Effect of temozolomide on central nervous system relapse in patients with advanced melanoma

Paul, Mazhuvanchary Jacob; Summers, Yvonne; Calvert, A. Hilary; Rustin, G. J. S.; Brampton, M.; Thatcher, Nick; Middleton, Mark R.

doi:10.1097/00008390-200204000-00011

Cited by 94 publications

(49 citation statements)

References 13 publications

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“…Two prior published reports have indicated brain metastasis as a first site of progressive disease in four out of nine patients with a complete remission (Legha et al, 1998;O'Day et al, 1999). Moreover, in a retrospective case-controlled study of responders to DTIC or TMZ, it was found that responders to TMZ developed significantly less CNS relapses than responders to DTIC (Paul et al, 2002). Importantly, low-dose IL-2 did not appear to cause signs or symptoms of brain oedema in patients with CNS disease.…”

Section: Discussionmentioning

confidence: 75%

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

et al. 2003

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The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) lowdose interleukin-2 (IL2), granulocyte -monocyte colony stimulating factor (GM-CSF) and interferon-a 2b (IFNa) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150 -250 mg m À2 ) for 5 days followed by s.c. IL2 (4 MIU m À2 ), GM-CSF (2.5 mg kg À1 ) and IFNa (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12 -30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8 -42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose-and patientdependent. Lymphocytopenia (grade 3 -4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basis.

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Section: Discussionmentioning

confidence: 75%

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

et al. 2003

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“…28 Accordingly, patients with metastatic melanoma who respond to temozolomide develop less CNS metastases as the first site of recurrence compared with responders to dacarbazine. 14,29 These results also suggest that small lesions probably are treated more successfully with temozolomide. We did not observe intracranial hemorrhagic complications in the 13 patients who responded.…”

Section: Toxicitymentioning

confidence: 74%

Temozolomide in advanced malignant melanoma with small brain metastases

Boogerd

Gast

Dalesio

2007

Cancer

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BACKGROUND.The efficacy of radiotherapy (RT) in patients who have brain metastases from melanoma is limited. In this study, the authors evaluated the efficacy of treatment with temozolomide in patients with metastatic melanoma, including small brain metastases, who did not require immediate RT and investigated the feasibility of deferring RT.METHODS.Patients with brain metastasis were identified from 3 prospective studies of temozolomide (with or without immunotherapy) for metastatic melanoma. Patients with brain metastasis that measured >2 cm, extensive edema, and localization in the brain stem were excluded from the study. For the current analysis, patients with leptomeningeal metastasis and patients who received previous stereotactic RT were excluded. In patients who achieved a systemic response or stabilization to temozolomide, the response of brain metastasis and the necessity for palliative cranial RT were evaluated.RESULTS.Among 179 patients who received temozolomide for advanced melanoma, 52 patients with brain metastasis were evaluable. Stabilization of systemic metastasis was noted in 7 of 52 patients (13%), and there were 6 responses (5 partial responses and 1 complete response; 11%); thus, in those 13 patients, 6 had stabilization of brain metastasis (11%) and 5 had a response (2 partial responses and 3 complete responses; 9%). Immunotherapy did not influence the neurologic response. The median time to neurologic progression was 7 months (range 2–15, months). RT for cerebral recurrence was required in 2 patients. The median survival of patients with brain metastases was 5.6 months (95% confidence interval, 4.4–6.8 months). Intracranial hemorrhagic complications were not observed.CONCLUSIONS.The current results indicated that it is feasible to treat patients who have advanced melanoma and small brain metastasis with temozolomide as the single treatment. The small subset of patients with systemic response usually showed durable stabilization or a response of brain metastasis. With this approach, neurologic disease can be controlled, and cranial irradiation may be deferred and even withheld in most of patients. Cancer 2007. © 2006 American Cancer Society.

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“…Likewise, Bafaloukos et al [5] reported antitumor activity in the CNS and a regression in brain metastases. In a retrospective study [36], where 20 patients responded to treatment with temozolomide and 21 to treatment with DTIC, only two patients (10%) treated with temozolomide developed brain metastases compared with nine patients (43%) treated with DTIC. That result was found to be statistically significant (p ϭ .03) despite the small number of patients used in the study.…”

Section: Discussionmentioning

confidence: 99%

Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

et al. 2007

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Background. This systematic review examines the role of temozolomide in patients with metastatic melanoma. Outcomes of interest include response rate, progression-free survival, overall survival, quality of life, and adverse effects.Methods. The MEDLINE, EMBASE, and Cochrane Library databases were searched from 1980 through to 2005 using variations on the search terms: melanoma, clinical trial, random, temozolomide, temodal, and temodar. The American Society of Clinical Oncology Annual Meeting proceedings were searched from 1996 to 2005. Relevant articles and abstracts were selected and reviewed by two reviewers, and the reference lists from these sources were searched for additional trials.Results. Two randomized phase III trials and three randomized phase II trials were located. In addition, 21 phase I or II trials investigating single-agent temozolomide, temozolomide plus interferon-␣, and temozolo-

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Effect of temozolomide on central nervous system relapse in patients with advanced melanoma

Cited by 94 publications

References 13 publications

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

Temozolomide in advanced malignant melanoma with small brain metastases

Temozolomide for the Treatment of Metastatic Melanoma: A Systematic Review

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