BACKGROUND: Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5-day oral schedule every 4 weeks. METHODS: A single-institution phase 2 clinical trial was conducted to determine the efficacy and the safety profile of a new regimen based on a dose-intensified, protracted course of TMZ after whole-brain radiotherapy (WBRT). Patients were eligible if they had at least 1 bidimensionally measurable brain metastasis from breast cancer and nonsmall cell lung cancer (NSCLC). Twenty-seven patients were treated with 30 grays (Gy) of WBRT with concomitant TMZ (75 mg/m(2)/day) for 10 days, and subsequent TMZ at a dose of 75 mg/m(2) per day for 21 days every 4 weeks, for up to 12 cycles. RESULTS: Two complete responses (7.4%) and 11 partial responses (40.7%) were achieved. The schedule appeared to be well tolerated, with grade 3 toxicity (graded according to National Cancer Institute Common Toxicity Criteria) observed in only 2 patients. The overall median survival was 8.8 months and the median progression-free survival was 6 months. CONCLUSIONS: The concomitant use of WBRT and protracted low-dose TMZ appears to be an active, well-tolerated regimen. The observed antitumor activity suggests the need for further investigation of this schedule in combination with other anticancer agents for the concomitant treatment of brain metastases and primary cancers.
BACKGROUND:Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5-day oral schedule every 4 weeks. METHODS: A single-institution phase 2 clinical trial was conducted to determine the efficacy and the safety profile of a new regimen based on a dose-intensified, protracted course of TMZ after whole-brain radiotherapy (WBRT). Patients were eligible if they had at least 1 bidimensionally measurable brain metastasis from breast cancer and nonsmall cell lung cancer (NSCLC). Twenty-seven patients were treated with 30 grays (Gy) of WBRT with concomitant TMZ (75 mg/m(2)/day) for 10 days, and subsequent TMZ at a dose of 75 mg/m(2) per day for 21 days every 4 weeks, for up to 12 cycles. RESULTS: Two complete responses (7.4%) and 11 partial responses (40.7%) were achieved. The schedule appeared to be well tolerated, with grade 3 toxicity (graded according to National Cancer Institute Common Toxicity Criteria) observed in only 2 patients. The overall median survival was 8.8 months and the median progression-free survival was 6 months. CONCLUSIONS: The concomitant use of WBRT and protracted low-dose TMZ appears to be an active, well-tolerated regimen. The observed antitumor activity suggests the need for further investigation of this schedule in combination with other anticancer agents for the concomitant treatment of brain metastases and primary cancers.
Authors: Taofeek K Owonikoko; Jack Arbiser; Amelia Zelnak; Hui-Kuo G Shu; Hyunsuk Shim; Adam M Robin; Steven N Kalkanis; Timothy G Whitsett; Bodour Salhia; Nhan L Tran; Timothy Ryken; Michael K Moore; Kathleen M Egan; Jeffrey J Olson Journal: Nat Rev Clin Oncol Date: 2014-02-25 Impact factor: 66.675
Authors: Diane Palmieri; Renata Duchnowska; Stephan Woditschka; Emily Hua; Yongzhen Qian; Wojciech Biernat; Katarzyna Sosińska-Mielcarek; Brunilde Gril; Andreas M Stark; Stephen M Hewitt; David J Liewehr; Seth M Steinberg; Jacek Jassem; Patricia S Steeg Journal: Clin Cancer Res Date: 2014-03-14 Impact factor: 12.531
Authors: Fancy C Thomas; Kunal Taskar; Vinay Rudraraju; Satyanarayana Goda; Helen R Thorsheim; Julie A Gaasch; Rajendar K Mittapalli; Diane Palmieri; Patricia S Steeg; Paul R Lockman; Quentin R Smith Journal: Pharm Res Date: 2009-09-23 Impact factor: 4.200