Temozolomide in advanced malignant melanoma with small brain metastases

Abstract

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.

Minimized Doses for Linear Accelerator Radiosurgery of Brainstem Metastasis

“…Nevertheless, surgical access to the brainstem is restricted to lesions located in contact with the fourth ventricle. Chemotherapy, except temozolomide, shows poor results because the blood-brain barrier limits transit of molecules inside the parenchyma (22). Therefore, radiation therapy plays an important role in treatment strategy for brainstem lesions.…”

Genomic and Molecular Profiling Predicts Response to Temozolomide in Melanoma

“…Temozolomide has the added advantage of oral delivery as well as the ability to -brain barrier (23, 24), a distinct advantage over DTIC given the high rate of central nervous system metastasis associated with melanoma (25,26). Furthermore, in an animal model of extremity melanoma, isolated limb infusion with temozolomide was more effective than with melphalan, the drug of choice for regional treatment of melanoma (27).…”

Dynamic Changes of Molecular Markers during Natural History in Metastatic Melanoma: Ethical Issues and Lessons to Learn

“…No details were provided from the authors of a different study about the rate of complete response at brain level; they included 132 metastatic melanoma patients and 10 to 17% of these individuals presented brain metastases at inclusion [13]. Moreover, some complete responses were observed in a medium-sized retrospective analysis of 179 melanoma patients with small brain metastases, less than 2 cm, treated with TMZ alone [14]. As showed by the same authors, median survival of patients with brain metastases was 5.6 months (95% confidence interval, 4.4-6.8 months).…”