mitolactol and Astrocytoma

This article covers chemotherapy of malignant astrocytomas, ependymoma, and medulloblastoma. The future direction of anticancer drugs is discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Brain Stem; Child; Eflornithine; Ependymoma; Fluorouracil; Glioblastoma; Humans; Hydroxyurea; Lomustine; Medulloblastoma; Methotrexate; Mitoguazone; Mitolactol; Neoplasm Recurrence, Local; Ornithine; Prednisone; Risk; Thioguanine; Vincristine

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.. 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.. 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].. 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

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

Our aim was to investigate the effect of BCNU and DBD combined chemotherapy in patients with recurrent malignant gliomas. Forty-six patients were treated with combined chemotherapy. Out of 26 patients with anaplastic astrocytomas 11 were originally low-grade where no postoperative radiotherapy was applied. Fifteen patients with anaplastic astrocytoma responded well to the chemotherapy and 9 survived longer than one year. Median survival time was 14 months. Complete response of recurrent glioblastoma did not occur and only 4 patients survived longer than one year. Median survival time was 7 months. Ratio of patients with response and stable disease was 70 and 55 %, respectively. BCNU and DBD combination proved to be an effective combination for recurrent malignant gliomas. It was remarkable that patients' survival with primary or secondary lower grade astrocytoma were significantly longer than that in patients with glioblastomas. Treatment of lower grade tumors, even at their malignant recurrences is promising.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Carmustine; Female; Glioblastoma; Humans; Male; Middle Aged; Mitolactol; Time Factors; Treatment Outcome

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

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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Combined Modality Therapy; Female; Glioma; Humans; Lomustine; Male; Middle Aged; Mitolactol; Procarbazine