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PubMed1975

Autoradiographic study of chick limb cartilage in vivo and in vitro and its response to mitomycin C (MMC).

Effect of mitomycin C on mucopolysaccharide synthesis by the cartilage cells of chick limb bud (5-9 days old) was investigated both in vivo and in vitro by the uptake study of 35S. Control specimens (both in vivo and in vitro) showed higher concentration of silver grains, mostly intercellular, in the initial stages. Hypertrophy of cartilage cells at later stages reduced the matrix, leading to a corresponding decrease in the accumulation of silver grains. In the treated groups, both in vivo and in vitro, the silver grains were found to be less in number during the initial stage of growth than in the corresponding controls, due to the suppressive effect of the mitomycin C. However, during the later period of growth, uptake of 35S was more in the matrix of treated specimens, which was apparently not reduced due to lack of hypertrophy of cartilage cells. The mechanism of the suppressive effect of mitomycin C seems similar in vivo and in vitro.

Animals↗
PubMedDate not supplied

Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon.

From October 1990 to September 1991, 20 consecutive patients with histologically proven malignant pleural mesothelioma (MPM), secondary to environmental exposure to asbestos or erionite, were treated with cisplatin, mitomycin C and alpha interferon (cisplatin 50 mg/m2 i.v. on day 1 of a 21-day cycle; mitomycin C 10 mg/m2 i.v. day 1 of cycles 1,3 and 5; alpha-2b-interferon 10 x 10(6) units i.m., 4 h prior to cisplatin and 10 x 10(6) units i.v. immediately prior to cisplatin day 1 of each cycle). Eighty-two treatment cycles were administered to 19 evaluable patients. Two patients attained a partial response. Eleven patients had stable disease and 6 had disease progression. Toxicities included interferon-related fever and flu-like symptoms, and vomiting. Actuarial median survival was 15 months. Three patients are alive at 20+, 21+ and 27+ months. We conclude that while the addition of alpha interferon to cisplatin and mitomycin C did not result in an objective response higher than previously reported with the cytotoxic agents alone, the trend towards an improvement in median survival as compared to a well-matched historical group suggests some benefit from the inclusion of interferon.

Adult↗
PubMed1982

Investigation about the penetration depth in the normal bladder wall and tumor by local instillation of mitomycin into the urinary bladder.

The penetration depth of mitomycin into the normal urinary bladder wall and tumor was determined in 21 bladder tumor patients. Either 20 mg mitomycin/20 ml distilled water or 40 mg/40 ml distilled water was locally instilled into the bladder with a catheter after emptying it and was left for about 25-l20 min. The individual concentrations of mitomycin within the various bladder layers (epithelial, lamina propria, up to the middle of the musculature) were determined with a thin-layer cup method specially modified for these investigations. The results show a high scatter of resorption from 2 up to 442 micrograms of mitomycin/g dry weight. With this method, mitomycin could be determined in the bladder musculature.

Administration, Topical↗
PubMed1993

Percutaneous mitomycin C perfusion of bilateral ureteral carcinoma in situ.

We treated a 61-year-old patient with a diagnosis of bilateral ureteral carcinoma in situ with percutaneous perfusions of mitomycin C. After 16 sessions of mitomycin C therapy instilled through bilateral nephrostomy tubes, the urine cytology results became negative for malignancy. Bilateral ureteroscopy and cold-cup punch biopsies of the ureter revealed no evidence of disease. The patient did not experience side effects. He has remained free of disease during a 12-month follow-up period. Percutaneous perfusion of mitomycin C appears to be one of the effective and safe treatments for the carcinoma in situ of the upper urinary tract.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Adjuvant intravesical chemotherapy of superficial bladder cancer with monthly doxorubicin or intensive mitomycin. A comparison of two consecutive series.

120 patients with the first occurrence of TNM stage Ta or T1 bladder carcinoma were given adjuvant intravesical treatment in 2 consecutive series. The first 60 received doxorubicin monthly for 6 months, then on the 9th and 12th month following surgery. The second series was given mitomycin weekly for 2 months, then monthly to the end of the first year. Median follow-up is 48 months in the first series and 15 in the second. In the doxorubicin group, 28 patients had recurrences. The recurrence rate is 1.86/100 patient-months. Seventeen of these first relapses occurred within the first year. In the 'intensive' mitomycin series, where 36 patients were observed for 12 months or more, 3 relapsed. The recurrence rate to date is 0.35. The relapse-free survival probability at 12 months is 75% in the first series and 93% in the second. Treatment was stopped due to toxicity in 4 patients in the doxorubicin group and in 10 of the mitomycin group.

