We surveyed neuro-oncologists regarding patients treated with temozolomide for at least 12 cycles or 12 months. Patients receiving first-line temozolomide for a median 13 cycles had a median progression-free survival (PFS) of 14 months. Patients with recurrent disease receiving a median 14 cycles had a median PFS of 15.5 months. A small percentage of patients experienced grade III to IV toxicity. These results suggest that long-term treatment with temozolomide is feasible and well tolerated.
Temozolomide (TMZ) is the standard of care for patients with newly diagnosed glioblastoma (GBM) as well as those with recurrent anaplastic glioma (AG) and GBM. It has become common practice to re-expose patients to TMZ who had been previously treated with TMZ, or to switch patients to alternative dosing regimens of TMZ when there are signs of relapse or progress on standard TMZ therapeutic regimens. To date, however, there is a scarcity of data on the efficacy of this therapeutic strategy, currently referred to as TMZ rechallenge. We have conducted a retrospective review of patients with recurrent glioma rechallenged with TMZ. Patients experiencing progressive disease (PD) during TMZ therapy who were rechallenged with alternative TMZ regimens and patients rechallenged after stable disease in a TMZ-free interval were evaluated separately. A total of 90 rechallenges were identified in 80 patients. The progression-free survival at 6 months (PFS-6) was 48% in patients with AG (12/25) and 27.7% in those with GBM (14/47). The PFS-6 was 16.7% in AG and 26.3% in GBM for patients switched during TMZ and 57.9 and 28.6% in patients rechallenged after a TMZ-free interval of at least 8 weeks. Relevant hematological toxicity (NCI-CTC grade 3-5) was observed in 22 of 90 rechallenges, and relevant non-hematological in ten of 90 rechallenges. Temozolomide was well tolerated and generated promising PFS-6 in patients who had previously failed TMZ, regardless if they progressed during TMZ treatment, or if they were rechallenged after a TMZ-free interval. These results suggest that the TMZ rechallenge strategy warrants further investigation in a prospective randomized trial.
Background: Recurrent malignant glioma has a dismal prognosis, and therapeutic options are scarce. After previous potentially encouraging reports on liposomal pegylated doxorubicin (PEG-DOX) in this setting, PEG-DOX was applied to patients with recurrent malignant glioma in an institutional series. Methods: In a retrospective analysis, 49 patients with recurrent high-grade glioma (WHO III, n = 18; WHO IV, n = 31) were treated with PEG-DOX (days 1 and 14/28, 20 mg/m2, n = 26) alone or in combination with temozolomide (days 1–5/28, 200 mg/m2, n = 23). The response rate, progression-free survival and overall survival were evaluated. Results: The rate of progression-free patients at 6 months after initiation of therapy was 27% (WHO III, 33%; WHO IV, 23%). The median overall survival (mOS) after initiation of PEG-DOX (monotherapy and combination therapy) was 8 months (WHO III, 16 months; WHO IV, 7 months). The mOS after initiation of PEG-DOX monotherapy was 8 months, and after initiation of combination therapy, 10 months. Both regimens were well tolerated, with the main side effect being hematologic toxicity (grade 1–2, 8%; grade 3–4, 18%). Conclusion: These data demonstrate the safety and moderate efficacy of PEG-DOX ± temozolomide therapy in recurrent malignant glioma. The potential of this nonalkylating chemotherapy should be further explored.
There is an urgent need for strategies maintaining remission in patients with malignant glioma. Maintenance therapy with high-dose cRA is feasible and well tolerated over long periods of time. A controlled clinical trial to test the efficacy of cRA as a maintenance treatment in malignant glioma is warranted.
2034 Background: TMZ is standard therapy for patients (pts) with HGG. Recent data suggest potentially enhanced efficacy of alternative schedules of TMZ administration based on optimizing depletion of MGMT. However, no prospective data have been published on the efficacy of TMZ regimens after failure of first-line TMZ (FL-TMZ). We therefore assessed the outcome of rechallenge with TMZ in pts with HGG. Methods: A retrospective review of pt with recurrent HGG who were rechallenged with TMZ between Jan 2000 and Oct 2006 was conducted. Standard criteria for rechallenge were as follows: if pts relapsed=8 wks after discontinuation of FL-TMZ, they were treated with the same or an alternative regimen of TMZ; however, if they progressed while still receiving TMZ, they were treated with an alternative regimen. Results: Of a total 81 pts identified, 54 intra-institutional pts were evaluable, 23 glioblastoma (GBM), 22 anaplastic glioma (AG). Median age was 44 yr with median KPS of 80. The response rate (RR) to FL-TMZ was 65% in GBM and 95% in AG using Macdonald criteria. At rechallenge, pts received one of four TMZ regimens: 150–200 mg/m2/d for 5/28 days (n=35), 150 mg/m2/d for 7/14 days (n=7), 75 mg/m2/d for 21/28 days (n=4), or continuous 50 mg/m2/d (n=7). All pts had progressed during FL-TMZ or after initial discontinuation of TMZ. Discontinuation during rechallenge TMZ was due to progressive disease in 36 pts and patient request in 6 pts. None of the pts discontinued due to toxicity. The response rates were 66% and 70% in GBM and AG, respectively. 8/12 non-responders to FL-TMZ responded to alternate regimens of TMZ. Median time to progression (TTP) was 20 weeks and 22 weeks, respectively. Six-month progression-free survival was 41% in GBM and 43% in AG. Conclusions: TMZ was well tolerated without major toxicities and had a good RR in pts who had previously failed TMZ. Durable responses were observed in patients who had not initially responded to front-line TMZ. These data suggest that rechallenge with TMZ in previous responders and non-responders warrants further investigation in a prospective study. No significant financial relationships to disclose.
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