This document discusses therapeutic options for first line treatment of advanced non-small cell lung cancer (NSCLC). It provides details on chemotherapy regimens such as platinum doublets with paclitaxel, gemcitabine or docetaxel. It also discusses targeted therapies like bevacizumab, erlotinib and gefitinib. The document reviews clinical trials that established current standard first line treatments and highlights the need for personalized treatment based on tumor markers and mutations.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
The document discusses lung cancer subtypes and molecular features that can guide treatment. It provides statistics on the distribution of histology types among lung cancer cases. It also summarizes several key studies investigating targeted therapies such as EGFR TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer, noting improved progression-free survival with TKIs in patients with EGFR mutations. Molecular testing is increasingly important for determining personalized treatment approaches in lung cancer.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC (Part II)Mohammed Fathy
1) The document discusses targeted therapies for non-small cell lung cancer (NSCLC) with ALK translocations, including crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib.
2) Alectinib is now considered the preferred first-line treatment for ALK-positive NSCLC based on Phase III trials showing it is more effective than crizotinib.
3) For patients who progress on a first-generation ALK inhibitor like crizotinib, later-generation ALK inhibitors such as ceritinib, brigatinib, and lorlatinib have demonstrated efficacy in clinical trials as subsequent therapies.
This document discusses evolving strategies for the personalized treatment of non-small cell lung cancer (NSCLC). It covers histological and molecular subtypes of NSCLC, key clinical trials of the EGFR tyrosine kinase inhibitor gefitinib, mechanisms of acquired resistance to EGFR TKIs, and approaches to managing resistance. A phase IV study showed gefitinib was effective first-line therapy for Caucasian patients with EGFR mutation-positive NSCLC, with a 69.8% response rate and favorable progression-free and overall survival. Exploratory analyses found plasma samples could accurately assess EGFR mutation status when tumor tissue was unavailable. The document reviews strategies for treating systemic and central nervous system progression after acquiring resistance to EGFR T
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
The document discusses lung cancer subtypes and molecular features that can guide treatment. It provides statistics on the distribution of histology types among lung cancer cases. It also summarizes several key studies investigating targeted therapies such as EGFR TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer, noting improved progression-free survival with TKIs in patients with EGFR mutations. Molecular testing is increasingly important for determining personalized treatment approaches in lung cancer.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC (Part II)Mohammed Fathy
1) The document discusses targeted therapies for non-small cell lung cancer (NSCLC) with ALK translocations, including crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib.
2) Alectinib is now considered the preferred first-line treatment for ALK-positive NSCLC based on Phase III trials showing it is more effective than crizotinib.
3) For patients who progress on a first-generation ALK inhibitor like crizotinib, later-generation ALK inhibitors such as ceritinib, brigatinib, and lorlatinib have demonstrated efficacy in clinical trials as subsequent therapies.
This document discusses evolving strategies for the personalized treatment of non-small cell lung cancer (NSCLC). It covers histological and molecular subtypes of NSCLC, key clinical trials of the EGFR tyrosine kinase inhibitor gefitinib, mechanisms of acquired resistance to EGFR TKIs, and approaches to managing resistance. A phase IV study showed gefitinib was effective first-line therapy for Caucasian patients with EGFR mutation-positive NSCLC, with a 69.8% response rate and favorable progression-free and overall survival. Exploratory analyses found plasma samples could accurately assess EGFR mutation status when tumor tissue was unavailable. The document reviews strategies for treating systemic and central nervous system progression after acquiring resistance to EGFR T
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
Estado actual de terapia sistémica en cáncer renal metastásicoMauricio Lema
This document discusses the current management of metastatic renal cell carcinoma (mRCC). It provides an overview of targeted therapies for mRCC including tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and cabozantinib that target the VEGF pathway. Clinical trial results are presented comparing TKIs in first-line mRCC. Active surveillance is also discussed as a treatment option for select asymptomatic or minimally symptomatic mRCC patients. Toxicities of TKIs like fatigue, diarrhea and hand-foot syndrome are reviewed along with their negative impact on quality of life.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
Lapatinib is an oral tyrosine kinase inhibitor that is effective for HER2-positive breast cancer patients, including those with brain metastases. A phase II trial found that lapatinib led to partial responses in 6% of patients with HER2-positive breast cancer and brain metastases who progressed on prior trastuzumab therapy. Volumetric reductions of at least 20% in brain lesions on MRI were associated with improved progression-free survival. The most common adverse events were diarrhea and rash, which were primarily grades 1-2 in severity. Lapatinib is an important treatment option for HER2-positive breast cancer patients with brain metastases.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.
1) EGFR mutations are found in 10-30% of NSCLC cases and are associated with response to EGFR TKIs as first-line treatment.
