Nasser Hanna

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States

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Publications (85)524.52 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Advanced lung cancer patients have high rates of multiple physical and psychological symptoms, and many of their family caregivers experience significant distress. However, little is known about strategies that these patients and their family caregivers employ to cope with physical and psychological symptoms. This study aimed to identify strategies for coping with various physical and psychological symptoms among advanced, symptomatic lung cancer patients and their primary family caregivers. Patients identified their primary family caregiver. Individual semi-structured qualitative interviews were conducted with 21 advanced, symptomatic lung cancer patients and primary family caregivers. Thematic analysis of interview data was framed by stress and coping theory. Patients and caregivers reported maintaining a normal routine and turning to family and friends for support with symptom management, which often varied in its effectiveness. Whereas support from health-care professionals and complementary and alternative medicine were viewed favorably, reactions to Internet and in-person support groups were mixed due to the tragic nature of participants' stories. Several cognitive coping strategies were frequently reported (i.e., changing expectations, maintaining positivity, and avoiding illness-related thoughts) as well as religious coping strategies. Results suggest that advanced lung cancer patients and caregivers may be more receptive to cognitive and religious approaches to symptom management and less receptive to peer support. Interventions should address the perceived effectiveness of support from family and friends.
    Supportive Care Cancer 12/2014; · 2.50 Impact Factor
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    ABSTRACT: Relapsed small cell lung cancer (SCLC) has limited treatment options. Anthracyclines and cyclophosphamide have shown synergy in many tumors. Amrubicin (AMR) and cyclophosphamide both have single-agent activity in SCLC. This phase I trial evaluated the combination of AMR and cyclophosphamide in refractory solid organ malignancies and in relapsed SCLC. The primary endpoint was to determine maximum-tolerated dose and dose-limiting toxicities of the combination. Eligible patients were enrolled in sequential dose escalation cohorts in a standard 3+3 design. Treatment consisted of cyclophosphamide IV at 500 mg/m on day 1 with escalating doses of AMR IV on days 1 to 3 (25 to 40 mg/m with increments of 5 mg/m per cohort). Cycles were repeated every 21 days. Exploratory objectives analyzed the presence of NQO1 polymorphisms and topoisomerase IIA amplification and correlation with response. Thirty-six patients were enrolled, of whom 18 patients had SCLC (50%). Maximum-tolerated dose was determined to be dose level 2 (cyclophosphamide 500 mg/m, AMR 30 mg/m) due to grade 4 thrombocytopenia. The main grade 3 to 4 toxicities were hematologic. Efficacy results are available for 34 patients. Partial responses, stable disease, and progressive disease rates in the overall study population were 20.6% (n=7), 38.2% (n=13), and 41.2% (n=14), respectively. Partial response, stable disease, and progressive disease rates in the SCLC patients and 1 patient with extrathoracic small cell were 36.8% (n=7), 26.3% (n=5), and 36.8% (n=7), respectively. There was no correlation between topoisomerase IIA amplification or NQO1 polymorphisms and response. AMR and cyclophosphamide can be safely combined with little activity observed in heavily pretreated SCLC patients.
    American Journal of Clinical Oncology 12/2014; · 2.61 Impact Factor
  • Nasser Hanna, Lawrence H Einhorn
    Journal of Clinical Oncology 07/2014; · 17.88 Impact Factor
  • Greg Durm, Nasser Hanna
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    ABSTRACT: Angiogenesis plays a major role in the growth and progression of non-small-cell lung cancer (NSCLC), and there is increasing interest in the development of therapies that block this particular aspect of tumorigenesis. Bevacizumab was the first US FDA-approved inhibitor of angiogenesis after demonstrating improved progression-free survival and overall survival in combination with chemotherapy in treating NSCLC. However, the benefit of bevacizumab is only modest and transient as the tumors inevitably develop resistance to this particular treatment. Therefore, new therapies are being developed that attempt to inhibit angiogenesis through several different pathways. One promising new drug, nintedanib, is an oral triple angiokinase inhibitor that acts by blocking not only VEGFR, but also FGFR and PDGFR, which are involved in the development of resistance to bevacizumab. This article discusses the rationale for this approach and summarizes the clinical trial data on nintedanib, including the two most recent Phase III trials.
