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PubMedDate not supplied

Phase II study of hexamethylmelamine alone and in combination with mitomycin C and vincristine in advanced breast carcinoma.

Fifty-three patients with metastatic breast carcinoma were randomized to treatment with hexamethylmelamine (HMM) as a single agent versus a three-drug reimen of HMM, vincristine, and mitomycin C (HOM). All patients had received prior treatment with 5-fluorouracil, Adriamycin, and cyclophosphamide with or without methotrexate. HMM alone was used in a dose of 300 mg/m2/day x 14 days every 21 days. In the HOM regimen, the HMM dose was 200 mg/m2/day x 21 days, the vincristine dose was 1.5 mg on Days 1, 8, and 15, and the mitomycin C dose was 12 mg/m2 once every 6 weeks. No objective responses were observed with HMM in 15 evaluable patients. The HOM regimen resulted in five partial responses among the 27 evaluable patients. Gastrointestinal toxicity was the limiting toxicity of HMM, and thrombocytopenia was the major toxicity of the HOM regimen.

Adult↗
PubMedDate not supplied

Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide in advanced adenocarcinoma and large cell carcinoma of the lung.

Thirty-six patients with advanced carcinoma of the lung (30 with adenocarcinoma and six with large cell carcinoma) were treated with a combination of mitomycin C, Adriamycin, and cyclophosphamide (MAC) in a phase II study. Seven partial remissions were observed in adenocarcinomas, while none were seen in large cell carcinomas. The survival of patients in remission was clearly prolonged (P less than 0.01), with responders living a median of at least 39 weeks compared to 17 weeks for nonresponders. The combination was well-tolerated with moderate anorexia, nausea, vomiting, and alopecia. Myelosuppression was manageable but was more pronounced in previously chemotherapeutically treated patients. MAC offers a reasonable response rate in patients with adenocarcinoma of the lung with significant prolongation of survival; however, there was no significant advantage when compared to mitomycin C used as a single agent.

Adenocarcinoma↗
PubMed1979

Adriamycin, mitomycin C, and 5-fluorouracil in combination for advanced colorectal adenocarcinoma previously treated with 5-fluorouracil.

Twenty-one patients with progressing colorectal carcinoma previously treated with 5-FU were given a combination of 5-FU, adriamycin, and mitomycin C in an attempt to produce an objective response. No response was observed; 24% of patients had an arrest of their disease for a median of 18 weeks. 5-FU, adriamycin, and mitomycin C in combination failed to produce a response in patients with colorectal carcinoma previously treated with 5-FU.

Adenocarcinoma↗
PubMed2026

Intravesical mitomycin-C administered immediately before transurethral resection of bladder tumor in non-muscle-invasive bladder cancer: Clinical outcomes and molecular predictors from over 3 years of extended follow-up in a phase II trial.

PURPOSE: To evaluate the long-term outcomes and molecular correlates of response after immediate preoperative intravesical chemotherapy (IPeIC) with mitomycin-C (MMC) in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In this single-center, open-label, randomized phase II trial, 33 patients received two split doses of IPeIC/MMC (40 mg/20 mL), whereas 38 patients underwent transurethral resection of bladder tumor (TURBT) alone. The primary endpoint was 3-year recurrence-free survival (RFS), and secondary endpoints included progression-free survival (PFS). Exploratory RNA sequencing was performed on IPeIC-treated patients (three with recurrence, 25 without) using a Monte Carlo-based resampling strategy. RESULTS: The median follow-up durations were comparable between the intervention (60.0 months) and control arms (60.4 months). IPeIC/MMC reduced recurrence risk by 76.8% versus TURBT alone (p=0.024), yielding a 3-year RFS rate of 90.7% versus 78.6%. On multivariable analysis, IPeIC/MMC independently improved RFS (hazard ratio [HR] 0.266, p=0.044). IPeIC was associated with superior PFS, with 3-year and 5-year rates of 100% versus 92.1% and 85.8%, respectively, in the controls (HR 0.078, p=0.014). Exploratory transcriptomics identified low Glutathione S-transferase Mu 1 (GSTM1) expression as the factor most strongly associated with recurrence. CONCLUSIONS: IPeIC/MMC is associated with improved long-term oncological outcomes compared with TURBT alone and represents a safe prophylactic option for patients with NMIBC who are unable to receive standard immediate postoperative intravesical chemotherapy because of safety concerns or practical constraints. The GSTM1 findings are hypothesis-generating and support future biomarker-driven validation studies.