2) Several studies including IPASS, EURTAC and LUX-Lung 3 have shown superior PFS for first-generation EGFR TKIs like gefitinib and erlotinib and the second-generation TKI afatinib compared to platinum-based chemotherapy as first-line treatment for EGFR mutation-positive NSCLC.
3) Meta-analyses of these studies demonstrate improved PFS for EGFR TKIs compared to chemotherapy in EGFR mutation-positive NSCLC, though OS is generally similar between the treatments
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
This document summarizes key findings from the SPARTAN clinical trial evaluating the efficacy of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer. The study found that apalutamide significantly reduced the risk of distant metastasis or death by 72% compared to placebo. Apalutamide also improved progression-free survival, time to symptomatic progression, and delayed the time to initiation of cytotoxic chemotherapy. The most common adverse events with apalutamide were fatigue, hypertension, and rash.
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINI...Alok Gupta
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINICAL OUTCOME INACUTE LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
TREATMENT OF NON-HIDGKIN'S LYMPHOMA IN ELDERLY PATIENTSspa718
This document summarizes treatment approaches for non-Hodgkin's lymphoma in elderly patients. It discusses palliative options for refractory/relapsed diffuse large B-cell lymphoma such as gemcitabine-based chemotherapy, low-dose oral chemotherapy, and hyperfractionated cyclophosphamide. It also reviews novel anti-CD20 monoclonal antibodies showing efficacy against relapsed/refractory indolent lymphoma, and brentuximab vedotin's mechanism of action and responses seen in relapsed/refractory systemic anaplastic large cell lymphoma. Finally, it provides a high-level overview of the MD Anderson Cancer Center's Department of Lymphoma/Myeloma and its disease-specific
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
Tyverb (lapatinib) is approved for use in combination with capecitabine for treatment of ErbB2-positive advanced or metastatic breast cancer in patients who have progressed on prior therapies including anthracyclines, taxanes, and trastuzumab. A pivotal study found that the combination of Tyverb and capecitabine significantly increased time to progression and overall response rate compared to capecitabine alone with manageable side effects. Quality of life was maintained with the combination therapy.
Head and neck cancer accounts for 5-6% of all cancers, with over 90% being squamous cell carcinomas. Risk factors include tobacco, alcohol, and HPV. Treatment options include surgery, radiation therapy, chemotherapy, or combinations. While early stage cancer has a good prognosis with single modality treatment, advanced stages generally require combined modality treatment, though 5-year survival remains below 35%. New targeted therapies and improved radiation techniques have provided benefits in recent years.
Pemetrexed (Alimta) is an intravenous chemotherapy drug used to treat nonsquamous non-small cell lung cancer and mesothelioma. It is given as a 10 minute infusion every 21 days at a dose of 500 mg/m2. Patients should take folic acid and vitamin B12 supplements to reduce side effects. Dose reductions may be needed for hematologic or nonhematologic toxicities. Pemetrexed can interact with NSAIDs and nephrotoxic drugs. It is not recommended in pregnancy or for pediatric patients.
The document discusses bevacizumab and its use in treating cancer. It provides details from several clinical trials that studied bevacizumab in combination with chemotherapy for various cancers. The trials showed improvements in progression-free survival and overall survival when bevacizumab was added to chemotherapy compared to chemotherapy alone. The document also discusses adverse effects seen with bevacizumab treatment and potential biomarkers of response and resistance.
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
Estado actual de terapia sistémica en cáncer renal metastásicoMauricio Lema
This document discusses the current management of metastatic renal cell carcinoma (mRCC). It provides an overview of targeted therapies for mRCC including tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and cabozantinib that target the VEGF pathway. Clinical trial results are presented comparing TKIs in first-line mRCC. Active surveillance is also discussed as a treatment option for select asymptomatic or minimally symptomatic mRCC patients. Toxicities of TKIs like fatigue, diarrhea and hand-foot syndrome are reviewed along with their negative impact on quality of life.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
Lapatinib is an oral tyrosine kinase inhibitor that is effective for HER2-positive breast cancer patients, including those with brain metastases. A phase II trial found that lapatinib led to partial responses in 6% of patients with HER2-positive breast cancer and brain metastases who progressed on prior trastuzumab therapy. Volumetric reductions of at least 20% in brain lesions on MRI were associated with improved progression-free survival. The most common adverse events were diarrhea and rash, which were primarily grades 1-2 in severity. Lapatinib is an important treatment option for HER2-positive breast cancer patients with brain metastases.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.
1) EGFR mutations are found in 10-30% of NSCLC cases and are associated with response to EGFR TKIs as first-line treatment.
2) Several studies including IPASS, EURTAC and LUX-Lung 3 have shown superior PFS for first-generation EGFR TKIs like gefitinib and erlotinib and the second-generation TKI afatinib compared to platinum-based chemotherapy as first-line treatment for EGFR mutation-positive NSCLC.