    Future Oncology 05/2014; 10(7):1167-73. · 2.61 Impact Factor
  • Sawsan Rashdan, Nasser Hanna
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    ABSTRACT: Introduction: In NSCLC, increased microvessel count, often used as a measure of angiogenesis, has been correlated with poor prognosis and associated with advanced disease and inferior outcomes. In the clinical development of antiangiogenic therapies, two approaches have been used; the first has been to inhibit ligand binding and receptor activation using targeted antibodies, whereas the second has been to inhibit receptor activation using tyrosine kinase inhibitors that target VEGF receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and/or fibroblast growth factor receptor (FGFR). Nintedanib is a triple angiokinase inhibitor that simultaneously acts on VEGFR, PDGFR and FGFR. It has shown significant antiangiogenic and antineoplastic activities in vitro, in preventing tumor growth and overcoming drug resistance. Areas covered: Medline search was used with the following keywords: non-small-cell lung cancer and nintedanib or BIBF 1120, ASCO abstracts 2013 with nintedanib, and Phase I and Phase II abstracts lung cancer and nintedanib. Expert opinion: Recent Phase III trials have shown promising efficacy results of nintedanib in NSCLC; however, many questions still need to be answered before it is put into routine use.
    Expert Opinion on Pharmacotherapy 03/2014; · 2.86 Impact Factor
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    ABSTRACT: This study examined barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients (N = 165) at two medical centers in the Midwestern United States. Lung cancer patients completed an assessment of anxiety and depressive symptoms, mental health service use, barriers to using these services, and preferences for addressing emotional concerns. Only 45% of distressed patients received mental health care since their lung cancer diagnosis. The most prevalent patient-reported barriers to mental health service use among non-users of these services (n = 110) included the desire to independently manage emotional concerns (58%) and inadequate knowledge of services (19%). In addition, 57% of distressed patients who did not access mental health services did not perceive the need for help. Seventy-five percent of respondents (123/164) preferred to talk to a primary care physician if they were to have an emotional concern. Preferences for counseling, psychiatric medication, peer support, spiritual care, or independently managing emotional concerns also were endorsed by many patients (range = 40-50%). Older age was associated with a lower likelihood of preferring to see a counselor. Findings suggest that many distressed lung cancer patients underuse mental health services and do not perceive the need for such services. Efforts to increase appropriate use of services should address patients' desire for autonomy and lack of awareness of services. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 02/2014; · 4.04 Impact Factor
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    ABSTRACT: On the basis of the promising activity of cetuximab and radiation therapy for head and neck cancers, we evaluated the efficacy of this regimen followed by surgery in patients with resectable esophageal cancer. This was a phase II, open-label, single-arm, multicenter study of patients with potentially resectable esophageal cancer. Patients received two weekly doses of cetuximab followed by weekly cetuximab combined with radiation therapy for 6 weeks. After a 6- to 8-week rest, patients' primary tumor was resected. The main objective was to evaluate pathologic complete response (pCR) rate in the primary tumor after cetuximab and radiation therapy. Thirty-nine patients completed the study. Most patients were men (93%), median age was 64 years, performance status was 0 to 1 (95%), patients had a histology of adenocarcinoma (78%), and tumors were located in the esophagus (63%). Grade 3 toxicities in more than 5% of patients included dysphagia (17%), anorexia and dehydration (7%), and dyspnea, fatigue, hypernatremia (5%). Grade 5 aspiration occurred in 2% (1 patient). Four patients died, two from disease progression, one from aspiration pneumonia postsurgery, and one from septic shock. Thirty-one patients (76%) underwent esophagectomy. The pCR rate was 36.6% by intention-to-treat and 48% for patients who underwent esophagectomy. The pCR by histology was 6 of 9 (67%) for squamous cell carcinomas and 9 of 32 (28%) for adenocarcinoma. Earlier-stage disease was associated with increased pCR (IIA 70%, IIB 29%, III 28%). Cetuximab and radiation therapy results in a pCR rate that seems at least comparable with that of chemotherapy and radiation therapy. This regimen may be better tolerated than preoperative chemotherapy and radiation therapy in patients with resectable esophageal cancers.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2013; · 4.55 Impact Factor
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    ABSTRACT: This study examined support service use and interest in support services among lung cancer patients (N=165) at two comprehensive medical centers in the midwestern United States. Patients completed an assessment of support service use (i.e., receipt of mental health services, complementary and alternative medicine [CAM], and help from a spiritual leader), interest in support services, and physical and psychological symptoms. Only 40% of patients with significant anxiety and depressive symptoms and 28% of the entire sample reported current mental health service use. However, nearly half (47%) of all patients were receiving support from a spiritual leader. Having late-stage lung cancer and a religious affiliation predicted receipt of spiritual support. Few patients who were not receiving mental health services or spiritual support were interested in these services (range=4-18%). Conversely, although interest in CAM was expressed by a substantial minority of patients (27%) who were not using these services, rates of CAM use were relatively low (22%). Findings suggest that distressed lung cancer patients underuse mental health services, but many patients receive help from spiritual leaders. Given the lack of interest in mental health services among patients who are not receiving them, efforts are needed to enhance palatability of services and identify and reduce barriers to evidence-based service use.
