Enzalutamide is an androgen receptor-signaling inhibitor that is reported to differ from conventional antiandrogen agents in that it inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment; exhibits increased affinity for the androgen receptor; and induces tumor reduction, rather than slowing growth, in preclinical models. The recently reported AFFIRM study showed that enzalutamide treatment after chemotherapy significantly prolonged overall survival (OS), radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and time to skeletal-related events (SREs) in men with castration-resistant prostate cancer. This trial formed the basis for the recent approval of enzalutamide for the treatment of patients with metastatic castrationresistant prostate cancer who have previously received docetaxel. In the double-blind AFFIRM trial, 1,199 patients with castration-resistant prostate cancer who had received at least 1 docetaxel-containing chemotherapy regimen were randomized (2:1) to oral enzalutamide 160 mg once daily (800 patients) or placebo (399 patients). Treatment was continued until radiographic confirmation of disease progression requiring initiation of new systemic antineoplastic treatment. Enzalutamide has been associated with a lowered seizure threshold; thus, patients with a history of or risk factors for seizure or who were taking medications known to decrease seizure threshold were excluded from the trial. All of the patients continued androgen deprivation therapy. Patients were permitted to start or continue corticosteroid treatment during the study. The primary endpoint of the trial was OS. The median age in both groups was 69 years, with 26% of enzalutamide patients and 27% of placebo patients being 75 years of age or older. Similar proportions of enzalutamide and placebo patients had a Gleason score 7 (50% vs 52%, respectively), and ECOG performance status of 0 or 1 (91% vs 92%), a pain score 4 (28% vs 29%), 1 prior chemotherapy regimen (72% vs 74%), bisphosphonate use at baseline (43% in both groups), prior radiation therapy (71% vs 72%), bone disease (92% vs 92%, with 38% in both groups having 20 lesions), soft tissue disease (71% vs 69%), PSA progression at baseline (89% vs 90%), and radiographic progression at baseline (59% in both groups). Median PSA levels at baseline were 108 ng/mL and 128 ng/mL. The median number of prior docetaxel cycles was 8.5 in the enzalutamide group and 8.0 in the placebo group. During the study, 48% of enzalutamide patients and 46% of placebo patients received corticosteroid treatment. At the time of a preplanned interim analysis, median durations of treatment were 8.3 months in the enzalutamide group and 3.0 months in the placebo group. The median duration of follow-up to assess survival outcomes
Enzalutamide是一种雄激素受体信号抑制剂，据报道，它与传统的抗雄激素药物不同，它抑制雄激素受体核易位、DNA结合和辅激活剂募集;对雄激素受体的亲和力增强;并在临床前模型中诱导肿瘤缩小，而不是减缓肿瘤生长。最近报道的AFFIRM研究表明，化疗后enzalutamide治疗显著延长了去势抵抗性前列腺癌男性的总生存期(OS)、放射学无进展生存期(PFS)、前列腺特异性抗原(PSA)进展时间和骨骼相关事件(SREs)时间。这项试验为最近批准enzalutamide用于治疗转移性去势抵抗性前列腺癌患者奠定了基础，这些患者之前接受过多西他赛。在双盲试验AFFIRM中，1199例接受过至少1种含多西他赛化疗方案的去雄抵抗性前列腺癌患者被随机(2:1)分配到每日一次口服enzalutamide 160 mg(800例)或安慰剂(399例)。治疗一直持续到x线摄影证实疾病进展，需要开始新的全身抗肿瘤治疗。恩杂鲁胺与癫痫发作阈值降低有关;因此，有癫痫发作史或危险因素或正在服用降低癫痫发作阈值药物的患者被排除在试验之外。所有患者继续雄激素剥夺治疗。在研究期间，允许患者开始或继续皮质类固醇治疗。试验的主要终点是OS。两组的中位年龄均为69岁，26%的enzalutamide患者和27%的安慰剂患者年龄在75岁或以上。类似比例的enzalutamide和安慰剂患者格里森评分7(分别为50%和52%),和ECOG性能状态0或1 (91% vs 92%),疼痛评分4 (28% vs 29%), 1之前化疗方案(72% vs 74%),二磷酸盐使用基线在两组(43%),放射治疗(71% vs 72%)之前,骨病(92% vs 92%, 38%,两组有20病变),软组织疾病(71% vs 69%), PSA进展在基线(89% vs 90%),基线放射学进展(两组均为59%)。基线时PSA水平中位数分别为108 ng/mL和128 ng/mL。先前多西他赛周期的中位数在恩杂鲁胺组为8.5，在安慰剂组为8.0。在研究期间，48%的enzalutamide患者和46%的安慰剂患者接受了皮质类固醇治疗。在预先计划的中期分析中，恩杂鲁胺组的中位治疗持续时间为8.3个月，安慰剂组为3.0个月。评估生存结果的中位随访时间
