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Journal of Clinical Oncology : Official... Sep 1989One thousand four hundred sixty patients with 2,590 patient-years of follow-up were treated on 15 protocols for metastatic breast cancer with dibromodulcitol... (Review)
Review
One thousand four hundred sixty patients with 2,590 patient-years of follow-up were treated on 15 protocols for metastatic breast cancer with dibromodulcitol (mitolactol; DBD)-containing regimens since 1976. Twenty-three patients developed myelodysplastic syndrome (MDS) and/or acute nonlymphocytic leukemia (ANLL). The overall risk of developing MDS or ANLL per person is 1.6%. In patients who had received more than 16,000 mg of DBD the risk per person is 6%, and in the high-dose subsets of patients who received no prior radiation or alkylator therapy, it is 7.9%. The risk per person increases to a maximum by 30 to 36 months (5.3%). The high risk was seen despite a study population of metastatic breast cancer patients with a median survival of 16 months. This analysis strongly suggests that DBD is one of the most potent of the reported leukemogenic-inducing agents. Further use of this drug in both the adjuvant and metastatic situation should be reconsidered.
Topics: Adult; Aged; Breast Neoplasms; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mitolactol; Myelodysplastic Syndromes; Risk
PubMed: 2671284
DOI: 10.1200/JCO.1989.7.9.1252 -
Cancer Treatment Reviews Sep 1979
Clinical Trial Review
Topics: Animals; Bone Marrow; Chemical Phenomena; Chemistry; Clinical Trials as Topic; DNA, Neoplasm; Drug Resistance; Female; Humans; Immunity; Mitolactol; Neoplasms; Neoplasms, Experimental
PubMed: 394837
DOI: 10.1016/s0305-7372(79)80070-5 -
Magyar Onkologia Dec 2017The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines... (Review)
Review
The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action. Myelobromol with selective action on the myeloid elements of bone marrow has been justified for its application in chronic myeloid leukemia therapy and also in bone marrow ablation before transplantation. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors. 5-etil-2'-deoxyuridine by reducing dihydropyrimidine dehydrogenase activity is able to increase 5-fluorouracil concentration in the blood, resulting in improved antitumor effect. In contrast, 5-hexil-2'-deoxyuridine, as an inhibitor of glycoconjugate pathway by reducing heparan sulfate production, has the ability to prevent metastasis. Noteworthy, the remarkable effects of vinca alkaloids, antiestrogens, and GNRH analogues were also presented in this review.
Topics: Antineoplastic Agents, Alkylating; Databases, Factual; Drug Design; Forecasting; Humans; Hungary; Mannomustine; Mitobronitol; Mitolactol; Pharmaceutical Research; Pharmacology, Clinical; Quality Improvement; Retrospective Studies
PubMed: 29257158
DOI: No ID Found -
Journal of Clinical Oncology : Official... Jan 1997Cisplatin, mitolactol (dibromodulcitol), and ifosfamide have been the most active single agents in squamous carcinoma of the cervix identified so far by the Gynecologic... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study.
PURPOSE
Cisplatin, mitolactol (dibromodulcitol), and ifosfamide have been the most active single agents in squamous carcinoma of the cervix identified so far by the Gynecologic Oncology Group (GOG). Combinations of cisplatin plus ifosfamide and cisplatin plus mitolactol are prospectively compared with cisplatin alone.
PATIENTS AND METHODS
Patients were randomized to receive cisplatin 50 mg/m2 or the same dose of cisplatin plus mitolactol (C + M) 180 mg/m2 orally on days 2 to 6, or cisplatin plus ifosfamide (CIFX) 5 g/m2 given as a 24-hour infusion plus mesna 6 g/m2 during and for 12 hours after the ifosfamide infusion, every 3 weeks for up to six courses. Of 454 patients entered, 438 were eligible and analyzed for response and survival.
RESULTS
CIFX had a higher response rate (31.1% v 17.8%, p = .004) and longer progression-free survival (PFS) time (P = .003) compared with cisplatin alone. The median times to progression or death were 4.6 and 3.2 months, respectively. C + M showed no significant improvement in these parameters compared with cisplatin alone. Survival was associated with initial performance score (PS; 0 was more favorable; P < .001) and with age (younger was unfavorable, P = .025). There was no significant difference in overall survival between cisplatin and either of the combinations. Leukopenia, renal toxicity, peripheral neurotoxicity, and CNS toxicity were more frequent with CIFX (P < .05).
CONCLUSION
CIFX improved the response rate and PFS duration in advanced cervix cancer compared with cisplatin alone, but at the cost of greater toxicity and with no improvement in survival.
Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Ifosfamide; Middle Aged; Mitolactol; Prospective Studies; Remission Induction; Survival Analysis; Uterine Cervical Neoplasms
PubMed: 8996138
DOI: 10.1200/JCO.1997.15.1.165 -
Journal of Pharmaceutical Sciences Sep 1985A method involving precolumn derivatization and high-performance liquid chromatography is described for the measurement of mitolactol levels in plasma. The basis of the...
