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At least 73 records · Page 4Linked to original sources
PubMed1989

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.

Adenocarcinoma↗
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↗
PubMed1981

Adriamycin, vincristine, dibromodulcitol, and hexamethylmelamine in advanced previously treated breast cancer: an ECOG pilot study.

A combination of adriamycin, vincristine, dibromodulcitol, and hexamethylmelamine was piloted in patients with advanced breast cancer who had failed prior CMFP chemotherapy, as a part of ongoing trials by the Eastern Cooperative Oncology Group to improve second-line chemotherapy for this disease. The vincristine was given as an intensive 5 week induction regimen and hexamethylmelamine was administered on days 15-27 of a 28 day cycle, at the time of anticipated nadir peripheral blood counts. The study was terminated early after only 9 patients had been entered because of severe neurotoxicity related to the intensive schedule of vincristine as well as hematologic and gastrointestinal side effects. Three patients responded for 11, 18 and 21 weeks. The limited therapeutic benefit did not justify the toxicity produced, and suggested that intensive dosage schedules of vincristine, and use of low dose hexamethylmelamine during the time of anticipated hematologic nadir counts would not be of substantial benefit.

Aged↗
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↗
PubMed1993

The treatment of malignant scala posterior tumors in children: II. Preliminary result of the pre- and postoperative adjuvant chemotherapy of scala posterior tumors.

Ten children with posterior scala tumor infiltrating the surrounding brain substance and/or the brain stem entered in the present study with preoperative chemotherapy. In 8 of the 10 cases regression and necrosis of the tumor were seen by CT examination after the preoperative therapy. The diameter of the tumor decreased on the average by 35.6% (14.0-74.3%). The main side effect was granulocytopenia. According to our observation, the preoperative therapy enables a more radical surgery in some cases of medulloblastoma and ependymoma. Further observations are necessary to confirm these preliminary results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Apoptotic and mitotic activity in squamous cell carcinoma cells after combined modality treatment with gamma-irradiation and dibromodulcitol.

A-431 squamous cell carcinoma cells were treated in vitro with either 4 Gy radiation of 15 (or 45) microg/ml dibromodulcitol (DBD), as well as with combined 4 Gy irradiation and DBD, with the latter as either a pretreatment or post-treatment. DBD alone or in combination with radiation had a greater effect on cell proliferation than the effect of radiation alone. The difference is due to a higher level of apoptosis induced by DBD, especially in conjunction with radiation. Such a combination may therefore be useful in the treatment of squamous cell carcinoma, which in general responds poorly to radiation therapy.

Antineoplastic Agents, Alkylating↗
PubMed1987

Phase II evaluation of dibromodulcitol and actinomycin D, hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma.

In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma.

Adolescent↗
PubMed1988

In vitro chemosensitivity of brain tumors to cisplatin and its analogues, iproplatin and carboplatin.

The human tumor stem-cell assay was used to investigate the in vitro chemosensitivity of 27 evaluable samples to cisplatin and its analogues, iproplatin and carboplatin, as well as to BCNU, teniposide, vindesine, and dibromodulcitol. All agents exhibited some antitumor activity with the exception of dibromodulcitol (zero response out of 19 evaluable samples). Vindesine, BCNU, and carboplatin were the three most active compounds, with response rates of 29%, 23%, and 22%, respectively. There was a lack of complete cross-resistance between carboplatin and cisplatin as well as between carboplatin and BCNU. Our data suggest that clinical studies with carboplatin and combinations of vindesine plus cisplatin and its analogues may be worthwhile.

Brain Neoplasms↗
PubMed1982

Dibromodulcitol plus bleomycin compared with bleomycin alone in head and neck cancer.

Advanced recurrent squamous cell head and neck cancer patients were prospectively randomized to receive or not receive dibromodulcitol 10 mg/kg PO weekly for 8 consecutive weeks in addition to bleomycin chemotherapy. Patients initially entered in the study received bleomycin 15 mu/m2 three times weekly for 8 weeks. This was later changed to 15 mu/m2 twice weekly for 8 weeks because of unacceptable stomatitis. Most patients had relapsed following surgery and/or radiotherapy, but none had received prior chemotherapy. A2 : 1 randomization in favor of the dibromodulcitol-containing therapy was used. There were 12 partial responses in the 44 evaluable patients receiving the combination (27%), and 4 partial responses in the 18 patients receiving single-agent bleomycin chemotherapy (22%). This difference was not statistically significant. Response durations were also relatively short for both therapies. Within the limitations of this study, we were unable to demonstrate that patient benefit resulted from the addition of dibromodulcitol to bleomycin chemotherapy for this patient population.

Adult↗
PubMed1982

Chemotherapeutic approaches to brain tumors. Experimental observations with dianhydrogalactitol and dibromodulcitol.

