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J. Morris



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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-087 - A Phase I Study of Chloroquine with Carboplatin and Gemcitabine in Advanced Solid Tumors and NSCLC (ID 1628)

      09:30 - 17:00  |  Author(s): J. Morris

      • Abstract

      Background:
      Autophagy is the catabolic degradation of cellular constituents that can promote cancer cell survival by maintaining cellular energy levels during periods of stress, including exposure to radiation or chemotherapy. The antimalarial, chloroquine (CQ), has received attention as an inhibitor of autophagy. The lysosomotropic properties of CQ are probably responsible for many of its biological effects. Manipulation of autophagy is a potentially exciting area for the development of new cancer treatments. Recently, accumulating evidence suggest that CQ can effectively sensitize cancer cells to the cell-killing effects of ionizing radiation and chemotherapeutic agents, thus suggesting its use as a sensitizer for conventional therapies. Hypothesis: CQ may sensitize chemotherapy-resistant tumor cells by inhibiting autophagy and enhance tumor response and survival of patients with solid tumors. Patients with non small cell lung cancer (NSCLC) squamous cell carcinoma subtype will be enrolled and followed for possible improved outcome with the addition of choloroquine to platinum doublet especially agents as Bevacuzimab can not be added to their standard doublet therapy. Patients with other advanced solid tumors will be eligible as long as carboplatin and Gemcitabine are considered an acceptable therapeutic option.

      Methods:

      Dose Level Patients(N) CQ mg/dl D-7-D21 Carboplatin AUC D1 Gemcitabine mg/m2 D1 &D8
      1 3-6 50 5 1,000
      2 3-6 100 5 1,000
      3 3-6 150 5 1,000
      4 3-6 200 5 1,000
      Expansion cohort 10-12 MTD 5 1,000
      Primary Objectives: The aim of this phase I study is to determine the adverse events (AE) and maximum tolerated dose (MTD) associated with adding chloroquine (CQ) to carboplatin and gemcitabine (CG) in patients with previously treated advanced solid tumors. Secondary Objectives: To estimate overall response rate (ORR), progression-free survival (PFS), and overall survival (OS); to determine the pharmacokinetics of CQ in combination with CG, and its effect on tumor burden by measurement of circulating tumor cells (CTCs). Methods: A single institution phase I dose-escalation study. Patients with advanced solid malignancies with no available standard of care treatment options, and ECOG performance status 0-2 are eligible. Sequential cohorts of 3-6 patients will be treated with escalating daily doses of oral CQ in addition to carboplatin and gemcitabine (Table 1). The study is ongoing and patient accrual is in the first cohort.

      Results:
      Not applicable

      Conclusion:
      Not applicable

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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-053 - The Role of Systemic Therapy in Sarcomatoid Carcinoma of the Lung (ID 890)

      09:30 - 17:00  |  Author(s): J. Morris

      • Abstract

      Background:
      Primary sarcomatoid carcinoma (PSC) accounts for 2% to 3% of all lung cancers. Stage-for-stage, PSC carries a poorer prognosis compared to the more common types of lung cancer. It typically occurs in older heavy smoking men and has a predilection for upper lobe involvement. PSC of the lung was initially described by Virchow in 1865 as a “biphasic” lesion of adenocarcinomatous or squamous cell components along with spindle cell or giant cell elements forming at least 10% of the tumor mass. This description fulfills the current WHO criteria for the diagnosis of PSC. Mutational analysis has revealed a common origin of both elements and it is thought that epithelial-mesenchymal transition (EMT) is the mechanism of that gives rise to this tumor, with the epithelial elements (adenocarcinoma or squamous component) that has undergone a transition to a poorly-differentiated mesenchymal type (sarcomatoid) with the expression of mesenchymal proteins such as vimentin. Efforts to study PSC has been hindered by the rarity of this variant. Aim of the study: To assess the impact of surgery and various systemic therapies on patients with PSC of the lung at the University of Cincinnati Medical Center (UCMC).

      Methods:
      This retrospective study included all patients identified with a pathologically confirmed diagnosis of PSC of the lung treated at UCMC between the years 2000-2014. Death was considered as the study endpoint. Kaplan-Meier analysis was used to calculate median overall survival (OS) and 95% confidence intervals (CI). Cox model was used to test the chemotherapy effect adjusted for age, sex and surgery, and determine hazard ratios (HR). Data was analyzed using SAS® Version 9.4.