A method involving precolumn derivatization and high-performance liquid chromatography is described for the measurement of mitolactol levels in plasma. The basis of the assay is the reaction at pH 7.4 and 50 degrees C of mitolactol with diethyldithiocarbamate to form 1,6-bis(diethyldithiocarbamoyl)-2,3,4,5-tetrahydroxyhexane. This derivative is then extracted into chloroform, resolved by normal-phase chromatography, and detected by UV (254 nm) absorbance. The method quantitates the sum of mitolactol and its active bifunctional metabolites, bromoepoxydulcitol and dianhydrogalactitol, in plasma down to concentrations of 0.5 microM. The pharmacokinetic parameters of the drug in mice have been determined following the intraperitoneal injection of either 20 or 100 mg/kg of body weight. Absorption from the peritoneal cavity was largely complete by 5 min. Parameters obtained include a first-order elimination constant, k = 0.92 X 10(-2) min-1 and an apparent volume of distribution, Vd = 0.78 L/kg. For a 100-mg/kg dose, the area under the concentration-time curve was 49 mM X min, and the mean peak drug concentration was reached at 40 min following intraperitoneal injection. Concentrations of mitolactol in total plasma and in plasma ultrafiltrates were identical, indicating that the drug is not (less than 4%) reversibly bound to plasma proteins.
Topics: Alkylation; Animals; Biotransformation; Body Fluids; Buffers; Chromatography, High Pressure Liquid; Cross-Linking Reagents; Ditiocarb; Drug Stability; Humans; Kinetics; Male; Mice; Mice, Inbred Strains; Mitolactol; Spectrophotometry, Ultraviolet
PubMed: 2999377
DOI: 10.1002/jps.2600740915 -
American Journal of Clinical Oncology Aug 1985One hundred fifty-one women with advanced breast cancer who had failed prior chemotherapy were randomized to monthly courses of doxorubicin (60 mg/m2 I.V. day 1,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
One hundred fifty-one women with advanced breast cancer who had failed prior chemotherapy were randomized to monthly courses of doxorubicin (60 mg/m2 I.V. day 1, observation after 500 mg/m2) or doxorubicin (40 mg/m2 I.V. day 1; maximum 500 mg/m2) and mitolactol (135 mg/m2 orally, days 1-10; 180 mg/m2 after maximum doxorubicin). Median survival times were 232 days for doxorubicin and 225 days for doxorubicin + mitolactol, and median times to progression were 112 days and 97 days, respectively. Results are inconsistent with a 25% improvement in survival or time to progression for doxorubicin + mitolactol (p = 0.04 and 0.02, respectively, adjusted for stratification factors but not multiple testing). Regression rates for all patients, both measurable and evaluable, were 30% for doxorubicin alone and 26% for doxorubicin + mitolactol. Regression rates were significantly higher in patients with measurable indicator lesions. Cardiac toxicity was seen in four patients, all of whom were receiving doxorubicin alone. It appears that the combination of doxorubicin + mitolactol is not substantially more effective than doxorubicin alone in women with advanced breast cancer and prior chemotherapy exposure.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Doxorubicin; Drug Evaluation; Female; Humans; Leukopenia; Middle Aged; Mitolactol; Random Allocation; Thrombocytopenia
PubMed: 3909798
DOI: 10.1097/00000421-198508000-00001 -
Neurologic Clinics Nov 1985This article covers chemotherapy of malignant astrocytomas, ependymoma, and medulloblastoma. The future direction of anticancer drugs is discussed. (Comparative Study)
Comparative Study Review
This article covers chemotherapy of malignant astrocytomas, ependymoma, and medulloblastoma. The future direction of anticancer drugs is discussed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Brain Stem; Child; Eflornithine; Ependymoma; Fluorouracil; Glioblastoma; Humans; Hydroxyurea; Lomustine; Medulloblastoma; Methotrexate; Mitoguazone; Mitolactol; Neoplasm Recurrence, Local; Ornithine; Prednisone; Risk; Thioguanine; Vincristine
PubMed: 3001491
DOI: No ID Found -
British Medical Journal (Clinical... Jul 1983
Topics: Alkylating Agents; Altretamine; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Etoposide; Humans; Mitobronitol; Mitolactol; Nitrosourea Compounds; Razoxane; Vinca Alkaloids
PubMed: 6407699
DOI: 10.1136/bmj.287.6385.110 -
Therapia Hungarica (English Edition) 1977
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Mitolactol; Neoplasms; Remission, Spontaneous
PubMed: 854865
DOI: No ID Found -
American Journal of Clinical Oncology Jun 1992In this Phase I study, thirteen women with advanced cervix cancer were treated with mitolactol (dibromodulcitol) plus cisplatin to determine a maximum tolerable dose... (Clinical Trial)
Clinical Trial
In this Phase I study, thirteen women with advanced cervix cancer were treated with mitolactol (dibromodulcitol) plus cisplatin to determine a maximum tolerable dose schedule. Response was not an objective of this study, but four partial responses were seen in nine patients with measurable lesions. In general, the therapy was well tolerated, but of the ten patients treated at the first dose level (cisplatin 50 mg/m2 intravenously on day 1 plus mitolactol 180 mg/m2 orally on days 2-6 every 3-4 weeks), 5 required de-escalations and 8 required delays because of toxicity. All three patients treated with cisplatin plus a higher dose of mitolactol (270 mg/m2 x 5) required dose reductions and delays for hematologic toxicity. The first dose level appears tolerable by patients with, and promising in treating, advanced cervix cancer.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Evaluation; Female; Humans; Middle Aged; Mitolactol; Uterine Cervical Neoplasms
PubMed: 1590269
DOI: 10.1097/00000421-199206000-00001