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Journal of Neuro-oncology Apr 1998Twenty six (17 males) patients with glioblastoma (GBL), median age 55 years, median Karnofsky Index (KI) 70/100, and 11 patients (9 males) with anaplastic astrocytoma... (Clinical Trial)
Clinical Trial
Twenty six (17 males) patients with glioblastoma (GBL), median age 55 years, median Karnofsky Index (KI) 70/100, and 11 patients (9 males) with anaplastic astrocytoma (AA), median age 56 years, median KI 70/100 were treated at recurrence with dibromodulcitol (DBD) 1400 mg/m2 on day 1, BCNU 150 mg/m2 on day 2, and procarbazine (PCZ) 150 mg/day on days 1 to 15. The course was repeated every 4 weeks, but was delayed or decreased by 25% according to hematological toxicity. Response to treatment was evaluated by the criteria of MacDonald et al. (J Clin Oncol 1990; 8: 1277-1280). All GBL-patients were followed until death. One patient with complete response (CR) survived one year, and 2 patients with partial response (PR) survived 1 and 3 years. Ten patients who stabilized (SD) survived 7.5 months, and 13 patients who progressed under chemotherapy had a median survival of 3.5 months. In AA-group 3 patients were alive at the time of the analyses. Six patients: 1 CR and 5 PR survived 6 to 40+ months. Two patients with SD survived 4 and 14 months. Three patients with progressive disease had a mean survived of less than 3 months. The response rate of 55% in AA was significantly higher (p = 0.011) than the 12% response rate seen in GBL. We conclude that the regimen tested appears particularly promising in AA. The results in GBL are comparable to those obtained with a single nitrosourea, despite an increased but reversible toxicity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carmustine; Female; Glioblastoma; Hematologic Diseases; Humans; Male; Middle Aged; Mitolactol; Neoplasm Recurrence, Local; Procarbazine; Survival Analysis
PubMed: 9524094
DOI: 10.1023/a:1005952925378 -
Journal of Clinical Oncology : Official... Dec 1991Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
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.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Middle Aged; Mitolactol; Multivariate Analysis; Prognosis; Proportional Hazards Models; Survival Analysis; Tamoxifen; Treatment Outcome; Vincristine
PubMed: 1960558
DOI: 10.1200/JCO.1991.9.12.2153 -
Neuro-oncology Jan 2000We conducted a single-arm phase II study to evaluate the efficacy and safety of radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and... (Clinical Trial)
Clinical Trial
We conducted a single-arm phase II study to evaluate the efficacy and safety of radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and vincristine (TPDCV) chemotherapy for treating malignant astrocytoma in children and anaplastic ependymoma in patients of all ages. Between 1984 and 1992, 42 patients who had malignant astrocytomas (glioblastomas multiforme, anaplastic astrocytomas, or mixed anaplastic oligoastrocytomas) were treated with TPDCV chemotherapy and radiation therapy. Of these patients, 40 were younger than 18 years, but 2 were older (22 and 23 years) when treated. Cranial radiation averaged 58 Gy. TPDCV chemotherapy was given for 1 year or until progression. Between 1989 and 1991, 17 patients with malignant ependymoma were treated with TPDCV chemotherapy and craniospinal radiation. Radiation was given at an average dose of 54 Gy to the tumor, 28 Gy to the whole brain, and 31 Gy to the spinal axis. TPDCV chemotherapy was given for 1 year or until tumor progressed. Of the patients with glioblastoma multiforme, 13 of 17 died; the median time to progression was 49 weeks, and median survival was 85 weeks. The four patients surviving at this writing were followed a median 537 weeks (range 364-635 weeks). Of the patients with nonglioblastoma malignant astrocytoma, 14 of 25 died; the median time to progression was 224 weeks. Median survival was not reached in this group. The median follow-up for those surviving was 494 weeks. For the patients with ependymoma, 11 of 17 died with a median time to progression of 141 weeks. The median follow-up for the eight who survive was 469 weeks. Nine patients died with a median survival of 183 weeks. The combination of TPDCV and radiotherapy has activity against childhood anaplastic astrocytoma, glioblastoma multiforme, and anaplastic ependymoma. The results of this study for children with glioblastoma were comparable to results in the literature, while the results for children with anaplastic astrocytoma appeared better than most reports. The combination of TPDCV chemotherapy and radiation therapy for anaplastic ependymomas appears to be active and at least as good as published reports using radiation therapy alone.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Glioma; Humans; Lomustine; Male; Mitolactol; Procarbazine; Survival Analysis; Thioguanine; Treatment Outcome; Vincristine
PubMed: 11302250
DOI: 10.1093/neuonc/2.1.22 -
Series Haematologica (1968) 1973
Review
Topics: Adrenal Cortex Hormones; Alopecia; Antineoplastic Agents; Bleomycin; Blood Platelet Disorders; Carmustine; Chlorambucil; Cyclophosphamide; Daunorubicin; Drug Evaluation; Drug Therapy, Combination; Hodgkin Disease; Humans; Leukopenia; Mechlorethamine; Mitolactol; Nervous System Diseases; Procarbazine; Remission, Spontaneous; Streptonigrin; Vinblastine; Vincristine
PubMed: 4131662
DOI: No ID Found -
European Journal of Cancer (Oxford,... Jun 2008In a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic... (Randomized Controlled Trial)
Randomized Controlled Trial
Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882).
