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Oncology 1991Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other...
Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other cytostatics. Sister chromatid exchanges (SCE) in the lymphocytes in peripheral blood as well as other haematological parameters were measured in women with breast cancer to investigate whether women who had previously been treated with DBD as a part of their treatment regime had an increased frequency of SCE or another haematological abnormality attributable to DBD. SCE levels were elevated in women treated with DBD as well as in those treated with other cytostatics compared to the untreated control group. All other haematological parameters were normal. There was no significant difference in the number of SCEs between the patients who received DBD and those treated with other cytostatics. The increased frequencies of SCE in the treated patients are attributable to various cytostatic agents, and there is no significant permanent increase in the frequency of SCE after exposure to DBD.
Topics: Breast Neoplasms; Female; Humans; Lymphocytes; Mitolactol; Neoplasm Metastasis; Sister Chromatid Exchange
PubMed: 2023706
DOI: 10.1159/000226937 -
European Journal of Cancer (Oxford,... 1991Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF or CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Methotrexate; Middle Aged; Mitolactol; Prognosis; Prospective Studies; Time Factors; Vincristine
PubMed: 1832906
DOI: 10.1016/0277-5379(91)90261-b -
Anticancer Research 1990Dibromodulcitol (DBD) is an anticancer agent that is cytotoxic against animal and human brain tumors in vivo. Clinical trials of combination therapy with radiation, DBD,...
Dibromodulcitol (DBD) is an anticancer agent that is cytotoxic against animal and human brain tumors in vivo. Clinical trials of combination therapy with radiation, DBD, and a nitrosourea have shown some efficacy, but the mechanisms that lead to enhanced cytotoxicity are poorly understood. We investigated the effects of pretreatment with DBD on cell survival and sister chromatid exchange (SCE) caused by subsequent treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) in 9L rat brain tumor cells. Pretreatment of 9L cells for 24 hr with 5 microM DBD potentiated the cell kill produced by a 1-hr treatment with BCNU; the dose enhancement ratio was 1.7 at the 10% survival level. Treatment of 9L cells for 24 hr with 1 microM DBD induced 39 +/- 12 SCEs/metaphase. There was a 50-75% increase in BCNU-induced SCEs, compared with BCNU alone, after a 24 hr pretreatment with DBD. Thus DBD potentiation of BCNU cytotoxicity appears to be related to increased DNA damage.
Topics: Animals; Brain Neoplasms; Carmustine; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Drug Synergism; Kinetics; Mitolactol; Sister Chromatid Exchange
PubMed: 2285238
DOI: No ID Found -
Casopis Lekaru Ceskych Oct 1990A combination of cytostatics--Rubomycin (Medexport), Alcysten (Spofa) and LANVIS (Wellcome) was used to treat 44 patients with the diagnosis AML. A total of 66% CR was...
A combination of cytostatics--Rubomycin (Medexport), Alcysten (Spofa) and LANVIS (Wellcome) was used to treat 44 patients with the diagnosis AML. A total of 66% CR was achieved. The median duration of CR was 15 months and the median of survival of patients with CR was 25 months. 20% of the patients died in induction mostly from infectious complications. The authors assume that this combination with the use of the Czech preparation Alcysten and the Soviet preparation Rubomycin is suitable induction treatment in AML. Treatment, however, calls for perfect supporting therapy and therefore should by concentrated in selected departments.
Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Leukemia, Myeloid; Middle Aged; Mitolactol; Tamoxifen
PubMed: 2249232
DOI: No ID Found -
Journal of Clinical Oncology : Official... Apr 1990
Topics: Breast Neoplasms; Female; Humans; Leukemia, Myeloid, Acute; Mitolactol; Myelodysplastic Syndromes
PubMed: 2313338
DOI: 10.1200/JCO.1990.8.4.751 -
European Journal of Cancer (Oxford,... Feb 1990The bromine content of human gliomas and white matter was determined by neutron activation analysis (NAA) following p.o. administration of a single dose of 400-500 mg/m2...
The bromine content of human gliomas and white matter was determined by neutron activation analysis (NAA) following p.o. administration of a single dose of 400-500 mg/m2 dibromodulcitol (DBD). In another group of patients with brain gliomas, the bromine content was measured subsequent to application of a single dose of 334 mg/m2 of sodium bromide (equivalent dose regarding the bromine content of DBD). The bromine content of these two groups was compared to the values found in a third control group of untreated patients. The amount of bromine after DBD application was three to four times higher than in the untreated samples and the average accumulation ratio of 1.8 +/- 0.4 proved to be nearly identical both in tumour and white matter. The bromine values after NaBr treatment showed a different pattern of distribution. The accumulation was higher in the tumour tissue than in the normal white matter. These findings demonstrate that the pharmacokinetic properties of DBD- and NaBr-derived bromine are different, suggesting that the increase of bromine after DBD administration could be due to covalently bound bromine in DBD.