Aged↗
PubMed1978

Phase II trial of streptozotocin, mitomycin-C and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer.

Ten of 23 patients with advanced measureable adenocarcinoma of the pancreas achieved an objective response after treatment with a regimen consisting of streptozotocin, mitomycin-C and 5-fluorouracil (SMF). The median duration of response is in excess of 7 months and responding patients have lived significantly longer than patients with progressive disease (7.5 + months vs. 3 months). The SMF regimen was adequately tolerated. Principal toxicities included myelosuppression, which was generally mild, nausea and vomiting. There was reversible nephrotoxicity in the form of proteinuria in 30% of patients and persistent axotemia in 9% of patients.

Adult↗
PubMed1979

5-Fluorouracil, adriamycin, and mitomycin-C (FAM) chemotherapy for adenocarcinoma of the lung.

Twenty-five patients with advanced measurable adenocarcinoma of the lung were treated with combination chemotherapy consisting of 5-fluorouracil, adriamycin, and mitomycin-C (FAM). Objective response (1CR, 8PR) was obtained in 36% of patients. The median duration of response was 7.0 months and the median survival for responders is greater than 8.5 months. Five responders are alive 5.5 to 23.5 months after starting therapy. Three of four patients evidencing stabilization of disease are alive at 10-23 months. Non-responding patients had a median survival of 2.5 months and none lived beyond seven months. Tumor response and survival suggested correlation with initial performance status and limited disease. The FAM regimen was tolerated well, with moderate bone marrow suppression and gastrointestinal symptoms being the only clinically significant toxicities. These results indicate that patients with advanced pulmonary adenocarcinoma can obtain objective tumor regression with FAM chemotherapy.

Adenocarcinoma↗
PubMed1979

5-fluorouracil, adriamycin, and mitomycin-C (FAM) combination chemotherapy in the treatment of advanced gastric cancer.

Thirty-six patients with advanced measurable gastric cancer were treated with a new combination chemotherapy program consisting of 5-fluorouracil, Adriamycin and mitomycin-C (FAM). Fifty percent of patients achieved an objective partial response. The median duration of remission was 9.5 months and the median survival for responding patients was 13.5 months, with 2 remaining alive at 14 and 26 months. The median survival for nonresponding patients was 3.0 months and all were dead by 6 months after initiation of therapy. The median survival of all 36 patients treated with FAM was 5.5 months. An analysis of possible prognostic variables including initial performance status, resectability of the primary gastric tumor and histologic differentiation of the neoplasm failed to account for differences in patient response and survival. The FAM regimen was well tolerated, and produced only moderate bone marrow suppression. These results demonstrate that some patients with advanced gastric cancer can be effectively palliated with FAM chemotherapy. Phase III trials are warranted to assess the effect of the FAM regimen on the survival of patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1979

A phase II trial of ftorafur: adriamycin and mitomycin-C (FAM II) in advanced gastric adenocarcinoma.

Fifteen patients with advanced gastric cancer were treated with the combination of Ftorafur, Adriamycin and mitomycin-C (FAM II). Three patients showed partial responses, in five the disease remained stable for at least 3 months and seven showed progression while on treatment. All responding patients showed survival in excess of 12 months. Hematologic toxicity was of only moderate severity. Median white count nadir was 3500 cells/mm3 and median platelet nadir was 187,000 cells/mm3. Four patients had white count nadirs from 2000--2500 cells/mm3 and three had nadirs from 500--1500 cells/mm3; also there were four with platelet nadirs less than 100,000/mm3. However, no drug-related infections occurred and no platelet transfusions were required. The major non-hematologic toxicities of the regimen were nausea, vomiting, dizziness, vertigo, and rhinorrhea. These toxicities were limiting and resulted in termination of the trial because of poor patient acceptance and the failure of the combination to exhibit a therapeutic advantage over the similar combination (FAM) that employed weekly 5-fluorouracil in place of Ftorafur.

