thioguanine-anhydrous and Medulloblastoma

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

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.. 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.. 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.. 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

A number of chemotherapeutic agents have been shown to have anti-tumor activity against childhood medulloblastoma. Ten-year survival with optimal surgery and radiation therapy ranges from 5% to 25%. Carefully controlled clinical trials utilizing a combination of surgery, radiation therapy, and chemotherapy should be employed in the early stages of the disease in an attempt to define which drugs are most effective, and to improve the survival rate.

Topics: Adolescent; Adult; Antineoplastic Agents; Brain Neoplasms; Child; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Gold Radioisotopes; Humans; Male; Medulloblastoma; Methotrexate; Nitrosourea Compounds; Podophyllotoxin; Procarbazine; Radioisotope Teletherapy; Semustine; Thioguanine; Triethylenemelamine; Vincristine