Researchers at the Odense University Hospital, Denmark, have found that combining thalidomide with temozolomide may double its effectiveness, over temozolomide alone, for malignant melanoma with brain metastases.
The non-randomised phase II trial, published in the online journal ecancermedicalscience, investigated the combination of thalidomide and temozolomide. It is the first phase II study combining a new cyclic regimen of temozolomide (150mg /m2 daily, 7 days on 7days off) and thalidomide, for patients with malignant melanoma suffering from brain metastases, to show a meaningful response rate.
Melanoma is the third most common cause of metastases in the central nervous system. Thalidomide is known to prevent new blood vessels growing from pre-existing vessels and thus inhibit tumour growth, and is also known to adjust the body's immune response. Temozolomide is a chemotherapy alkylating agent commonly used for primary brain tumours, but also active in melanoma.
The researchers observed a response rate of 17.5% for temozolomide and thalidomide combined, around twice the response rate of the standard schedule of temozolomide alone (6-9% established in a previous study).
A statistically significant correlation was found between efficacy and lymphopenia (lowered white blood cell count).
Lead author Dr Lene Vestermark concluded: "The combination of temozolomide using the dose-intense schedule and thalidomide at 100-200 mg/day is a safe regimen leading to clinical efficacy in patients with brain metastases from malignant melanoma.
Most importantly it seems that patients who develop lymphopenia during therapy have a higher chance of obtaining objective response. The potential immunologic mechanism behind this will be the subject of future investigations, focusing on the potential benefit of regulatory T Cell down-regulation. The correlation between lymphopenia and objective response needs further investigation."
Further evaluations using larger patient numbers and including different therapy schedules will be considered for the future.
Temozolomide also known as Temodal or Thalomid
ecancermedicalscience