    Lung cancer (Amsterdam, Netherlands) 08/2013; · 3.14 Impact Factor
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    ABSTRACT: PURPOSE: BMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. This phase I-IIa study was designed to identify the maximum tolerated dose (MTD) and assess safety, antitumour activity, pharmacokinetics and pharmacodynamics of BMS-690514. PATIENTS AND METHODS: In phase I, patients with advanced solid tumours received escalating doses of once-daily BMS-690514. In phase IIa, erlotinib-naïve (cohort A) or erlotinib-resistant (cohort B) patients with advanced non-small-cell lung cancer (NSCLC) received BMS-690514 once-daily at the MTD. RESULTS: In phase I (n=28), the MTD was determined to be 200mg daily. BMS-690514 was rapidly absorbed and highly metabolised after repeated oral administration with minimum drug accumulation. In phase IIa (n=62), the most frequent treatment-related adverse events were diarrhoea and acneiform rash. Adverse events that led to >1 discontinuation were diarrhoea (n=4; 4%) and rash (n=2; 2%). Disease control (⩾4months) and objective response rates, respectively, were 43.3% and 3.3% (cohort A) and 22.6% and 3.2% (cohort B). Six of 21 (29%) NSCLC patients with wild-type EGFR achieved disease control versus seven of 10 (70%) patients with EGFR mutations (including T790M). At MTD, BMS-690514 modulated pharmacodynamic biomarkers associated with inhibition of VEGFR- and EGFR-signalling pathways. CONCLUSION: This phase I-IIa study suggests that BMS-690514 has manageable safety profile and antitumour activity in patients with NSCLC at 200mg/d, including those with EGFR mutations conferring resistance to erlotinib.
    European journal of cancer (Oxford, England: 1990) 03/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: Poor PS is a negative prognostic factor for survival and a risk factor for treatment-related toxicity with standard platinum-doublet chemotherapy for advanced NSCLC. A phase II study combining erlotinib and bevacizumab for treatment of recurrent NSCLC showed encouraging efficacy and acceptable toxicity. PATIENTS AND METHODS: This single-arm phase II study evaluated erlotinib and bevacizumab as first-line therapy for newly diagnosed nonsquamous advanced NSCLC patients with Eastern Cooperative Oncology Group PS ≥ 2 or age 70 or older. Only patients eligible for bevacizumab per label were enrolled. Patients received erlotinib 150 mg orally daily and bevacizumab 15 mg/kg intravenously on day 1 every 21 days for up to 6 cycles. The primary end point was the rate of nonprogressive disease at 4 months (alternative hypothesis > 60%). RESULTS: Twenty-five patients were enrolled, with median age 77 years (range, 52-90 years), 44% female, 20% never- or remote-smokers. Ninety-two percent of patients enrolled had PS of 2 per investigator assessment. The rate of nonprogressive disease at 4 months was 28%. There were no complete responses, 1 patient achieved a partial response, and 11 patients (44%) experienced stable disease as best response. Rash, fatigue, and diarrhea were the most common toxicities. CONCLUSION: The combination of erlotinib and bevacizumab had insufficient activity in the absence of known activating epidermal growth factor receptor gene mutations to warrant study in newly diagnosed elderly or poor PS patients with nonsquamous NSCLC.
