Hematologic adverse events associated with temozolomide

Villanó, John L.; Letarte, Nathalie; Yu, J.; Abdur, Shakir; Bressler, Linda R.

doi:10.1007/s00280-011-1679-8

Cited by 49 publications

(41 citation statements)

References 33 publications

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“…Although lymphopenia was noted, no patient developed P. carinii pneumonia. Two patients developed MDS, an adverse effect reported previously (17)(18)(19). It is difficult to establish with certainty whether this complication was due to temozolomide, prior etoposide, or the combination.…”

Section: Discussionmentioning

confidence: 81%

Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine-DNA Methyltransferase as a Potential Biomarker

Pietanza

Kadota

Huberman

et al. 2012

Clinical Cancer Research

151

109

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Purpose: This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC).Experimental Design: Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m 2 /d for 21 days of a 28-day cycle. The primary endpoint was the overall response rate [ORR; complete response (CR) plus partial response (PR)], which was evaluated separately in sensitive and refractory cohorts. In the available tissue, we assessed O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation status by PCR and MGMT expression by immunohistochemistry. Results: Sixty-four patients were accrued: 48 patients in the sensitive cohort and 16 in the refractory group. One CR and 10 PRs were noted in sensitive patients [ORR, 23%; 95% confidence interval (CI), 12%-37%]. Two PRs were seen in the refractory cohort (ORR, 13%; 95% CI, 2%-38%). As second-and third-line treatment, the ORR was 22% (95% CI, 9%-40%) and 19% (95% CI, 7%-36%), respectively. Among patients with target brain lesions, 38% had a CR or PR (95% CI, 14%-68%). Grade !3 thrombocytopenia and neutropenia were observed in nine patients (14%). A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT (38% vs. 7%; P ¼ 0.08).Conclusion: Temozolomide has activity in relapsed SCLC, particularly for brain metastases. Response to temozolomide may correlate with MGMT methylation in SCLC.

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Section: Discussionmentioning

confidence: 81%

Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine-DNA Methyltransferase as a Potential Biomarker

Pietanza

Kadota

Huberman

et al. 2012

Clinical Cancer Research

151

109

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“…The United States Food and Drug Administration approved TMZ as a treatment for glioblastoma in 1999 (22). However, TMZ is a relatively new alkylating agent and its long-term safety is not fully characterized.…”

Section: Discussionmentioning

confidence: 99%

“…The leukemogenic potential of alkylating agents is well-known and it usually takes 5-10 years after exposure for leukemia to develop (10-12). Following prolonged TMZ treatment, t-MDS and t-AML have been widely reported in patients (22)(23)(24). Results from phase I and II clinical trials suggest that the primary toxicity associated with TMZ is myelotoxicity (13).…”

Section: Discussionmentioning

confidence: 99%

Acute lymphoblastic leukemia following temozolomide treatment in a patient with glioblastoma: A case report and review of the literature

Liu

Lei

et al. 2018

Oncol Lett

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Abstract. Temozolomide (TMZ) is a second-generation oral alkylating agent that functions against a number of central nervous system neoplasms, and is generally used to treat high-grade gliomas, including anaplastic astrocytoma and glioblastoma multiforme. Therapy-related secondary myelodysplastic syndrome and acute myeloid leukemia have been reported in patients following prolonged exposure to TMZ. However, TMZ-related acute lymphoblastic leukemia (ALL) is extremely rare. The present study describes the case of an 11-year-old boy with a 3-day history of generalized tonic-clonic seizures and a contrast-enhanced lesion in the left temporooccipital region with focal cystic degeneration, as detected by magnetic resonance imaging. The patient underwent craniotomy and gross-total resection andpathological analysis confirmed the diagnosis of giant cell glioblastoma. Postoperatively, the patient received TMZ-based concurrent chemoradiation during radiotherapy, and developed B-cell ALL 6 months following TMZ treatment. A thorough literature search identified only six published cases of TMZ-related ALL. The chemotherapeutic efficacy of TMZ has been identified, however, its leukemogenic potential should be emphasized among practitioners and patients. Further studies are required to determine the specific pathogenic mechanism of TMZ-related ALL. Close hematological monitoring of patients following TMZ treatment is vital and a high index of suspicion is necessary. IntroductionTemozolomide (TMZ) is a second-generation oral alkylating agent with the ability to penetrate the blood-brain barrier, and is widely used in the management of high-grade brain neoplasms, including anaplastic astrocytoma and glioblastoma multiforme, in addition to brain metastasis from solid tumors (1,2). TMZ is a prodrug and imidazotetrazine analog that exerts its action following spontaneous conversion to its active form, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3). This active drug subsequently exerts its antitumor effect by methylating the purine bases of chromosomal DNA including O6-guanine, which results in the failure of DNA replication, cell cycle arrest and subsequent apoptosis (4,5). TMZ is generally considered effective and relatively safe (6-8); however, increased survival rates in certain patients have uncovered toxicities arising from the long-term use of alkylating agents, including TMZ (9). Treatment-related secondary myelodysplastic syndrome (t-MDS) and treatment-related acute myeloid leukemia (t-AML) have been recorded in patients following prolonged (5-10 years) exposure to alkylating agents (10-12).TMZ is a relatively new drug and glioblastoma is an aggressive neoplasm with poor prognosis, thus the types of secondary cancer arising due to TMZ treatment have not yet been fully characterized. A review of the existing literature demonstrated that only 7 cases of TMZ-related acute lymphoblastic leukemia (ALL) have been reported thus far (13-18). The current case describes an 11-year-old boy with glioblastoma multiforme, who develo...

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“…5 patients died because of complications from aplastic anemia or from bone marrow transplant. Villano et al [46] reviewed all the TMZ-associated HAEs reported in the FDA Med-Watch database between November 1, 1997 and September 4, 2008, and found that aplastic anemia was the most frequently observed major HAE with 39 out of 112 reported cases. The median duration of TMZ treatment was 6 weeks.…”

Section: Resultsmentioning

confidence: 99%

Temozolomide-Related Hematologic Toxicity

Scaringi¹,

Sanctis²,

Minniti³

et al. 2013

Oncol Res Treat

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Temozolomide (TMZ) is an oral alkylating agent used for the treatment of recurrent or newly diagnosed malignant gliomas with significant survival benefit. TMZ is generally well tolerated and safe. The most common side effects are mild to moderate, and are represented by fatigue, nausea, vomiting, thrombocytopenia, and neutropenia. However severe hematologic adverse events (HAEs), including myelodysplastic syndrome and aplastic anemia, have also been reported. In this review we present an overview of the available literature of HAEs after exposure to TMZ.

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Hematologic adverse events associated with temozolomide

Cited by 49 publications

References 33 publications

Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine-DNA Methyltransferase as a Potential Biomarker

Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine-DNA Methyltransferase as a Potential Biomarker

Acute lymphoblastic leukemia following temozolomide treatment in a patient with glioblastoma: A case report and review of the literature

Temozolomide-Related Hematologic Toxicity

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