Administration, Intravesical↗
PubMed1992

4'-epidoxorubicin versus mitomycin C intravesical chemoprophylaxis of superficial bladder cancer.

The authors report the preliminary data concerning a phase III study comparing the chemoprophylactic effects of mitomycin C and epirubicin in Ta-T1 primary and recurrent superficial bladder tumors. 60 patients were treated, 32 with epirubicin and 28 with mitomycin C, with a medium follow-up of 17.7 and 16.2 months, respectively. There were no systemic side effects. The remission rate was 62.5% in the epirubicin group and 64.2% in the mitomycin C group. Both drugs were equally useful in the chemoprophylaxis of superficial bladder cancer.

Administration, Intravesical↗
PubMed1992

Topical chemoprophylaxis of superficial bladder cancer with mitomycin C and adjuvant hyaluronidase.

The effect of intravesical instillation of 200,000 IU hyaluronidase in addition to mitomycin C as chemoprophylaxis of superficial bladder cancer was evaluated. Based on our result of a previous study that this approach results in a significantly reduced recurrence rate (7.1 versus 32.1%), 43 patients undergoing transurethral resection of Ta-T1 tumors were retrospectively analyzed after a mean observation period of 48.5 months. During the 2 years of prophylactic therapy, tumor recurrence was seen in 6 patients (13.9%). Of the 37 patients who remained recurrence-free under treatment, 5 (13.5%) had recurrent tumors later during a mean observation period of 24.5 (18-42) months after treatment. These values are significantly lower than those obtained previously from a group of 63 patients treated with mitomycin alone, with recurrence rates of 33.3% during chemoprophylaxis and 26.2% thereafter (mean observation period 50.4 months). It appears that additive hyaluronidase enhances the local effect of mitomycin C in the intravesical chemoprophylaxis of bladder cancer, presumably by improving diffusion into the bladder mucosa and catalyzing the breakdown of a hyaluronic acid contained in a protective halo around malignant urothelial cells.

Administration, Intravesical↗
PubMed2006

Human serum reduces mitomycin-C cytotoxicity in human tenon's fibroblasts.

PURPOSE: To determine the effect of human serum factors on mitomycin-C (MMC) cytotoxicity in cultured human subconjunctival Tenon's capsule fibroblasts. METHODS: Fibroblast monolayers were treated with 5-minute applications of mitomycin-C (0.4 mg/mL) and incubated in culture medium with or without additional human serum. Fibroblast apoptosis was quantified by direct cell counts based on nuclear morphology, flow cytometry with annexin-V/propidium iodide, and a lactate dehydrogenase release assay. The number of viable fibroblasts and fibroblast proliferation were measured with a colorimetric MTT assay and by bromodeoxyuridine (BrdU) labeling. RESULTS: Mitomycin-C induced significant levels of fibroblast apoptosis. The addition of human serum resulted in a 40% reduction in MMC-induced fibroblast apoptosis (range, 31.3%-55.3%; P = 0.021) as determined by nuclear morphology and a 32.4% reduction measured by annexin-V/PI. There was a corresponding dose-dependent increase in the number of viable fibroblasts. Serum did not restore proliferation in MMC-treated fibroblasts. CONCLUSIONS: Factors present in human serum reduce MMC cytotoxicity in cultured human Tenon's fibroblasts. Human serum increased the number of viable fibroblasts by inhibiting MMC-induced fibroblast apoptosis. Serum factors access aqueous humor after trabeculectomy and may therefore influence the clinical outcome of MMC treatment.

Annexin A5↗
PubMedDate not supplied

Mitomycin C and vinblastine in anthracycline-resistant metastatic breast cancer: a phase II study.

