Caleb Chu - Academia.edu (original) (raw)
Papers by Caleb Chu
Future directions of monoclonal antibody use in personalized lung cancer therapy
Oncology, Nov 30, 2010
... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodr... more ... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodrigues Pereira J, et al: Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in nonsmall-cell lung cancer (NSCLC) (Abstract B2.3). J Thorac ...
Novel Statistical Models for NSCLC Clinical Trials
Vandetanib for the treatment of lung cancer
Expert Opinion on Investigational Drugs, Jun 6, 2012
VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). ... more VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.
Although the frequentist paradigm has been the predominant approach to clinical trial design sinc... more Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial ...
Future directions of monoclonal antibody use in personalized lung cancer therapy
Oncology, 2010
With the new direction in research and clinical trials, treating patients who most benefit from t... more With the new direction in research and clinical trials, treating patients who most benefit from treatment with minimal toxicity will continue to be the mainstay of personalized cancer therapy.
Journal of Thoracic Oncology
were considered significant. Non-parametric correlation analysis was performed to explore the sig... more were considered significant. Non-parametric correlation analysis was performed to explore the signaling interconnection within each group of patients. Only correlations with p<0.0001 were considered significant. Results: This preliminary analysis revealed a statistically significant different activation level of 20 proteins between the KRAS-MUT and KRAS-WT samples. Five of the proteins that were statistically different in the KRAS-MUT group are involved in the inflammatory immunoresponse (ASK1 S83 p<0.01, Axl Y702 p¼0.01, Stat2 Y690 p<0.01, Tyk2 Y1054/Y1055 p¼0.01 and Twist p<0.01) and six in cell cycle control and DNA repair (ATM S1981 p¼0.01; Bcl-xL p¼0.03; Cleaved Caspase 3 D175 p¼0.02; Histone H3 S10 p<0.01; p53 S15 p<0.01; p27 T187 p¼0.04). The analytes that were statistically significant were all lower in the KRAS-MUT group compared to the WT (except for p27 T187 which decreased in the KRAS-MUT group compared to KRAS-WT). Pair-wise correlation analysis of the signaling proteins showed an overall more complex protein-protein interaction network and pathway activation (included AKT/mTOR signaling pathway) in the KRAS-MUT population with high number of statistically significant correlations compared to the KRAS-WT group. Conclusion: This pilot study indicated that the effect of KRAS mutation status on protein signaling in NSCLC was an alteration of the immunoresponse axis and DNA repair network. If validated in a larger cohort of patients, these results could have important clinical implications for stratification KRAS-MUT advanced NSCLC patients towards more efficacious targeted treatment and to identify new therapeutic targets based on multi-targets/ multi-pathways KRAS inhibitory approach. (AIRC-supported study).
Future Directions of Monoclonal Antibody Use in Personalized Lung Cancer Therapy
Oncology, Nov 1, 2010
... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodr... more ... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodrigues Pereira J, et al: Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in nonsmall-cell lung cancer (NSCLC) (Abstract B2.3). J Thorac ...
Future directions of monoclonal antibody use in personalized lung cancer therapy
Oncology (Williston Park, N.Y.), Jan 30, 2010
... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodr... more ... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodrigues Pereira J, et al: Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in nonsmall-cell lung cancer (NSCLC) (Abstract B2.3). J Thorac ...
Statistics in Medicine, 2012
Although the frequentist paradigm has been the predominant approach to clinical trial design sinc... more Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More Bayesian trials should be designed and conducted to refine the approach and demonstrate their real benefit in action.
Vandetanib for the treatment of lung cancer
Expert Opinion on Investigational Drugs, 2012
VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). ... more VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.
Novel Statistical Models for NSCLC Clinical Trials
Future directions of monoclonal antibody use in personalized lung cancer therapy
Oncology, Nov 30, 2010
... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodr... more ... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodrigues Pereira J, et al: Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in nonsmall-cell lung cancer (NSCLC) (Abstract B2.3). J Thorac ...
Novel Statistical Models for NSCLC Clinical Trials
Vandetanib for the treatment of lung cancer
Expert Opinion on Investigational Drugs, Jun 6, 2012
VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). ... more VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.
Although the frequentist paradigm has been the predominant approach to clinical trial design sinc... more Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial ...
Future directions of monoclonal antibody use in personalized lung cancer therapy
Oncology, 2010
With the new direction in research and clinical trials, treating patients who most benefit from t... more With the new direction in research and clinical trials, treating patients who most benefit from treatment with minimal toxicity will continue to be the mainstay of personalized cancer therapy.
Journal of Thoracic Oncology
were considered significant. Non-parametric correlation analysis was performed to explore the sig... more were considered significant. Non-parametric correlation analysis was performed to explore the signaling interconnection within each group of patients. Only correlations with p<0.0001 were considered significant. Results: This preliminary analysis revealed a statistically significant different activation level of 20 proteins between the KRAS-MUT and KRAS-WT samples. Five of the proteins that were statistically different in the KRAS-MUT group are involved in the inflammatory immunoresponse (ASK1 S83 p<0.01, Axl Y702 p¼0.01, Stat2 Y690 p<0.01, Tyk2 Y1054/Y1055 p¼0.01 and Twist p<0.01) and six in cell cycle control and DNA repair (ATM S1981 p¼0.01; Bcl-xL p¼0.03; Cleaved Caspase 3 D175 p¼0.02; Histone H3 S10 p<0.01; p53 S15 p<0.01; p27 T187 p¼0.04). The analytes that were statistically significant were all lower in the KRAS-MUT group compared to the WT (except for p27 T187 which decreased in the KRAS-MUT group compared to KRAS-WT). Pair-wise correlation analysis of the signaling proteins showed an overall more complex protein-protein interaction network and pathway activation (included AKT/mTOR signaling pathway) in the KRAS-MUT population with high number of statistically significant correlations compared to the KRAS-WT group. Conclusion: This pilot study indicated that the effect of KRAS mutation status on protein signaling in NSCLC was an alteration of the immunoresponse axis and DNA repair network. If validated in a larger cohort of patients, these results could have important clinical implications for stratification KRAS-MUT advanced NSCLC patients towards more efficacious targeted treatment and to identify new therapeutic targets based on multi-targets/ multi-pathways KRAS inhibitory approach. (AIRC-supported study).
Future Directions of Monoclonal Antibody Use in Personalized Lung Cancer Therapy
Oncology, Nov 1, 2010
... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodr... more ... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodrigues Pereira J, et al: Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in nonsmall-cell lung cancer (NSCLC) (Abstract B2.3). J Thorac ...
Future directions of monoclonal antibody use in personalized lung cancer therapy
Oncology (Williston Park, N.Y.), Jan 30, 2010
... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodr... more ... Caleb T. Chu, MD Jörg J. Jacoby, PhD Roy S. Herbst, MD, PhD. ... 10. Gatzemeier U P-AL,Rodrigues Pereira J, et al: Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in nonsmall-cell lung cancer (NSCLC) (Abstract B2.3). J Thorac ...
Statistics in Medicine, 2012
Although the frequentist paradigm has been the predominant approach to clinical trial design sinc... more Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More Bayesian trials should be designed and conducted to refine the approach and demonstrate their real benefit in action.
Vandetanib for the treatment of lung cancer
Expert Opinion on Investigational Drugs, 2012
VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). ... more VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.
Novel Statistical Models for NSCLC Clinical Trials