrence following curative surgery for gastric cancer. The Austrian Working Group for Stomach Cancer, a subgroup of the Austrian Working Group for Surgical Oncology, initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen. PATIENTS AND METHODS: A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were randomly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound (n = 46) or served as a surgical control group (n = 45). Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment. RESULTS: After a median observation period of 597 days (range, 72 to 1,096), a significantly higher postoperative complication rate was observed in the M-CH group (35%) compared with the control group (16%) (P < .02). In accordance with this finding, the postoperative (60 days) mortality rate was also significantly elevated in the M-CH group (11% v 2% in the control group). Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy, the protocol committee decided to stop further recruitment of patients onto this study. CONCLUSION: Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications. However, no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial.

Adenocarcinoma↗
PubMed2001

Induction chemotherapy with mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin followed by radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS: Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (> 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS: From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis-free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis-free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION: The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.

Adolescent↗
PubMed1995

Properties of water-insoluble mitomycin C-albumin conjugate as a sustained release drug delivery system in mice inoculated with Sarcoma 180.

In order to improve the deposition of mitomycin C (MMC) in the administered site, water-insoluble mitomycin C-albumin conjugate (MMC-G-BSA) was prepared. MMC was covalently attached to the glutarylated bovine serum albumin (G-BSA) in the presence of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide hydrochloride (EDC) to give MMC-G-BSA. The MMC content of the conjugate (16.3% (w/w)) was higher than that of water-soluble mitomycin C-albumin conjugates. MMC was liberated from MMC-G-BSA suspended in a phosphate buffer (pH 7.4, 37 degrees C) with a half-life of 155.3 h. In the same buffer system containing alpha-chymotrypsin, MMC-G-BSA was dissolved perfectly within 24 h due to enzymatic degradation, and the liberation of MMC from the conjugate was significantly accelerated (t1/2 = 24.5 h). After intraperitoneal injection in mice, most of the MMC-G-BSA was retained in the abdominal cavity. Furthermore, the survival time of mice inoculated with Sarcoma 180 was significantly increased by the intraperitoneal injection of MMC-G-BSA. These findings suggest that MMC-G-BSA is a biodegradable macromolecular hybrid which acts as a sustained release delivery system of MMC.

Albumins↗
PubMed2001

Stability of cisplatin, doxorubicin, and mitomycin combined with loversol for chemoembolization.

OBJECTIVE: To evaluate the chemical stability of a mixture of cisplatin 10 mg/mL, doxorubicin 5 mg/mL, and mitomycin 1 mg/mL in sodium chloride 0.9% (NS), and sodium chloride 0.9% and ioversol 68% (NSI). METHODS: The agents were reconstituted with NS and NSI in two groups. One syringe was made and stored protected from light at 4, 25, and 37 degrees C. Triplicate HPLC determinations were performed on each syringe at each time period. Drug concentration at T0, 4, 12, 24, 72, and 120 hours were recorded. RESULTS: Cisplatin in NS remained stable for five days at all three temperatures and lost 12.7% at 37 degrees C in 120 hours in NSI. Doxorubicin in NS remained stable throughout the five days at 4 and 25 degrees C, but lost 13.1% at 37 degrees C in 24 hours. Doxorubicin in NSI remained stable for five days at 4 degrees C and lost 16.3% at 25 degrees C by day 5, and 18.8% at 37 degrees C in 24 hours. Mitomycin in NS lost 15.8% at 4 degrees C within 24 hours, and 24.7% at 25 degrees C and 36% at 37 degrees C within four hours. Mitomycin in NSI was stable for 72 hours at 4 degrees C, 24 hours at 25 degrees C, and less than four hours at 37 degrees C. CONCLUSIONS: These agents in NS are stable for 12 hours at 4 degrees C. In NSI, they are stable for 72 hours at 4 degrees C.

Analysis of Variance↗
PubMed1985

Trial of vindesine plus mitomycin in stage-3 non-small cell lung cancer. An active regimen for outpatient treatment.