    Clinical Lung Cancer 10/2012; · 2.04 Impact Factor
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    ABSTRACT: INTRODUCTION:: Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase-II study in heavily pretreated non-small-cell lung cancer (NSCLC) patients (≥ 2 prior therapies) used a randomized discontinuation design. METHODS:: Patients received 400 mg of sorafenib orally twice daily for two cycles (2 months) (step 1). Responding patients on step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease 2 months after randomization. RESULTS:: There were 299 patients evaluated for step 1; of these, 81 eligible patients were randomized on step 2 and received sorafenib (n = 50) or placebo (n = 31). The 2-month disease control rates after randomization were 54% and 23% for patients initially receiving sorafenib and placebo, respectively, p = 0.005. The hazard ratio for progression on step 2 was 0.51 (95% [confidence interval] CI 0.30, 0.87, p = 0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), hazard ratio 0.67 (95% CI 0.40-1.11), p = 0.117. A dispensing error occurred, which resulted in the unblinding of some patients, but not before completion of the 8-week initial step 2 therapy. Toxicities were manageable and as expected. CONCLUSIONS:: The results of this randomized discontinuation trial suggest that sorafenib has single-agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1574-1582. · 4.55 Impact Factor
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    ABSTRACT: PURPOSE: Although costs of lung cancer care have been documented, economic and social changes among lung cancer patients' family caregivers have yet to be fully examined. In addition, research has not focused on caregivers with greater need for support services. This study examined various economic and social changes among distressed family caregivers of lung cancer patients during the initial months of cancer care in the USA. METHODS: Lung cancer patients' primary family caregivers with significant anxiety or depressive symptoms were recruited from three medical centers within 12 weeks of the patient's new oncology visit. Caregivers (N = 83) reported demographic and medical information and caregiving burden at baseline. Seventy-four caregivers reported anxiety and depressive symptoms and economic and social changes 3 months later. RESULTS: Seventy-four percent of distressed caregivers experienced one or more adverse economic or social changes since the patient's illness. Common changes included caregivers' disengagement from most social and leisure activities (56 %) and, among employed caregivers (n = 49), reduced hours of work (45 %). In 18 % of cases, a family member quit work or made another major lifestyle change due to caregiving. Additionally, 28 % of caregivers reported losing the main source of family income, and 18 % reported losing most or all of the family savings. Loss of the main source of family income and disengagement from most social and leisure activities predicted greater caregiver distress. CONCLUSIONS: Findings suggest that distressed caregivers of lung cancer patients experience high rates of adverse economic and social changes that warrant clinical and research attention.
    Supportive Care in Cancer 09/2012; · 2.09 Impact Factor
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    ABSTRACT: OBJECTIVE: This study examined support service use and interest in support services among distressed family caregivers of patients recently entering comprehensive cancer care facilities. METHODS: Primary family caregivers of lung cancer patients (N = 83) were recruited from three medical centers within 12 weeks of the patient's new visit to the oncology clinic. All family caregivers were screened for psychological distress, and those reporting significant anxiety or depressive symptoms were eligible for this study. Caregivers completed a baseline assessment of support service use (i.e., use of mental health services and complementary and alternative medicine [CAM]) and interest in support services. Support service use was also assessed 3 months later. RESULTS: Although all caregivers reported clinically meaningful distress, only 26% used mental health and 39% used CAM services during the 3-month study period. Patients' receipt of chemotherapy was positively associated with caregivers' mental health service use, whereas greater education and receiving assistance with caregiving tasks were associated with CAM use. Forty percent of caregivers who did not use CAM at baseline were interested in CAM. In addition, 29% of caregivers who did not receive mental health services at baseline were interested in professional psychosocial support, and 29% of caregivers who did not receive staff assistance with practical needs at baseline were interested in this service. CONCLUSIONS: Findings suggest that distressed family caregivers of lung cancer patients underuse mental health services and that a sizable minority are interested in professional help with psychosocial and practical needs. Copyright © 2012 John Wiley & Sons, Ltd.
    Psycho-Oncology 09/2012; 22(7). · 4.04 Impact Factor
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    ABSTRACT: PURPOSE: Lung cancer and its treatment impose many demands on family caregivers, which may increase their risk for distress. However, little research has documented aspects of the caregiving experience that are especially challenging for distressed caregivers of lung cancer patients. This study aimed to explore caregivers' key challenges in coping with their family member's lung cancer. METHODS: Single, semi-structured qualitative interviews were conducted with 21 distressed family caregivers of lung cancer patients. RESULTS: Caregivers described three key challenges in coping with their family member's lung cancer. The most common challenge, identified by 38 % of caregivers, was a profound sense of uncertainty regarding the future as they attempted to understand the patient's prognosis and potential for functional decline. Another key challenge, identified by 33 % of caregivers, involved time-consuming efforts to manage the patient's emotional reactions to the illness. Other caregivers (14 %) characterized practical tasks, such as coordinating the patient's medical care, as their greatest challenge. CONCLUSIONS: Results suggest that clinical efforts are needed to assist distressed caregivers in providing practical and emotional support to the patient and attending to their own emotional needs.