3) Meta-analyses of these studies demonstrate improved PFS for EGFR TKIs compared to chemotherapy in EGFR mutation-positive NSCLC, though OS is generally similar between the treatments
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
This document summarizes key findings from the SPARTAN clinical trial evaluating the efficacy of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer. The study found that apalutamide significantly reduced the risk of distant metastasis or death by 72% compared to placebo. Apalutamide also improved progression-free survival, time to symptomatic progression, and delayed the time to initiation of cytotoxic chemotherapy. The most common adverse events with apalutamide were fatigue, hypertension, and rash.
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINI...Alok Gupta
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINICAL OUTCOME INACUTE LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
TREATMENT OF NON-HIDGKIN'S LYMPHOMA IN ELDERLY PATIENTSspa718
This document summarizes treatment approaches for non-Hodgkin's lymphoma in elderly patients. It discusses palliative options for refractory/relapsed diffuse large B-cell lymphoma such as gemcitabine-based chemotherapy, low-dose oral chemotherapy, and hyperfractionated cyclophosphamide. It also reviews novel anti-CD20 monoclonal antibodies showing efficacy against relapsed/refractory indolent lymphoma, and brentuximab vedotin's mechanism of action and responses seen in relapsed/refractory systemic anaplastic large cell lymphoma. Finally, it provides a high-level overview of the MD Anderson Cancer Center's Department of Lymphoma/Myeloma and its disease-specific
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
Tyverb (lapatinib) is approved for use in combination with capecitabine for treatment of ErbB2-positive advanced or metastatic breast cancer in patients who have progressed on prior therapies including anthracyclines, taxanes, and trastuzumab. A pivotal study found that the combination of Tyverb and capecitabine significantly increased time to progression and overall response rate compared to capecitabine alone with manageable side effects. Quality of life was maintained with the combination therapy.
Head and neck cancer accounts for 5-6% of all cancers, with over 90% being squamous cell carcinomas. Risk factors include tobacco, alcohol, and HPV. Treatment options include surgery, radiation therapy, chemotherapy, or combinations. While early stage cancer has a good prognosis with single modality treatment, advanced stages generally require combined modality treatment, though 5-year survival remains below 35%. New targeted therapies and improved radiation techniques have provided benefits in recent years.
Pemetrexed (Alimta) is an intravenous chemotherapy drug used to treat nonsquamous non-small cell lung cancer and mesothelioma. It is given as a 10 minute infusion every 21 days at a dose of 500 mg/m2. Patients should take folic acid and vitamin B12 supplements to reduce side effects. Dose reductions may be needed for hematologic or nonhematologic toxicities. Pemetrexed can interact with NSAIDs and nephrotoxic drugs. It is not recommended in pregnancy or for pediatric patients.
The document discusses bevacizumab and its use in treating cancer. It provides details from several clinical trials that studied bevacizumab in combination with chemotherapy for various cancers. The trials showed improvements in progression-free survival and overall survival when bevacizumab was added to chemotherapy compared to chemotherapy alone. The document also discusses adverse effects seen with bevacizumab treatment and potential biomarkers of response and resistance.
Lung Cancer : Update on Diagnosis and Treatment Lung Cancer : Update on Dia...MedicineAndHealthCancer
- Lung cancer is one of the leading causes of cancer death worldwide, with over 1.5 million new cases and 1.5 million deaths per year globally. In the US there are over 164,000 new cases and 156,900 deaths per year.
- The main types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC makes up 80% of cases and SCLC 20%. NSCLC subtypes include squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and bronchioloalveolar carcinoma.
- Treatment depends on the cancer type and stage. For early stage NSCLC, surgery is usually recommended. Later stage NSCLC may
This document summarizes several classes of antimetabolite drugs, including their mechanisms of action and clinical uses. It discusses antifolate drugs like methotrexate and pemetrexed, which inhibit dihydrofolate reductase and other folate-dependent enzymes. It also covers fluoropyrimidines like 5-fluorouracil and capecitabine, which interfere with thymidylate synthase during DNA synthesis. Deoxycytidine analogs such as cytarabine and gemcitabine are described as inhibiting DNA polymerase. The document concludes by discussing purine antagonists including mercaptopurine, fludarabine, and cladribine, which
This document discusses a clinical trial (JMEI) comparing the efficacy and safety of Alimta versus docetaxel as a second-line treatment for non-small cell lung cancer (NSCLC). The trial aimed to show that Alimta has similar efficacy to docetaxel but a superior safety profile. Results showed Alimta had consistently similar efficacy to docetaxel across all endpoints and subgroups. Alimta also had a significantly better safety profile than docetaxel.
