Pseudoprogression following chemoradiotherapy for glioblastoma multiforme.

PURPOSE: Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis. MATERIALS/METHODS: All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups. RESULTS: Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p = 0.0286). CONCLUSIONS: Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the "rescue" approach.

BACKGROUND: Despite advances in first-line therapy, there are few data on treatment of glioblastoma multiforme (GBM) at recurrence. Temozolomide (TMZ) is well tolerated and may have activity despite prior TMZ exposure if novel dose schedules are used. METHODS: The authors reviewed their experience with a continuous TMZ schedule (50 mg/m(2) daily), given at progression after conventional 5-day TMZ. Patients were reported in 3 groups: 1) GBM after progression on conventional TMZ; 2) GBM at first recurrence after completion of standard concomitant and adjuvant TMZ; and 3) patients with other anaplastic gliomas at second relapse on conventional TMZ. RESULTS: In Group 1, 21 patients with a median age of 54 years (range, 33 years-68 years) received a median of 3 cycles (range, 2-12 cycles) of continuous TMZ at 50 mg/m(2). Overall clinical benefit (complete response, partial response, and stable disease) was 47%, with 6-month progression-free survival (PFS) of 17%. In Group 2, 14 patients with GBM, median age 52 years (range, 38 years-62 years) received continuous TMZ at progression after initial TMZ/radiotherapy (RT) and adjuvant TMZ. The median interval after adjuvant TMZ was 3 months (range, 2 months-10 months). A median of 5 cycles of TMZ was given, and 6-month PFS was 57%. In Group 3, 14 patients with a median age of 49 years (range, 34 years-56 years) received continuous TMZ; 2 partial responses and 6 with stable disease were seen, with a 6-month PFS of 42%. Toxicities were mild and well tolerated; lymphopenia was common but no serious opportunistic infections were identified. CONCLUSIONS: Although retrospective, our results demonstrate that continuous daily administration of TMZ is an active regimen despite prior TMZ therapy. The excellent tolerability of this regimen may allow future combination with other alkylating agents or with novel therapies.