Adenocarcinoma↗
PubMed1978

A sequential combination of bleomycin and mitomycin C in the treatment of advanced squamous cancers.

The 49 patients with squamous cell type of cervical, lung, esophagus and head and neck cancers were treated with a sequential combination of bleomycin (BLM) and mitomycin C (MMC) as follows; 5 mg of BLM daily for 5 or 7 days followed by a single injection of 10 mg of MMC on day 6 or day 8. After one week of rest period, this course was repeated two to five times depending on the response or adverse effects. For cervical cancer, 17 patients out of 18 (94%) responded with complete remission (CR) in 13 (72%) and partial remission (PR) in 4 (22%). For lung cancer, four patients out of five responded. In two of the responders, metastatic tumors disappeared completely, but primary tumors decrease to about 10% in volume. For esophagal cancer, one patient out of 3 had CR after combining the BLM and MMC treatment with radiotherapy. For head and neck cancer, these were some differences in the response rates between two hospitals. In one hospital, 12 patients out of 22 (53%) responded, with CR in 4 (18%), whereas in the other hospital, 10 patients out of 11 (94%) responded, including eight with CR (72%). Regarding the toxicity, the overall incidence was very low, although lung complications were frequent. These results are promising with hopeful prospects for the control of advanced squamous cancers with metastasis.

Adult↗
PubMed1977

The distribution of mitomycin C-induced sister chromatid exchanges in the euchromatin and heterochromatin of the Indian muntjac.

The frequency of sister chromatid exchanges (SCEs) induced by mitomycin C (MMC) in Indian Muntjac chromosomes was determined by the fluorescence plus Giemsa (FPG) technique. Using scanning cytophotometry the relative DNA content of each chromosome was measured with and without acid or alkali pretreatments for C-banding. During acid and alkali treatments, euchromatin lost 20 to 30% of its DNA, while heterochromatin lost less than 5%; an intermediate DNA loss was observed for the short arm of the X chromosome. After growth of cells in the presence of MMC during the first cycle and in the presence of bromodeoxyuridine (BrdU) during the first and second cycles of DNA replication, SCEs in the euchromatin were proportional to DNA content. SCEs at the junctions between the neck of the X chromosome and the long and short arms occurred more frequently than expected. A threshold effect for the induction of SCEs was observed in regions resistant to DNA extraction by acid and alkali treatments (i.e., the neck and short arm of the X chromosome). At high concentrations of MMC, the frequency of SCE at each junction appears to plateau at 0.5.

Animals↗
PubMed1979

ColE1 DNA sequences interacting in cis, essential for mitomycin-C induced lethality.

Protein synthesis and survival of colicinogenic bacteria carrying different ColE1 deletion and insertion mutants, were followed in presence or absence of the inducing agent mitomycin-C. It is concluded that active colicin is not involved in the process leading to death of the induced colicinogenic cell. The region of ColE1, essential for cell induced lethality, is carried on the DNA between map positions 0.74 to 0.27. In this region the DNA sequences carried between 0.74 to 0.79 and 0.0 to 0.27 are essential, while those located between 0.79 to 0.0 are nonessential for commitment to death. A cis interaction of the ColE1 DNA sequences in the essential regions is probably necessary for cell induced lethality. Some possibilities for such a cis interaction are suggested and discussed.

Bacterial Proteins↗
PubMed1977

Induction of protein synthesis in Escherichia coli following UV- or gamma-irradiation, mitomycin C treatment or tif Expression.