BACKGROUND
In a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), a clinically significant trend towards a longer overall survival (OS) and a progression-free survival (PFS) was observed in the subgroup of AA. The aim of the present study was to test this adjuvant regimen in a larger number of AA patients.
METHODS
Continuation of the previous phase III trial for newly diagnosed AA according to the local pathologist. Patients were randomised to either radiotherapy only or to radiotherapy in combination with BCNU on day 2 and weekly DBD, followed by adjuvant DBD and BCNU in cycles of six weeks for a maximum total treatment duration of one year. OS was the primary end-point.
RESULTS
Patients (193 ) with newly diagnosed AA according to local pathological assessment were randomised to radiotherapy (RT) alone (n=99), or to RT plus DBD/BCNU (n=94); 12 patients were considered not eligible. At central pathology review, over half (53%) of the locally diagnosed AA cases could not be confirmed. On intent-to-treat analysis, no statistically significant differences in OS (p=0.111) and PFS (p=0.087) were observed, median OS after RT was only 23.9 months 95% confidence interval (CI), [18.4-34.0] after RT plus DBD/BCNU 27.3 months 95% CI [21.4-46.8].
CONCLUSION
No statistically significant improvement in survival was observed after BCNU/DBD adjuvant chemotherapy in AA patients. The trend towards improved survival is consistent with previous reports. Central pathology review of grade 3 tumours remains crucial.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Carmustine; Chemotherapy, Adjuvant; Female; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitolactol; Treatment Failure
PubMed: 18248979
DOI: 10.1016/j.ejca.2007.12.005 -
Pathology Oncology Research : POR Jun 2010The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100... (Clinical Trial)
Clinical Trial
The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100 consecutively treated squamous cell cancer patients receiving a combined neoadjuvant therapy were selected (Bleomycin-Vincristin-Methotrexate (BVM) or BVM + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the patients were operated on. The largest diameter of the primary tumors was compared before and after chemotherapy. In the surgical specimen, the involvement of surgical margin was assessed. The largest diameter before chemotherapy was: T2 30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the surgical specimen as: no rest 11%; <2 cm 57%; 2-4 cm 28%; 4-6 cm 4%. The no rest and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the T4A: 0%. Severe side effects (Grade III-IV) were not observed. There was a significant decrease in size (P < 0.0001). Of the 100 surgical specimens, 83% had clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients) involved margin. Based on the significantly better size and operability of primary T2-3, the mild side effects and the high (83%) percentage of clear surgical margins, that is better than other (without preoperative chemotherapy) results, sought the use of chemotherapy is recommended before surgery. Due to the 40% involved margin, we don't suggest surgery in T4A.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Male; Methotrexate; Middle Aged; Mitolactol; Mouth Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Oral Surgical Procedures; Physicians; Surgery, Oral; Vincristine
PubMed: 19757193
DOI: 10.1007/s12253-009-9208-3 -
Ideggyogyaszati Szemle Jan 2002At the Hungarian National Institute of Neurosurgery 73 recurrent supratentorial malignant tumours were treated by chemotherapy during the last ten years. Chemotherapy... (Clinical Trial)
Clinical Trial
At the Hungarian National Institute of Neurosurgery 73 recurrent supratentorial malignant tumours were treated by chemotherapy during the last ten years. Chemotherapy was applied after postoperative radiotherapy but in some cases following reoperation only. All cases were clinically and by CT or MRI verified recurrences. Forty-three patients received BCNU-DBD (dibromodulcitol) treatment (23 anaplastic astrocytoma--AA, and 20 glioblastoma multiforme--GM): day 1. BCNU 150 mg/sq.m. in i.v. infusion, day 2. dibromdulcitol 1000 mg/sq orally was given. This course was repeated every six weeks, altogether 2-8 times. Sixteen patients with AA responded with complete or partial regression but only 6 did with GM. Median survival was 14 and 7 months, the difference proved to be significant, p = 0.0091. PCV combination (procarbazine, CCNU, vincristine) was applied to 16 patients with AA and 14 cases with recurrent oligodendroglioma (O). Treatment started with vincristine 1.5 mg/sq.m. i.v. (2.0 mg maximum), the next day CCNU 100 mg/sq.m. was given, followed by procarbazine 60 mg/sq.m. on days 8-22. and finished by the same dose of vincristine on day 30. The course was repeated after one month, mostly six times. Six patients with AA did not respond; in cases of oligodendroglioma all but one responded with complete or partial improvement. It is remarkable that no significant difference was found between the survivals of BCNU-DBD or PCV treated AA patients. Chemotherapy of supratentorial malignant glioma recurrences with nitroso-ureas and their combination proved to be efficacious. It also seems, that in recurrent cases lower grade gliomas show better response rate than glioblastomas.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Carmustine; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Glioblastoma; Humans; Male; Middle Aged; Mitolactol; Neoplasm Recurrence, Local; Procarbazine; Radiotherapy, Adjuvant; Reoperation; Supratentorial Neoplasms; Survival Analysis; Treatment Outcome; Vincristine
PubMed: 12122942
DOI: No ID Found -
American Journal of Clinical Oncology Feb 1998Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to... (Clinical Trial)
Clinical Trial
Induction chemotherapy of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin with methotrexate in metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1181).
Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Methotrexate; Middle Aged; Mitolactol; Neoplasm Metastasis; Pilot Projects; Remission Induction; Survival Analysis; Tamoxifen; Vincristine
PubMed: 9499270
DOI: 10.1097/00000421-199802000-00023 -
Blood Feb 2006Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free... (Randomized Controlled Trial)
Randomized Controlled Trial
Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free survival (EFS) and overall survival (OS). Patients were randomized to receive standard-dose DAT (daunorubicin, cytarabine, and thioguanine) or high-dose DAT during induction. To interfere with P-glycoprotein (P-gp)-dependent drug efflux, the second randomization tested the benefit of cyclosporine (CsA) added to consolidation chemotherapy. Of the 282 children randomly assigned to receive standard DAT induction, 248 (87.9%) achieved remission compared to 253 (91%) of the 278 receiving high-dose DAT (P = ns). Children with HLA-identical sibling donors who achieved a complete remission received an allogeneic bone marrow transplant as consolidation. For the 83 patients receiving a matched related donor bone marrow transplantation (BMT), the 3-year disease-free survival (DFS) is 67%. Of the 418 children who achieved remission and went on to consolidation with and without CsA, the DFS was 40.6% and 33.9%, respectively (P = .24). Overexpression of P-gp was infrequent (14%) in this pediatric population. In this study, intensifying induction with high-dose DAT and the addition of CsA to consolidation chemotherapy did not prolong the durations of remission or improve overall survival for children with AML.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclosporine; Disease-Free Survival; Doxorubicin; Female; Humans; Immunosuppressive Agents; Infant; Karyotyping; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mitolactol; Remission Induction; Survival Analysis; Tamoxifen; Treatment Outcome
PubMed: 16254147
DOI: 10.1182/blood-2004-08-3218 -
Pediatric Neurosurgery Oct 1996To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive...
Treatment of high-risk medulloblastoma and other primitive neuroectodermal tumors with reduced dose craniospinal radiation therapy and multi-agent nitrosourea-based chemotherapy.
PURPOSE
To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive neuroectodermal tumors (PNET) with a combined modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy.
PATIENTS AND METHODS
Between 1984 and 1992, 34 evaluable patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniospinal radiotherapy (CSA). Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) to enhance CCNU-induced tumor cell kill and to reduce alkyltransferase repair of ethylated DNA. Vincristine was given 1 and 3 weeks after CCNU to kill cells that began to cycle after the challenge of the first four drugs. Chemotherapy was given in the outpatient setting. CSA radiation was planned to deliver a dose of 54 Gy to the primary tumor site and 24 Gy to the rest of the neuroaxis. Additional radiation was given to bulky disease outside the primary site if present. Hydroxyurea was used during radiotherapy as a radiosensitizer.
RESULTS
Patients treated included 27 with medulloblastoma, 5 with pineoblastoma, and 2 with supratentorial PNET. All but 3 medulloblastoma cases were considered high risk either because of bulky residual disease remaining after surgery and/or metastatic disease detected during staging. For the 34 patients, 24 have progressed, 20 have died. Overall estimated PFS was 55% at 3 years and 35% at 5 years. The 5-year survival estimate is 56%. One patient had inadequate staging to determine M stage. Of the remaining 33 patients, there were 19 patients who had metastatic disease at diagnosis (M1 or higher stage) who had a 3- and 5-year PFS of 42 and 21% respectively and 5-year survival of 42%. There were 14 patients who had negative staging (M0 stage) who had a 3- and 5-year PFS of 69 and 52% respectively and 5-year survival of 71%. Of the 27 patients with medulloblastoma, 15 had M1 or higher stage. These 15 patients had a 5-year PFS and overall survival of only 20 and 40% respectively. Medulloblastoma patients with M0 staging had a 5-year PFS and overall survival of 52 and 73% respectively. Overall toxicity was primarily due to mild hematological toxicity and related to the use of the chemotherapy.
CONCLUSIONS
The results using this therapy in high-risk groups of patients does not offer any improvement over results reported in other recent studies. The reason for these results may be due to the lowered craniospinal radiation dose.
Topics: Adolescent; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Brain Neoplasms; Chemotherapy, Adjuvant; Child; Child, Preschool; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Follow-Up Studies; Humans; Infant; Male; Medulloblastoma; Middle Aged; Mitolactol; Neoplasm Staging; Neuroectodermal Tumors, Primitive; Nitrosourea Compounds; Procarbazine; Retrospective Studies; Risk Factors; Thioguanine; Vincristine
PubMed: 9293544
DOI: 10.1159/000121120