The purpose of this phase II study was to evaluate the clinical efficacy of mitomycin C and vinblastine in patients with anthracycline-resistant metastatic breast cancer. This single-center, non-randomized trial enrolled 39 patients. Eligible patients must have received at least three chemotherapy regimens with epirubicin or CAF and had treatment failure while on chemotherapy or within 6 months of completing therapy. Treatment consisted of mitomycin C at a starting dose of 8 mg/m2 on day 1 and vinblastine (8 mg/m2, days 1 and 28). The regimen was repeated every 6 weeks with a 20% dose escalation of both drugs after the first cycle in the absence of grade III hematologic or other toxicity. On an intent-to-treat basis, 38 patients were eligible for assessment; 9 (23.7%, 95% confidence interval 1.92-2.45%) achieved a partial response and 13 (34.2%) had stable disease. The median time to disease progression was 6.21+/-4.26 months (range, 1-15; 95% confidence interval, 4.81-7.61), and the median survival was 10.76+/-7.6 (range, 1-29; 95% confidence interval 8.0-13.1%). Responsive patients had a significantly better survival than those with stable and progressive disease. Treatment was well tolerated. Anemia and neutropenia (grade I-III) developed in 28.9% and 26.3% of the patients, respectively. One patient with grade III granulocytopenia developed fever and infection that required hospitalization. Moderate neurotoxicity, myalgia, constipation, diarrhea and alopecia were observed. No toxic death occurred. Mitomycin C plus vinblastine is an effective and well-tolerated regimen for anthracycline resistant cancer.

Adult↗
PubMedDate not supplied

Capecitabine and mitomycin C may be an effective treatment option for third-line chemotherapy in advanced colorectal cancer.

AIMS AND BACKGROUND: We evaluated the activity in terms of time to progression (TTP) of mitomycin C and capecitabine in patients with advanced colorectal cancer who progressed after 2 lines of chemotherapy. METHODS: Patients with advanced colorectal cancer undergoing third-line chemotherapy after failure of 5-FU with CPT-11 or oxaliplatin-based chemotherapy regimens were treated with capecitabine and mitomycin C. RESULTS: Sixty-one patients were enrolled in this study. The median age was 55 years (range, 26-78 years) and the male:female ratio 21:40. We observed partial remissions in 5 patients (8%), stable disease in 25 patients (40%) and progression of disease in 31 patients (52%). Median TTP was 3 months and median survival was 6 months. Global toxicity was mild and entirely acceptable. Grade 3-4 hematological toxicity occurred in 12 patients and grade 3-4 nonhematological toxicity in 5 patients. CONCLUSIONS: The combination of capecitabine and mitomycin C could represent an effective and manageable treatment option for colorectal cancer patients failing previous chemotherapy regimens.

Adult↗
PubMed1980

Mitomycin C in metastatic breast cancer resistant to hormone therapy and conventional chemotherapy.

Mitomycin C was administered to 22 patients with metastatic breast cancer, refractory to hormonal therapy and conventional chemotherapy. Treatment was given by intravenous bolus injection at 20 mg/m2 of the drug and repeated at 6-week intervals. The overall response rate was 23%. Two complete remissions were seen in soft tissue lesions. Leukopenia occurred in 68% of the patients, thrombocytopenia in 36%, and anemia in 14%. One case of cardiotoxicity after previous treatment with adriamycin was observed. We conclude that mitomycin C is an active agent in disseminated breast cancer resistant to hormone therapy and chemotherapy. Combination of mitomycin C with other chemotherapeutic drugs will be tested.

Adult↗
PubMed1994

Mitomycin "C" and vinorelbine as second line chemotherapy for metastatic breast carcinoma.

