Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: A phase II study

Brandes, Alba A.; Ermani, Mario; Basso, Umberto; Amistà, Pietro; Berti, Franco; Scienza, Renato; Rotilio, Antonino; Pinna, Giampietro; Gardiman, Marina Paola; Monfardini, S.

doi:10.1023/a:1008336732273

Cited by 81 publications

(43 citation statements)

References 8 publications

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“…Not only oligodendroglial tumours respond to TMZ, as was demonstrated by Yung et al (1999), who reported a response rate of 35% and disease stabilisation in 26% of their series of predominantly anaplastic astrocytoma. These response rates are higher as compared with our results that are more comparable with the response rates of 11 and 23%, respectively as observed in other phase II trials in high-grade glioma (Bower et al, 1997;Brandes et al, 2001). Even if the reported response rates of the various clinical trials are not homogeneously high, we must consider that TMZ is one of the few drugs that have shown activity as single drug in high-grade glioma.…”

Section: Discussionsupporting

confidence: 79%

“…In children, the MTD is 180 mg m À2 day À1 for patients with previous CSI (Nicholson et al, 1998) and 200 -215 mg m À2 day À1 , respectively for patients without prior CSI (Estlin et al, 1998;Nicholson et al, 1998, respectively). The reports of phase II trials of TMZ using comparable administration regimens of 150 -200 mg m À2 day À1 Â 5 every 28 days in adults with recurrent or progressive grade III or grade IV (oligodendro-) glioma showed objective response rates varying from 8, 11, 23, 35 and 44%, respectively (Brada et al, 2001;Bower et al, 1997;Brandes et al, 2001;Yung et al, 1999;Chinot et al, 2001, respectively). A phase II clinical trial by the UKCCSG New Agents Group/SFOP 'Groupe de Pharmacologie' with this regimen of TMZ in paediatric patients with recurrent or progressive high-grade glioma showed a lower response rate of 12% for supratentorial high-grade glioma and 6% for brainstem glioma, respectively (Lashford et al, 2002).…”

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confidence: 99%

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Temozolomide in paediatric high-grade glioma: a key for combination therapy?

et al. 2004

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This report describes a single-centre study with temozolomide (TMZ) (200 mg m À2 day À1 Â 5 per cycle of 28 days) in children with (recurrent) high-grade glioma. Magnetic resonance imaging was performed every two cycles. In all, 20 patients were treated between 1998 and 2001 after the UKCCSG/SFOP TMZ phase II trial. All patients had measurable disease. Totally, 15 patients had a relapse after surgery7radiotherapy7chemotherapy. Overall, five patients received TMZ after surgery or biopsy, awaiting radiotherapy. There were one clinically malignant grade II glioma, 11 grade III and eight grade IV gliomas. Seven tumours had oligodendroglial features. Mean age at start of TMZ was 12.0 years (range 3 -20.5 years). In total, eight patients had 48 cycles (range 3 -30). One VGPR (currently in CR after surgery), three PRs (with a PFS of 4, 4 and 11 months, respectively) and one MR (PFS 14 months) were observed. Three out of five responses occurred after 44 courses. The overall response rate was 20%. Median progression-free survival (PFS) was 2.0 months (range 3 weeks -34 þ months). PFS rate was 20% after 6 months. Median overall survival (OS) was 10 months. Nine patients showed a clinical improvement. Three patients vomitted shortly after TMZ administration, eight patients (13 cycles) experienced grade III/IV thrombocytopenia, occurring predominantly during the fourth week of the first two cycles. Five patients experienced neutropenia, and three patients febrile neutropenia. TMZ is a well-tolerated ambulatory treatment for children with malignant glial tumours. This drug warrants further study in these highly chemoresistant tumours and should be studied either as upfront therapy or in combination therapy. (Stevens et al, 1987), which is also the cytotoxic metabolite of dimethyl triazeno imidazole carboxamide (DTIC, dacarbazine). The cytotoxic effect of MTIC is caused by alkylation of deoxyguanosine nucleotides, mostly at the O 6 position, leading to DNA mismatch (G -T match instead of G -C match) (Catapano et al, 1987), DNA strand breaks and subsequently apoptosis (Tentori et al, 1997).Several phase I studies with TMZ single drug have been published in adults and children with solid tumours (Newlands et al, 1992;O'Reilly et al, 1993;Dhodapkar et al, 1997;Brock et al, 1998;Estlin et al, 1998;Nicholson et al, 1998;Brada et al, 1999), showing haematological dose-limiting toxicity (DLT). Maximally tolerated doses (MTD) were between 150 and 250 mg m À2 day À1 when using the once daily oral administration on 5 consecutive days every 4 weeks, depending on whether or not patients had been previously treated with nitrosureas (Dhodapkar et al, 1997) or craniospinal irradiation (CSI) (Nicholson et al, 1998). In children, the MTD is 180 mg m À2 day À1 for patients with previous CSI (Nicholson et al, 1998) and 200 -215 mg m À2 day À1 , respectively for patients without prior CSI (Estlin et al, 1998; Nicholson et al, 1998, respectively). The reports of phase II trials of TMZ using comparable administration regimens of 150 -200 mg m À2...

