Rapid alkalinisation for flavone acetic acid administration: a potentially hazardous procedure.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
J Verweij
Publications and source records attributed to J Verweij.
Indium 111 antimyosin for the detection of leiomyosarcoma and rhabdomyosarcoma.
111In-antimyosin monoclonal antibody complex passes through damaged myocardial cell membranes and binds to the intracellular myosin. Normal myocardial and other muscle cells show no uptake. Rhabdomyosarcoma and Leiomyosarcoma cells also contain intracellular myosin and the cell membrane permeability is greater than normal. Significant uptake of 111In-antimyosin was observed in patients with Leiomyosarcoma and Rhabdomyosarcoma suggesting that the reagent has a potential for the in vivo detection of these tumour types. Tumour to background ratios of 10:1 were measured in one case and in view of the fact that the site of accumulation is intracellular, antimyosin may have a potential as a carrier for therapeutic agents.
Adult↗
Mitomycin C-induced organ toxicity in Wistar rats: a study with special focus on the kidney.
Two studies were performed to investigate acute and chronic organ toxicity after Mitomycin C (MMC) administration in Wistar rats. Six rats received 2.5 mg/kg MMC i.p. once and were followed for 5 consecutive days. The alanine aminopeptidase (AAP)/creatinine ratio increased significantly, compared to a control group receiving saline. Four groups of rats were injected i.p. weekly for 5 weeks; 6 control rats with saline, 7 rats with 1.7 mg/kg of MMC, 7 rats with 10 mg/kg 5-fluorouracil (5-FU) and 7 rats with MMC as well as 5-FU. The latter two groups were included to study possible toxicity synergism between the two drugs. A significant decrease in AAP excretion in the MMC group, as well as a nonsignificant decrease in the MMC/5-FU group were the most remarkable observations. Light microscopy did not show renal changes, but did not show alveolar septal congestion after repeated MMC injections. It is concluded that MMC causes tubular damage in Wistar rats, with acute leakage of enzyme from the cells, followed by enzyme depletion during chronic treatment. Also MMC induces pulmonary changes in Wistar rats. To what extent these changes represent early stages of toxicity remains to be elucidated.
Alanine Transaminase↗
A prospective study on the dose dependency of cardiotoxicity induced by mitomycin C.
Since 1975 mitomycin C (MMC) has been suggested to be cardiotoxic, especially when combined with or given following doxorubicin. Data on dose dependency or incidence concerning this side effect were not known. We have initiated a prospective study to obtain some more data on these subjects. Forty-four MMC-treated patients were studied, 37 of them could be evaluated. All patients were studied by repeated physical examinations, chest X-rays, electro- and echocardiography and radionuclide left ventricular ejection fraction (EF) determinations. The results were evaluated per cumulative dose level. One of the patients developed cardiac failure after 30 mg m-2 MMC and only 150 mg m-2 doxorubicin. The cardiac failure was predicted by a drop in EF determined during a cold pressor test. None of the other patients developed clinical cardiotoxicity, nor did the studied parameters change. The literature on this subject was also reviewed. Based on the combined data from the present study and the literature, we suggest that MMC-related cardiotoxicity is dose dependent, occurring at cumulative dose levels of 30 mg m-2 or more, mainly in patients also (previously or simultaneously) treated with doxorubicin. The incidence is likely to be less than 10% even for this risk group.
Adult↗
The chemistry of 9 alpha-hydroxysteroids. 1. Preparation of 9 alpha,17 beta-dihydroxy-17 alpha-ethynylandrost-4-en-3-one.
9 alpha-Hydroxyandrost-4-ene-3,17-dione 1, when allowed to react with dipotassium acetylide in tetrahydrofuran, resulted, after chromatographic separation, in 4-methyl-19-norandrosta-4,9-diene-1,17-dione 2, 4 xi-methyl-19-norandrosta-5(10),9(11)-diene-1,17-dione 3, 4-methyl-17 alpha-ethynyl-17 beta-hydroxy-19-norandrosta-4,9-dien-1-one 4, 4 xi-methyl-17 alpha-ethynyl-17 beta-hydroxy-19-norandrosta-5(10),9(11)-dien- 1-one 5, and 17 alpha-ethynyl-17 beta-hydroxy-9,10-secoandrost-4-ene-3,9-dione 6. Selective protection of delta 4-3-ketone of 9 alpha-hydroxyandrost-4-ene-3,17-dione 1 as its dienol methyl ether 7, and subsequent reaction with lithium acetylide-ethylenediamine followed by acidic hydrolysis, afforded 9 alpha,17 beta-dihydroxy-17 alpha- ethynylandrost-4-en-3-one 8.
