Multicenter phase II study of temozolomide therapy for brain metastasis in patients with malignant melanoma, breast cancer......

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2003 ASCO Annual Meeting


Abstract No: 407 Citation: Proc Am Soc Clin Oncol 22: 2003 (abstr 407)

Author(s):S. Siena, G. Landonio, E. Baietta, M. Vitali, L. Crino', M. Danova, A. Musolino, G. Gardin, P. Foa, G. Fincato; Ospedale Niguarda Ca' Granda, Milan, Italy; Istituto Nazionale Tumori, Milan, Italy; Ospedale Maggiore Bellaria, Bologna, Italy; IRCCS San Matteo I, Pavia, Italy; Ospedale Regionale Torrette, Ancona, Italy; Istutito Nazionale Per la Ricerca sul Cancro, Genova, Italy; Unita' di Terapia Biomolecolare, Schering-Plough, Milano, Italy


Brain metastasis is a major factor in reducing the survival of patients with advanced cancer, especially in patients with lung cancer, breast cancer, or malignant melanoma. The brain is a frequent site of metastatic relapse, and since those recurrences are generally the most refractory sites of disease, more effective therapies are necessary. In an effort to improve effects of systemic chemotherapy on brain metastases in patients with advanced non-small cell lung cancer (NSCLC), breast cancer, and melanoma, a dose-intense regimen of temozolomide was investigated in a phase II study. An alternating weekly regimen was chosen based on preclinical evidence that temozolomide efficacy could be improved by more frequent administration.

A total of 63 patients were enrolled, 21 for each tumor type, all with measurable brain metastases. Treatment was with oral temozolomide 150 mg/m2/d on days 1-7 and 15-21 every 28 days, until disease progression or for 1 year.

For 62 evaluable patients, the overall response rate for brain metastases (partial responses plus stable disease) was 24% (24% for NSCLC, 19% for breast cancer, and 40% for melanoma). The most frequent adverse events were thrombocytopenia (NSCLC) and vomiting (breast cancer and melanoma), and the most severe were grade 3-4 thrombocytopenia and leukopenia. The high response rates for established brain metastases and manageable adverse events warrant further evaluation of dose-intense temozolomide for treatment of advanced NSCLC, breast cancer, or melanoma that includes brain metastases.