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Section: Discussionsupporting

confidence: 79%

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confidence: 99%

Temozolomide in paediatric high-grade glioma: a key for combination therapy?

et al. 2004

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“…Both trials used a schedule of TMZ 150-200 mg/m 2 for 5 out of 28 days. Other prospective studies mainly without previous TMZ treatment using this schedule showed similar PFS-6 rates ranging from 21 to 24% [64][65][66][67].…”

Section: Temozolomide Monotherapy and Combination Regimensmentioning

confidence: 54%

Therapeutic options in recurrent glioblastoma—An update

Seystahl

Wick

Weller

2016

Critical Reviews in Oncology/Hematology

177

134

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“…11,12 In a few studies, patients who received previous therapy with nitrosoureas remained at the 150 mg/m 2 per day dose and responses at this lower dose have been reported. 22 Overall, this regimen was reasonably well tolerated. Most of the serious study drug-related toxicities were hematologic or infectious.…”

Section: Discussionmentioning

confidence: 85%

Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma

Korones

Benita-Weiss

Coyle

et al. 2003

Cancer

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BACKGROUND Although temozolomide is active against recurrent malignant glioma, responses in many patients are modest and short‐lived. Temozolomide may prove more effective in combination with other agents. Therefore, combination oral chemotherapy for these patients is a particularly attractive approach. METHODS The authors conducted a Phase I study of temozolomide in combination with escalating doses of oral etoposide (VP‐16) to determine the maximum tolerated doses of these two agents when given together. The temozolomide dose was fixed at 150 mg/m2 per day on Days 1–5. The oral VP‐16 was escalated in cohorts of 3 to 6 patients by numbers of days of VP‐16 administered: 50 mg/m2 per day, Days 1–5 (dose level 1), Days 1–8 (dose level 2), Days 1–12 (dose level 3), Days 1–16 (dose level 4), and Days 1–20 (dose level 5). Therapy was given in 28‐day cycles. RESULTS Of the 29 patients enrolled, 26 were fully evaluable and 3 were partially evaluable for toxicity. The 29 patients received a total of 92 cycles. The median age of the patients was 49 years (range, 28–76 years). Diagnoses included glioblastoma (n = 19), gliosarcoma (n = 3), anaplastic astrocytoma (n = 5), and anaplastic oligoastrocytoma (n = 2). The median time from diagnosis to disease recurrence was 8 months (3–188 months). Twenty patients were treated at the first disease recurrence, seven at the second, and two at the third. Twenty‐four patients (83%) were receiving anticonvulsants and 24 were receiving dexamethasone. All patients had received previous radiation, and 25 of 29 had been treated with chemotherapy previously. Of the 3 patients at dose level 1, none had dose‐limiting toxicity (DLT). Of the 6 patients at dose level 2, 1 patient had DLT: Grade 3 thrombocytopenia resulting in a > 2‐week delay in starting the next cycle of chemotherapy. Of the 6 patients at dose level 3, 1 patient had DLT: death due to pneumonia. There were 2 DLTs in the 7 patients at dose level 4: fever, neutropenia, and herpes zoster infection in 1 patient and death due to pneumonia in another. Seven patients had been started at dose level 5 when DLT was established at dose level 4: of the 5 fully evaluable and 2 partially evaluable patients at dose level 5, there was no DLT. CONCLUSIONS The maximum tolerated dose of temozolomide and oral VP‐16 in this heavily treated group of patients with recurrent malignant glioma is temozolomide 150 mg/m2 per day for 5 days and oral VP‐16 50 mg/m2 per day for 12 days. Cancer 2003;97:1963–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11260

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Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: A phase II study

Cited by 81 publications

References 8 publications

Temozolomide in paediatric high-grade glioma: a key for combination therapy?

Temozolomide in paediatric high-grade glioma: a key for combination therapy?

Therapeutic options in recurrent glioblastoma—An update

Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma

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