This document discusses lung cancer epidemiology, risk factors, pathology, and smoking cessation. It notes that lung cancer is largely caused by tobacco consumption and was rare before the 20th century. While smoking is the primary risk factor, some people who develop lung cancer have never smoked. The four main histological types are small cell lung cancer, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Stopping smoking can avoid over 90% of lung cancer risk from tobacco. Occupational exposures like asbestos and radiation also increase lung cancer risk.
Prostate Cancer . Castration resistanceLuis Toache
The document discusses castrate-resistant prostate cancer (mCPRC). Some key points:
- mCPRC is the leading cause of death in men with prostate cancer and most deaths are due to mCPRC. Median survival is around 2 years.
- New treatments have improved survival for mCPRC. About 90% of prostate cancers initially respond to androgen deprivation therapy (ADT) but mCPRC often rapidly develops, especially if PSA nadir is >4 ng/mL.
- mCPRC occurs when tumor progression continues despite castrate levels of testosterone (<50 ng/dL). Most mCPRC is still dependent on the androgen receptor
This document provides an overview of cholangiocarcinoma, a rare and deadly form of cancer. It discusses risk factors and increasing incidence rates. For localized disease, surgical resection is standard but outcomes remain poor. For advanced disease, gemcitabine-based chemotherapy is the standard first-line treatment based on results from the ABC-02 trial showing improved survival with gemcitabine and cisplatin. Retrospective data on second-line therapies and combination of pazopanib and trametinib show some benefit. Adding radiation therapy may also improve outcomes based on another retrospective review. Next generation sequencing is helping identify molecular alterations to guide targeted therapy trials. Ongoing clinical trials at MD Anderson include testing new
1. The document discusses individualized systemic therapy for non-small cell lung cancer (NSCLC), focusing on biomarkers like ERCC1, BRCA1, and EGFR mutations that can help customize chemotherapy based on a patient's tumor genetics.
2. Clinical trials show that targeting therapies like EGFR tyrosine kinase inhibitors provide significant benefits for NSCLC patients with EGFR mutations, with response rates over 70% in some studies.
3. Ongoing research aims to identify additional biomarkers to further personalize treatment selection and overcome resistance to targeted therapies.
This document provides a summary of neuroendocrine tumors (NETs):
- NETs arise from neuroendocrine cells throughout the body and can be functional or nonfunctional. Gastroenteropancreatic NETs are the most prevalent.
- NET incidence has increased 5-fold over the past 30 years. They are often advanced at diagnosis due to nonspecific symptoms and long diagnostic delays.
- Treatment options include surgery, chemotherapy, targeted therapies like somatostatin analogues, interferon, and newer agents inhibiting angiogenesis and mTOR pathways. Clinical trials are evaluating these targeted agents.
- The PI3K/Akt/mTOR pathway is frequently deregulated in cancers including NETs and represents a
Radiation therapy plays an evolving role in the treatment of lung cancer beyond just causing DNA double strand breaks.
1) Stereotactic body radiation therapy (SBRT) can provide curative treatment for early stage lung cancer with high local control rates.
2) For locally advanced lung cancer, dose escalation with conventional fractionation in RTOG 0617 did not improve overall survival, highlighting the importance of fractionation and sequencing with other therapies.
3) Radiation induces tumor cell death that can elicit anti-tumor immune responses, known as abscopal effects, especially when combined with immunotherapy like anti-CTLA4 and anti-PD1/PDL1 agents which play complementary roles.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ ΡΟΔΟΥ: Εξελίξεις στη θεραπεία του πλακώδους κα...isrodoy isr
The document discusses recent developments in the treatment of non-small cell lung cancer (NSCLC). It summarizes several key studies that have established new standards of care and treatment options for NSCLC. These include the use of pemetrexed or albumin-bound paclitaxel in combination with platinum chemotherapy as first-line options. Targeted therapies such as necitumumab for squamous cell NSCLC and the addition of bevacizumab or cetuximab to chemotherapy based on tumor biomarkers are also discussed. Studies establishing the role of the anti-VEGF antibody ramucirumab in combination with docetaxel in the second-line setting are summarized.
This document discusses advanced non-small cell lung cancer and targeted therapies. It provides an overview of lung cancer epidemiology and risk factors like smoking. It also reviews molecular targets in NSCLC like EGFR, KRAS, and EML4-ALK and associated targeted therapies. The document outlines NSCLC diagnosis, staging, and management approaches including surgery, chemotherapy, and newer targeted therapies based on molecular profiling.
The document provides guidelines for the treatment of advanced non-small cell lung cancer. It recommends that first-line therapy should consist of platinum-based combination chemotherapy for patients with good performance status. For patients with EGFR mutations, an EGFR tyrosine kinase inhibitor is the preferred first-line treatment. It also recommends the addition of bevacizumab or cetuximab to platinum-based chemotherapy for certain patients.
