Phase I Dose Escalation Trial in Patients With Brain Metastases Using IMRT
Traditionally, whole brain radiation therapy (WBRT) has been the primary therapy for
patients with brain metastases. Despite this therapy, patients still have poor survival of
four to six months. Untreated patients have a median survival of one month. Up to one half
of these patients die of causes related to the presence of brain metastases. In a Phase
I/II RTOG trial, the efficacy and safety of delivering accelerated fractionation was
investigated in patients with good prognostic factors. No toxicity was observed with
escalating dose of irradiation up 70.40Gy in 1.6Gy twice daily treatments. However, in a
randomized trial, the use of hyperfractionation did not appear to improve survival when
compared to 30Gy whole brain irradiation delivered in 10 fractions.
Current therapeutic approach also includes stereotactic radiosurgery (SRS). Several
retrospective studies have demonstrated improved local tumor control of 80% with addition of
SRS to WBRT. These local control rates were comparable to surgery. In a recently published
randomized trial by RTOG 95-08 (TJU accrued 42 patients to this trial), Andrews et al.
demonstrated improved survival in patients with solitary brain lesion treated with SRS.
Median survival was 6.5 months in patients treated with WBRT and SRS compared to 4.9 months
in patients treated with WBRT alone. Also, these patients were more likely to have stable
or improved performance status.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Unacceptable Acute CNS Toxicity
The primary endpoint is the frequency of patients developing unacceptable acute CNS toxicity.
Wenyin Shi, MD, PhD
Thomas Jefferson University
United States: Institutional Review Board
|Thomas Jefferson University||Philadelphia, Pennsylvania 19107-6541|