Older patients with newly diagnosed glioblastoma and
poor performance status tolerated temozolomide well, according to results from
a phase 2 study.
Additionally, patients assigned to temozolomide
(Temodar, Schering-Plough) had superior OS and PFS compared with those assigned
to supportive care.
Seventy patients with newly diagnosed
glioblastoma and a Karnofsky performance score of less than
70 were enrolled in the study from July 2007 to February 2009. The median age
was 77 years, and the median Karnofsky performance score was 60.
All patients underwent prior surgery. Chemotherapy with
up to 12 cycles of
temozolomide began within the first month after diagnostic
biopsy or resection. The first dose was 150 mg/m2 for 5 consecutive
days every 28 days, with dose escalation up to 200 mg/m2 at the
second cycle in the absence of hematologic toxic effects.
Fourteen patients (20%) had dose delays and 17 patients
(24%) had dose reductions caused by acute or prolonged hematologic toxicity.
Treatment-related toxicity did not lead to permanent discontinuation of
chemotherapy. Five patients refused to continue treatment after completing at
least one cycle of chemotherapy.
All patients had died by final analysis. Sixty-one
patients (87.1%) died of tumor progression. Three of the remaining patients
died of pulmonary embolism, two of aspiration pneumonia, one each from diabetic
ketoacidosis and septic shock, and two of unknown causes.
The median OS was 25 weeks (95% CI, 19-28). The 6-month
survival rate was 44.3% (95% CI, 32.7-55.9) and the 12-month survival rate was
11.4% (95% CI, 3.9-18.8). The median PFS was 16.1 weeks (95% CI, 10.2-20). The
6-month PFS rate was 29.9% (95% CI, 18.9-40.9) and the 12-month PFS rate was
6.5% (95% CI, 0.6-12.3).
Four patients experienced grade-3 nonhematologic adverse
events. Three patients had severe infections, and one patient died of septic
shock before beginning treatment. Three patients experienced thromboembolic