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Retreatment with erlotinib in NSCLC harboring EGFR mutation—Case report
Abstracts / Lung Cancer 77 (2012) S28–S43
Autophagy execution protein beclin1 regulates radiation-induced osteopontin in human lung cancer cell Seung-Hee Chang 1,∗ , Kyeong-Nam Yu 1 , Kyung-A. Lee 1 , Myung-Haing Cho 1,2,3,4,5 . 1 Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea, 2 Department of Nanofusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea, 3 Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea, 4 Center for Food Safety and Toxicology, Seoul National University National Institute of Food and Drug Safety, Seoul, Republic of Korea, 5 Advanced Institute of Convergence Technology, Seoul National University, Suwon, Republic of Korea Background: Lung cancer is still the leading cause of cancer-related deaths worldwide. Radiation in combination with chemotherapy has long been used as a reasonably effective treatment regimen for lung cancer. However, some malignancies are relatively resistant to radiation upon repeated treatment and may eventually recover proliferative capacity. In general, autophagy is known to play a key role in radiosensitization of cancer cells. Materials and methods: A549 cells were exposed to 5 Gy of gamma-radiation and transfected with beclin1 (BECN1) plasmid. The effects of BECN1 on expression level of OPN and pro-autophagic proteins (BECN1, ATG5, and LC3) were evaluated. Results: We report that the increased OPN levels through induction of nuclear p53 following irradiation could be inhibited by exogenous BECN1. In addition, induction of autophagy through stable expression of BECN1 resulted in elevated cytosolic p53 protein and the inhibition of cell growth and angiogenesis. Conclusions: Our work provides the basis for rational approach to cope with the relatively poor cure rate in lung cancer patients associated with a radioresistance because exploitation of autophagy should have the capacity to improve the therapeutic gain of current classical therapies. Acknowledgements: This work was supported by the National Research Foundation (NRF-2012-0000102) of the Ministry of Education, Science and Technology (MEST) and the R&D Program of MKE/KEIT (10035333, Development of anti-cancer therapeutic agent based on regulating cell cycle or cell death) in Korea. http://dx.doi.org/10.1016/j.lungcan.2012.05.051 Retrospective analysis of pain management in an in-hospital setting in cancer patients Dominique Lossignol 1,3 , Cristina Dumitrescu 1,∗,3 , Dirk Schrijvers 2,3 . 1 Jules Bordet Institute – Free University of Brussels, Belgium, 2 ZNA Middelheim, Belgium Background: This retrospective study evaluates the data on breakthrough pain (BTP) and the pharmacological pain treatment in hospitalized cancer patients. Methods: Breakthrough cancer pain (BTCP) has been evaluated by a general questionnaire per centre. The number of cancer patients seen monthly, the type of opioids used, the presence of BTP syndrome and hospitalisations have been recorded. 156 consecutive patients (32 centres) have been evaluated and completed the questionnaire. BTP is defined as follows: rapid onset of acute pain, lasting from seconds to hours, known factors or unknown, co-existing chronic pain syndrome and/or an inadequate chronic treatment.
3
For the Survey Pain Management Study.
S29
Results: 80% of patients received opioids for cancer related pain but 50% remained uncontrolled. The need for specific BTP medication is 94%. 75% of patients in hospital setting have BTCP. The need for hospitalization should be reduced by 78% with an adequate BTCP medication. The use of opioids remains the corner stone for the management of chronic cancer pain (93% of patients) and for rescue medication (69% of patients) as well. Toxicity of long-term used opioids remains of concern Conclusions: BTCP remains a challenge in terms of diagnosis and management. An effective treatment may (1) reduce the number and duration of hospitalizations, (2) reduce the overall opioids’ toxicity and (3) improve the quality of life. Note that most BTCP medications are not available in Belgium and if they are, there is no reimbursement foreseen, this explaining, in part, our data. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.lungcan.2012.05.052 Retreatment with erlotinib in NSCLC harboring EGFR mutation—Case report Ondrej Fiala 1,∗ , Milos Pesek 2 , Jindrich Finek 1 , Lucie Benesova 3 , Marek Minarik 3 . 1 Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic, 2 Department of Tuberculosis and Respiratory Diseases, University Hospital in Pilsen, Czech Republic, 3 Center for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague, Czech Republic Background: Erlotinib is EGFR tyrosine kinase inhibitor used for treatment of advanced stage NSCLC. Clinical trials have shown high efficacy of erlotinib, particularly in patients harboring activating mutations in the EGFR gene. Here we describe a case report of a patient with metastatic NSCLC harboring EGFR mutation who developed resistance to erlotinib in the first line and was successfully retreated with erlotinib after 6 cycles of second line chemotherapy. Case presentation: A 42-year-old female smoker was diagnosed with adenocarcinoma of the upper lobe of left lung with pleural metastases, malignant pleural fluid and metastases in the thoracic vertebrae, T4NXM1, stage IV. Genetic testing showed the presence of activating EGFR mutation (exon 19 deletion). The patient was treated with erlotinib (150 mg/day) from December 2009. A partial regression was achieved. Because of severe skin toxicity, the dose had to be reduced (100 mg/day). In February 2011 disease progression was discovered. The patient was subsequently treated with chemotherapy. Six cycles of pemetrexed/carboplatin were administered, partial regression was achieved. In June 2011 further disease progression was observed. Subsequently erlotinib in reduced dose (100 mg/day) was re-administered. Recently, in April 2012 the disease remained stable without any sign of progression and the treatment is still ongoing. The treatment is well tolerated and the patient is still able to live an active life. Conclusion: Retreatment with erlotinib in a patient with adenocarcinoma of the lung, harboring EGFR mutation was effective. Therefore it should be considered as a good treatment option for patients with NSCLC harboring EGFR mutation. http://dx.doi.org/10.1016/j.lungcan.2012.05.053