    Supportive Care in Cancer 07/2012; 21(2). · 2.09 Impact Factor
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    ABSTRACT: The combination of sunitinb (37.5 mg orally daily) + paclitaxel (90 mg/m intravenously on days 1, 8, 15 every 4 weeks) was examined in patients with advanced esophageal or gastroesophageal junction cancer, and progression-free survival (PFS) was compared to that of historical controls. The end points included response rate, overall survival, and toxicities. Twenty-eight patients were enrolled at six centers. Median age was 59.5 years. The 24-week PFS rate was 25% (90% confidence interval [CI], 12-42%). Three (11%) of 23 evaluable patients had a response (1 complete response and 2 partial response) (90% CI, 3-25%). Median overall survival was 228 days (90% CI, 140-283 days). Grade 3/4 toxicities included leukopenia/neutropenia (25%), anemia (18%), fatigue (11%), and hemorrhage (11%). There were four grade 5 toxicities including upper gastrointestinal hemorrhage (n = 2), gastrointestinal/esophageal fistula (n = 1), and unexplained death (n = 1). In our study, we found that sunitinib + paclitaxel in patients with advanced esophageal or gastroesophageal junction cancer had a 24-week PFS no better than the PFS of historical controls. The combination also had a high rate of serious toxicities and will not be pursued.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2012; 7(4):760-3. · 4.55 Impact Factor
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    ABSTRACT: Concurrent chemoradiation with etoposide and cisplatin (EP/XRT) is standard treatment for inoperable stage III locally advanced non-small-cell lung cancer (LA-NSCLC). Consolidation docetaxel (D; Taxotere) after EP/XRT resulted in increased toxicity but no improvement in survival compared with observation (O). We report updated survival for the entire study population and include an analysis of efficacy and tolerability of EP/XRT with or without D in patients aged ≥ 70 years. Hoosier Oncology Group LUN 01-24 enrolled 243 patients with LA-NSCLC and randomized 166 after EP/XRT to three cycles of D versus O. the trial was terminated after an analysis of the first 203 patients demonstrated futility of D. Median survival time (MST) for the overall study population was 21.5 months, and 3-, 4-, and 5-year survival rates were 30.7%, 18.0%, and 13.9%, respectively. No differences in MST or 3-year survival were noted between D and O arms. Older patients had similar MST (17.1 versus 22.8 months for younger patients, P = 0.15) but higher rates of grade 3/4 toxicity and hospitalization during induction. Consolidation docetaxel after EP/XRT does not improve survival in LA-NSCLC. Fit older adults with LA-NSCLC benefit from concurrent chemoradiation similarly as younger patients but experience higher rates of hospitalization and toxicity.