The document describes a case study of a 72-year-old male patient with metastatic gastric cancer who showed a partial response after 20 months of treatment with pembrolizumab immunotherapy, with reduction in tumor size of multiple lesions of over 70%. It then reviews the KEYNOTE-012 trial which found that pembrolizumab achieved an objective response rate of 33% in patients with advanced gastric cancer. Ongoing trials are investigating nivolumab as a potential treatment for gastric cancer patients who have progressed on two or more prior chemotherapy regimens.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
This document summarizes the evolution of systemic therapy for non-small cell lung cancer (NSCLC) from empiric chemotherapy to molecularly-driven approaches. It discusses:
1) How histological classification is now necessary for treatment decisions, as different chemotherapy regimens have different efficacy depending on adenocarcinoma or squamous cell carcinoma subtype.
2) How maintenance therapy and extended duration of therapy have shown survival benefits compared to stopping treatment after a set number of cycles.
3) The need for molecular classification of NSCLC to guide targeted therapies, including determining EGFR and ALK status to select appropriate first-line tyrosine kinase inhibitors or chemotherapy. Ongoing research aims to identify more driver mutations
This document summarizes the evolution of systemic therapy for non-small cell lung cancer (NSCLC) from empiric chemotherapy to molecularly-driven approaches. It discusses:
1) How histological classification is now necessary for treatment decisions, as different chemotherapy regimens have different efficacy depending on adenocarcinoma or squamous cell carcinoma subtype.
2) How maintenance therapy and extended duration of therapy have shown survival benefits compared to stopping treatment after a set number of cycles.
3) The need for molecular classification of NSCLC to guide targeted therapies, including determining EGFR and ALK status to select appropriate first-line tyrosine kinase inhibitors or chemotherapy. Ongoing research aims to identify more driver mutations
1) Targeted kinase inhibitors such as sorafenib show promise in treating radioactive iodine refractory thyroid cancer, with sorafenib demonstrating a partial response rate of 36% and clinical benefit in 82% of patients in one study.
2) Management of radioactive iodine refractory thyroid cancer involves local therapies when possible and enrollment in clinical trials of small molecule tyrosine kinase inhibitors like sorafenib, which target pathways important in thyroid cancer signaling and growth.
3) Guidelines recommend targeted kinase inhibitors as first-line treatment for radioactive iodine refractory thyroid cancer based on their improved efficacy over chemotherapy and ability to potentially prolong progression-free and overall survival.
Personalized vs. Precision, let’s call it Medicineflasco_org
This document discusses the integration of precision oncology and hematology into clinical practice. It begins by outlining the clinical problem of multiple treatment options for most diseases and unpredictable toxicity. It then discusses practical choices in selecting amongst equivalent options and using clinical trial data and probabilistic risk assessment to guide interventions. Examples are given of pharmacogenomic biomarkers that can guide cancer treatment selection. Next-generation sequencing is discussed as a tool to further analyze tumor genomes. Implementation challenges and opportunities in clinical practice are reviewed including multidisciplinary tumor boards and tracking results. The need to validate biomarkers in robust data and apply them is emphasized to determine the potential of precision oncology.
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
Similar to มะเร็งปอด ประชุมองค์กรแพทย์ 2003 ppt (20)
This document presents recommendations from the Eighth Joint National Committee for the management of high blood pressure in adults. It finds that pharmacologic treatment should be initiated for hypertension at or over certain blood pressure thresholds. It recommends treating to specific blood pressure goals based on age and health status. Initial treatment should include certain classes of antihypertensive drugs, particularly thiazide-type diuretics, calcium channel blockers, ACE inhibitors or ARB's. The recommendations seek to lower blood pressure and improve health outcomes through an evidence-based approach to hypertension management.
Glaucoma is a group of diseases that cause damage to the retinal ganglion cells from increased intraocular pressure. It is a leading cause of blindness. The anatomy involves aqueous humor production and outflow, with factors like age, race, family history, drugs, and surgery affecting IOP. Normal IOP is typically below 21 mmHg. Treatment options include beta blockers, alpha agonists, carbonic anhydrase inhibitors, and prostaglandins, while surgical options include laser trabeculoplasty and filtration procedures. Screening is recommended for those over 40, with a family history, underlying diseases, on certain medications, history of eye trauma, or signs/symptoms of suspected glaucoma.
This document discusses Middle East Respiratory Syndrome Coronavirus (MERS-CoV). It notes that the first case was identified in Saudi Arabia in 2012 and presented as acute pneumonia with renal failure. Most cases have links to the Middle East and common symptoms include severe respiratory illness, fever, cough and gastrointestinal issues. Chest imaging often shows signs of viral pneumonia. While human-to-human transmission is possible, current spread has been limited to close contacts. Treatment focuses on organ support and no medications have proven clearly effective. Infection control requires standard, contact and airborne precautions.