Ninety patients with stage-3 non-small cell lung cancer were given vindesine (3 mg/sq m) plus mitomycin (10 mg/sq m). Data on response are available for 84 adequately treated individuals (93 percent). For patients who had received no prior chemotherapy, the rate of major objective response was 36 percent (20/55). For previously treated patients the rate of major response was 17 percent (5/29). The drugs were routinely administered in the outpatient department without difficulty. Moderate or severe myelosuppression, neurotoxic, nephrotoxic, or pulmonary toxic effects, nausea, and vomiting occurred in less than 15 percent of all studied patients. Three-drug extravasation ulcerations occurred in 1,129 administrations of chemotherapy (0.3 percent). There were two treatment-related deaths, one from sepsis and one from the combination of mitomycin-induced pulmonary and renal toxic effects. The combination of vindesine plus mitomycin is an active, well-tolerated outpatient regimen for patients with non-small cell lung cancer who have not previously received chemotherapy. Further trials are warranted to compare this regimen to other active combinations and to use it as a component of a program of treatment using alternating regimens of chemotherapy.

Adenocarcinoma↗
PubMedDate not supplied

[Use of mitomycin C for corneal-conjunctival intraepithelial neoplasia: management options--case reports].

Three cases of corneal-conjunctival intraepithelial neoplasia treated differently with mitomycin C based on clinical presentation are reported. The selected patients were followed at the Department of Ophthalmology of the Casa de Saúde Santo Inácio. According to the clinical appearance of the lesions, 0.04% mitomycin C was employed in three different ways: 1) postoperative chemoablation; 2) preoperative chemoreduction; and 3) isolated chemoablation. Regression of the neoplastic lesion was observed in all cases with no recurrence detected during a follow-up time ranging from 18 to 29 months. Conjunctival hyperemia was the single side effect. The use of mitomycin C seems to be efficient and safe for the treatment of corneal-conjunctival intraepithelial neoplasia under several approaches.

Administration, Topical↗
PubMed1999

Distant and delayed mitomycin C extravasation.

Mitomycin C is a vesicant chemotherapeutic agent used to treat solid tumors. Its ability to cause delayed and remote tissue injury after intravenous administration is reported in the literature. Two cases of delayed and distant mitomycin C extravasation injury occurred in our institution. In both patients, no evidence of acute extravasation was visible during or immediately after administration. Within 48 hours, one patient reported erythema, burning, and pain in the hand contralateral to the administration site. The second patient developed three distinct ulcerated lesions on her forearm within 6 weeks of receiving the agent. The lesions, located at sites of venipunctures, occurred 12-15 cm proximal to the site of mitomycin infusion. Because the drug has the potential to cause such unusual and unanticipated tissue injuries, health care professionals and patients should be aware of this hazard.

Adult↗
PubMed1980

Mechanism of the development of resistance to mitomycin C in Hirosaki sarcoma.

In the peritoneal cavity of the rat, Hirosaki sarcoma, as ascites tumor of the rat, acquired a resistance to the essentially effective dose of 100 microgram/kg of mitomycin C by means of the daily treatment with the ineffective dose of 10 or 1 microgram/kg of mitomycin C. It is considered that most of Hirosaki sarcoma cells may have gradually acquired a hereditary resistance to mitomycin C in the course of the contact with the drug.

Animals↗
PubMed2000

A phase II study of mitomycin C, etoposide, and cisplatin in advanced non-small cell lung cancer.

Standard chemotherapeutic regimens, such as cisplatin and etoposide, may improve quality of life and prolong survival in patients with incurable non-small cell lung cancer (NSCLC). This trial was designed to evaluate the activity and toxicity of a regimen combining three of the most active agents against advanced-stage NSCLC: mitomycin C, etoposide, and cisplatin (MEP). Sixty-eight patients with stage IIIB (pleural effusion) or IV NSCLC received cisplatin 80 mg/m2 i.v. on day 1 and etoposide 80 mg/m2 i.v. on days 1, 2, and 3 every 3 weeks along with mitomycin C 10 mg/m2 i.v. on day 1 of the first and third cycles for a median of four cycles (range, 1-11). Median age was 59 years, and nine patients were enrolled after relapse from previously treated early-stage NSCLC. Eighty-eight percent of patients had stage IV disease, and 14 (21%) had brain metastases at diagnosis. Palliative radiotherapy was given to 10 patients (15%) before MEP and to 17 (25%) concurrent with MEP. The major toxicity of MEP was myelosuppression, with grade 3-4 neutropenia in 74% of patients. Sixteen patients (24%) had documented infections, and there were eight (12%) treatment-related deaths. Partial response was observed in 24 patients (35%) with a median duration of 4.4 months, (range 1.4-13 months). Median survival was 8.1 months (range, 1-34 months), and 1-year survival was 32%. The addition of mitomycin C to cisplatin and etoposide resulted in response and survival rates comparable with those achieved with standard regimens in patients with advanced NSCLC but was associated with substantial hematologic toxicity and unacceptable treatment-related mortality.