    Annals of Oncology 12/2011; 23(7):1730-8. · 6.58 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Clinical Lung Cancer 08/2011; 13(1):24-30. · 2.04 Impact Factor
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    ABSTRACT: This study assessed activity and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, in patients with locally advanced or metastatic non-small cell lung cancer. In this open-label trial (NCT00517790), patients who received one to two prior lines of systemic therapy were randomized to oral linifanib 0.10 mg/kg (low dose) or 0.25 mg/kg (high dose) once daily. Tumor responses were assessed by independent central imaging review every 8 weeks. The primary end point was progression-free rate at 16 weeks. Secondary end points included objective response rate, time to progression, progression-free survival, and overall survival. Safety was also assessed. Between August 2007 and October 2008, 139 patients were enrolled; 60% had two or more prior regimens, and 88% had nonsquamous cell carcinoma. The objective response rate (low dose and high dose) was 5.0% (3.1 and 6.8%), progression-free rate at 16 weeks was 33.1% (32.3 and 33.8%), median time to progression was 3.6 months (3.6 and 3.7 months), median progression-free survival was 3.6 months (3.5 and 3.6 months), and median overall survival was 9.0 months (10.0 and 8.3 months). The most common linifanib-related adverse events were fatigue (42%), decreased appetite (38%), hypertension (37%), diarrhea (32%), nausea (27%), palmar-plantar erythrodysesthesia (24%), and proteinuria (22%). These events were more common in the high-dose group. The most common linifanib-related grade 3 or 4 adverse event was hypertension (14%). Linifanib is active in advanced non-small cell lung cancer as second- or third-line therapy. Increased adverse event rates were observed at the high dose of linifanib.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2011; 6(8):1418-25. · 4.55 Impact Factor
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    ABSTRACT: Bevacizumab when combined with carboplatin and paclitaxel improves response rates (RRs) and overall survival in patients with advanced non-small cell lung cancer. Paclitaxel has single-agent activity in relapsed small cell lung cancer (SCLC). Angiogenesis seems to play an important role in the pathogenesis of SCLC. This study evaluated the safety and efficacy of paclitaxel plus bevacizumab in patients with chemosensitive relapsed SCLC. Patients with relapsed chemosensitive SCLC with an Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. They received paclitaxel 90 mg/m intravenously on days 1, 8, and 15. Bevacizumab was administered at 10 mg/kg intravenously on days 1 and 15. Cycles were every 28 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included RRs, toxicity, and overall survival. Correlative studies evaluated vascular endothelial growth factor polymorphisms. Thirty-four patients were enrolled in the study. Median age was 66.5 (range, 38-88) years, male:female: 61.8%:38.2%, Eastern Cooperative Oncology Group performance status 0:1 47.1%:52.9%. Median progression-free survival was 14.7 weeks (equivalent to historical controls). Median survival time was 30 weeks. The overall RR was 18.1%. Stable disease rate was 39.3%, and 45.4% of patients had progressive disease. No unexpected toxicities were noted, and grade 3/4 toxicities were limited to neutropenia, fatigue, and dyspnea. None of the vascular endothelial growth factor polymorphisms evaluated were significantly associated with response. The addition of bevacizumab to paclitaxel does not improve outcomes in relapsed chemosensitive SCLC.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2010; 5(12):2008-11. · 4.55 Impact Factor
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    ABSTRACT: : Bevacizumab is approved in combination with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC). Preclinical data suggest that enzastaurin and bevacizumab may have complementary effects in inhibiting angiogenesis. : Eligibility criteria: ≥18 years of age, chemonaïve, stage IIIB/IV nonsquamous NSCLC, and Eastern Cooperative Oncology Group performance status 0 to 1. Patients were randomized to placebo or enzastaurin 500 mg orally daily (after a loading dose), plus pemetrexed 500 mg/m, carboplatin area under the curve 6, and bevacizumab 15 mg/kg, intravenously, every 21 days for four cycles. Patients without progression received maintenance therapy with bevacizumab and placebo or enzastaurin. The primary objective was progression-free survival (PFS). Planned sample size was 90 patients, one-sided alpha of 0.20, with two interim analyses: one for safety and the second for futility, with a PFS hazard ratio of 0.8857. : Forty patients were randomized. No unique safety concerns were noted at the first interim analysis. The early stopping rule for futility was met at the second interim analysis. Median PFS was 3.5 months and 4.3 months (hazard ratio: 1.04, 95% confidence interval: 0.49-2.21), and response rates were 20% and 30% (p = 0.462) for enzastaurin and placebo, respectively. Grade 3 or 4 toxicity was similar between the two arms. Two patients died on study because of respiratory arrest and pulmonary embolism. An additional patient died of sepsis secondary to a gastrointestinal perforation >30 days after study treatment discontinuation. : Enzastaurin does not improve efficacy when combined with pemetrexed, carboplatin, and bevacizumab. This combination does not warrant further study in NSCLC.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2010; 5(11):1815-20. · 4.55 Impact Factor

Publication Stats

4k Citations
524.52 Total Impact Points


  • 2002–2014
    • Indiana University-Purdue University Indianapolis
      • • Division of Hematology/Oncology
      • • Department of Medicine
      • • Division of General Internal Medicine and Geriatrics
      Indianapolis, Indiana, United States
  • 2012
    • Memorial Sloan-Kettering Cancer Center
      • Department of Psychiatry & Behavioral Sciences
      New York City, NY, United States
    • Indiana University-Purdue University School of Medicine
      • Department of Medicine
      Indianapolis, Indiana, United States
  • 2010
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy