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PubMed1980

Pulmonary toxicity of mitomycin.

Six patients with breast cancer developed pulmonary toxicity following mitomycin therapy. The presenting symptoms were shortness of breath and a dry cough. The radiological pictures varied from a normal chest x-ray to extensive bilateral pneumonitis. The histological findings consisted of diffuse alveolar damage progressing to interstitial pulmonary fibrosis. Corticosteroid therapy resulted in complete resolution of pneumonia in one patient. Respiratory symptoms improved in 3 patients following discontinuation of the drug. Two patients with extensive bilateral pneumonitis, who were not treated with steroids, died of respiratory failure. Mitomycin-induced lung toxicity appears to be reversible with the discontinuation of drug and the administration of corticosteroids. Lung biopsy is necessary in order to rule out other diagnoses.

Adrenal Cortex Hormones↗

PubMed1980

Surgical adjuvant chemotherapy with mitomycin C and cyclophosphamide in Japanese patients with breast cancer.

A controlled trial of surgical adjuvant chemotherapy for breast cancer was carried out using 551 Japanese patients. Single or combined treatment with mitomycin C (0.2 mg/kg i.v. three times within five days postoperatively) and cyclophosphamide (100 mg postoperatively daily for four months or longer) was used after radical surgery. In patients of the chemotherapy group with one to three lymph nodes involved in the axilla, the five-year cancer-free survival rate was 84.8% compared with 57.3% in the control group (P < 0.05), and the five-year cumulative recurrence in distant sites was 5.1% compared with 31.1% in the control (P < 0.05). The effectiveness of chemotherapy was much less marked in patients without nodal metastasis and with four or more nodes involved. Histologically, scirrhous cancer was the type that responded most favorably to chemotherapy, even in patients without axillary involvement. Premenopausal patients benefited more than postmenopausal patients from chemotherapy. A combination of mitomycin C and cyclophosphamide was more effective than their use singly. The present chemotherapy regimen was effective primarily in moderately advanced stages of breast cancer with decreased incidence of distant metastasis.

Adenocarcinoma, Scirrhous↗

PubMed1985

Mitomycin in metastatic breast cancer refractory to hormonal and combination chemotherapy.

Forty-three patients with evaluable metastatic breast cancer refractory to hormonal agents and extensive combination chemotherapy including doxorubicin were treated with mitomycin, 20 mg/m2 intravenously every 6 weeks. There were five partial responses (12%) and three minor responses (7%), with a mean time to progression of 5 months and 3.5 months, respectively. Thrombocytopenia was the major dose-limiting toxicity, and myelosuppression was cumulative. Cardiac dysfunction was observed in 12% of patients. Mitomycin had some antitumor activity in this group of metastatic breast cancer patients refractory to extensive combination chemotherapy including doxorubicin.

Adult↗

PubMed1992

Treatment of unresectable primary liver cancer with intrahepatic fluorodeoxyuridine and mitomycin C through an implantable pump.

Ten patients with unresectable primary liver cancer, eight of whom had elevated serum alpha-fetoprotein levels, were treated with intrahepatic fluorodeoxyuridine (FUDR) and mitomycin C administered through an implantable pump. Four patients had a partial response, and two had a minor response. The median survival from initiation of treatment was 14.5 months (range, 2 to 32 months), with patients receiving therapy for a median of 11.2 months. In general, the therapy was well tolerated; only one patient had treatment-related biliary sclerosis. In conclusion, the combination of intrahepatic FUDR and mitomycin C was an effective palliative regimen for unresectable primary liver cancer, even in the presence of elevated serum alpha-fetoprotein levels. Further studies are needed to confirm these findings and compare this regimen with other methods of treatment for hepatocellular carcinoma.

Adolescent↗

PubMed2001

Regional chemotherapy of nonresectable colorectal liver metastases with mitoxantrone, 5-fluorouracil, folinic acid, and mitomycin C may prolong survival.

BACKGROUND: Regional chemotherapy of isolated, nonresectable colorectal liver metastases (CRLMs) by hepatic artery infusion (HAI) has the advantages of high response rates and the possibility of downstaging and resection of CRLMs. 5-Fluorodeoxyuridine (5-FUDR) has been the drug studied in most Phase II and III trials. The meta-analysis of the Phase III trials comparing HAI with systemic or supportive therapy confirmed an advantage for response and even survival for HAI. Hepatic artery infusion with 5-FUDR, however, is hepatotoxic, inducing sclerosing cholangitis (SC). The authors have introduced 5-fluorouracil (5-FU) with folinic acid for HAI and found equal effectivity but no SC when compared with HAI with 5-FUDR. Now, they report a new combination chemotherapy protocol based on HAI with 5-FU with FA and on in vitro Phase II studies suggesting mitoxantrone and mitomycin C as active drugs for HAI in CRLM. PATIENTS AND METHODS Between February 1993 and August 2000, 63 patients with CRLM were treated with HAI using mitoxantrone, 5-FU with FA, and mitomycin C (MFFM) via port catheters with a protocol planing up to 11 cycles of treatment. Toxicity and response were analyzed according to World Health Organization (WHO) criteria, and survival was analyzed according to Kaplan-Meier. All patients were treated with more than two HAI cycles. RESULTS: The objective response rate (complete remission and partial remission) was 54% and primary intrahepatic progression (progressive disease) occurred in 4.8%, whereas in 41.3% of the patients the intrahepatic disease was evaluated as no change. Median survival times from the first diagnosis of CRLM or start of HAI were 25.7 months and 23.7 months, respectively, and 7 patients lived longer than 40 months. Grade 3 toxicity according to WHO occurred in 34.9%, and Grade 4 occurred in 3.2%. No toxic death or SC occurred. CONCLUSIONS: Our new HAI protocol with MFFM seems to be superior to HAI with 5-FUDR, 5-FU with FA, and systemic chemotherapy with 5-FU and FA at acceptable toxicity. Currently, HAI with MFFM is compared with systemic chemotherapy using 5-FU and FA intravenously in a randomized Phase III trial.

Adult↗

PubMed2005

Intra-operative mitomycin C for glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for glaucoma to lower the intraocular pressure (IOP). Mitomycin C (MMC) is an antimetabolite used during the initial stages of a trabeculectomy to prevent excessive postoperative scarring and thus reduce the risk of failure. OBJECTIVES: To assess the effects of intraoperative MMC compared to placebo in trabeculectomy. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1985 to 20 March 2005), SIGLE (1980 to December 2004), the National Research Register (Issue 1, 2005), LILACS (29 March 2005) and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised trials of intraoperative MMC compared to placebo in trabeculectomy surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted trial investigators for missing information. MAIN RESULTS: Eleven trials, involving a total of 698 participants, were included. The trials enrolled three types of participants (high risk of failure, trabeculectomy combined with cataract surgery, no previous surgical intervention). Mitomycin C appears to reduce the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean IOP was significantly reduced at 12 months in all three participant groups receiving MMC compared to placebo. No significant increase in permanent sight-threatening complications was detected. However, none of the trials were large enough or of sufficient duration to address the long-term risk of bleb infection and endophthalmitis which has been reported in observational studies. Some evidence exists that MMC increases the risk of cataract. AUTHORS' CONCLUSIONS: Intraoperative MMC reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean IOP at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following MMC, there was insufficient power to detect any increase in other serious side effects such as endophthalmitis.

Antimetabolites↗

PubMed1994

Effects of spermine on formation of HGPRT- mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C in V79 Chinese hamster cells.

Spermine is a polyamine found in bacteria, animal, and plant tissues. It is involved in a variety of biological processes, and its interaction with DNA stabilizes the secondary structure of the double helix. Spermine is one of the first reported antimutagens, reducing the mutation rate in several prokaryotic test systems, while in eukaryotic organisms conflicting results have been obtained. In light of the significant antimutagenic effect of spermine, it is important to evaluate its activity in mammalian cells in culture. The present study was undertaken to evaluate the ability of spermine to suppress the level of HGPRT- mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C. Spermine reduced the mutation frequency induced by ethylmethanesulfonate and methylmethanesulfonate but did not affect survival; with mitomycin C survival was reduced but mutation rate was not influenced.