Adult↗
PubMed1992

Kidney cortical necrosis induced by mitomycin-C: a morphologic experimental study.

Experimental studies on mitomycin-C nephrotoxicity are scanty and mention the occurrence of cortical hemorrhage, tubular necrosis, or hydronephrosis secondary to papillomatous hyperplasia of the uroepithelium. To our knowledge, only one experimental study has mentioned morphological lesions similar to the hemolytic uremic syndrome in the human. In the present study 40 female Wistar rats were studied following unilateral renal perfusion of the left kidney with 2 mg/kg of mitomycin-C. Renal lesions corresponded to cortical necrosis with the presence of large bizarre nuclei. The presence of these nuclear atypias supports a direct toxic effect (alkylation) of the mitomycin or its metabolites on cells.

Animals↗
PubMed2002

Arterial chemotherapy of 5-fluorouracil and mitomycin C in the treatment of liver metastases of colorectal cancer.

AIM: Regional chemotherapy using hepatic artery catheters is a good method of treating patients with colorectal cancer liver metastases. We investigated the survival of patients with liver metastases from colorectal cancer using 5-fluorouracil (5-FU) and mitomycin C Cthrough implantable hepatic arterial infusion port. METHODS: Seventy-five patients with inoperable liver metastases from colorectal cancer were included between March, 1992 and November, 2001. We placed implantable hepatic arterial catheter (HAC) port by laparotomy. 5-FU, 1 000 mg/ m(2)/d continuous infusion for five days every four weeks, was delivered in the hepatic arterial catheter through the port. Mitomycin C, 30 mg/m(2)/d infusion in the first day every cycle through the port. Response to the treatment was evaluated by serial determinations of plasma CEA and imaging techniques consisting of computerized tomography and sonography of liver. RESULTS: Sixty-eight were performed hepatic artery chemotherapy and fifty-six were followed up among seventy-five HAC patients. Twenty-six patients(46.4 %) have responded and 4 complete remission were achieved. Eight patients (14.3 %) had stable liver metastases. Twenty-two patients (39.3 %) were progressed with increased tumor size and number. Twenty-nine patients(51.8%) had a decreased serum CEA level, while 10 patients (17.9 %) were stable and 17 patients (30.4 %) had an increased serum CEA level. There were no operative death in this series. Complications, which occurred in 18 patients (32.1 %), were as followed: hepatic artery thrombosis in 11, Upper gastric and intestinal bleeding in 3, liver abscess in 1, pocket infection in 1, cholangitis in 1, and hepatic artery pseudo-aneurysm in one patient. CONCLUSION: Combined infusion of 5-FU and mitomycin C by hepatic artery catheter port is an effective treatment for liver metastases from colorectal cancer. The high response and lower complication rates prove the adjuvant treatment of colorectal cancer with this treatment.

Adult↗
PubMed2004

Phase III study of mitomycin-C with protracted venous infusion or circadian-timed infusion of 5-fluorouracil in advanced colorectal carcinoma.

The combination of protracted venous infusion (PVI) fluorouracil (5-FU) and mitomycin-C has previously been shown to be superior to PVI 5-FU alone in terms of response rate and failure-free survival. This study explores the effect of dose intensification by circadian timing of 5-FU in this combination on response, toxicity, and survival. Patients with advanced colorectal carcinoma were randomized to receive PVI 5-FU 300 mg/m2 daily or circadian-timed infusion (CTI) of 5-FU, beginning at 600 mg/m2 and subsequently reduced to 450 mg/m2, delivered as a flat-rate infusion from 10:15 PM to 9:45 AM. Both groups received mitomycin-C at a dose of 7 mg/m2 given every 6 weeks. From April 1996 to August 1998, 320 patients were randomized, including 263 with metastatic disease and 21 with circumferential margin involvement. The overall response rate for the PVI 5-FU group was 38%, compared with 30.3% for the CTI group (P = 0.176). There was no statistically significant difference in terms of failure-free survival (8.0 months vs. 9.9 months; P = 0.131) or overall survival (15.8 months vs. 16.3 months; P = 0.275) between the treatment groups. There were no differences in global quality of life. Grade 3/4 diarrhea occurred significantly more frequently with CTI 5-FU (6.5% vs. 19.8%; P < 0.001); a nonsignificant trend toward increased incidences of grade 3/4 infection and palmar plantar erythema were observed with CTI 5-FU. This study confirms the high response rate and overall survival figures for the combination of PVI 5-FU and mitomycin-C in colorectal cancer. However, dose intensification of 5-FU using a circadian-timed, flat-rate infusion did not lead to improved response or survival.