Acute gout causes sudden and severe pain and inflammation in joints, especially those in the big toe. Lowering high levels of uric acid in the blood through urate lowering therapies can help prevent future gout attacks. Common urate lowering therapies include medications such as allopurinol and febuxostat that inhibit uric acid production or increase uric acid excretion from the body.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
3. นพ.จิรเจษฎ์ สุขสุเพิ่ม
อายุรแพทย์โรคมะเร็ง ศูนย์มะเร็ง รพ.จุฬารัตน์ 9
ศูนย์มะเร็ง รักษามะเร็งปอด และ ให ้คาแนะนาเกี่ยวกับ
Growth factors support :
- Filgastrim for Neutropenia (มี PEG filgastrim form ฉีดเข็มเดียว=แบบ ODx5)
- Oral Eltrombopax for Thrombocytopenia (Platelet drop from chemo)
- PAIN control Solution Non Opioid to all Opioid (MO syrup is in process)
- Zoledronic acid (Zometa/Local brand) for releive Bone PAIN
- RadioTherapy : Convention, IMRT 3มิติ (ศูนย์มะเร็งกรุงเทพ ซ.อารีย์)
- ให ้คาแนะนา BrachyTherapy (ฝังแร่) และ ประสานส่งตัว
- Contact of Bone scan (อุรุพงษ์) PET Scan (ศูนย์จุฬาภรณ์)
- Genetic test : EGFR mutation, ALK rearrange (N-health)
4. Lung Cancer: A Leading Cause of
Cancer-Related Deaths
221,130 new
cases of lung
cancer
156,940 deaths
due to lung
cancer
Men
Lung and bronchus 28%
Prostate 11%
Colon and rectum 8%
Pancreas 6%
Leukemia 4%
Women
Lung and bronchus 26%
Breast 15%
Colon and rectum 9%
Pancreas 7%
Ovary 6%
Leading Sites* by Sex, United States, 2010 Estimates
*Excludes basal and squamous cell skin cancer, and in situ carcinomas except urinary bladder.
American Cancer Society. Cancer Facts & Figures 2011.
5. Risk Factors for Lung Cancer
Smoking
Lung cancer deaths due to smoking
~ 91% males and 80% females[1]
Environmental factors[2]
Second-hand smoke 3% to 5%
Radon 3% to 5%
Industrial pollution 0% to 5%
Radiation exposureRare
Asbestos, radon, radiation, silicosis, and berylliosis
Arsenic exposure, talc, obesity, genetic factors
1. CDC. Lung Cancer. 2011.
2. American Cancer Society. Lung Cancer. 2011.
6.
7. Lung Cancer Subtypes
The WHO classification for primary lung cancer recognizes 4 major
histology types[1]
Small-cell
carcinoma
13.0%
Large-cell
carcinoma
5.0%
Adenocarcinoma
38.3%
19.7%
Squamous cell
carcinoma
Other*
24.0%
Percent distribution by histology among histologically
confirmed lung cancer cases, 2001-2004[2]
1. Brambilla E, et al. Eur Respir J. 2001;18:1059-1068.2. SEER Database. Lung and Bronchus Cancer
(Invasive), 1975-2004.
*Including adenosquamous
carcinoma; carcinomas with
pleomorphic, sarcomatoid or
sarcomatous elements;
carcinoid tumor; carcinomas of
salivary gland type; and
unclassified carcinoma
8. 6th Edition Descriptor 7th Edition N0 N1 N2 N3
T1 (≤ 2 cm) T1a IA IIA IIIA IIIB
T1 (> 2-3 cm) T1b IA IIA IIIA IIIB
T2 (> 3 to ≤ 5 cm) T2a IB IIA IIIA IIIB
T2 (> 5-7) T2b IIA IIB IIIA IIIB
T2 (> 7 cm) T3 IIB IIIA IIIA IIIB
T3 invasion IIB IIIA IIIA IIIB
T4 (same lobe nodules) IIB IIIA IIIA IIIB
T4 (extension) T4 IIIA IIIA IIIB IIIB
M1 (ipsilateral lung) IIIA IIIA IIIB IIIB
T4 (pleural effusion) M1a IV IV IV IV
M1 (contralateral lung) IV IV IV IV
M1 (distant) M1b IV IV IV IV
7th Edition of TNM Staging
Goldstraw P, et al. J Thorac Oncol. 2007;2:706-714.
9. Chemotherapy vs Best Supportive
Care in Advanced NSCLC: Meta-
Analysis
Meta-analysis of 8 trials (778 patients) using
cisplatin-based chemotherapy[1]
Absolute improvement in survival of 10% at 1 yr[1]
Median survival, BSC vs chemo: 4 vs 8+ mos,
respectively
Median survival now 12+ mos in more recent
trials
VEGF-targeted therapy plus platinum doublet[2]
Quality-of-life benefit from chemotherapy[3]
1. NSCLC Collaborative Group, et al. BMJ. 1995;311:899-909. 2. Herbst R, et al. Clin Lung Cancer.
2009;10:20-27 3. Klastersky J, et al. Lung Cancer. 2001;34(suppl 4):S95-S101.