AIMS AND BACKGROUND: Patients with metastatic breast carcinoma resistant to first line chemotherapy may require further treatment. Results o second line chemotherapy are still largely unsatisfactory. For this reason a phase II study on the combination of mitomycin C and vinorelbine was carried out. METHODS: Forty patients with anthracycline pretreated metastatic breast cancer were treated with a combination of mitomycin C 10 mg/m2 i.v. on day 1, and vinorelbine 25 mg/m2 i.v. on days 1 and 8. This cycle was repeated every 28 days. Responses were evaluated according to the WHO criteria. RESULTS: A major objective response was recorded in 16 cases (40%; 95% confidence limits 32%-48%), with 2 patients (5%) obtaining a complete response with a median duration of 8.0+ months, and 14 (35%) a partial response with a median duration of 7.3+ months. Nine patients (23%) showed no change, and 15 progressed. Patients who did not meet the minimal required criteria to be evaluable were considered as treatment failures. Responses were seen at all sites of disease, but skin, nodal, and soft tissue lesion were more chemosensitive than liver, lung, and bone ones. The mean survival of patients with complete and partial responses was 8.9+ months, whereas that of patients with no change or progressive disease was 7.8 and 6.0 months respectively. Treatment was very well tolerated by most patients. Gastrointestinal toxicity was mild. Grade 2 leukopenia was recorder in 45% of patients, and grade 3 leukopenia in only 10%. Grade 2 thrombocytopenia was seen in 5%. Reversible mild to moderate constipation occurred in 45%, but no case of severe neurotoxicity was observed. CONCLUSIONS: Our data suggest that the combination of mitomycin C and vinorelbine is active in metastatic breast carcinoma refractory to first line chemotherapy containing anthracyclines, and may be safely administered on an outpatient basis.

Adult↗
PubMedDate not supplied

Mitomycin-C and lonidamine as second-line therapy for colorectal cancer: a phase II study.

AIMS AND BACKGROUND: Recent preclinical data have suggested that lonidamine may potentiate the acitivity of mitomycin C in human colon cancer cell lines LoVo and HT29. STUDY DESIGN: A phase II study was carried out in 14 patients with advanced colorectal cancer pretreated with fluorouracil and folinic acid. Treatment consisted of lonidamine, 600 mg po, followed after 2 h by mitomycin, 20 mg/m2 by iv bolus, followed by lonidamine, 150 mg tio for 5 days; the cycle was repeated every 6 weeks. RESULTS: No objective response was seen. Three patients had stable disease; the median survival for the whole group was 4 months. Although hematologic toxicity was negligible, lonidamine-related side effects were moderate to severe in most patients and mainly represented by myalgia and gastric pain. DISCUSSION: Despite a sound preclinical rationale, this schedule of lonidamine and mitomycin C was ineffective and toxic in patients with advanced colorectal cancer. More experimental data about lonidamine are needed in order to design more effective regimens based on the combination of this interesting drug with other anticancer agents.

Adult↗
PubMedDate not supplied

A phase II study of mitomycin C, vindesine and cisplatin combined with alpha interferon in advanced non-small cell lung cancer.

AIMS AND BACKGROUND: MVP chemotherapy (mitomycin C, vindesine or vinblastine, cisplatin) is one of the most commonly used regimens for advanced non-small cell lung cancer (NSLCLC). Experimental data suggest a synergistic cytotoxic activity of alpha-interferon (alpha-IFN) when combined with cisplatin, mitomycin C and vinca alkaloids. In an effort to improve MVP chemotherapy activity, we have combined this regimen with alpha-IFN. PATIENTS AND METHODS: Thirty-five patients with advanced NSCLC (19 stage IV) were treated with the MVP regimen (mitomycin C, 8 mg/m2; vindesine, 3 mg/m2, cisplatin, 75 mg/m2, all on day 1) plus alpha-2a-IFN, 3x10(6) U from day 1 to 7. The cycles were repeated every 28 days. RESULTS: There were no complete responses and 18 partial responses, for an overall response rate of 51%. Median time to treatment failure was 6 months (range, 1-18), and the median survival was 9.5 months (range, 1-32). WHO grade 3 toxicity was recorded in up to 8% of patients, flu-like syndrome was a common complaint; one toxic death occurred. CONCLUSIONS: The combination yielded a level of response comparable to that of other cisplatin-based regimens. Larger randomized trials are needed to assess the role of alpha-IFN combined with chemotherapy in advanced NSCLC.

Adult↗
PubMedDate not supplied

Mitomycin C and vinorelbine in pretreated breast cancer.

