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At least 19 recordsLinked to original sources
PubMed1992

Chemotherapy of cervix cancer with mitolactol (dibromodulcitol, NSC 104800) and cisplatin. A phase I study of the Gynecologic Oncology Group.

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.

Adult↗
PubMed1976

Preliminary experience with Mitolactol in advanced tumors of the orofacial region and the larynx.

Mitolactol (Dibromodulcitol "DBD"; RlobromolR) an alkylating agent was applied in a clinical series of twenty advanced or relapsing cases of malignant tumors of the orofacial region and the larynx. It was administered orally in a mean total dose of 127 mg/kg/30 days. In 45% of the patients the treatment resulted in a diminution of tumors by more than 50%, with remission lasting 1-4 months. 30% of the patients responded by a retreat of the tumor volume smaller than 50%, while no therapeutic effect was noted in 25% of the patients, or the objective finding proved to be worse. Subsequent radiotherapy improved the results, and remissions which followed combined chemo-radiotherapy were prolonged up to 9 months. The effect of DBD treatment proved better in orofacial than in laryngeal carcinoma.

Adult↗
PubMed1991

Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer.

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study.

Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with mitolactol, doxorubicin, vincristine (DAV), tamoxifen, and fluoxymesterone (DAVTH). Nine patients were canceled, and 114 were ineligible (half because of concomitant diseases). Among the 501 eligible patients, the overall response rate was 54% (14% complete response and 5% not assessable). The median time to treatment failure (TTF) was 9.0 months, and the median survival was 20.9 months. Multivariate models were fit on a randomly chosen half of the eligible cases and then verified on the other half. About half of the variables that were significant in the models remained significant in the verification data set. In the verification data set the variables that remained significantly associated with lower probability of response were three or more organ sites of disease and lack of nodal metastases; the variables associated with a significantly shorter TTF were liver metastases, estrogen receptor (ER)-negativity, and prior adjuvant therapy. The variables associated with significantly shorter survival were liver metastases, ER negativity, three or more organ sites of disease, and prior adjuvant chemotherapy. None of the variables in the data set had a significant influence on toxicity. The 125 patients aged over 65 years did not have worse toxicity or worse prognosis than younger patients. Ineligible patients had significantly less response but virtually identical TTF curves, survival curves, and toxicities. Therefore, patient discriminants are of paramount importance in predicting the outcome of treatment. Many of the current criteria for eligibility for entry on study may not be justified.

Adenocarcinoma↗
PubMed1975

Bone changes in young mice with impaired lymphoid system.

Disturbances of osseal growth were observed in young mice with their lymphoid system affected by antihymocyte serum or mitolactol (dibromodulcitol) treatment. These bone changes were similar to those observed in germ-free and neonatally thymectomized mice as well as in mice suffering from a graft vs. host reaction. Their severity was in direct correlation with the disturbance of the thymus dependent lymphoid system. Not only immunological adaptation but also normal bone growth appears to require an intact thymus and thymus dependent lymphoid system.

Animals↗
PubMed1979

Intra-arterial chemotherapy of head and neck tumours.

The benefits and complications of regional chemotherapy in the treatment of head and neck tumours are discussed. Intra-arterial chemotherapy has been employed in 72 cases of preoperative, postoperative and palliative management. Cytostatic treatment consisted of combined Vincristine, bleomycin, methotrexate, and mitolactol administration by a Watkins-USCI or Sharp chronofusor. In cases of preoperative treatment the tumour regression was in the range of 50-80%. Tumours of the gingiva, parotid gland, maxilla and tonsil responded very well, tumours of the tongue less well to the treatment. The most dangerous complication is thrombosis of the common carotid artery; to avoid this complication the prothrombin index was reduced and kept at the 30-40% level.

Antineoplastic Agents↗
PubMed1992

Treatment of recurrent gliomas and metastatic brain tumors with a polydrug protocol designed to combat nitrosourea resistance.

PURPOSE: The study was undertaken to evaluate a chemotherapy protocol against recurrent malignant gliomas that was designed to combat presumed chloroethyl-nitrosourea (NU) resistance. PATIENTS AND METHODS: All patients had malignant gliomas and had failed prior therapy. Patients were stratified as having either glioblastoma multiforme (GM) or anaplastic gliomas (AG) and as having failed radiotherapy (RT) only or both RT and chemotherapy. Chemotherapy consisted of six drugs: before lomustine (CCNU), thioguanine (TG), dibromodulcitol (mitolactol; DBD), and procarbazine (PCB) were given to enhance CCNU-induced tumor-cell kill and to reduce alkyltransferase repair of ethylated DNA. A fluorouracil-hydroxyurea (FUHU) combination was given 2 weeks later to kill cells that began to cycle after the challenge of the first four drugs (TPDC-FUHU chemotherapy). RESULTS: Of the 88 assessable patients, 37 had GM, 38 had AG, and 13 had other primary and metastatic brain tumors. For GM patients, 61% had a partial response (PR) or stable disease (SD) for a median of 9.3 months if RT only failed, and 58% had a PR or SD for a median of 5.1 months if they had previously been treated with an NU. For AG patients, 92% had a PR or SD for a median of 15 months if RT only had failed, but only 38% had a PR or SD for a median of 10.6 months if they had been previously treated with a NU. Activity was also seen against other recurrent or progressive primary and metastatic brain tumors. CONCLUSIONS: TDPC-FUHU chemotherapy is a highly effective form of chemotherapy for both recurrent GM and AG patients. This study suggests but does not prove that this combination may be superior to other NU-based treatments for recurrent malignant glioma patients who fail RT. Because of the activity of this chemotherapy, we intend to evaluate more fully this approach in a randomized study.