10. First-line Treatment: 2 Agents Are
More Effective Than 1
Meta-analysis: 65 trials (N = 13,601) between
1980-2001
Compared efficacy of
Doublet vs single-agent regimens
Triplet vs doublet regimens
Delbaldo C, et al. JAMA. 2004;292:470-484.
Survival Outcome Doublet vs Single-Agent
Regimens
Triplet vs Doublet
Regimens
1-yr OS
Doublet > single-agent
OR: 0.80; 95% CI: 0.70-0.91;
P < .001
5% absolute benefit
Triplet = doublet
OR: 1.01; 95% CI: 0.85-1.21;
P = .88
Median OS
Doublet > single-agent
MR: 0.83; 95% CI: 0.79-0.89;
P < .001
Triplet = doublet
MR: 1.00; 95% CI: 0.94-1.06;
P = .97
11. Agents With Activity in Advanced
NSCLC
*Not all drugs listed have FDA approval.
Older Agents* Newer Agents*
Carboplatin
Cisplatin
Etoposide
Ifosfamide
Mitomycin C
Vinblastine
Vindesine
Docetaxel
Gemcitabine
Irinotecan
Paclitaxel
Topotecan
Vinorelbine
Pemetrexed
Gefitinib
Erlotinib
Bevacizumab
Cetuximab
Crizotinib
12. History of Therapy in Advanced
NSCLC: FDA Approval Dates
First line
Second line
Third line
Maintenance
Not approved
1970 1980 1990 2000
Median
OS (mos)
12+
~ 6
~ 2-4
BSC Single-agent platinum Doublets
Bevacizumab + PC
Carboplatin*
1989
Erlotinib
Pemetrexed
2004
Docetaxel
1999
Paclitaxel
Gemcitabine
1998
Vinorelbine
1994
Docetaxel
2002
Bevacizumab
2006
Gefitinib
2003
Standard therapies
*Label does not include
NSCLC-specific indication
Pemetrexed
2008/2009
Histology-directed therapy
~ 8-10
Cisplatin*
1978
1. FDA Web site. 2. NCCN. Clinical practice guidelines in oncology. v.3.2011. 3. Schrump, et al. Non-small
cell lung cancer. In: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2005.
13. Paclitaxel 225 mg/m2 over 3 hrs on Day 1
Carboplatin AUC 6.0 mg/mL/min on Day 1
3-wk cycle
Docetaxel 75 mg/m2 on Day 1
Cisplatin 75 mg/m2 on Day 1
3-wk cycle
Gemcitabine 1000 mg/m2 on Days 1, 8, 15
Cisplatin 100 mg/m2 on Day 1
4-wk cycle
Reference Arm
Paclitaxel 135 mg/m2 over 24 hrs on Day 1
Cisplatin 75 mg/m2 on Day 2
3-wk cycle
ECOG 1594: Comparison of 4
First-line Doublet Regimens in
Advanced NSCLC
Stratified by:
ECOG PS (0/1 vs 2)
Weight loss in previous 6 mos
(< 5% vs ≥ 5%)
Disease stage (IIIB vs IV or recurrent)
Brain metastases (yes vs no)
Advanced-stage, previously
untreated NSCLC patients
(N = 1207)
Schiller JH, et al. N Engl J Med. 2002;346:92-98.
14. ECOG 1594: OS
Schiller JH, et al. N Engl J Med. 2002;346:92-98.
1.0
0.8
0.6
0.4
0.2
0
Proportionofpatients
Mos
0 5 10 15 20 25 30
Survival by Treatment Group
All Randomized Cases
Cisplatin/paclitaxel
Cisplatin/gemcitabine
Cisplatin/docetaxel
Carboplatin/paclitaxel
15. Advanced-stage, previously
untreated NSCLC patients
(N = 1725)
Cisplatin 75 mg/m2 on Day 1
Gemcitabine 1250 mg/m2 on Days 1 and 8
Six 3-wk cycles
Cisplatin 75 mg/m2 on Day 1
Pemetrexed 500 mg/m2 on Day 1
Six 3-wk cycles
Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551.