AIMS AND BACKGROUND: Vinorelbine, a new semi-synthetic vinca alkaloid, has demonstrated high activity as a single agent in pretreated metastatic breast cancer. PATIENTS AND METHODS: To evaluate the activity of the combination vinorelbine-mitomycin C and to reduce the incidence of side effects, in particular myelotoxicity, patients with metastatic breast cancer pretreated with 1 or more chemotherapy regimens for metastatic disease were treated according to the following schedule: mitomycin C, 10 mg/m2 day 1, and vinorelbine, 25 mg/m2, days 1, 8 and 15, every 28 days. RESULTS: Twenty-seven patients were enrolled and were evaluable for activity and side effects. A total of 157 cycles were delivered (median 5 cycles per patient). There were 10 partial remissions (37%; 95% confidence interval 20-59%), 5 instances of stable disease and 12 of disease progression. Grade III-IV toxicity was mostly hematological and included thrombocytopenia (4%) and neutropenia (42%). CONCLUSION: Our results indicate that the combination of mitomycin C and vinorelbine has moderate activity in pretreated breast cancer.

Adult↗
PubMedDate not supplied

Instillation of mitomycin C after recurrent pterygium surgery.

PURPOSE: The aim of the study was to evaluate the safety and effectiveness of postoperative instillation of Mitomycin C eye drops in patients with recurrent pterygium. METHODS: Between October 1993 and November 1994, we operated 12 patients with recurrent pterygium using the conjunctival autografting technique, and after the operation patients instilled 0.02% or 0.04% Mitomycin C eye drops two or four times a day for one or two weeks. RESULTS: Early complications were 2 wound dehiscences, 7 corneal epithelial defects, 5 reported eye discomforts and 2 glaucoma. Late, there were 2 recurrences of pterygium after 6 and 9 months, one simplex glaucoma, one cataract and one alopecia areata. CONCLUSIONS: In cases of aggressive or severe pterygia, postoperative use of Mitomycin C eye-drops appears to be safe, effective and acceptable, but good surgical technique, careful observation and a long follow-up is indispensable for these patients.

Adult↗
PubMed2006

Synergistic effects of valproic acid and mitomycin C in adenocarcinoma cell lines and fresh tumor cells of patients with colon cancer.

Valproic acid has been demonstrated to mediate cytotoxic effects against tumor cells by acting as a histone-deacetylase inhibitor. However, to date, there are only limited data on the effects of valproic acid in colon cancer. Moreover, information regarding combinations of the drug with chemotherapeutic agents is very limited. The latter is of interest as there is increasing evidence for synergism between so-called "molecular targeting drugs" and chemotherapy. We first demonstrated that valproic acid dose-dependently reduced the viability of adenocarcimona cell lines. After co-incubation with a variety of chemotherapeutic agents, only valproic acid in combination with mitomycin C consistently induced synergistic growth inhibition in all cell lines. To confirm these results in an ex vivo situation, five samples of fresh colon cancer cells were studied. Again, the effect of valproic acid on the viability of the fresh tumor cells was dose dependent. In four of five samples of freshly isolated colon cancer cells, the synergistic effect of valproic acid and mitomycin C on the inhibition of cell growth was confirmed by calculation of the combination index by multiple drug effect analysis. In conclusion, this is the first demonstration that valproic acid as a model substance for histone-deacetylase inhibitors is effective in tumor cells freshly isolated from patients with colon cancer and that the combination of mitomycin C and valproic acid synergistically decreases viability of colon cancer cells.

Adenocarcinoma↗
PubMed1985

Mitomycin: ten years after approval for marketing.

Mitomycin was approved for marketing by the Food and Drug Administration in 1974 for use in gastric and pancreatic carcinomas when combined with other chemotherapeutic agents. Since then, mitomycin has been used extensively in combination chemotherapy for a variety of tumors, particularly in the past seven years. However, the contribution of this agent to the various drug regimens has not been adequately defined. Clear evidence of the drug's activity as a single agent has been seen in the intravesical treatment of superficial bladder carcinoma. Common toxicities include anorexia, vomiting, and myelosuppression. Less common, but potentially lethal, toxicities in the form of fibrosing alveolitis and microangiopathic hemolytic anemia with renal failure are being reported with increasing frequency. These potentially severe adverse effects, coupled with the still undefined role of mitomycin in systemic cancer chemotherapy, suggest that selection of this drug for other than investigational use should be made with care.

Antineoplastic Agents↗