Adolescent↗
PubMed1992

[Comparative study of preoperative chemotherapy and radiotherapy in squamous cell carcinoma of the oral cavity].

The results of the preoperative Co 60 irradiation and BVMM (bleomycin, vincristine, mitolactol, methotrexate) chemotherapy were compared. Both treatments were used in 50-50 advanced squamous cell cancer of the oral cavity. The general condition, size of lesion and age of the patients were similar. Surgery in the irradiated group was significantly more radical at the primary sites. Local recurrences during a three-year follow-up period were diagnosed in 36% from the radiotherapy group, whilst 8% such recurrences diagnosed in the chemotherapy group. There was no significant difference in the radicality of lymph node surgery. Lymph node recurrences occurred in 8% from the irradiated group, whilst 22% was diagnosed in the chemotherapy group. The main opinion is that BVMM chemotherapy and irradiation can be used to support one another in the interest of better result, like preoperative chemo- and postoperative radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1975

Cytostatic treatment of polycythaemia rubra vera. Comparison of the effects of some cytostatics in 100 patients in a period of five years.

Experience with cytostatic treatment performed in patients with polycythaemia rubra vera is reviewed. The effectivity and side effects of the drugs applied are evaluated. Mannosulfan and mitobromitol were the drugs most sutiable for treatment. In certain special cases, 5-hydroxyurea was also satisfactory, while mitolactol was the least suitable.

Adolescent↗
PubMed1975

Enhancement by drugs of metastatic lung nodule formation after intravenous tumour cell injection.

In studies on a model of induced pulmonary metastasis in mice a tumour host system was analysed which was not affected by immunogenicity of the tumour for the host; neither intensive immunosuppression nor immunization caused a significant change in the quantity of pulmonary metastatic nodules. In contrast the application of cytostatic drugs and of Corynebacterium parvum could modify the pulmonary resistance to the formation of tumour nodules by a factor greater than 100 in either direction. This finding confirms the observation of others that major modification of the resistance to metastatic tumour formation can occur independently of classical immunological mechanisms. Special attention is drawn to the fact that cyclophosphamide enhances the formation of metastatic nodules in this model by factors of 100 to more than 1,000 whereas other cytostatic drugs including the cyclophosphamide congeners iphosphamide and trophosphamide are active only factors between 2 and 12. The possible practical significance of these findings is discussed.

Alkylating Agents↗
PubMed1992

Treatment of malignant scala posterior brain tumors in children: the chemotherapy of relapsed medulloblastoma with a dibromdulcitol containing drug regime and pharmacokinetic studies of dibromdulcitol in children.

Dibromdulcitol (Elobromol) has favorable pharmacokinetic parameters for the treatment of brain tumors: high spinal fluid/plasma ratio and long half-life in spinal fluid. Oral application makes its administration easy. The drug combination vincristine, procarbazine, and dibromdulcitol proved to be effective in a pilot trial on relapsed medulloblastomas: 8 complete and 4 partial remissions were achieved from 16 cases. The main side effect was granulocytopenia, which was in some cases severe. However, in the dose-schedule we used it did not delay the treatment longer than 1 week.

Adolescent↗
PubMed1976

The effect of dibromodulcitol on the template activity of DNA chromatin and nuclei from Yoshida sarcoma cells.

It has been shown earlier that after in vivo administration, dibromodulcitol (DBD) reacts with DNA and to a greater extent with chromosomal proteins of Yoshida sarcoma cells. The present experiments were designed to show if the binding of DBD to the chromatin elements of Yoshida sarcoma cells causes any changes in RNA synthesis using either DNA or chromatin as template in bacterial RNA polymerase system. During 4 to 24 h following in vivo administration, DBD reduces the template activity of dna without detectable single-strand breaks in the template DNA in alkaline sucrose gradients. Using chromatin as template the same dose of DBD produces no or very slight inhibition of RNA synthesis. Measuring the DNA-dependent RNA synthesis in nuclei isolated from Yoshida cells of treated rats, the dose of DBD which markedly inhibited the template activity of DNA, resulted in a significant stimulation of the nuclear RNA synthesis. The increased RNA synthesis was not due to an inhibition of ribonuclease activity. The observed alterations of the transcriptive properties of chromatin and nuclei produced by DBD are interpreted as being due to a modification of the whole nucleoprotein structure caused by the interaction of DBD with both DNA and chromosomal proteins.

Animals↗
PubMed1976

The effect of dibromodulcitol on resting and dividing lymphoid cells.

The effect of dibromodulcitol (DBD) on the incorporation of labelled precursors into DNA and RNA fractions of PHA-stimulated human lymphocytes and of P388F lymphoma cells at various stages of their growth was studied. Both cell systems showed sensitivity to the drug within the concentration rage of 1-10 mug/ml. When DBD was added before phytohaemagglutinin (PHA), h.han RNA. In contrast, by adding DBD after PHA, RNA labelling was much more inhibited than DNA. In the latter case, the decrease in DNA labelling occurred only 24 h after drug treatment whereas RNA labelling was decreased 1 h after treatment. Levels of DBD which normally produced 30% inhibition in plating efficiency of P388F lymphoma cells affected uridine-5-T incorporation to a different extent at different stages of growth of the culture. Enhanced RNA labelling occurred in early exponential stage while at later stages of growth, RNA synthesis was depressed.

Adult↗