Clin Lung Cancer. 2012 Jan;13(1):24-30. doi: 10.1016/j.cllc.2011.05.007. Epub 2011 Aug 10.
Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced non-small-cell lung cancer.
Ortuzar W, Hanna N, Pennella E, Peng G, Langer C, Monberg M, Scagliotti G.
SourceEli Lilly and Company or one of its subsidiaries, Indianapolis, IN 46285, USA. ortuzarwa@lilly.com
Abstract
BACKGROUND: Symptomatic brain metastases (BM) frequently occurs after initial treatment of non-small-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence.
METHODS: Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors.
RESULTS: Overall, 71.5% of patients in pemetrexed-containing arms (819 of 1145), and 68.2% of patients in non-pemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2% (95% confidence interval [CI], 2.1%-4.6%) in the pemetrexed-containing arms vs. 6.6% (95% CI, 5.0%-8.6%) in the non-pemetrexed-containing arms (P = .002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95% CI, 0.32-0.76; P = .001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC.
CONCLUSIONS: Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.
Outcomes associated with brain metastases in a three-arm phase III trial of gemcitabine-containing regimens versus paclitaxel plus carboplatin for advanced non-small cell lung cancer.
Edelman MJ, Belani CP, Socinski MA, Ansari RH, Obasaju CK, Chen R, Monberg MJ, Treat J; Alpha Oncology Research Network.
SourceUniversity of Maryland Greenebaum Cancer Center, Baltimore, Maryland 21201-1595, USA, medelman@umm.edu
Abstract
BACKGROUND: Brain metastases (BMs) are a common complication of non-small cell lung cancer (NSCLC). Because of historical data indicating a poor prognosis for patients with BM, few randomized phase III studies of advanced NSCLC have included patients with BM at presentation. Because the potential benefits of systemic therapy in patients with BM are uncertain, we analyzed data from a recent phase III study.
METHODS: One thousand one hundred thirty-five chemonaïve patients with stage IIIB/IV NSCLC were randomized to receive gemcitabine/carboplatin, gemcitabine/paclitaxel, or paclitaxel/carboplatin. Stratification was based on presence or absence of BM, stage, and baseline weight loss. Patients with BM were required to be clinically stable after treatment with radiotherapy or surgery before entry. Results were retrospectively analyzed by presence or absence of BM at study entry.
RESULTS: Rate of BM was 17.1% overall. The response rate was 28.9% for patients with BM (n = 194) versus 29.1% without BM (n = 941). Time to progression was 4.3 months with BM and 4.6 months without BM (p = 0.03). Median survival was 7.7 months (95% confidence interval: 6.7-9.3) among patients with BM (n = 194) and 8.6 months (95% confidence interval: 7.9-9.5) for patients without BM (n = 941), p = 0.09. Rates of hematologic adverse events were not different among patients with and without BM.
CONCLUSIONS: There were no significant differences in response, survival, or hematologic toxicity for patients with or without BM; however, patients with BM had a small but significantly shorter time to progression. Nonprogressing patients with treated BM are appropriate candidates for systemic therapy and entry into clinical trials.
Continuous pemetrexed treatment for brain metastasis in non-small cell lung cancer-A report of two cases.
Nobuaki Ochi, Hiromichi Yamane, Tomoko Yamagishi, Nagio Takigawa
Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
Lung cancer (Amsterdam, Netherlands) (Impact Factor: 3.14). 12/2012; DOI:10.1016/j.lungcan.2012.12.010
Source: PubMed
ABSTRACT Brain metastasis is a major complication in patients with advanced non-small cell lung cancer (NSCLC), which is the malignancy that metastasizes most frequently to the central nervous system (CNS). Although the CNS is protected from cytotoxic agents by the blood-brain barrier under normal conditions, the blood-brain barrier is thought to become less functional in the presence of brain metastasis. Here, we describe two NSCLC patients who relapsed with brain metastases. Following brain stereotactic irradiation, salvage chemotherapy using pemetrexed was given. Continuous pemetrexed treatment resulted in no recurrence, including brain metastasis, over 2 years without whole-brain irradiation. Our experience suggests that pemetrexed suppresses brain metastasis after stereotactic irradiation.
罗氏的Brain Shuttle技术 http://www.roche.com/research_an ... s/brain_shuttle.htm
Brain Shuttle is a technology that we have developed at Roche to increase penetration of large molecules such as antibodies into the brain. Access of large molecules to the brain is restricted by the blood brain barrier (BBB), a gatekeeper between the blood and the brain tissue that carefully filters which molecules can enter the brain. By using the Roche antibody engineering platform, we have created antibodies that are able to cross the blood brain barrier by binding to one of the protein receptors located on its surface. The so-called “brain shuttle” technology could potentially transport all types of therapeutic molecules into the brain, regardless of their intrinsic ability to cross the blood brain barrier.
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