      Results:
      We identified 21 patients with a diagnosis of PSC of the lung that were eligible for chart review and analysis. The 14 men and 7 women had a median age of 59 (range, 31-84 years). Treatment with systemic chemotherapy showed a trend in improvement in outcome among all stages of disease (p=0.08 and HR 0.04) but chemotherapy was most often used in advanced stages. Female gender demonstrated a trend for improved OS (p=0.1), and older patients demonstrated a better OS (HR=0.849; p=0.041) by a one-year increase in age. The median OS of the patients with PSC treated with systemic chemotherapy was 375 days (95% CI 114-600 days). Patients with early stage disease who were eligible for surgical resection, with or without the addition of systemic chemotherapy had a median survival of 457.5 days (95% CI 206.-1187 days), only slightly different from patients with advanced disease that received systemic chemotherapy. Patients who did not receive systemic chemotherapy had a lower median OS of 256 days (95% CI 98-999 days). Two patients demonstrated EML-4/ALK translocations. The patient with the longest OS of about three years was treated with systemic therapies including cisplatin, gemcitabine, docetaxel and crizotinib.

      Conclusion:
      Patients with PSC of the lung may benefit from systemic therapy. Larger prospective studies are needed to confirm this benefit especially if used as an adjuvant therapy in early stage disease.

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    P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P3.01-037 - Impact of Endobronchial Stents on Patients with NSCLC and Central Airway Obstruction (CAO) (ID 819)

      09:30 - 17:00  |  Author(s): J. Morris

      • Abstract

      Background:
      Approximately 30% of lung cancer patients develop central airway obstruction (CAO) increasing the risk of post-obstructive pneumonia and respiratory failure. Therapeutic interventional bronchoscopy including airway stenting (AS) can provide immediate and effective palliation to improve patient quality of life (QoL). Unfortunately, there is little data about the impact on OS or the risk of hospitalization in patients with CAO mandating stent placement versus patients with CAO lesions that did not require stent placement.

      Methods:
      Between 2011-2014, twenty five patients with advanced lung cancer were evaluated by the Interventional Pulmonary (IP) Service at the University of Cincinnati for endobronchial stent placement for CAO. We retrospectively reviewed the OS and the risk of hospitalization in patients with lung cancer with CAO mandating stent placements versus patients who did not have lesions requiring stent placement. Death was considered as the endpoint. Kaplan-Meier method was used to calculate median overall survival and 95% CI. Cox model was used to test the overall survival difference between the patients who need stent and patients who do not need stent adjusted for age and sex. Logistic regression was used to test the hospitalization rate difference between the patients who need stent and patients who do not need stent adjusted for age and sex. Data were analyzed using the SAS ® Version 9.4.

      Results:
      Between 2011-2014, twenty five patients with advanced lung cancer were evaluated by the Interventional Pulmonary (IP) Service at the University of Cincinnati for endobronchial stent placement for CAO. Eight patients did not require placement of a stent and 17 patients had obstructive lesions that required stenting. Age and gender did not have any impact on the risk of hospitalization or OS of both of these groups of patients. The eight patients whose lesions did not mandate stent placement had a significantly lower risk of hospitalization compared to the 17 patients with CAO requiring a stent (OR 15.9, 95%CI 1.2, 209.1; p =0.035). Patients with advanced NSCLC and CAO that required IP stent placement had a median OS of 424 days (95%CI, 119-606 days) compared to a median OS of 729 days (95%CI, 426-. days) for patients with CAO not requiring a stent. Even with a lower survival in patients with stent placement, their OS of 424 days was slightly longer than the reported one-year survival for patients with stage IV NSCLC suggestive of improved outcome of patients with advanced stage NSCLC supported by IP.

      Conclusion:
      Lung cancer patients with less severe CAO have a lower risk of hospitalization and have better OS compared to patients with CAO mandating stent placement; however, CAO patients with IP evaluation and management in addition, may have improved OS suggesting that IP consultation may offer both improvements in QoL and OS to patients with advanced NSCLC and CAO.