Whole Brain Radiotherapy Alone or in Combination with Temozolomide (TMZ) for Brain Metastases. A Phase III Study

Reviewer: Heather Jones, MD
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Ultima Vez Modificado: 9 de octubre del 2002

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Presenter: D. Antonadou
Presenter's Affiliation: Radiation Oncology Department, Metaxas Cancer Hospital, Pireus, GR
Type of Session: Scientific

Background

    Brain metastases are a common phenomenon in cancer patients and an increasingly important cause of morbidity and mortality. One of the most attractive advantage of using temozolomide, as an adjuvant ot whole brain radiation (WBRT), is its well- documented penetration of third spaces such as the central nervous system (CNS). This study is a confirmatory phase III multicenter randomized trial, base on this institution's previous positive phase II study.

Materials and Methods

  • Eligibles patients had untreated brain metastases from various primary tumors
  • Patients were randomized to receive WBRT with or without TMZ.
  • TMZ 75mg/m2 was administered daily during WBRT (10 fractions of 3Gy) and at 1 month interval after WBRT 200mg/m2 from days 1-5 for 6 consecutive cycles.
  • Objective response was evaluated with computerized tomography or magnetic resonance imaging.
  • Response rate was further evaluated with respect to prognostic factors, such as age and Karnofsky performance status.

Results

  • 134 eligible patients were randomized, 82% with lung primaries.
  • The two arms were well balanced in terms of well known prognostic factors such as, primary tumor size, age, gender and performance status.
  • The response rate in the combined modality (TMZ + WBRT) arm was 53.4% compared to 33.3 % in the WBRT arm
  • Patients less than 60 years of age had a 76.7% response rate compared to 37% the WBRT arm (p=0.003).
  • Patients with a Karnofsky performance score of 90-100 had a 70.6% response rate in the combined modality arm compared to 32.4% in the WBRT arm (p=0.003).
  • Time to progression in the combined modality arm was 7.4 months compared to 5.9 months in the WBRT arm (p= 0.007)
  • Median survival is 7.9 months in the combined modality arm and 4.3 months in the WBRT arm (p=0.006).

Author's Conclusions

    Significantly higher response rates were seen with the addition of TMZ to WBRT for the treatment of brain metastases. The beneficial effect of TMZ administration was more pronounced in patients younger than 60 years of age and with good performance status.

Clinical/Scientific Implications

    Brain metastases constitute more than 25% of all observed recurrences in cancer patients. Brain metastases are a common complication in cancer patients and an increasingly important cause of morbidity and mortality. While WBRT has proven to be an effective treatment modality for brain metastases often it does not yield durable control for young, good performance status patients. Temozolomide (TMZ) is an attractive drug for combined modality treatment because it is oral, fairly well tolerated and has a predictable and short nadir period. This provocative phase III trial suggests that TMZ may indeed lead to more durable control rates than whole brain radiation therapy alone. We look forward to further studies evaluating TMZ in the palliative setting.

Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.


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