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Neoplasma 1996From January 1976, 50 patients with squamous cell cancer of the head and neck were treated with telecobalt preoperative irradiation followed by appropriate surgery.... (Clinical Trial)
Clinical Trial Comparative Study
From January 1976, 50 patients with squamous cell cancer of the head and neck were treated with telecobalt preoperative irradiation followed by appropriate surgery. Another group of 50 patients, who matched in risk factors and stage of disease, were treated with preoperative chemotherapy and surgery. Chemotherapy consisted of bleomycin, vincristine, mitolactol and methotrexate. All patients received 3 courses. Surgery was performed 2-3 weeks post-chemotherapy or 4-6 weeks postradiotherapy. Forty-four percent of the patients in the radiotherapy group showed recurrences, while 30% of the patients had recurrence in the chemotherapy group. The overall 3-year survival rate was 66% in the chemotherapy group and 57% in the radiation therapy group, with no statistical difference.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Male; Methotrexate; Middle Aged; Mitolactol; Mouth Neoplasms; Preoperative Care; Vincristine
PubMed: 8843961
DOI: No ID Found -
British Journal of Cancer Feb 1995The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival... (Comparative Study)
Comparative Study
The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival time in mice bearing P388 solid lymphomas than either of the drugs alone. In the human metastatic melanoma HT-168 xenograft model the combined application of DBD and CDDP was also very effective, inducing a reduction in the number and volume of metastatic nodules. For V79 spheroids, DBD was mainly cytotoxic against the internal, quiescent cells, whereas cisplatin primarily killed cells in the proliferating, external regions of the spheroids. When combined, the drugs appeared to act synergistically throughout the spheroids. Studies on plasmid DNA showed that CDDP primarily generates cross-links, whereas single-strand breaks were dominant after DBD treatment. Upon using an assay for cleavage by restriction nuclease, antagonistic action of DBD and CDDP in combination may occur, nevertheless more strand breaks were always observed in these samples. These results suggest that the efficacy of combined DBD and CDDP is in part a result of 'spatial cooperation' by the drugs (i.e. affecting different cells) and in part the result of DNA damage produced by the combination treatments.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Cisplatin; DNA Damage; DNA, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Leukemia P388; Male; Melanoma; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mitolactol; Neoplasm Metastasis; Neoplasm Transplantation; Tumor Cells, Cultured
PubMed: 7841047
DOI: 10.1038/bjc.1995.63 -
Orvosi Hetilap Nov 1994Systemic pharmacokinetics of high-dose (500 mg/m2), orally administered dibromodulcitol (Elobromol) were studied in 16 chemotherapeutic courses administered to 5...
Systemic pharmacokinetics of high-dose (500 mg/m2), orally administered dibromodulcitol (Elobromol) were studied in 16 chemotherapeutic courses administered to 5 patients. Cerebrospinal fluid dibromodulcitol levels were also analysed in two patients. Bromoepoxydulcitol, dianhydrodulcitol are cytotoxic, whereas bromoanhydrodulcitol, andhydroepoxydulcitol are inactive metabolites detectable during the biotransformation of dibromodulcitol. The HPLC method, developed by our team, is suitable for the determination of both dibromodulcitol and its main metabolites (dianhydrodulcitol and bromoanhydrodulcitol). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexite-derivatives in pediatric patients. With the exception of one patient, concentration-time curves were analysed by the one-compartment model. From the 30th minute following administration, dibromodulcitol was detectable in all plasma samples for at least 12 hours, its concentration however was usually undetectable by the 24th hour. Though highly variable in value, dianhydrodulcitol concentrations were detectable during all but one therapeutic courses. The following peak concentrations were observed: dibromodulcitol: 3.46-30.63 microM; dianhydroldulcitol: 1.70-6.17 microM; bromoanhydrodulcitol: 0-5.63 microM. The correlation of area under the curve for bromoanhydrodulcitol and dibromodulcitol was exponential up to 200 microMxh with no additional increase detectable above this limit; the distribution of dianhydrodulcitol values were described by a maximum-curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives were detectable in the cerebrospinal fluid even if the concentration of the individual metabolite remained undetectable in plasma. The cerebrospinal fluid concentrations of dibromodulcitol were almost constant in the period from 2.5 to 8 hours following administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Biotransformation; Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Mitolactol
