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At least 1,243 records · Page 69Linked to original sources
PubMed1984

[Combination chemotherapy of mitomycin C and cytosine arabinoside in the intravesical treatment for superficial bladder tumors: report 2. Evaluation of prophylactic intravesical infusion therapy].

Combined chemotherapy of Mitomycin C (20 mg to 30 mg) and Cytosine Arabinoside (200 mg) was given by intravesical infusion to 25 patients with superficial bladder tumor who underwent transurethral treatment for prevention of postoperative recurrence. The prophylactic effect of this therapy was evaluated as follows. 1) The postoperative recurrence rates by the actuarial method were 4.0% in six months, 8.1% in one year, 22.2% in two years, 37.4% in three years and 37.4% in five years. 2) The prophylactic effect on recurrence tended to be marked on primary tumors, solitary tumors, low grade tumors and relatively large tumors. 3) The correlation of doses and the recurrence rate was significantly observed: prophylactic effect tended to increase in proportion to increase of doses of both Mitomycin C and Cytosine Arabinoside.

Adult↗
PubMed1984

[Pharmacokinetics of mitomycin C in cancer patients during prolonged administration of the preparation].

The mitomycin C levels in the blood of patients subjected to prolonged intravenous injection of the drug in 200-300 ml of isotonic sodium chloride solution for 15-50 minutes were determined in the microbiological test system consisting of E. coli and 1.5 per cent of agar in the meat-peptone broth with restricted contents of the nutrients. Such administration of the drug usually provided lower blood levels than intravenous injections of the drug in analogous doses. However, the drug renal excretion was also less intensive. It suggested that the drug administered for a prolonged period was more completely absorbed by the host tissues. This was confirmed by much lower blood levels of the drug, when the tumors were large, as compared to those in patients with insignificant residues of the tumor tissue after surgical resections. The curves of mitomycin C distribution in the blood indicate that the pharmacokinetics of the drug in patients with tumors is a multi-factorial function.

Breast Neoplasms↗
PubMed1984

Antitumor activity and toxicity in animals of RR-150 (7-cysteaminomitosane), a new mitomycin derivative.

The experimental antitumor activity of a new mitomycin derivative, 7-cysteaminomitosane (RR-150), was evaluated in mice. When administered i.p. to mice bearing i.p.-implanted tumors, RR-150 was superior to mitomycin C (MMC) in increasing the life span of animals bearing P388 leukemia, B16 melanoma, and a line of L1210 leukemia partially resistant to MMC. RR-150 appeared comparable to MMC in increasing life span of mice bearing Madison 109 lung carcinoma, Colon 26 carcinoma, or parental (nonresistant) L1210 leukemia. Mice immunosuppressed with 550 rads whole-body irradiation prior to i.p. implantation of B16 still benefited (e.g., 40% cure rate) following optimal RR-150 therapy when compared to nonirradiated, B16-implanted mice given RR-150 (e.g., 70% cure rate). RR-150 had inconsistent activity in the treatment of s.c.-implanted tumors. In toxicity evaluations, RR-150 was comparable to MMC in suppression of total while blood cell counts but appeared to be less neutropenic. RR-150 also caused less cumulative leukopenia than did MMC in a weekly chronic dose experiment. Based on serum chemistries, RR-150 did not have significant nephrotoxicity, but there was evidence of possible liver toxicity at doses near the 50% lethal dose. Because of the balance of favorable antitumor and toxicity properties of RR-150, work is under way to prepare a more bioavailable form for advanced evaluation.

Animals↗
PubMed1984

[Influence of family history, irradiation and anti-cancer drug (mitomycin C) on the occurrence of multiple primary neoplasms in breast carcinoma patients].

The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilateral breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period.

Adult↗
PubMedDate not supplied

Conjugates of mitomycin C with the immunoglobulin M monomer fragment of a monoclonal anti-MM46 immunoglobulin M antibody with or without serum albumin as intermediary.