Alkylation↗

PubMed2004

Concomitant radiochemotherapy in primary inoperable advanced head and neck cancer with 5-fluorouracil and mitomycin-C.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy and concomitant 5-fluorouracil (5-FU) and mitomycin-C infusion in inoperable head and neck cancer. METHODS: Seventy-six patients (86% men, 14% women), mean age 57 years, with primary inoperable head and neck cancer were treated with 70 Gy plus simultaneous intravenous chemotherapy with 5-FU (600 mg/m(2)/d, days 1 to 5) and mitomycin-C (10 mg/m(2), day 5 plus 36). RESULTS: After a mean follow-up of 13 months, 31 patients were alive. Complete response (CR) was seen in 63%. The 1- and 2-year overall survival rates were 67.7% and 39.5%, and locoregional control rates were 51.7% and 35.6%. Pretreatment hemoglobin <13.9 g/dL was associated with lower locoregional control rates (p = .03). Therapy was well tolerated (grade 3 mucositis in 21%, grade 4 in 1%, grade 3 leukopenia in 11%). CONCLUSIONS: Our radiochemotherapy regimen offers a curative option for this group of patients with a poor prognosis. Hemoglobin levels before therapy have an influence on prognosis.

Adult↗

PubMed1978

Combination therapy with mitomycin C, 5-fluorouracil, and cytosine arabinoside for nonresectable malignant tumor in man.

The effectiveness of MFC (mitomycin C, 5-fluorouracil and cytosine arabinoside) therapy for nonresectable cancers and cancers recurring after surgery was investigated in 60 patients with solid cancers aged 26 to 69 years. Treatment was effective in 28 patients (47%) including seven (12%) who showed a very good response. Side effects included anorexia, vomiting, melena, anemia, decreased leukocyte and platelet counts, and impaired renal function. In particular, hemorrhage of the digestive tract should be watched carefully during MFC therapy. MFC therapy is suitable for solid tumors of the breast and digestive organs, especially with metastases to the lymph nodes. Response to treatment is generally seen after 6--10 doses. If there is no response at this time, treatment should be changed. In cases where induction of remission is successful, maintenance therapy should be continued keeping the frequency of administration to a minimum. Remission is readily induced with MFC therapy, but because of the problems of hemorrhage of the digestive tract, and bone marrow suppression, its use for outpatient treatment is not considered safe. Therefore, alternative treatment should be given for long term maintenance of remission. FAMT (5-fluorouracil, cyclophosphamide-endoxan, mitomycin C, chromomycin A3 -toyomycin) therapy is considered safe and suitable for maintenance therapy in outpatients. Three cases in which MFC therapy was very effective are described to illustrate the treatment program.

Adult↗

PubMed1982

Treatment of advanced gastric cancer with 5-fluorouracil versus mitomycin C.

Thirty-eight patients of advanced adenocarcinoma of the stomach were randomly administered intensive courses of either 5-FU or mitomycin C by intravenous route, The 5-FU administration resulted in a slightly better response than mitomycin C, although the toxic effects of the two drugs were more or less the same. The selection of drug regime in the present study has been based on cost, availability, potential toxicity, and minimal alteration of the patients' life style.

Adenocarcinoma↗

PubMed1992

Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C.

Two kinds of immunoconjugate (T-3M and T-11M) of murine monoclonal antibody with mitomycin C (MMC) were developed using spacers containing a disulfide (T-3M) or thiocarbamate (T-11M) bond. A murine monoclonal antibody (NCC-LU-243) raised against a human small cell lung carcinoma cell line, Lu-24, in nude mice, is an IgG2a monoclonal antibody that recognizes a 145-kDa protein on the cell surface membrane. T-3M and T-11M showed affinity for the LU-243 antigen-positive H-69 cell line but not for the antigen-negative Lu-65 cell line in vitro. In the in vitro MTT assay, the order of efficacy of these compounds was T-11M > T-3M > MMC against antigen positive H-69 and T-11M = MMC > T-3M against antigen-negative K562. When antigen-positive H-69 was transplanted into nude mice for in vivo assay, the maximum tolerated dose of T-3M was twice as high than that of the parent compound MMC. Furthermore, T-3M showed higher antitumor activity against antigen-positive H-69 than MMC conjugated with a non-specific rabbit IgG in vivo. When the maximum tolerated doses of T-3M and MMC were administered to H-69-bearing nude mice, the effect of T-3M was superior to that of MMC, whereas no differences were observed between the antitumor activity of T-3M and MMC against antigen- negative MX-1, a human breast carcinoma. These two immunoconjugates of monoclonal antibody with mitomycin C are thought to be useful for targeting cancer chemotherapy against human small cell lung carcinomas.