Adenocarcinoma↗
PubMed2002

A phase II study of vinorelbine, mitomycin C and cisplatin chemotherapy for advanced non-small cell lung cancer.

BACKGROUND: This prospective phase II trial was performed to determine the efficacy and toxicity of mitomycin C, vinorelbine and cisplatin combination chemotherapy for patients with previously untreated stage IIIB or IV non-small cell lung cancer (NSCLC). METHODS: Between January 1999 and April 2001, 30 patients with chemotherapy-naive stage IIIB or IV NSCLC were entered into this study. Mitomycin C at a dose of 7 mg/m2, vinorelbine at a dose of 25 mg/m2 and cisplatin at a dose of 75 mg/m2 on day 1 and vinorelbine at a dose of 25 mg/m2 on day 8 were administered. This regimen was repeated every 4 weeks. RESULTS: 29 patients out of 30 patients were assessable. Among the assessable patients, 15 (51.7%) patients had a partial response. The median duration of response and survival was 22 weeks and 39 weeks, respectively. Grade 3 or 4 leukopenia and thrombocytopenia were observed in 28.3% and 4.7% of all the cycles, respectively. Nausea and vomiting of grade 3 occurred only in 2.4% of all the cycles. CONCLUSION: The regimen of mitomycin C, vinorelbine and cisplatin for non-small cell lung cancer is active against advanced NSCLC with tolerable toxicities.

Adult↗
PubMedDate not supplied

Scraping and mitomycin C to treat haze and regression after photorefractive keratectomy for myopia.

PURPOSE: To evaluate the efficacy, safety, and predictability of therapeutic scraping and application of a diluted 0.02% mitomycin C solution to treat haze and regression after photorefractive keratectomy (PRK) for myopia. METHODS: We performed a non-comparative, non-randomized retrospective study of 35 eyes of 30 patients who had previously undergone PRK for myopia and developed haze and regression after treatment. The range of refractive error after regression was -0.75 to -5.50 D (mean -2.92 D). Haze, ranging from grade 3 to 4 (scale: 0 to 4) caused a best spectacle-corrected visual acuity loss of 1 to 6 Snellen lines. All eyes were treated 6 to 12 months after PRK by scraping the stromal surface and application of a 0.02% mitomycin C solution for 2 minutes using a soaked merocel sponge. No laser ablation was performed. Corneal transparency, refractive error, and visual outcomes were evaluated over a 12-month follow-up period. RESULTS: All eyes had significant improvement in corneal transparency. Thirty-one eyes had haze grades lower than 1, which were maintained over time. Only four eyes showed haze grades 1 to 2 and two of them needed further treatment using the same technique. At 12 months after treatment, all eyes were within +/-1.50 of original intended correction (mean 0.04 +/- 0.63 D). BSCVA improved in all eyes. No toxic effects were observed during re-epithelialization or during follow-up. CONCLUSION: Single application of diluted mitomycin C 0.02% solution following scraping of the corneal surface was effective and safe in treating haze and regression after PRK.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

High-risk human papillomavirus, tumor suppressor protein p53 and mitomycin-C in invasive squamous cell carcinoma cervix.

