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Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer: a multicentric Austrian phase II study

Radiochemotherapie mit Temozolomid für Patienten mit Hirnmetastasen bei nicht kleinzelligem Lungenkarzinom

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Summary

Background

This multicentric randomized phase II study investigated the feasibility and toxicity of temozolomide (TMZ) added to whole brain radiotherapy (WBRT) followed by adjuvant TMZ in patients with multiple brain metastases of non-small-cell lung cancer (NSCLC).

Methods

Patients with multiple brain metastases from NSCLC aged ≥ 18 years, classified according to recursive partitioning analysis class I or II and with adequate organ functions were eligible. Treatment consisted of WBRT + TMZ 75 mg/m2 for 2 weeks followed at day 28 by TMZ 100 mg/m2/day 2 weeks on/2 weeks off for up to 6 months (radiochemotherapy, RCT) or WBRT alone (radiotherapy, RT).

Results

The study enrolled only 35 patients (22 patients in RCT and 13 in RT) and had to be closed prematurely due to poor accrual. The toxicity was mainly due to TMZ with WHO grade 3 and 4 thrombocytopenia in 3/22 versus 0/13, leucocytopenia in 1/22 versus 0/13 and lymphocytopenia in 7/22 versus 12/13 patients in RCT and RT respectively. Thirteen patients in RCT and six in RT progressed systemically and dropped out before first restaging of the response in brain. Median time to progression (TTP) was 2.4 months (95 % CI: 2–2.6 months) and 2.0 months (95 % CI: 0.5–3.5 months), median overall survival (OAS) was 3 months (95 % CI: 1.7–3.1 months) and 6.3.months (95 % CI: 0.2–7.6 months) in RCT and RT, respectively.

Conclusions

Like other studies before on patients with brain metastases, insufficient number of recruited patients does not allow conclusions on efficacy and toxicity as the study closed prematurely.

Zusammenfassung

Grundlagen Wir berichten über die Ergebnisse einer multizentrischen randomisierten österreichischen Phase II Studie über Verträglichkeit und Toxizität der Zugabe von Temozolomid (TMZ) zur Ganzhirnbestrahlung (WBRT) bei PatientInnen mit multiplen Hirnmetastasen des nicht kleinzelligen Lungenkarzinoms (NSCLC):

Methodik Das Studienprotokoll sah vor, 92 erwachsene PatientInnen mit multiplen Hirnmetastasen bei NSCLC entweder mit WBRT alleine (RT) oder mit WBRT + TMZ 75 mg/m2 konkomitant zur Bestrahlung und nach 28 Tagen Pause 100 mg/m2, Tag 1–14/q28 (RCT) zu behandeln.

Ergebnisse Die Studie musste wegen fehlender Rekrutierung vorzeitig geschlossen werden. 35 PatientInnen wurden in die Studie aufgenommen, 22 in den RCT und 13 in den RT Arm. Die beobachteten Toxizitäten waren überwiegend auf TMZ zurückzuführen mit jeweils WHO Grade 3 und 4 Thrombocytopenie in 3/22 gegenüber 0/13, Leucocytopenie in 1/22 gegenüber 0/13 and Lymphocytopenie in 7/22 verglichen mit 12/13 PatientInnen im RCT Arm gegenüber dem RT Arm. Dreizehn PatientInnen des RCT Arms und sechs im RT Arm erreichten wegen systemischer Progression das erste Restaging zehn Wochen nach Therapiebeginn nicht. Die mediane Zeit bis zur Tumorprogression betrug 73 Tage (95 % CI: 63–80) im RCT Arm und 62 Tage im RT Arm, (95 % CI: 15–108), die mittlere Überlebenszeit 3 Monate in RCT (95 % CI: 1,7–3,1 Monate) gegenüber 6,3 Monate (95 % CI: 0,2–7,6 Monate) im RT Arm.

Schlussfolgerungen Diese Studie konnte ihr Rekrutierungsziel nicht erreichen. Wegen der zu geringen PatientInnenanzahl können auch keine Aussagen über die Wertigkeit der Zugabe von Temozolomide zur WBRT bei Hirnmetastasen von NSCLC gemacht werden.

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Conflict of interest

All authors declare that they have no conflict interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence this work.

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Authors and Affiliations

  1. Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Marco Ronald Hassler MD &  Christine Marosi MD

  2. Department Pulmology, General Hospital Linz, Krankenhausstr 9, 4020, Linz, Austria

    Wolfgang Pfeifer MD

  3. Department of Radiotherapy, Hospital Hietzing, Vienna, Austria

    Thomas Hendrik Knocke-Abulesz MD

  4. Department of Internal Medicine 5, Hospital Hietzing, Wolkersbergenstr 1, 1130, Vienna, Austria

    Klaus Geissler MD

  5. Department of Radiotherapy and Radiobiology, Comprehensive Cancer Center-Central Nervous System Tumours Unit (CCC-CNS), Medical University Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Gabriele Altorjai MD & Karin Dieckmann MD

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  1. Marco Ronald Hassler MD
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Correspondence to Christine Marosi MD.

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Hassler, M., Pfeifer, W., Knocke-Abulesz, T. et al. Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer: a multicentric Austrian phase II study. Wien Klin Wochenschr 125, 481–486 (2013). https://doi.org/10.1007/s00508-013-0402-7

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