Adrenal Cortex Hormones↗
The pharmacokinetic plasma profile of mitomycin C, measured after sequential intermittent intravenous administration.
The pharmacokinetic plasma profile of mitomycin C (MMC) was studied during sequential courses in man. MMC was given repeatedly as i.v. bolus injections at fixed dose levels to the same patient either as a single agent or as part of different combination chemotherapy regimens. Large interindividual variations between the various pharmacokinetic parameters were observed. Statistical analysis showed no significant differences between average pharmacokinetic parameters when comparing the first and the second MMC injection, except for the total body clearance (Cltot). The Cltot was higher for the second injection when compared to the first injection in a group of patients who received MMC as a single agent (10 patients). For a group of patients receiving MMC as part of a combination therapy the average values of Cltot of the first when compared to the second injection were not statistically different (nine patients). This observation could not be correlated with clinical observations on toxicities.
Adult↗
5-Fluorouracil, doxorubicin and mitomycin C (FAM) combination chemotherapy for metastatic adenocarcinoma of unknown primary.
The prognosis of patients with adenocarcinoma of unknown primary (ACUP) is dismal. Various chemotherapy regimens have yielded disappointing response rates and survival. Based on a promising report of Goldberg et al. (J Clin Oncol 1986, 4, 395-399) we performed a phase II study with 5-fluorouracil, adriamycin and mitomycin C (FAM). Only three out of 22 evaluable patients achieved a partial response (14%) for a duration of 22, 30 and 74+ weeks. Median survival was 54+ weeks (range 35-74+ weeks) for responding patients and 33+ weeks (range 9-74+ weeks) for all treated patients. One patient (5%) developed mitomycin C induced hemolytic uremic syndrome. FAM cannot be recommended for routine use in patients with ACUP.
Adenocarcinoma↗
Ifosfamide in advanced head and neck cancer. A phase II study of the Rotterdam Cooperative Head and Neck Cancer Study Group.
Explore the source record for details and available documents.
Adult↗
Etoposide and cisplatin in advanced esophageal cancer. A preliminary report.
In order to find an effective and suitable chemotherapy regimen for preoperative treatment of esophageal cancer, patients with inoperable or metastatic disease were treated with a combination of etoposide and cisplatin. Of 27 evaluable patients, 13 had squamous cell carcinoma, 13 adenocarcinoma, and 1 muco-epidermoid carcinoma. No complete responses were noted. Nine of 13 patients with squamous cell carcinoma and only one of 13 with adenocarcinoma showed a partial response. Nine of 10 responders achieved a partial response after 2 courses, one after 4 courses. There was one toxic death, due to sepsis during leukopenia. Other toxicities were alopecia, nausea and vomiting, nephrotoxicity, thrombocytopenia and leukopenia.
Adult↗
Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis.
Lung damage after mitomycin C (MMC) was first reported in 1978. Although this side effect has been frequently reported since then, there are no data on dose dependency nor on incidence. Therefore, the authors initiated a prospective study to obtain more data on this subject. Forty-four patients treated with MMC entered the study; 37 were evaluable. All patients were subjected to repeated physical examinations, chest x-rays, chest computed tomography (CT) scan and pulmonary function tests. The results were evaluated per cumulative dose level. None of the patients had clinical pulmonary toxicity develop; one patient had pulmonary changes on CT scan, the significance of which remained unclarified. The world literature on this subject was also reviewed. Based on the combined data of the present study as well as the literature review, the authors concluded that MMC-related lung toxicity is a dose-dependent side effect, occurring at cumulative dose levels of 20 mg/m2 or more. The incidence is likely to be less than 10%.
Adult↗
[Severe tissue necrosis due to extravasation of mitomycin].
Explore the source record for details and available documents.
Extravasation of Diagnostic and Therapeutic Materi↗
Absence of interaction between furosemide and mitomycin C.