BACKGROUND: Clinical data relating to human papillomavirus (HPV) infection and p53 status in cervical cancer has been sparse and confusing. AIM: To evaluate high-risk HPV and expression of tumor suppressor protein p53 in squamous cell carcinoma of cervix and to assess response to mitomycin-C in neo-adjuvant chemotherapy. SETTING AND DESIGN: Teaching College Hospital; Gynecologic Oncology Unit and Department of Pathology. Prospective, randomized. MATERIALS AND METHODS: Expression of p53 protein was assessed, using immunohistochemistry with mouse monoclonal antibody in 30 consecutive patients undergoing radical hysterectomy or admitted for neo-adjuvant chemotherapy. Human papillomavirus DNA (HPV DNA) was assessed using hybrid capture II technology. Patients eligible for chemotherapy were randomized into vincristine, bleomycin and cisplatin (VBP) group and VBP with mitomycin C group. STATISTICAL ANALYSIS: Chi-square test, one-way ANOVA, Pearson's correlation; Mann-Whitney, McNemar and Fischer's exact tests were used for statistical analysis. RESULTS: All patients with cancer cervix were positive for high-risk HPV DNA having relative light units/cut off values ranging from 3.4-2389.21 (P value = 0.006). High viral load of high risk HPV DNA was seen in advanced stages (P = 0.05) and an association of viral load with tumor volume was also seen (r = 0.361, P = 0.05). Analysis of p53 protein in cervical carcinoma patient showed expression in 50% of cancer specimens (P value < 0.001). McNemar's and Fischer's exact test showed no change in p53 status post-chemotherapy; however 66% of stage II B patients in VBP-M group became operable. CONCLUSION: High-risk HPV was universally present in all cases of cancer cervix and viral load was associated with stage and tumor volume while p53 protein was expressed in 50% of cases suggesting deregulation. More studies using mitomycin-C in cervical cancer treatment protocols are needed.

Adolescent↗
PubMed1981

Induction of single strand scission in bacteriophage phi X174 replicative form I DNA by mitomycin C.

The action of mitomycin C on double-stranded replicative form I DNA (RF I DNA; supercoiled, covalently closed, circular duplex DNA) of bacteriophage phi X174 was investigated using the technique of agarose gel electrophoresis. Mitomycin C reduced with sodium hydrosulfite (sodium dithionite, Na2S2O4) caused single strand scission in phi X174 RF I DNA in the presence of Cu2+. Cu2+ was essential for this DNA cleave action, and other transition metal ions such as Fe2+, Fe3+, Mn2+, Co2+ and Zn2+ were of no effect. This DNA strand scission was inhibited by catalase (EC 1.11.1.6) and various radical scavengers. This DNA strand scission was caused by free oxygen radicals generated during autoxidation of reduced mitomycin C in the presence of Cu2+.

Bacteriophage phi X 174↗
PubMed1991

The derivation of a novel mitomycin skeleton: 3 alpha-alkoxymitomycin.

The first example of C-3 alkoxylation in mitomycins has been achieved. 3 alpha-iso-Propoxy-10-O-decarbamoylmitomycin D (4) and 3 alpha-iso-propoxymitomycin D (5) were derived from mitomycin D (3) under decarbamoylation conditions with iso-propoxide. Under similar conditions 3 alpha-iso-propoxy-10-O-decarbamoylporfiromycin (8) and 3 alpha-methoxy-10-O-decarbamoylmitomycin B (11) were also derived from porfiromycin (6) and mitomycin B (9), respectively. The mechanism of generation of these novel analogs was based on the premise that the key intermediate of hydroquinone iminium salt (14) was led through the iminium salt (13), followed by alkoxide addition and oxidation.

Mass Spectrometry↗
PubMed1999

[Respiratory complications of the vinorelbine-mitomycin combination].

The respiratory toxicity of vinca alkaloids only appears when they are associated with mitomycin. Few reports have been noted with vinorelbine, the last molecule of this class. We report 4 cases of acute dyspnea induced by the association mitomycin-vinorelbin, The 4 patients were treated for lung cancer. At the end of the injection of vinorelbin appeared an acute bronchospasm. In 3 cases, the symptoms disappeared with broncho-dilatators and corticoids. The fourth patient needed an additional respiratory support. After the acute syndrome, a chronic respiratory insufficiency developed in three patients. Two patients required continuous oxygenotherapy. The pulmonary toxicity of the mitomyin-vinca alkaloids association is characterized by an acute dyspnea. The dyspnea appears within 2 hours after the end of the administration of vinorelbine. The frequent existence of airflow obstruction in patients with lung cancer exposes to high risk of severes incidents. These treatments must be stopped at onset of the first pulmonary symptom. The association of mitomycin with vinorelbine (as for all vinca alkaloids) in chemotherapy protocols for treatment of non-small-cell lung cancer should not be indicated because there is an increase of the toxicity without increase of efficiency.

Aged↗