title: Tamoxifen and carboplatin combinational treatment of high-grade gliomas. Results of a clinical trial on newly diagnosed patients.
abstract: Between April, 1992 and December, 1995, forty consecutive patients with a cerebral malignant glioma (WHO Grade III and IV) were enrolled in a trial consisting in surgery and post-operative administration of radiotherapy (4500-6000 cGy), carboplatin (CBDCA; dose of 450-600 mg/m2), and oral tamoxifen (TAM; at doses of 40, 80 or 120 mg/day). Two patients of the TAM group died in the postoperative period from a pulmonary embolism and myocardial infarction, respectively. The patients (all dosages combined) had a median survival time of 13 months from the time of diagnosis. The 12-month and 24-month survival rates were 52% and 32%, respectively. The median relapse-free survival time was 7 months. Patients treated with higher doses of TAM (80-120 mg/day) demonstrated a longer median survival rate (13 months both) and a longer 12-month survival result (58% and 76%, respectively). Patients who assumed TAM for a period longer than 3 months (group +3) have a higher median survival rate (16 months) and better 12-month and 24-month results (62% and 40%, respectively). Moreover, the median relapse-free survival time was 10 months (versus 6 months in group -3; p = 0.0038). However, it is not possible to exclude that patients of group +3 had a slower growing or a stable tumor and were well enough to assume TAM for a longer period. The results observed in the TAM-group have been compared with those of 40 matched controls treated with surgery, radiotherapy and CBDCA. These patients had a median survival time of 9 months (p = 0.04) and the 12-month and 24-month survival rates were 30% and 0%, respectively. The median relapse-free survival time was 4 months (p = 0.0014). These data suggest a potential role for combinational TAM-CBDCA therapy in the post-operative treatment of cerebral malignant gliomas; further clinical phase III trials, especially those with higher dosages of TAM are warranted.
authors.affiliation: Department of Neurological Sciences, Civilian Hospital of Terni, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mastronardi
authors.forename: F
authors.initials: F
authors.lastname: Puzzilli
authors.forename: W T
authors.initials: WT
authors.lastname: Couldwell
authors.forename: J O
authors.initials: JO
authors.lastname: Farah
authors.forename: P
authors.initials: P
authors.lastname: Lunardi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D016190:Carboplatin