Animals↗

PubMed1976

Mitomycin C in large infrequent doses in breast cancer.

Seventy-one women with far-advanced breast cancer resistant to standard chemotherapeutic agents were administered mitomycin C using an intermittent high dose schedule. One group consisted of 54 patients with measurable metastatic tumor; a second group consisted of 18 patients with nonmeasurable osseous metastases. Objective response rate in group 1 was 26% for an average duration of 2 1/2 months. Subjective response rate in group 2 was 44% for an average duration of 3 months. Response and toxicity data were similar to those of studies employing the less convenient protracted low-dose schedule. Prior treatment with other alkylating agents did not adversely affect response. Further investigation into the role of mitomycin in combination chemotherapy programs is recommended.

Adult↗

PubMed1981

Phase II evaluation of mitomycin C (MMC) in children with refractory solid tumors using the single high-intermittent-dose schedule.

Nine evaluable patients with refractory solid tumors received mitomycin C as a single intravenous injection at a dose of 20 mg/m2 at 6- to 8-week intervals. Toxicity was tolerable. One patient with Wilms' tumor had a transient decrease in liver size. Pharmacokinetic data on three patients have suggested that the disposition of mitomycin C were comparable to those obtained in adults.

Adolescent↗

PubMed2003

Ascorbic acid potentiates mitomycin C-induced micronuclei and sister chromatid exchanges in human peripheral blood lymphocytes in vitro.

Vitamin C (l-ascorbic acid), an effective free radical scavenger present as ascorbate in most biological systems, is one of the most extensively studied antioxidant vitamins. Vitamin C acts as either a free radical scavenger or a pro-oxidant producing hydrogen peroxide and free radicals. The modulatory effect of L-ascorbic acid (AA) on Mitomycin C (MMC) induced chromosome damage has been evaluated in human peripheral blood lymphocytes in vitro. The effect of L-ascorbic acid, 200 microg/ml as 1- and 2-h pretreatment on the frequencies of the biomarkers micronuclei (MN), sister chromatid exchanges (SCEs), and chromosome aberrations (CA) induced by mitomycin C 0.1 and 0.2 microg/ml has been studied. AA pretreatment caused a statistically significant increase in MMC-induced MN and SCE frequencies for all treatment groups, but did not show an increase in induced chromosome aberrations compared to MMC treatment alone. Cell division delays caused by MMC was reversed in the presence of AA. Interindividual variability in MMC as well as AA plus MMC-induced MN, SCE, and CA frequencies were evident. Ascorbic acid potentiated MMC-induced chromosome damage in human lymphocytes in vitro. The potentiation observed has to be viewed in the light of metal ion catalysed autooxidation of AA in oxygenated media and the existence of an antioxidant system in vivo that inactivates oxyradicals before their interaction with DNA.

Adult↗

PubMed1995

Gene targeting of DT-diaphorase in mouse embryonic stem cells: establishment of null mutant and its mitomycin C-resistance.

It is generally accepted that DT-diaphorase is primarily involved in the detoxification of quinone compounds and is capable of metabolically activating some cancer chemotherapeutic quinones including mitomycin C. However, these conclusions have mainly been drawn from the experiments using the DT-diaphorase inhibitor, dicoumarol. To understand directly the roles of this enzyme in quinone metabolism, we have established heterozygously and homozygously DT-diaphorase-targeted mutant embryonic stem (ES) cells by homologous recombination. Cytotoxicity experiments using these cells clearly demonstrated that DT-diaphorase acts as an activator of mitomycin C in ES cells. These mutant cell lines seem to be very useful for investigating the functions of DT-diaphorase including the bioactivation and detoxification of quinone species. The generation of a DT-diaphorase-targeted mouse is under investigation.

Animals↗

PubMed1997

Transconjunctival application of mitomycin C in combination with laser sclerostomy ab interno: a long-term morphological study of the postoperative healing process.