The possible interaction between furosemide and mitomycin C (MMC) was studied in five patients. The pharmacokinetics of MMC were studied using an HPLC assay. Furosemide was administered prior to, or 120 min after MMC. Furosemide did not change the pharmacokinetics of MMC, nor did it change the amount of MMC excreted in the urine. There appears to be no interaction between the two drugs.
Adult↗
Relationship between clinical parameters and pharmacokinetics of mitomycin C.
Although the number of reports on mitomycin C (MMC) pharmacokinetics is increasing, data on possible relations between clinical parameters and pharmacokinetics are usually lacking. The present report concerns the results of a detailed study on this subject in 35 patients receiving MMC, either as a single agent or as a part of combination chemotherapy. MMC concentrations were determined by HPLC. T1/2 beta varied from 23 to 78 min, VD from 11 to 48 l/m2, Cl tot from 12 to 42 l/h per m2, and AUC from 138 to 1221 micrograms/h per l, confirming previously reported data. Infusion time, cholestasis, and urinary pH did not influence the pharmacokinetic data. There were no relations between other clinical data and pharmacokinetics, nor between AUC and bone marrow toxicity. An interaction between MMC and furosemide could not be excluded, but there was no interaction with other comedication. Consecutive pharmacokinetics in 6 patients showed consistent results. Because renal impairment does not alter MMC pharmacokinetics and renal excretion is not a major route of elimination, it is suggested that renal impairment does not call for dose adjustment.
Adult↗
Mitomycin C is an inactive drug in the third-line treatment of hormone and chemotherapy refractory breast cancer.
Mitomycin C (MMC) is rarely used in first-line chemotherapy for advanced breast cancer, although the drug is reported to be active. Treatment with MMC is usually reserved for second- or third-line treatment. We have given MMC as second- or third-line treatment to 59 patients. Fifty-six patients were evaluable for response. No complete and only 3 partial responses were observed for an overall response rate of 5%. The median time to progression was 2 months and median survival time was 6 months. In this retrospective study MMC is demonstrated to be inactive in third-line chemotherapy.
Adult↗
Cyclophosphamide, hexamethylmelamine, adriamycin and cisplatin combination chemotherapy in mixed mesodermal sarcoma of the female genital tract.
Clinically mixed mesodermal sarcoma is a different entity among the other subtypes of soft tissue sarcomas. Although adriamycin is considered to be the most active single agent in the treatment of adult soft tissue sarcomas, the drug has only limited activity in mixed mesodermal sarcomas. On the other hand, cisplatin is inactive in soft tissue sarcomas, but was reported to be active in mixed mesodermal sarcomas. Therefore combinations including both adriamycin and cisplatin appear attractive for testing in the treatment of mixed mesodermal sarcomas. We have performed a pilot study with two combinations in mixed mesodermal sarcomas of the female genital tract. Two patients treated with adriamycin and cisplatin showed rapid progression. Of 7 patients treated with cyclophosphamide, hexamethylmelamine, adriamycin and cisplatin (CHAP-5), 6 had measurable disease, of whom 5 yielded a response (2 complete responses for 19+ and 40 months and 3 partial responses for 4, 7 and 8 months). The patient with non-measurable disease had a progression-free survival of 27 months. The median survival for all CHAP-5-treated patients was 20 months. This regimen is recommended for further phase II studies.
Aged↗
Mitomycin C-induced hemolytic uremic syndrome. Six case reports and review of the literature on renal, pulmonary and cardiac side effects of the drug.
Six new cases of mitomycin C (MMC)-induced hemolytic uremic syndrome are reported and the literature on renal-, pulmonary- and cardiotoxicity of the drug is reviewed. The number of reports concerning these side effects is still increasing. The incidence of all three side effects will be below 10%, while there appears to be a dose-dependency, with toxicity mainly occurring at cumulative doses of 20-30 mg/m2 or more. Toxicity often develops very sudden and the mortality rate especially of HUS is very high despite supportive care. The pathogenesis of toxicity is still unknown, although for HUS there are indications for a role of circulating immune complexes. The pulmonary toxicity can often be treated by corticosteroids, while the left ventricular cardiac failure can be treated with diuretics. The possible role of oxygen radicals in the development of MMC side effects is mentioned.
Adult↗
Severe side effects of the cytotoxic drug mitomycin-C.
Explore the source record for details and available documents.
Animals↗