ocytoma were enrolled. All patients had failed surgery and radiation therapy, while 31% also failed chemotherapy. In a second Phase 2 open label study conducted by the Children's Oncology Group (COG), 122 patients were enrolled, including medulloblastoma/PNET (29), high grade astrocytoma (23), low grade astrocytoma (22), brain stem glioma (16), ependymoma (14), other CNS tumors (9) and non-CNS tumors (9). The TEMODAR toxicity profile in children is similar to adults. Table 1 shows the adverse events in 122 children in the COG Phase 2 study.
Table 1 Adverse Events Reported in Pediatric Cooperative Group Trial (>/=10%)
No. (%) of TEMODAR
Patients (N=122) a
Body System/Organ Class
Adverse Event All Events Gr 3/4
Subjects Reporting an AE
Body as a Whole 107 (88) 69 (57)
Central and Peripheral Nervous System
Central cerebral CNS cortex 22 (18) 13 (11)
Gastrointestinal System
Nausea 56 (46) 5 (4)
Vomiting 62 (51) 4 (3)
Platelet, Bleeding and Clotting
Thrombocytopenia 71 (58) 31 (25)
Red Blood Cell Disorders
Decreased Hemoglobin 62 (51) 7 (6)
White Cell and RES Disorders
Decreased WBC 71 (58) 21 (17)
Lymphopenia 73 (60) 48 (39)
Neutropenia 62 (51) 24 (20)
a These various tumors included the following: PNET-medulloblastoma, glioblastoma, low grade astrocytoma, brain stem tumor, ependymoma, mixed glioma, oligodendroglioma, neuroblastoma, Ewing's sarcoma, pineoblastoma, alveolar soft part sarcoma, neurofibrosarcoma, optic glioma, and osteosarcoma.
ADVERSE REACTIONS IN ADULTS
Newly Diagnosed Glioblastoma Multiforme
During the concomitant phase (TEMODAR + radiotherapy), adverse events including thrombocytopenia, nausea, vomiting, anorexia and constipation, were more frequent in the TEMODAR + RT arm. The incidence of other adverse events was comparable in the two arms. The most common adverse events across the cumulative TEMODAR experience were alopecia, nausea, vomiting, anorexia, headache, and constipation (see Table 2 ). Forty-nine percent (49%) of patients treated with TEMODAR reported one or more severe or life-threatening events, most commonly fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%). Overall, the pattern of events during the maintenance phase was consistent with the known safety profile of TEMODAR.
Table 2 Number (%) of Patients with Adverse Events: All and Severe/Life Threatening
(Incidence of 5% or Greater)
Concomitant Phase
RT Alone
(n=285) Concomitant Phase
RT + TMZ
(n=288) * Maintenance Phase
TMZ
(n=224)
All Grade >/= 3 All Grade >/= 3 All Grade >/= 3
Subjects Reporting any Adverse Event 258 (91) 74 (26) 266 (92) 80 (28) 206 (92)& |