Dianhydrogalactitol (DAG) or its active cell-killing moiety has a relatively long biological half-life in 9L cells cultured in vitro. The shape of the DAG dose-response curves was similar to that of those observed for most oncolytic agents. The prominent shoulder on the 24-h dose-response curve indicates that 9L cells can accumulate a reasonable amount of DAG-induced sublethal damage before they are killed. The appearance of 9L colonies in petri dishes was delayed 3-5 days after a DAG treatment that killed more than 99% of the cells, an observation not previously made with radiation, hyperthermia, the nitrosoureas, or other chemotherapeutic agents. Comparison of the in vitro exposure integral and the in vivo tumor tissue integral indicated that DAG would have to be administered at a dose in excess of its LD10 to achieve an in vivo 2 log cell kill. The lack of a significant increase in lifespan after a LD10 dose confirmed this prediction. While DAG alone is active against IC ependymoblastoma, it had very limited activity against IC glioma 26; however, the combination of DAG with BCNU was curative in 85%-100% of animals at 120 days. BCNU alone achieved no more than 4%-16% survival at 120 days. The combination of DBD and BCNU was not consistently better than BCNU alone against IC glioma 26. It appears that DAG may have a limited place in CNS chemotherapy for specific kinds of tumors. BCNU-DAG combination studies suggest that we may, under the right conditions, enhance the antitumor activity of the hexitol epoxides by drug combination therapies, although the mechanism for this enhanced antitumor activity is presently unknown.

Animals↗
PubMed1987

Polychemotherapy of acute myelogenous leukemia in a patient with acute intermittent porphyria.

The safety of drugs in hepatic porphyrias has largely been established by clinical experience, which is very limited in the case of antineoplastic agents. We administered three cycles of polychemotherapy consisting of daunorubicin, cytarabine and 6-thioguanine, and modified supportive care to a 33-year-old Turkish woman suffering from acute myelogenous leukemia. The urinary excretion of total porphyrins, porphobilinogen, and aminolevulinic acid was continuously monitored. Excretion of these metabolites was permanently elevated, but the values were comparatively low during cytotoxic therapy while peak values were recorded at the onset of fever during bone marrow aplasia; yet there were no clinical signs of porphyritic attacks at that time. A few potentially unsafe drugs were tolerated without an increase in porphyrin excretion. Although the susceptibility to drugs is highly variable in patients with hepatic porphyrias, the treatment of malignancy in these patients seems justified as long as porphyrin excretion under therapy is not grossly elevated over baseline values and appropriately modified supportive care is administered.

Acute Disease↗
PubMed1985

Short term high density systemic therapy for metastatic breast cancer.

Twenty-three patients with metastatic breast carcinoma were induced with a complex systemic therapy regimen in an attempt to ascertain if a complete remission rate greater than 50% could be obtained with intensive drug exposure. The durability of the remissions was observed by discontinuing therapy after 3 cycles in complete remission or after 6 cycles of treatment, whichever was longer. In 13 patients consolidation radiation therapy to the pre-treatment sites of disease was administered after discontinuing systemic therapy. Each 28 day cycle of the drug regimen consisted of pulses of adriamycin, vincristine, dibromodulcitol, prednisone, methotrexate with leukovorin rescue, hexamethylmelamine, bleomycin (discontinued after entry #17), fluoxymesterone, and tamoxifen. Eighteen of the 23 patients achieved complete remissions (78%) and 3 had partial remissions. The median times to treatment failure and survival were, respectively, 12.3 and 19.4 mos. The times for complete remission patients were, respectively, 13.5 and 23.9 mos. Consolidation radiotherapy at greater than or equal to 40 Gy to drug induced pre-study sites of complete remission was associated with first relapses at pre-study sites in 5/30 (17%) instances, compared to 21/35 (60%) in sites not receiving radiotherapy. Side-effects were commensurate with the intensity of the treatment program and are detailed in the text. Although the achievement of a high complete remission rate is promising, the failure to extend their duration beyond that of historical data suggests that additional conceptual and therapeutic approaches need to be explored.

Altretamine↗
PubMed1986

Dibromodulcitol-based combined postoperative chemotherapy of malignant astrocytomas and glioblastomas.

Continuing our earlier studies with dibromodulcitol (DBD), in a series of 38 evaluable consecutive patients who were operated on for malignant supratentorial gliomas, radiotherapy with smaller daily but higher total doses of DBD has been started 3-5 weeks after surgery. This was followed alternately by a combination chemotherapy of CCNU and DBD or CCNU and Procarbazine. No severe myelotoxicity occurred. Survivals were compared with a group of patients who got irradiation alone. Statistical analysis showed a significantly better survival in the presently treated group: median survival was 55 weeks, p = 0.02. These values were very similar to those groups which were treated by intermittent DBD schedule during irradiation. This study seems to confirm our previous suggestion that the concurrent use of DBD during irradiation might be an important factor in improving survival times.

Adult↗
PubMed2000

Possibilities of preventing osteoradionecrosis during complex therapy of tumors of the oral cavity.

In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for physicians dealing with oncotherapy. An organic part of the complex therapy is preoperative or postoperative irradiation. Application of this is accompanied by a lower risk of recurrences, and by a higher proportion of cured patients. Unfortunately, irradiation also has a disadvantage: the development of osteoradionecrosis, a special form of osteomyelitis, in some patients (mainly in those cases where irradiation occurs after bone resection or after partial removal of the periosteum). Once the clinical picture of this irradiation complication has developed, its treatment is very difficult. A significant result or complete freedom from complaints can be attained only rarely. Attention must therefore be focussed primarily on prevention, and the oral surgeon, the oncoradiologist and the patient too can all do much to help prevent the occurrence of osteoradionecrosis. Through coupling of an up-to-date, functional surgical attitude with knowledge relating to modern radiology and radiation physics, the way may be opened to forestall this complication that is so difficult to cure.

Antineoplastic Agents, Alkylating↗