CONSORT: Phase III Gemcitabine or
Pemetrexed + Cisplatin as First-line Therapy
Stratified by:
ECOG PS (0 vs 1)
Disease stage (IIIB vs IV)
Brain metastases (yes vs no)
Sex (male vs female)
Pathologic diagnosis (histologic vs cytologic)
Treatment center
17. Chemotherapy Today and the
Need for Targeted Therapies
Doublet chemotherapy for 4-6 cycles is standard
Can now select chemotherapy based on histology
Future selection by other markers (ie, ERCC1)
There is a need for “targeted” chemotherapy and
other agents
Antiangiogenesis: VEGF targeted (bevacizumab, etc)
EGFR-targeted antibody (cetuximab), TKI (erlotinib,
etc)
Newer targets (ALK and others)
Recent identification of “driver mutations” in 50% of
NSCLC adenocarcinomas
18. The Angiogenic Switch
Small tumor
Nonvascular
“Dormant”
Larger tumor
Vascular
Metastatic potential
1-2 mm
Angiogenic
Switch
VEGF
21. E4599: Efficacy
RR: 15% for Paclitaxel/Carboplatin vs
35% for Paclitaxel/Carboplatin + Bevacizumab
PFS(%)
0
20
40
60
80
100
OS(%)
0 6 12 18 24 30 42
Mos
PCB group
(305 events in 417 patients)
PC group
(344 events in 433 patients)
.Sandler A, et al. N Engl J Med. 2006;355:2542-2550.
0
20
40
60
80
100
0 6 12 18 24 30
Mos
36
HR: 0.79 (P = .003)
HR: 0.66 (P < .001)
PCB group
(374 events in 417 patients)
PC group
(405 events in 433 patients)
22. Bevacizumab in Special
Populations: Summary
Caution with elderly patients; ongoing trials
Hemoptysis remains an issue, but
anticoagulation can be considered cautiously
Safe in patients with treated brain metastases
Squamous histology still a major bleeding risk
23. EGFR and NSCLC
EGF binds to the EGFR
to regulate cell growth, proliferation, and differentiation
Erlotinib and gefitinib are inhibitors of the TK enzyme in the
EGFR
Cetuximab is a monoclonal human-murine chimeric antibody
against EGFR with some NSCLC activity
Baselga J. Oncologist. 2002;7(suppl 4):2-8. Lynch TJ, et al. N Engl J Med. 2004;350:2129-2139. Shepherd
FA, et al. N Engl J Med. 2005;353:123-132. Rosell R, et al. N Engl J Med. 2009;361:958-967.
31. Previously
untreated patients
with stage IIIB/IV
NSCLC; never or
light ex-smokers;
PS 0-2
(N = 1217)
Up to six
3-wk cycles
Gefitinib 250 mg/day PO
(n = 609)
Paclitaxel 200 mg/m2 IV on Day 1 +
Carboplatin AUC 5-6 mg/mL/min IV on Day 1
(n = 608)
Mok TS, et al. N Engl J Med. 2009;361:247-257.
IPASS: Gefitinib vs
Carboplatin/Paclitaxel in Select
Patients With Advanced NSCLC
Primary endpoint: PFS (noninferiority)
Secondary endpoints: ORR, OS, QoL, safety, disease-related symptoms
Exploratory endpoints: EGFR mutation, EGFR gene copy number, EGFR protein
expression
Randomized from
March 2006 to October 2007
33. EURTAC: First-line Erlotinib vs
Chemo in European Patients With
EGFR Mutations
174 patients
Trial run in Europe (lead by Spanish group)
Outcome CT Erlotinib HR P Value
Response rate, % 15 58 - NR
Median PFS, mos 5.2 9.7 0.37 < .0001
Median OS, mos NR NR 0.80 .42
Most common
toxicities, %
ALT elevation: 72
Anemia: 46
Neutropenia: 36
ALT elevation: 80
Rash: 80
Diarrhea: 57
Rosell R, et al. ASCO 2011. Abstract 7503.
35. EURTAC vs Asian Trials in EGFR
Mutated NSCLC: RR and PFS
None of the EGFR-TKI vs chemo as first-line
therapy trials in EGFR mut NSCLC have shown
a significant OS benefit
Study Response Rate, % PFS, Mos (HR)
EURTAC 58.0 vs 14.9 9.7 vs 5.2 (0.37)
OPTIMAL 83 vs 36 13.1 vs 4.6 (0.16)
NEJ 002 74 vs 31 10.8 vs 5.4 (0.30)
WJTOG 3405 62 vs 31 9.2 vs 6.3 (0.49)
Rosell R, et al. J Clin Oncol. 2011;29(suppl). Abstract 7503.
36.
37. Summary: First-line NSCLC
Therapy
Doublet chemotherapy still standard backbone
regimen
Some selection possible; histology
Targeted drugs can add to doublet chemotherapy
Bevacizumab and cetuximab with survival benefit
MANY with NO benefit in unselected patients in this
setting
EGFR-TKIs, VEGFR-TKIs, MMPs, immunomodulators
Targeted agents where target is known can
replace first-line chemotherapy (EGFR-TKI in
EGFR mutants)
Better biomarkers will lead to better targeting