In studies on antitumor antibody-drug conjugates as potential antitumor agents with improved tumor specificity, conjugates of mitomycin C (MMC) with the IgMs fragment of a monoclonal IgM antibody to a tumor-associated antigen (MM antigen) on mouse mammary tumor MM46 cell (anti-MM46 IgMs) were prepared by direct and bovine serum albumin (BSA)-mediated indirect conjugation. MMC was linked to the IgMs and BSA by the use of 1a-[4-(N-succinimidoxycarbonyl)butyryl]mitomycin C, which allowed the slow release of MMC. In the indirect conjugation, the thiol group of BSA was first protected as the 2-pyridyldithio group and, after the MMC binding, regenerated with dithiothreitol, and the resulting BSA-MMC was reacted with the IgMs having the maleimide group introduced with N-succinimidyl m-(N-maleimido)benzoate. Anti-MM46 IgMs-MMC was more cytotoxic against the target MM antigen-positive but Thy 1.2 antigen-negative MM46 cells than control anti-Thy 1.2 IgM-MMC. No such selective cytotoxicity was observed between anti-MM46 IgMs-MMC and anti-Thy 1.2 IgMs-MMC against the MM antigen- and Thy 1.2 antigen-negative MM48 cells. Anti-MM46 IgMs-BSA-MMC was more cytotoxic against MM46 cells than was a mixture of unconjugated anti-MM46 IgMs and BSA-MMC.

Animals↗
PubMed1984

[Phase II study of KW 2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with various cancers].

A phase II study of KW 2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C] was carried out in 14 cases of stomach cancer, 5 of lung cancer, 5 of colon cancer and 5 other types of cancer. KW 2083 was intravenously injected at a dose of 40 mg/body weekly in 26 cases. Among 23 evaluable cases, partial response was obtained in 6 cases (26%). The PR cases were 4 of stomach cancer and 2 of lung cancer, the former being all undifferentiated adenocarcinoma. Regarding hematologic toxicities, thrombocytopenia was the most principal toxicity and an important weak point of KW 2083. Thrombocytopenia (less than 75,000/mm3) was observed in 13 cases (50%). Recovery took about 4 weeks, but by that time 3 cases had still not recovered to 75,000/mm3. leukocytopenia (less than 3,000/mm3) was observed in 17 cases (65%). Concerning gastrointestinal symptoms, anorexia occurred in 11 cases (42%), nausea and vomiting in 11 cases (42%), diarrhea in 1 case and stomatitis in 1 case. T1/2 (beta-phase) of KW 2083 was half that of Mitomycin C.

Adolescent↗
PubMed1984

[Effect of 7-N-(P-hydroxyphenyl)-mitomycin C (KW-2083) against pleuritis carcinomatosa].

Fourteen cases of adenocarcinoma with pleuritis carcinomatosa (lung cancer 10 cases, ovarian cancer 2 cases, colon cancer 2 cases) were treated with intra-pleural instillation of 7-N-(p-hydroxyphenyl)-mitomycin C (KW-2083), a derivative of mitomycin C. KW-2083 was administered at a dose of 40 mg once or twice weekly. In 14 evaluable patients, the rate of decrease of pleural fluid was 79%, and that of disappearance of tumor cells in pleural fluid was 64%. Median survival time (MST) from the beginning of treatment in all cases was 163 days. The toxicities of intrapleural instillation of KW-2083 were chest pain (86%), transient fever (64%), anorexia (64%), fatigability (29%), nausea (21%), vomiting (21%) and thrombocytopenia (nadir: 3.5 X 10(4)/mm3; 7%). Serum and pleural fluid KW-2083 concentrations have been measured in 3 patients after intrapleural administration of KW-2083. The mean half life of KW-2083 in serum and pleural fluid was 74 min (69-78 min) and 56 min (33-70 min), respectively. The peak serum KW-2083 concentration was 0.18 microgram/ml (0.06-0.24 microgram/ml).

Adenocarcinoma↗
PubMed1981

Phagovar determination of Pseudomonas aeruginosa and a comparison of the results with mitomycin C induced pyocin production.