PubMed: 7800388
DOI: No ID Found -
Anti-cancer Drugs Oct 1994Systemic pharmacokinetics of high dose (500 mg/m2), orally administered Elobromol (dibromodulcitol, DBD) were studied in 16 chemotherapeutic courses administered to five... (Clinical Trial)
Clinical Trial
Systemic pharmacokinetics of high dose (500 mg/m2), orally administered Elobromol (dibromodulcitol, DBD) were studied in 16 chemotherapeutic courses administered to five patients. Cerebrospinal fluid (CSF) DBD levels were also analyzed in two patients. Bromoepoxydulcitol (BED), dianhydrodulcitol (DAD) are cytotoxic, whereas bromoanhydrodulcitol (BAD) and anhydroepoxydulcitol (AED) are inactive metabolites detectable during the biotransformation of DBD. The HPLC method, developed by our team, is suitable for the determination of both DBD and its main metabolites (DAD and BAD). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexitol derivatives in pediatric patients. With the exception of one patient, concentration time curves were analyzed by the one-compartment model. From 30 min following administration, DBD was detectable in all plasma samples for at least 12 h; its concentration, however, was usually undetectable by 24 h. Though highly variable in value, DAD concentrations were detectable during all but one of the therapeutic courses. The following peak concentrations were observed: DBD = 3.46-30.63 microM, DAD = 1.70-6.17 microM and BAD = 0-5.63 microM. The correlation of AUCBAD and AUCDBD values were exponential up to 200 microM h with no additional increase detectable above this limit: the distribution of AUCBAD and AUCDBD was described by a maximum curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives was detectable in CSF even if the concentration of the individual metabolite remained undetectable in plasma. DBD CSF concentrations were almost constant in the period from 2.5 to 8 h following administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aging; Biotransformation; Brain Neoplasms; Child; Child, Preschool; Chromatography, High Pressure Liquid; Enterohepatic Circulation; Female; Half-Life; Humans; Medulloblastoma; Mitolactol
PubMed: 7858286
DOI: No ID Found -
Seminars in Oncology Aug 1994Squamous cell cancer of the cervix is a relatively drug-resistant tumor. Therefore, chemotherapy is predominantly reserved for cervical cancer patients with recurrent or... (Review)
Review
Squamous cell cancer of the cervix is a relatively drug-resistant tumor. Therefore, chemotherapy is predominantly reserved for cervical cancer patients with recurrent or refractory disease following surgery and/or radiation therapy or for patients who present with far advanced, incurable disease. Objective responses to salvage chemotherapy are generally short lived (4 to 6 months) with few patients surviving more than 1 year. Complete clinical remissions primarily occur at extrapelvic sites (eg, lung, lymph node, and soft tissue metastases). Bulky pelvic tumor in an area of prior irradiation remains largely refractory to further therapy. At present, no chemotherapy regimen has proven superior to single-agent cisplatin, which is associated with an approximately 30% objective response rate. The most effective nonplatinum agents appear to be doxorubicin, ifosfamide, mitolactol, and vincristine. Multiple studies have documented improved partial response rates with platinum-based multiagent chemotherapy, but no regimen has been associated with an improved survival duration. To improve the poor prognosis of this patient group, identification of new agents with at least equivalent activity to cisplatin is mandatory. The development of new platinum-based regimens using currently available agents is unlikely to substantially improve patient survival, although better palliative therapy may result from this approach.
Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Clinical Trials as Topic; Female; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Salvage Therapy; Uterine Neoplasms
PubMed: 8091240
DOI: No ID Found -
Neurology Aug 1994We tested adjuvant chemotherapy combining dibromodulcitol (DBD) and bischloroethylnitrosourea (BCNU) given postoperatively to adults with newly diagnosed supratentorial... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
We tested adjuvant chemotherapy combining dibromodulcitol (DBD) and bischloroethylnitrosourea (BCNU) given postoperatively to adults with newly diagnosed supratentorial malignant gliomas.
