“One week on–one week off”: efficacy and side effects of dose-intensified temozolomide chemotherapy: experiences of a single center

Abstract

To evaluate in a single center retrospectively the efficacy and tolerability of a weekly regimen, which alternates temozolomide (TMZ) in patients with recurrent or progressive high-grade glioma (HGG). From January 2005 until June 2011, 54 patients with recurrent or progressive HGG were treated with TMZ 150 mg/m²/day on days 1-7 and 15-21 of a 28-day cycle ("one week on-one week off" scheme; TMZ 7/14) with individual dose adjustment depending on toxicity. The majority of patients (n = 48, 89 %) was treated at first tumor recurrence or progression. All patients had received prior radiotherapy with or without concomitantly administered TMZ and, optionally, adjuvant chemotherapy. After initiation of TMZ 7/14, MRI was obtained every 8-12 weeks. Tumor response or progression was assessed according to Macdonald criteria. Blood examinations were performed weekly. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE; version 3.0). A total of 434 treatment weeks with TMZ 7/14 were delivered. The median number of treatment weeks was 7 (range, 1-41 weeks). No grade 4 hematological toxicity and no opportunistic infections occurred. Patients with neutropenia were not observed. Two patients developed grade 3 and 4 patients grade 2 leukocytopenia. Thrombocytopenia grade 3 and grade 2 occurred in 4 patients and 6 patients, respectively. The progression-free survival (PFS) rate at 6 months was 43 %. Median PFS from treatment initiation was 18 weeks (95 % CI, 14-22 weeks) and median overall survival (OS) was 37 weeks (95 % CI, 31-42 weeks). The rates for PFS and OS at 1 year were 24 and 28 %, respectively. Our data suggest that treatment with TMZ 7/14 is safe and effective in patients with recurrent or progressive HGG.

Successful treatment with apatinib for refractory recurrent malignant gliomas: a case series

“…Recently, a Phase II clinical trial reported that TMZ dose-dense regimen treated rMG with a certain efficacy. 12 However, TMZ dose-dense regimen was not effective for case 1 in this report.…”

Successful Second-Line Metronomic Temozolomide in Metastatic Paraganglioma: Case Reports and Review of the Literature

“…48,49 The benefit of MGMT gene silencing in patients with glioma undergoing chemotherapy with TMZ is well elucidated. 26 Efforts to deplete MGMT activity to increase the cytotoxic potential of alkylating agents led to exploration of metronomic TMZ schedules in patients with glioma 26,50,51 with the goal of improving antitumor activity and overcoming resistance. [52][53][54][55] Several regimens consisting of MS TMZ in both newly diagnosed and recurrent gliomas as well as in melanoma have been investigated.…”

Long-term temozolomide might be an optimal choice for patient with multifocal glioblastoma, especially with deep-seated structure involvement: a case report and literature review

“…Multifocal glioblastoma is defined as intracranial GBM with multiple synchronous foci, and there is a known anatomical route for spread of diseases between lesions. It only consists of a small part of glioblastoma, with an incidence of 0.5% to 20% [ 7 , 10 , 11 ]. Thomas et al .…”

“…[ 29 ] mentioned that temozolomide treatment was continued for more than 6 cycles by 80.5% of neuro-oncologists in Spain. There are many kinds of long-term usage of temozolomide nowadays, three distinctive regimens are standard ‘5/28’ protocol (150 to 200 mg/m 2 on days 1 to 5 every 28 days) [ 6 ], ‘1 week on-1 week off’ protocol (150 mg/m 2 on days 1 to 7 and 15 to 21 of a 28-day cycle) [ 7 ], and dose-dense protocol (75 to 100 mg/m 2 on days 1 to 21 every 28 days) [ 30 ].…”