Topics: Brain Chemistry; Brain Neoplasms; Bromine; Glioblastoma; Humans; Mitolactol; Neutron Activation Analysis
PubMed: 2157475
DOI: 10.1016/0277-5379(90)90286-3 -
Haematologia 1990Seventy-two consecutive and previously untreated adults with acute non-lymphoblastic leukaemia (ANLL), having a median age of 36 years (range 12 to 71), were... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Seventy-two consecutive and previously untreated adults with acute non-lymphoblastic leukaemia (ANLL), having a median age of 36 years (range 12 to 71), were prospectively randomised to receive conventional doses of cytosine arabinoside and doxorubicin combined with either etoposide (CTR III) or 6-thioguanine (DAT). Morbidity was comparable between the two regimens and complete remission (CR) rates of 52% and 62% respectively (p greater than 0.50) were not influenced by age above or below 50 years, initial white cell count, French-American-British classification, or race. However, growth pattern in the GM: CFUc assay was found to identify a subgroup of patients who had a significantly higher CR rate. Similarly, the secretion of tissue plasminogen activator by leukaemic blasts in vitro uniformly predicted for primary drug resistance, whereas a CR rate of 68% was associated with production of the urokinase type or a mixture of both enzymes. Remission duration and survival did not differ between these two forms of chemotherapy, nor were they influenced by immunotherapy with C. parvum or the duration of maintenance therapy, whereas age below 50 and the species of plasminogen activator secreted were significant prognostic factors. It is concluded that etoposide can be substituted for 6-thioguanine in these cytosine arabinoside and doxorubicin-containing regimens and that for both combinations the most sensitive prognostic factor for CR and survival is the species of plasminogen activator secreted in vitro by the leukaemic blasts.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Doxorubicin; Etoposide; Female; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitolactol; Prospective Studies; Randomized Controlled Trials as Topic; Remission Induction; Survival Rate; Tamoxifen
PubMed: 2204594
DOI: No ID Found -
Journal of Clinical Oncology : Official... Dec 1989Sixty patients with advanced squamous cell carcinoma of the cervix (SCC) who had received no prior chemotherapy were entered onto a study of mitolactol (dibromodulcitol... (Clinical Trial)
Clinical Trial
Sixty patients with advanced squamous cell carcinoma of the cervix (SCC) who had received no prior chemotherapy were entered onto a study of mitolactol (dibromodulcitol [DBD]). The drug was administered orally at an initial dose of 180 mg/m2 per day for 10 days and repeated every 4 weeks. There were 55 evaluable patients, of whom one (2%) had a complete response (CR), and 15 (27%) had a partial response (PR), (CR plus PR, 29%). A 95% confidence interval for the true response rate is 18.8% to 42.1%. Myelosuppression was appreciable at this dose and schedule, with 13 patients experiencing life-threatening thrombocytopenia and two drug-related deaths. The level of activity in this disease encourages us to determine a tolerable dose of this drug in combination with cisplatin for further study.
Topics: Adult; Aged; Bone Marrow; Carcinoma, Squamous Cell; Drug Evaluation; Female; Humans; Middle Aged; Mitolactol; Multicenter Studies as Topic; Uterine Cervical Neoplasms
PubMed: 2685182
DOI: 10.1200/JCO.1989.7.12.1892 -
Carbohydrate Research Dec 1989
Topics: Calorimetry; Kinetics; Mitolactol; Molecular Structure; Solubility; Solutions
PubMed: 2620304
DOI: 10.1016/0008-6215(89)85030-x -
Cancer Oct 1989Two Adriamycin (doxorubicin)-based chemotherapy regimens were investigated in patients with carcinoma of the breast who had failed prior systemic therapy. The two... (Comparative Study)
Comparative Study
Combination chemotherapy of advanced breast cancer. Comparison of dibromodulcitol, doxorubicin, vincristine, and fluoxymesterone to thiotepa, doxorubicin, vinblastine, and fluoxymesterone: an Eastern Cooperative Oncology Group Study.
Two Adriamycin (doxorubicin)-based chemotherapy regimens were investigated in patients with carcinoma of the breast who had failed prior systemic therapy. The two chemotherapy programs, dibromodulcitol, Adriamycin, vincristine, and Halotestin (fluoxymesterone) (DAVH), and thiotepa, Adriamycin, vinblastine, and Halotestin (TAVH), were chosen for comparison on the basis of reported response rates of 40% to 50% with remission durations of 11 months in patients refractory to other cytotoxic chemotherapy. Cycles of DAVH were repeated every 4 weeks. Cycles of TAVH were repeated every 3 weeks. Of 184 patients evaluable for response, 32% of patients treated with DAVH and 38% of patients treated with TAVH had a complete response (CR) or partial response (PR). An additional 5% of patients had nonmeasurable improvement in osseous disease for an overall rate of response (CR + PR + improvement) of 40%. Patients who had previously received cytotoxic chemotherapy for metastatic disease or had early failure after adjuvant therapy had a lower response rate to DAVH, but not to TAVH than those who did not fail prior chemotherapy. Duration of response and survival were similar with the two treatments. There were seven treatment-related deaths, five among patients receiving DAVH and two among patients receiving TAVH. Patients receiving DAVH had significantly more thrombocytopenia and neurologic toxicity than those receiving TAVH. These treatments appear to be reasonable second-line regimens and are good candidates to be used in initial therapy of metastatic disease or adjuvant therapy studies that explore the use of alternating non-cross-resistant combinations with cyclophosphamide, methotrexate, and 5-fluorouracil.
Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Evaluation; Female; Fluoxymesterone; Humans; Leukopenia; Middle Aged; Mitolactol; Neoplasm Recurrence, Local; Nervous System Diseases; Thiotepa; Thrombocytopenia; Vinblastine; Vincristine
PubMed: 2505919
DOI: 10.1002/1097-0142(19891001)64:7<1393::aid-cncr2820640704>3.0.co;2-b