The precise mechanism whereby mitomycin C enhances IOP reduction in glaucoma filtering surgery still eludes us. Ten rabbits received full-thickness Nd:YAG laser sclerostomy ab interno and adjunctive intraoperative treatment with mitomycin C (MMC) applied topically over the intact conjunctiva (0.5 mg ml-1 for 5 min). A systematic ultrastructural analysis of the fistulas and surrounding tissue was then conducted in conjunction with clinical observations, over the ensuing 10 weeks. In order to investigate also the extent to which MMC impedes fistula occlusion in the absence of percolating aqueous humour, we created non-perforating ('half-thickness') sclerostomies ab interno in three additional rabbits, one with and two without MMC therapy. Transconjunctival MMC application resulted in no serious complications. Eight of the ten full-thickness fistulas remained patent throughout the study, maintaining significant IOP reduction; the other two sclerostomies were compromised by iris incarceration. The MMC-treated, half-thickness canal remained as a tissue-free cul de sac; the two non-treated ones became completely occluded within one week without having recourse to extraocular cell populations. MMC suppressed the migration and proliferation of fibroblasts, macrophages and clump cells from the episclera, sclera, ciliary body and iris root. Repolymerization of heat-damaged collagen was abortive; neosynthesis was not observed. Myofibroblasts were encountered in the vicinity of the sclerostomy canals, and, after the fifth week, these cells were also found to be deployed as a canal-lining layer, delimiting the lumen from the surrounding stroma along most of the fistula length. Towards the external ostium, this layer of myofibroblasts was incomplete or absent. Near the internal ostium, lining cells were derived from the corneal endothelium. The transconjunctival mode of applying MMC appears to be efficient. This antifibrotic drug exerts its inhibitory influence by suppressing not only cell migration and proliferation, but also phagocytic and synthetic activities. However, exposed tissues are not acellular, and amongst the populations present, myofibroblasts are found to dominate the scene. The canal-delimiting cellular lining may play a role in maintaining fistula patency in MMC-treated eyes.

Administration, Topical↗

PubMed1993

Treatment of advanced or recurrent squamous cell carcinoma of the uterine cervix with mitomycin-C, bleomycin, and cisplatin chemotherapy.

Fifty-nine patients with recurrent/persistent, or advanced local/metastatic squamous cell cancer of the cervix were treated with combination chemotherapy consisting of mitomycin-C, bleomycin, and cisplatin. Response to therapy and survival analysis was determined for 44 of 49 patients who had previously been treated with radiation therapy and/or surgery and for 10 patients with advanced, previously untreated disease. Seven (16%) of the 44 previously treated patients experienced either complete response (CR) or partial response (PR). The median progression-free interval for responders (CR + PR) was 14.5 months, compared with 2.6 months for the nonresponders (significant, P < 0.001). The median survival time for responders (CR + PR) was 15.9 months, compared with 5.9 months for nonresponders (significant, P < 0.01). The 10 previously untreated patients were separately evaluated for response to chemotherapy. Of these, there was 1 CR, 2 PR, 1 < PR, and 6 SD. The 3 responders (CR + PR), who subsequently underwent radiation therapy, were alive and without evidence of disease 7.9, 13.7, and 27.6 months after treatment. Toxicities were mild to moderate, with no treatment-related deaths. In this study, this combination of mitomycin-C, bleomycin, and cisplatin chemotherapy was found to have activity in local, previously untreated disease and in patients with disease recurrence outside pelvic radiation fields.

Adult↗

PubMed1995

Phase II trial of mitomycin-C in squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

Fifty-six patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix not previously exposed to cytotoxic drugs, other than as radiosensitizers, were entered into a study of single-agent 20 mg/m2 mitomycin-C every 6 weeks. The overall response rate among the 52 patients evaluable for response was 12% (three complete and three partial responses). Median response duration was 7.3 months. For the entire population, median progression-free interval was 3.0 months, and median survival was 4.9 months. Among 27 patients with pelvic disease only in previously radiated fields, two responses were observed (7%), whereas four responses were observed among 25 patients with extrapelvic disease in nonradiated fields (16%). The most frequent and severe adverse effects were the result of myelosuppression. Based on the modest level of activity observed, no further study of mitomycin-C in squamous cell carcinoma of the cervix is planned.

Adult↗