This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) and age > or = 70 years who were treated with erlotinib and evaluated to ...determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement.
Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS.
Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival.
Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.
Empire's Twin Tyrrell, Ian; Sexton, Jay
08/2015
eBook
Across the course of American history, imperialism and anti-imperialism have been awkwardly paired as influences on the politics, culture, and diplomacy of the United States. The Declaration of ...Independence, after all, is an anti-imperial document, cataloguing the sins of the metropolitan government against the colonies. With the Revolution, and again in 1812, the nation stood against the most powerful empire in the world and declared itself independent. As noted by Ian Tyrrell and Jay Sexton, however, American "anti-imperialism was clearly selective, geographically, racially, and constitutionally."Empire's Twinbroadens our conception of anti-imperialist actors, ideas, and actions; it charts this story across the range of American history, from the Revolution to our own era; and it opens up the transnational and global dimensions of American anti-imperialism.
By tracking the diverse manifestations of American anti-imperialism, this book highlights the different ways in which historians can approach it in their research and teaching. The contributors cover a wide range of subjects, including the discourse of anti-imperialism in the Early Republic and Civil War, anti-imperialist actions in the U.S. during the Mexican Revolution, the anti-imperial dimensions of early U.S. encounters in the Middle East, and the transnational nature of anti-imperialist public sentiment during the Cold War and beyond.
Across the course of American history, imperialism and anti-imperialism have been awkwardly paired as influences on the politics, culture, and diplomacy of the United States. The Declaration of Independence, after all, is an anti-imperial document, cataloguing the sins of the metropolitan government against the colonies. With the Revolution, and again in 1812, the nation stood against the most powerful empire in the world and declared itself independent. As noted by Ian Tyrrell and Jay Sexton, however, American "anti-imperialism was clearly selective, geographically, racially, and constitutionally."Empire's Twinbroadens our conception of anti-imperialist actors, ideas, and actions; it charts this story across the range of American history, from the Revolution to our own era; and it opens up the transnational and global dimensions of American anti-imperialism.By tracking the diverse manifestations of American anti-imperialism, this book highlights the different ways in which historians can approach it in their research and teaching. The contributors cover a wide range of subjects, including the discourse of anti-imperialism in the Early Republic and Civil War, anti-imperialist actions in the U.S. during the Mexican Revolution, the anti-imperial dimensions of early U.S. encounters in the Middle East, and the transnational nature of anti-imperialist public sentiment during the Cold War and beyond.Contributors:Laura Belmonte, Oklahoma State University; Robert Buzzanco, University of Houston; Julian Go, Boston University; Alan Knight, University of Oxford; Ussama Makdisi, Rice University; Erez Manela, Harvard University; Peter Onuf, Robert H. Smith International Center for Jefferson Studies, Monticello, and University of Virginia; Jeffrey Ostler, University of Oregon; Patricia Schechter, Portland State University; Jay Sexton, University of Oxford; Ian Tyrrell, University of New South Wales
To assess the feasibility of early palliative care in the ambulatory setting in patients with newly diagnosed advanced non-small-cell lung cancer (NSCLC).
Patients were eligible if they had a ...performance status of 0 to 1 and were within 8 weeks of diagnosis of advanced NSCLC. Participants received integrated care from oncology and palliative care throughout the course of their disease. Participants were scheduled to meet with the palliative care team (PCT) and complete quality-of-life (QOL) and mood questionnaires monthly for 6 months. The study was deemed feasible if 64% of patients completed at least 50% of their scheduled visits and QOL assessments.
Fifty-one patients were enrolled onto the trial. One died within 72 hours and was not assessable. Ninety percent (95% CI, 0.78 to 0.96) of study participants complied with at least 50% of the palliative care visits. Eight-six percent (95% CI, 0.73 to 0.94) of the participants met the full feasibility requirements by both meeting with the PCT and completing QOL assessments at least 50% of the time. QOL and mood analyses confirmed the high symptom burden in patients with newly diagnosed advanced NSCLC. At least 50% of participants experienced some degree of shortness of breath, cough, difficulty breathing, appetite loss, weight loss, or unclear thinking at their baseline assessment. More than one third of patients had a probable mood disorder at baseline.
Integrated palliative and oncology care is feasible in ambulatory patients with advanced NSCLC.
To evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer.
Ten strictures were identified in 213 patients treated with ...HDRBT alone receiving 34Gy in four fractions, 36Gy in four fractions, 31.5Gy in 3 fractions or 26Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra.
Stricture rates were 3% in the 34Gy group, 4% in the 36Gy group, 6% in the 31.5Gy group and 4% in the 26Gy group. The median time to stricture formation was 26months (range 8-40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule.
Urethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions.
Purpose: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly
patients with lung cancer.
Experimental Design: Previously ...untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least
70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m 2 for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week
of therapy in a subgroup of eight patients.
Results: A total of 35 patients (median age, 76 years; range, 70–85) were enrolled. The overall response rate was 23%. Median time
to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and
22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection
(8.8%). Two patients died from treatment-related toxicity. There was no significant difference ( P = 0.18) between the total body clearance of paclitaxel on the first (17.4 ± 2.9 liters/h/m 2 , mean ± SD) and sixth (15.8 ± 4.1 liters/h/m 2 ) week of therapy.
Conclusion: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m 2 is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly
patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug
clearance after repeated weekly dosing.
Purpose: To investigate the anti-tumor activity and toxicity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839 or Iressa™; AstraZeneca Pharmaceuticals, Wilmington, DE), in ...patients with advanced non-small cell lung cancer (NSCLC).
Methods: This was an open label, expanded access program (EAP) of oral gefitinib administered at 250
mg per day continuously until evidence of undue toxicity or disease progression.
Results: Two hundred consecutive patients with advanced NSCLC were enrolled in this study. The median number of prior chemotherapy regimens was 2 (range 0–6). One hundred seventy-two patients were treated with gefitinib; 23 expired from disease progression prior to treatment and 5 withdrew their consent. One hundred fifty-four patients are evaluable for toxicity; 8 (5.2%) experienced grade 3/4 toxicity; 2 patients discontinued therapy for grade 3 rash and one for grade 3 nausea. Of 172 patients evaluable for efficacy, 7 (4.1%; 95% CI; 1.7–8.2%) experienced a partial response (PR); 60 patients (34.9%) had stable disease (SD) as their best response. Median survival for all patients was 4.5 months (95% CI; 4.1–4.9 months). One-year survival was 29%. Significant independent prognostic factors associated with improved survival were female gender, good performance status (0/1), and adenocarcinoma histology.
Conclusion: Gefitinib has anti-tumor activity, in a heterogeneous population of NSCLC patients treated on the EAP study. Treatment with gefitinib in this population is associated with a longer survival in women, those with good performance status and in patients with adenocarcinomas. These findings need to be further validated in additional clinical studies.
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