Abstract 1792: Identification of synergistic drug combinations with the oral HSP90 inhibitor Debio 0932 in non-small cell lung cancer and renal cell cancer

Author(s):  
Casey G. Langdon ◽  
Norbert Wiedemann ◽  
Hélène Maby-El Hajjami ◽  
Mathew A. Held ◽  
James T. Platt ◽  
...  
CHEST Journal ◽  
2014 ◽  
Vol 145 (3) ◽  
pp. 317A
Author(s):  
Eric Toloza ◽  
Anna Cheng ◽  
Domenico Coppola ◽  
Yuan Shan ◽  
Carla Moodie ◽  
...  

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
A. Kartolo ◽  
J. Sattar ◽  
V. Sahai ◽  
T. Baetz ◽  
J. M. Lakoff

Purpose We aimed to elucidate predictive factors for the development of immune-related adverse events (iraes) in patients receiving immunotherapies for the management of advanced solid cancers.Methods This retrospective study involved all patients with histologically confirmed metastatic or inoperable melanoma, non-small-cell lung cancer, or renal cell carcinoma receiving immunotherapy at the Cancer Centre of Southeastern Ontario. The type and severity of iraes, as well as potential protective and exacerbating factors, were collected from patient charts.ResultsThe study included 78 patients receiving ipilimumab (32%), nivolumab (33%), or pembrolizumab (35%). Melanoma, non-small-cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the cancers in the study population. In 41 patients (53%) iraes developed, with multiple iraes developing in 12 patients (15%). In most patients (70%), the iraes were of severity grade 1 or 2. Female sex [adjusted odds ratio (oradj): 0.094; 95% confidence interval (ci): 0.021 to 0.415; p = 0.002] and corticosteroid use before immunotherapy (oradj: 0.143; 95% ci: 0.036 to 0.562; p = 0.005) were found to be associated with a protective effect against iraes. In contrast, a history of autoimmune disease (oradj: 9.55; 95% ci: 1.34 to 68.22; p = 0.025), use of ctla-4 inhibitors (oradj: 6.25; 95% ci: 1.61 to 24.25; p = 0.008), and poor kidney function of grade 3 or greater (oradj: 10.66; 95% ci: 2.41 to 47.12; p = 0.025) were associated with a higher risk of developing iraes. A Hosmer–Lemeshow goodness-of-fit test demonstrated that the logistic regression model was effective at predicting the development of iraes (chi-square: 1.596; df = 7; p = 0.979).Conclusions Our study highlights several factors that affect the development of iraes in patients receiving immunotherapy. Although future studies are needed to validate the resulting model, findings from the study can help to guide risk stratification, monitoring, and management of iraes in patients given immunotherapy for advanced cancer.


1996 ◽  
Vol 14 (3) ◽  
pp. 806-813 ◽  
Author(s):  
B E Johnson ◽  
J D Bridges ◽  
M Sobczeck ◽  
J Gray ◽  
R I Linnoila ◽  
...  

PURPOSE A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. PATIENTS AND METHODS Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. RESULTS Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. CONCLUSION This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.


2014 ◽  
Vol 322 (2) ◽  
pp. 345-354 ◽  
Author(s):  
Chun-Liang Tung ◽  
Hsien-Chun Chiu ◽  
Yi-Jun Jian ◽  
Yun-Ting Jian ◽  
Chien-Yu Chen ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Seung Yeob Hyun ◽  
Huong Thuy Le ◽  
Cong-Truong Nguyen ◽  
Young-Sik Yong ◽  
Hye-Jin Boo ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17128-17128
Author(s):  
B. Lu

17128 Background: Small cell lung cancer (SCLC) carries an extremely poor prognosis and treatment options for this disease remain poor. PDGF and PDGFR-β are expressed and have been found to have prognostic value in several human cancers. Data in non-small cell cancer cell lines have suggested that PDGFR is a therapeutic target for drug development. In the current study PDGFR-β expression and prognostic value in SCLC was investigated. Methods: Paraffin embedded tissue blocks from 53 patients with limited and extensive stage SCLC were obtained for immunohistochemical staining. Tumors from each patient were sampled three times and stained with PDGFR-β specific antibody. Patients were divided into low and high staining groups based on intensity. Results: There was high intensity PDGFR-β staining in 20 patients with SCLC. Another 29 expressed low intensity PDGFR- β staining, with only 4 patients showing no PDGFR- β staining. There was no statistically significant difference in five year overall survival between patients with low levels of PDGFR-β staining versus those with high level staining SCLC tumors (P = 0.538). Conclusions: Though expression of PDGFR-β may not be a predictor of prognosis, due to its high expression in SCLC it may represent an important target for improved tumor control, however, further studies are required to confirm this. No significant financial relationships to disclose.


2012 ◽  
Vol 18 (18) ◽  
pp. 4973-4985 ◽  
Author(s):  
Takeshi Shimamura ◽  
Samanthi A. Perera ◽  
Kevin P. Foley ◽  
Jim Sang ◽  
Scott J. Rodig ◽  
...  

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