One hundred Pseudomonas aeruginosa isolates recovered from intensive care areas of a university hospital and other clinical sites were characterized on the basis of their susceptibility to a set of twenty one phages. These strains were previously mitomycin C induced for their pyocin production and their serovars were also determined. All isolates identified on the basis of belonging to the same O-serovars and pyocin patterns, belonged to oe phagovar group. Strains which were non-identifiable with commercial antisera, had to be typed by both phagovar assay and mitomycin C induced pyocin production. Neither phagovar assay nor pyocin production alone gave enough individual characteristics of any one isolate, as to allow proper identification. Patterns with the same configurations in both phagovar and pyocin groups were detected among strains within entirely different O-serovar groups.

Bacteriocins↗
PubMed1981

Antitumor activity of 7-n-(p-hydroxyphenyl)-mitomycin C in experimental tumor systems.

The antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) was compared with that of mitomycin C (MMC) in rodent tumor systems. M-83 exhibited more potent activity than MMC against the ascitic form of lymphocytic leukemia P388 and fibrosarcoma Meth 1, and doses of over 5 mg/kg of M-83 (1/6 LD50) resulted in some 60-day survivors. The chemotherapeutic ratio (optimal dose/MED) of M-83 was around 64 and was estimated to be approximately 5 to 8 times higher than that of MMC. Upon intravenous administration, M-83 also gave a better survival and showed a higher chemotherapeutic ratio than MMC against intravenously implanted P388. M-83 inhibited the growth of solid form of sarcoma 180 to the same extent as MMC at an equivalent dose, but showed a higher safety margin than MMC. M-83 was as effective as MMC against Lewis lung carcinoma at dose levels giving the same degree of toxicity. In vitro studies on tumor growth inhibition demonstrated that the cytotoxic effects of M-83 against leukemia P388 and fibrosarcoma Meth 1 cells were similar to and stronger than those of MMC, respectively.

Animals↗
PubMed1982

Distribution and excretion of 7-N-(p-hydroxyphenyl)-mitomycin C in normal mice.

Tissue distribution, excretion and stability of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) in normal mice were compared with those of mitomycin C (MMC) by microbiological assay. M-83 was more rapidly inactivated by mouse liver homogenate in vitro than MMC. MMC could not be detected by thin-layer chromatography-bioautography in the reaction mixture of M-83 incubated with mouse liver homogenate, or in the mouse urine. Both M-83 and MMC exhibited biphasic serum elimination characteristics after iv bolus injection. When these compounds were administered at their approximate LD50 (M-83, 20 mg/kg; MMC, 8 mg/kg) iv into mice, their half-lives were 17.9 and 19.8 min, respectively. However, the half-life of M-83 (10.2 mg/kg) after iv bolus injection was 7.5 min and was shorter than that of MMC (8 mg/kg) at the molar equivalent dose. In ip administration of an approximate LD50, M-83 and MMC exhibited similar drug absorption and elimination patterns. When both compounds were administered iv at the approximate LD50, the 24-hr urinary recoveries of unchanged M-83 and MMC were 2.85 and 19.26%, respectively. The distribution of M-83 in various tissues was similar to that of MMC.

Animals↗
PubMed1982

[Periodic prophylactic bladder instillation (PPI) of mitomycin C].

The effect of preoperative bladder instillation (POI) and periodic prophylactic bladder instillation (PPI) of anticancerous drugs was evaluated in connection with the prevention of recurrent bladder tumors after surgery. A total of 191 patients with pTa or pT1 tumors including patients submitted to TURbt and partial cystectomy from January, 1967, to December, 1980, was chosen for the study. They were divided into the following 4 groups: Group A (49 cases) was treated with PPI and POI, Group B (11 cases) with PPI but not POI, Group C (46 cases) with POI but not PPI and Group D (85 cases) with neither PPI nor POI. POI was performed three times a week for a total of 20 applications of anticancerous drugs from two months before surgery. PPI was performed twice a month from one month after TURbt or parital cystectomy with a combination of 20mg of Mitomycin C and 1,000mg of 5-FU. The non-recurrence rate in these 4 groups was estimated by the actuarial method. The 3 year non-recurrence rates in Groups A,B,C and D were 95.4%, 90.9%, 44.0%, and 45.6%, respectively. The 5 year non-recurrence rates in Groups A,B,C and D were 82.4%, 81.0%, 32.0% and 35.1%, respectively. It is presumed from our study that PPI was effective in preventing the recurrence of bladder tumors. In comparison, POI showed a very limited effect and only in the first two years after surgery. No carcinogenic action on the bladder epithelium was observed from the topical use of Mitomycin C.

Adolescent↗
PubMedDate not supplied

MVP (mitomycin, vinblastine, and progesterone): a second-line regimen in ovarian cancer with a high incidence of pulmonary toxicity.

Thirteen patients with epithelial ovarian cancer refractory to primary combination chemotherapy regimens were treated with a three-drug combination called MVP: mitomycin, vinblastine, and progesterone. None of the patients had an objective response to therapy. Five of the 13 patients (39%) developed signs and symptoms consistent with drug-induced pulmonary toxicity following therapy with MVP and histologic confirmation was obtained in two patients. Mitomycin and vinblastine therapy in heavily treated patients with ovarian cancer may be associated with a higher risk of pulmonary toxicity than that previously reported for patients with other tumors.

Antineoplastic Agents↗
PubMed1983

[Phase II study of KW2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with carcinoma of the lung and metastatic pulmonary tumor].

A phase II study of KW2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C], a derivative of Mitomycin C, was carried out in 20 patients with carcinoma of the lung and in 19 patients with metastatic pulmonary tumor. KW2083 was administered by single intravenous injection at a dose of 20-30 mg/m2 weekly or a single 70 mg/m2 dose. Patients treated with a dose of 20-30 mg/m2 should be given at least 3 doses for eligibility. Of 17 evaluable patients with carcinoma of the lung (11 adenocarcinomas, 3 squamous cell carcinomas, 2 small cell carcinomas and 1 large cell carcinoma), two patients with adenocarcinoma showed a partial response (11.8%). Two patients who achieved PR had adenocarcinoma without prior therapy received KW2083 at a single dose of 70 mg/m2 Objective response rates were 18.2% for 11 patients with adenocarcinoma and 25% for 8 patients with adenocarcinoma treated with a single dose of 70 mg/m2 of 15 evaluable patients with metastatic pulmonary tumor, no patients showed any objective responses. The hematologic toxicities were thrombocytopenia (less than 5 X 10(4)/mm3, 41.6%) and leukocytopenia (less than 2000/mm3, 28.1%); it was observed in 19% of the patients, that thrombocytopenia continued for more than 6 weeks after stopping therapy. Gastrointestinal symptoms such as anorexia (81%), nausea (66%) and vomiting (16%) were severe in patients treated with a single dose of 70 mg/m2. Fever in 19%, alopecia in 13%, phlebitis in 9%, eruption in 6%, stomatitis in 6% and liver insufficiency in 13% were also observed.

Adenocarcinoma↗
PubMed1996

Lack of a role of glutathione in cellular nonenzymatic activation of BMS-181174, a novel analogue of mitomycin C.