METHODS
We enrolled 269 patients, 255 of whom were eligible. After surgery, we treated all patients with radiation therapy, using a median dose of 60 Gy given in 30 fractions. After randomization, patients in the chemotherapy group also received (1) six weekly courses, administered during irradiation, of DBD 700 mg/m2 and (2) one to nine (median, four) courses, administered during the first year following radiation therapy, of DBD 1,000 mg/m2 on day 1 and BCNU 150 mg/m2 on day 2, with the course being repeated every 6 weeks.
RESULTS
Patients treated with radiation therapy along with DBD plus BCNU (group 2) had significantly longer survival time (p = 0.044) and time to progression (p = 0.003) than did those treated with radiation therapy alone (group 1). The median survival time was 13.0 months for group 2 and 10.4 months for group 1; the median time to progression was 8.1 months for group 2 and 6.7 months for group 1. The percentage of patients alive at 18 and 24 months was 34% and 21% in group 2 compared with 21% and 12% in group 1.
CONCLUSION
DBD plus BCNU is an effective adjuvant therapy for malignant glioma.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carmustine; Chemotherapy, Adjuvant; Female; Glioma; Humans; Male; Middle Aged; Mitolactol; Survival Analysis
PubMed: 8058153
DOI: 10.1212/wnl.44.8.1479 -
Journal of Clinical Oncology : Official... Apr 1994
Topics: Acute Disease; Adult; Aged; Breast Neoplasms; Female; Humans; Leukemia, Myeloid; Middle Aged; Mitolactol; Myelodysplastic Syndromes; Neoplasms, Second Primary; Risk Factors
PubMed: 8151329
DOI: 10.1200/JCO.1994.12.4.874 -
Journal of Clinical Oncology : Official... Jan 1994To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
PURPOSE
To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer.
MATERIALS AND METHODS
One hundred six women with metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction treatment, then randomized to receive one of two chemotherapy regimens if they had obtained an induction partial response (PR) or no change (NC), or to receive observation versus chemotherapy if they had obtained an induction complete response (CR). Patients were then retreated with DAVTH reinduction after relapse.
RESULTS
Seventy-four patients were eligible or had minor reasons for ineligibility. Severe or life-threatening toxicity was documented in 46%, and lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16 induction nonresponders, 15% induction PR, 44% induction CR). The median time to treatment failure (TTF) from reinduction was 3 months, and the median survival duration from reinduction was 14 months. In a logistic model, factors associated with more reinduction responses were observation after induction CR (P = .002) and age greater than 55 years (P = .04). Time since induction was not significant.
CONCLUSION
Reinduction of response after treatment failure remains a therapeutic problem. The need for better salvage treatment underlines the importance of developing new regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Logistic Models; Middle Aged; Mitolactol; Neoplasm Metastasis; Remission Induction; Survival Analysis; Tamoxifen; Treatment Outcome; Vincristine
PubMed: 8270982
DOI: 10.1200/JCO.1994.12.1.45 -
Medical and Pediatric Oncology 1993Ten children with posterior scala tumor infiltrating the surrounding brain substance and/or the brain stem entered in the present study with preoperative chemotherapy....
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain; Brain Neoplasms; Chemotherapy, Adjuvant; Child; Child, Preschool; Choroid Plexus Neoplasms; Ear Neoplasms; Ependymoma; Female; Humans; Infant; Male; Medulloblastoma; Methotrexate; Mitolactol; Procarbazine; Remission Induction; Tomography, X-Ray Computed; Vincristine
PubMed: 8469223
DOI: 10.1002/mpo.2950210408 -
Annals of Oncology : Official Journal... Nov 1992
Metastatic breast cancer: higher versus low dose maintenance treatment when only a partial response or a no change status is obtained following doxorubicin induction treatment. An Eastern Cooperative Oncology Group study.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Fluoxymesterone; Humans; Methotrexate; Mitolactol; Neoplasm Recurrence, Local; Prednisone; Prospective Studies; Remission Induction; Survival Rate; Tamoxifen
PubMed: 1450067
DOI: 10.1093/oxfordjournals.annonc.a058337