The rate of synthesis of total cellular proteins has been studied by pulse labelling cells at various periods after irradiation with UV or gamma-rays, after treatment with mitomycin C (MMC) or after expression of the temperature sensitive mutation tif. Subsequent gel electrophoresis and autoradiography reveals changes in the rate of synthesis of several proteins. The most striking change is in a protein of molecular weight 40,000, protein X, which has been previously most extensively studied in cells treated with nalidixic acid (Gudas, 1976). Synthesis of large quantities of protein X is induced by UV, gamma-rays, MMC treatment or tif expression in rec+ but not recA cells. A feature of recA cells is that they break down their DNA excessively after irradiation or MMC treatment. However, if protein synthesis following irradiation is prohibited by chloramphenicol, post-irradiation degradation becomes excessive in recA+ cells. This inverse relationship between DNA degradation and new protein synthesis consistent with the hypothesis that an induced protein such as X is responsible for controlling DNA degradation following irradiation. Protein X is not induced in a lexB mutant following MMC treatment. In this respect the lexB mutant behaves like lexA and recA mutants in that the ability to induce protein X can be correlated with excessive DNA degradation. Studies on the induction of proteins in inf, tif and tif sfi mutants fail to reveal any correlation between induction of protein X and either the induction of prophage lambda or septation.

Bacterial Proteins↗
PubMed1979

Post-operative long-term adjuvant immunochemotherapy with mitomycin-C, PSK and FT-207 in gastric cancer patients.

Long-term adjuvant immunochemotherapy carried out on the gastrectomized patients with stomach cancer was reported. The protocol comprises the administration of large-dose of Mitomycin-C (20+10) mg just after gastrectomy and the long-term administration of PSK, FT-207 or (PSK+FT-207). Almost no side effects were observed. According to the studies on the immunological parameters, the increased reactions in PPD skin test and lymphocyte blastogenesis induced by PHA and PWM were observed remarkably in group (P+F) 3 or 6 months after gastrectomy. As for the survival rate, group (P+F) showed the most preferable results at one year in stage IV, at two years in stage III and at three years in all the stages, respectively after gastrectomy.

Adjuvants, Immunologic↗
PubMed1978

Factors influencing the frequency of mitomycin C-induced sister-chromatid exchanges in 5-bromodeoxyuridine-substituted human lymphocytes in culture.

Newly developed techniques for the detection of sister-chromatid exchanges (SCE) require the substitution of 5-bromodeoxyuridine (BrdU) for thymidine in DNA. We investigated the possibility of interactions between BrdU and one mutagen--carcinogen, mitomycin C (MMC) for the induction of both chromosomal aberrations and SCE in human peripheral lymphocytes in culture. No effect on aberration yield was found. Neither comparisons between the yields of SCE by BrdU substitution and differential staining and those detected by tritiated thymidine incorporation and autoradiography nor between the yields of SCE for different levels of BrdU incorporation provided any evidence of synergism. It was found, however, that MMC persists in cultures and continues to increase SCE frequencies for about 30 h. It was also observed that some MMC-induced DNA lesions persist long enough so that some of those present prior to S phase of the first cell cycle cause additional SCE in the third cycle.

Bromodeoxyuridine↗
PubMed1979

Spontaneous and mitomycin-C induced sister-chromatid exchanges. Comparison of in vivo and in vitro systems.

Frequencies of sister-chromatid exchanges (SCE) were measured in vitro in mouse fibroblasts and in vivo in mouse bone-marrow cells. SCE levels in these cell systems were measured in response to varying concentrations of bromode-oxyuridine (BrdU) and mitomycin-C (MMC). Although BrdU was found to induce SCE in both cellular systems, baseline SCE levels were 2- to 3-fold higher in vitro than in vivo. SCE induction was found to be a linear function of MMC concentration in vivo and in vitro; however the slope of the vivo curve was 5-fold higher. The interaction of BrdU substituted DNA and MMC was examined by administering a fixed dose of MMC with increasing concentrations of BrdU. The induced SCE frequencies appeared to be additive. In addition to measuring drug-induced SCE, the BrdU differential staining technique allows concomitant measurement of the inhibition of cellular replication by the test drugs.

Animals↗