Recent studies, using a cell-free system, have suggested that thiol-dependent nonenzymatic bioactivation may be responsible for the superior antitumor activity of the mitomycin C analogue BMS-181174 [N-7-[2-(4-nitrophenyldithio)ethyl]mitomycin C] when compared to the parent compound. If operational in tumor cells, this pathway could have enormous clinical implications since tumor cell resistance to a variety of anticancer agents is often associated with increased glutathione (GSH) levels and BMS-181174 may be used to reverse this mechanism of resistance. The present study was undertaken to determine the role of GSH in cellular activation of BMS-181174 using a pair of well-characterized human bladder cancer cells (J82 and SCaBER) as a model. A 20-h pretreatment of J82 and SCaBER cells with a nontoxic concentration of D,L-buthionine-S,R-sulfoximine (BSO) caused about 80-88% reduction in cellular GSH levels. Surprisingly, the sensitivity of both cells to BMS-181174 was increased, not reduced, by BSO-induced GSH depletion. On the other hand, the cytotoxicity of BMS-181174 was significantly reduced in both cells by a 4-h pretreatment with 1 mM GSH. Like BSO, a 4-h pretreatment with another thiol compound (cysteine) resulted in a statistically significant sensitization of both cells to BMS-181174. Cellular GSH levels were not affected in either of the cell lines by pretreatment with GSH or cysteine. In conclusion, the results or the present study argue against a role of GSH in cellular nonenzymatic activation of BMS-181174 in J82 and SCaBER cells.

Antineoplastic Agents, Alkylating↗
PubMed1992

Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts.

Proliferating human Tenon's capsule fibroblasts were exposed for 5 minutes to a wide range of concentrations of fluorouracil, floxuridine, and mitomycin. High concentrations of all three agents had prolonged effects on cell proliferation and morphologic characteristics compared with untreated control cells up to 36 days. The highest concentrations of both floxuridine (15,000 micrograms/mL) and mitomycin (1000 micrograms/mL) had an apparent cidal effect, reducing cell numbers below initial cell density. In contrast, although the highest concentration of fluorouracil (25,000 micrograms/mL) inhibited cell proliferation by more than 50% relative to the untreated control cells at 36 days, the cell numbers still increased fourfold compared with the initial cell density. These results demonstrate that 5-minute treatments with high concentrations of these drugs have prolonged effects on the proliferation of human Tenon's capsule fibroblasts in vitro. Single-dose regimens using high concentrations of these drugs at the time of operation may achieve results similar to those of protocols that involve repeated applications.

Cell Division↗
PubMed1993

Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C.

Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90 degrees and 180 degrees from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed.

Animals↗
PubMed1976

Phase II study of mitomycin-C, vincristine, and bleomycin in advanced squamous cell carcinoma of the uterine cervix.

Utilizing the stathmokinetic principle of timed vincristine and bleomycin, we combined these two agents with Mitomycin-C. The dose schedule included vincristine 0.5 mg/m2 intravenously (i.v.) geginning on day 1 and repeated twice weekly for 12 weeks; each injection was followed in 6-12 hours by bleomycin 6 mg/m2 for 12 weeks. Mitomycin-C was administered as a 20 mg/m2 bolus beginning on day 2 and repeated at 6-week intervals. Thirty patients were entered into this study, 27 were fully available for response. Thirteen patients (48%) met criteria of response (greater than 50% reduction in volume of measurable tumor). Significant myelosuppression resulted from this therapy. Median leukopenia nadir was 3.8 X 10(3) cells/mm3 and median thrombocytopenia nadir was 116 X 10(3) cells/mm3. Additional toxic reactions included anemia, lassitude, anorexia, peripheral neuropath fever, and skin rash. Despite significant, but manageable, toxicity, this combination appears to represent an improvement in the chemotherapy of a traditionaly refractory solid tumor.

Adult↗
PubMed1978

Mitomycin-C and megestrol acetate in treatment of breast cancer refractory to hormonal and combination chemotherapy.

Fifty patients with breast cancer refractory to endocrine manipulation and/or combination chemotherapy were treated with mitomycin-C 20 mg/m2 I.V. every 4-6 weeks and megestrol acetate 160 mg daily. Of 48 evaluable patients, 4% achieved complete remission (CR), 23% had partial remission (PR). Median duration of response for CR and PR was 7 months. Non-responders had a median survival of 2 months. The difference in survival of responders (both CR and PR) and non-responders was statistically significant at p less than 0.01 level. Attenuated doses of mitomycin-C were administered at increasing intervals due to cumulative myelosuppressive toxicity.

Adult↗