Brain Metastases From Melanoma: Is There a Role for Concurrent Temozolomide in Addition to Whole Brain Radiation Therapy?

Objectives:This study was performed to evaluate the addition of temozolomide (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma. Methods:Seven patients with brain metastases from melanoma were treated on a North Central Cancer Treatment Group (NCCTG) trial (N0274) of TMZ plus WBRT. TMZ was given orally in doses of 200 mg/m2 for 5 days every 4 weeks for up to 8 cycles. WBRT was started on the first day of TMZ and included the delivery of 3750 cGy in 15 fractions. In addition, separately analyzed was a cohort of 53 patients treated at the Mayo Clinic who received WBRT alone (39 patients) or WBRT plus TMZ (14 patients). Results:The median survival of the 7 patients treated on N0274 was 3.6 months with 2 of 7 (29%) failing in brain and 5 of 7 (71%) failing elsewhere. For the other cohort of 53 patients, the median survival was 3.8 months with WBRT alone compared 4.3 months for WBRT plus TMZ (P = 0.5). Conclusions:Patients did not appear to benefit from the addition of TMZ to WBRT for the treatment of their brain metastases. Further improvements in outcome will require research to discover more effective systemic therapy and RT techniques.

[1]  D. Rades,et al.  Dose escalation of whole-brain radiotherapy for brain metastases from melanoma. , 2010, International journal of radiation oncology, biology, physics.

[2]  M. Atkins,et al.  Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma , 2008, Cancer.

[3]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[4]  P. Brown,et al.  A higher radiotherapy dose is associated with more durable palliation and longer survival in patients with metastatic melanoma , 2007, Cancer.

[5]  I. Quirt,et al.  Temozolomide for the treatment of metastatic melanoma: a systematic review. , 2007, The oncologist.

[6]  V. Suman,et al.  Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma , 2007 .

[7]  D. Rades,et al.  Stereotactic radiosurgery alone versus resection plus whole‐brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients , 2007, Cancer.

[8]  J. Malvehy,et al.  Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases , 2006, Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico.

[9]  M. Gore,et al.  Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Maria Werner-Wasik,et al.  Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial , 2004, The Lancet.

[11]  J. Earle,et al.  The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma , 2002 .

[12]  J. Sosman,et al.  Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group , 2002, Journal of Cancer Research and Clinical Oncology.

[13]  W R Markesbery,et al.  Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. , 1998, JAMA.

[14]  K. Ang,et al.  Radiation therapy for malignant melanoma. , 1996, The Surgical clinics of North America.

[15]  G. Duncan,et al.  A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis , 1996, Cancer.

[16]  Ronald Brand,et al.  Treatment of single brain metastasis: Radiotherapy alone or combined with neurosurgery , 1993, Annals of neurology.

[17]  A. Harwood Conventional fractionated radiotherapy for 51 patients with lentigo maligna and lentigo maligna melanoma. , 1983, International journal of radiation oncology, biology, physics.

[18]  R. Gelber,et al.  Value of radiation therapy in the management of patients with cerebral metastases from malignant melanoma. Radiation therapy oncology group brain metastases study I and II , 1980, Cancer.

[19]  M. Didolkar,et al.  Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. , 1978, American journal of surgery.

[20]  L. Stalpers,et al.  Comparison of Short-Course versus Long-Course Whole-Brain Radiotherapy in the Treatment of Brain Metastases , 2008, Strahlentherapie und Onkologie.

[21]  V. Budach,et al.  Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases , 2005, Journal of Neuro-Oncology.

[22]  N. Viñolas,et al.  Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. , 2005, International journal of radiation oncology, biology, physics.

[23]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[24]  E. Rofstad,et al.  Radiation sensitivity in vitro of cells isolated from human tumor surgical specimens. , 1987, Cancer research.