The Safety of the Temozolomide in Patients with Malignant Glioma

Dario, Alessandro; Tomei, G.

doi:10.2174/157488606776930535

Cited by 18 publications

(11 citation statements)

References 54 publications

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“…Myelodysplasia or leukemia developed after a median TMZ exposure of 15 Introduction Temozolomide (TMZ) has become an integral part of management in patients with malignant glioma. Randomized studies and a drug safety review have substantiated its excellent safety profile [1][2][3][4]. Common Terminology Criteria for Adverse Events (CTCAE) grades III and IV hematological toxicities are noncumulative and have been observed in less than 10% of patients.…”

Section: Sanjay Dixit Louise Baker Vicki Walmsley and Mohan Hingoranimentioning

confidence: 99%

“…However, idiosyncratic drug reactions (IDRs) such as aplastic anemia and profound myelosuppression [5,6], other nonhematological uncommon toxicities [7], and treatment-induced myelodysplasia (t-MDS) have been reported recently [8]. These toxicities were either not apparent or not reported in a phase III trial and in numerous preceding phase II studies [1,2,4]. Because these toxicities are rare and published either as a case series or as case reports, no associated risk factor could be identified.…”

Section: Sanjay Dixit Louise Baker Vicki Walmsley and Mohan Hingoranimentioning

confidence: 99%

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Temozolomide-related idiosyncratic and other uncommon toxicities

Dixit

Baker²,

Walmsley³

et al. 2012

Anti-Cancer Drugs

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Temozolomide (TMZ)-related idiosyncratic and other uncommon toxicities have been reported. To better characterize these toxicities and to identify any associated risk factors, we performed a systematic review. We searched the PubMed database, limited to the English language, published between 1999 and December 2011. We selected only those articles in which TMZ was temporally related and was the sole or main contributing chemotherapeutic drug to idiosyncratic drug reactions (IDRs) and other uncommon toxicities. Hematological IDRs are biopsy-proven aplastic anemia or grade V toxicity or grade IV toxicity with slow and incomplete hematological recovery. Seventy-three cases were identified, including 21 hematological IDRs, 31 nonhematological IDRs and uncommon infections, and 21 second primary cancers. With a caveat of publication and reporting bias, the following observations could be made. The hematological IDRs predominantly occurred in female patients (exact binomial two-tailed, P=0.0041) and most patients were receiving TMZ concomitantly with radiotherapy for glioma. The median duration of exposure to TMZ was 30 days and the median cumulative TMZ exposure was 2250 mg/m (range, 500-6900 mg/m). The sex predilection was not evident in nonhematological IDRs and other uncommon toxicities. TMZ-induced pneumonitis and cholestatic hepatitis are emerging as a nonhematological hypersensitive reaction and IDR, respectively. For TMZ-related myelodysplasia or leukemia, the cumulative dose of TMZ ranged from 1400 to 30 000 mg/m. The cumulative dose of TMZ was lower and latency was shorter with a previous exposure to other leukemogenic drugs, suggesting that TMZ may have augmented the leukemogenic potential of other drugs. Early appearance of profound myelosuppression during the course of TMZ and concurrent radiotherapy could be a hematological IDR, which warrants prompt investigations to exclude aplastic anemia. Myelodysplasia or leukemia developed after a median TMZ exposure of 15 g/m.

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Section: Sanjay Dixit Louise Baker Vicki Walmsley and Mohan Hingoranimentioning

confidence: 99%

Section: Sanjay Dixit Louise Baker Vicki Walmsley and Mohan Hingoranimentioning

confidence: 99%

Temozolomide-related idiosyncratic and other uncommon toxicities

Dixit

Baker²,

Walmsley³

et al. 2012

Anti-Cancer Drugs

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“…Chemotherapy, however, is not innocuous. Side effects of temozolomide and BCNU are myelosuppressive, with anemia and susceptibility to infection [29], while bevacizumab has been associated with coagulopathies and gastrointestinal toxicity [30]. …”

Section: Current Treatment For Glioblastomamentioning

confidence: 99%

Design and application of oncolytic HSV vectors for glioblastoma therapy

Grandi¹,

Peruzzi

Reinhart³

et al. 2009

Expert Review of Neurotherapeutics

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Glioblastoma multiforme is one of the most common human brain tumors. The tumor is generally highly infiltrative, making it extremely difficult to treat by surgical resection or radiotherapy. This feature contributes to recurrence and a very poor prognosis. Few anticancer drugs have been shown to alter rapid tumor growth and none are ultimately effective. Oncolytic vectors have been employed as a treatment alternative based on the ability to tailor virus replication to tumor cells. The human neurotropic herpes simplex virus (HSV) is especially attractive for development of oncolytic vectors (oHSV) because this virus is highly infectious, replicates rapidly and can be readily modified to achieve vector attenuation in normal brain tissue. Tumor specificity can be achieved by deleting viral genes that are only required for virus replication in normal cells and permit mutant virus replication selectively in tumor cells. The anti-tumor activity of oHSV can be enhanced by arming the vector with genes that either activate chemotherapeutic drugs within the tumor tissue or promote anti-tumor immunity. In this review, we describe current designs of oHSV and the experience thus far with their potential utility for glioblastoma therapy. In addition, we discuss the impediments to vector effectiveness and describe our view of future developments in vector improvement.

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“…Temozolomide (TMZ) is the standard therapeutic agent used to treat patients with malignant glioma (4). Severe adverse events such as leukopenia, anemia, thrombocytopenia, vomiting and nausea have been reported in patients who undergo TMZ therapy; however, unlike the adverse events associated with other chemotherapeutic agents previously used to treat malignant gliomas, the adverse events associated with TMZ are reversible and have rather low incidences (5). Severe lymphocytopenia induced by TMZ leads to opportunistic infections such as PCP (6,7) and fulminant hepatitis due to reactivation of the hepatitis B virus (HBV) (8,9).…”

Section: Introductionmentioning

confidence: 99%

Management of Cytomegalovirus Infection in a Patient with Malignant Glioma Treated with Temozolomide and Steroids

et al. 2012

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Temozolomide (TMZ) is the standard chemotherapy treatment for glioblastoma. Lymphocytopenia is reported to be the most frequent and severe adverse effect of TMZ and leads to opportunistic infections. Few cases of TMZ-induced cytomegalovirus (CMV) reactivation have so far been reported, and there are no guidelines regarding the use of chemotherapy after recovery from CMV reactivation. We herein report the case of a 45-year-old man with glioblastoma who developed CMV hepatitis following surgery and chemoradiotherapy with concomitant TMZ and steroids. After successful treatment of the CMV infection with an antiviral agent and recovery from the lymphocytopenia were achieved, the patient resumed maintenance therapy with TMZ under careful monitoring of his lymphocyte count and CMV pp65 antigenemia level.

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The Safety of the Temozolomide in Patients with Malignant Glioma

Cited by 18 publications

References 54 publications

Temozolomide-related idiosyncratic and other uncommon toxicities

Temozolomide-related idiosyncratic and other uncommon toxicities

Design and application of oncolytic HSV vectors for glioblastoma therapy

Management of Cytomegalovirus Infection in a Patient with Malignant Glioma Treated with Temozolomide and Steroids

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