Autophagy execution protein beclin1 regulates radiation-induced osteopontin in human lung cancer cell Seung-Hee Chang 1,∗ , Kyeong-Nam Yu 1 , Kyung-A. Lee 1 , Myung-Haing Cho 1,2,3,4,5 . 1 Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea, 2 Department of Nanofusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea, 3 Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea, 4 Center for Food Safety and Toxicology, Seoul National University National Institute of Food and Drug Safety, Seoul, Republic of Korea, 5 Advanced Institute of Convergence Technology, Seoul National University, Suwon, Republic of Korea Background: Lung cancer is still the leading cause of cancer-related deaths worldwide. Radiation in combination with chemotherapy has long been used as a reasonably effective treatment regimen for lung cancer. However, some malignancies are relatively resistant to radiation upon repeated treatment and may eventually recover proliferative capacity. In general, autophagy is known to play a key role in radiosensitization of cancer cells. Materials and methods: A549 cells were exposed to 5 Gy of gamma-radiation and transfected with beclin1 (BECN1) plasmid. The effects of BECN1 on expression level of OPN and pro-autophagic proteins (BECN1, ATG5, and LC3) were evaluated. Results: We report that the increased OPN levels through induction of nuclear p53 following irradiation could be inhibited by exogenous BECN1. In addition, induction of autophagy through stable expression of BECN1 resulted in elevated cytosolic p53 protein and the inhibition of cell growth and angiogenesis. Conclusions: Our work provides the basis for rational approach to cope with the relatively poor cure rate in lung cancer patients associated with a radioresistance because exploitation of autophagy should have the capacity to improve the therapeutic gain of current classical therapies. Acknowledgements: This work was supported by the National Research Foundation (NRF-2012-0000102) of the Ministry of Education, Science and Technology (MEST) and the R&D Program of MKE/KEIT (10035333, Development of anti-cancer therapeutic agent based on regulating cell cycle or cell death) in Korea. http://dx.doi.org/10.1016/j.lungcan.2012.05.051 Retrospective analysis of pain management in an in-hospital setting in cancer patients Dominique Lossignol 1,3 , Cristina Dumitrescu 1,∗,3 , Dirk Schrijvers 2,3 . 1 Jules Bordet Institute – Free University of Brussels, Belgium, 2 ZNA Middelheim, Belgium Background: This retrospective study evaluates the data on breakthrough pain (BTP) and the pharmacological pain treatment in hospitalized cancer patients. Methods: Breakthrough cancer pain (BTCP) has been evaluated by a general questionnaire per centre. The number of cancer patients seen monthly, the type of opioids used, the presence of BTP syndrome and hospitalisations have been recorded. 156 consecutive patients (32 centres) have been evaluated and completed the questionnaire. BTP is defined as follows: rapid onset of acute pain, lasting from seconds to hours, known factors or unknown, co-existing chronic pain syndrome and/or an inadequate chronic treatment.
3
For the Survey Pain Management Study.
S29
Results: 80% of patients received opioids for cancer related pain but 50% remained uncontrolled. The need for specific BTP medication is 94%. 75% of patients in hospital setting have BTCP. The need for hospitalization should be reduced by 78% with an adequate BTCP medication. The use of opioids remains the corner stone for the management of chronic cancer pain (93% of patients) and for rescue medication (69% of patients) as well. Toxicity of long-term used opioids remains of concern Conclusions: BTCP remains a challenge in terms of diagnosis and management. An effective treatment may (1) reduce the number and duration of hospitalizations, (2) reduce the overall opioids’ toxicity and (3) improve the quality of life. Note that most BTCP medications are not available in Belgium and if they are, there is no reimbursement foreseen, this explaining, in part, our data. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.lungcan.2012.05.052 Retreatment with erlotinib in NSCLC harboring EGFR mutation—Case report Ondrej Fiala 1,∗ , Milos Pesek 2 , Jindrich Finek 1 , Lucie Benesova 3 , Marek Minarik 3 . 1 Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic, 2 Department of Tuberculosis and Respiratory Diseases, University Hospital in Pilsen, Czech Republic, 3 Center for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague, Czech Republic Background: Erlotinib is EGFR tyrosine kinase inhibitor used for treatment of advanced stage NSCLC. Clinical trials have shown high efficacy of erlotinib, particularly in patients harboring activating mutations in the EGFR gene. Here we describe a case report of a patient with metastatic NSCLC harboring EGFR mutation who developed resistance to erlotinib in the first line and was successfully retreated with erlotinib after 6 cycles of second line chemotherapy. Case presentation: A 42-year-old female smoker was diagnosed with adenocarcinoma of the upper lobe of left lung with pleural metastases, malignant pleural fluid and metastases in the thoracic vertebrae, T4NXM1, stage IV. Genetic testing showed the presence of activating EGFR mutation (exon 19 deletion). The patient was treated with erlotinib (150 mg/day) from December 2009. A partial regression was achieved. Because of severe skin toxicity, the dose had to be reduced (100 mg/day). In February 2011 disease progression was discovered. The patient was subsequently treated with chemotherapy. Six cycles of pemetrexed/carboplatin were administered, partial regression was achieved. In June 2011 further disease progression was observed. Subsequently erlotinib in reduced dose (100 mg/day) was re-administered. Recently, in April 2012 the disease remained stable without any sign of progression and the treatment is still ongoing. The treatment is well tolerated and the patient is still able to live an active life. Conclusion: Retreatment with erlotinib in a patient with adenocarcinoma of the lung, harboring EGFR mutation was effective. Therefore it should be considered as a good treatment option for patients with NSCLC harboring EGFR mutation. http://dx.doi.org/10.1016/j.lungcan.2012.05.053