{"title":"Enzalutamide in castrate-resistant prostate cancer after chemotherapy","authors":"J. Abraham","doi":"10.12788/J.CMONC.0011","DOIUrl":"https://doi.org/10.12788/J.CMONC.0011","url":null,"abstract":"Enzalutamide is an androgen receptor-signaling inhibitor that is reported to differ from conventional antiandrogen agents in that it inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment; exhibits increased affinity for the androgen receptor; and induces tumor reduction, rather than slowing growth, in preclinical models. The recently reported AFFIRM study showed that enzalutamide treatment after chemotherapy significantly prolonged overall survival (OS), radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and time to skeletal-related events (SREs) in men with castration-resistant prostate cancer. This trial formed the basis for the recent approval of enzalutamide for the treatment of patients with metastatic castrationresistant prostate cancer who have previously received docetaxel. In the double-blind AFFIRM trial, 1,199 patients with castration-resistant prostate cancer who had received at least 1 docetaxel-containing chemotherapy regimen were randomized (2:1) to oral enzalutamide 160 mg once daily (800 patients) or placebo (399 patients). Treatment was continued until radiographic confirmation of disease progression requiring initiation of new systemic antineoplastic treatment. Enzalutamide has been associated with a lowered seizure threshold; thus, patients with a history of or risk factors for seizure or who were taking medications known to decrease seizure threshold were excluded from the trial. All of the patients continued androgen deprivation therapy. Patients were permitted to start or continue corticosteroid treatment during the study. The primary endpoint of the trial was OS. The median age in both groups was 69 years, with 26% of enzalutamide patients and 27% of placebo patients being 75 years of age or older. Similar proportions of enzalutamide and placebo patients had a Gleason score 7 (50% vs 52%, respectively), and ECOG performance status of 0 or 1 (91% vs 92%), a pain score 4 (28% vs 29%), 1 prior chemotherapy regimen (72% vs 74%), bisphosphonate use at baseline (43% in both groups), prior radiation therapy (71% vs 72%), bone disease (92% vs 92%, with 38% in both groups having 20 lesions), soft tissue disease (71% vs 69%), PSA progression at baseline (89% vs 90%), and radiographic progression at baseline (59% in both groups). Median PSA levels at baseline were 108 ng/mL and 128 ng/mL. The median number of prior docetaxel cycles was 8.5 in the enzalutamide group and 8.0 in the placebo group. During the study, 48% of enzalutamide patients and 46% of placebo patients received corticosteroid treatment. At the time of a preplanned interim analysis, median durations of treatment were 8.3 months in the enzalutamide group and 3.0 months in the placebo group. The median duration of follow-up to assess survival outcomes","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"135-137"},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The National Cancer Institute (NCI) has defined cancer health disparities as adverse differences in incidence, prevalence, mortality, survivorship, and burden of cancer or related health conditions that exist among specific populations in the United States. African Americans are more likely than members of any other racial or ethnic population to develop and die from cancer. African American women are more likely than are white women to die of breast cancer, although African American women have a lower incidence rate of this disease than white women. The most conspicuous factors that contribute to the observed disparities are associated with a lack of health care coverage, low socioeconomic status, and race/ethnicity. We recently provided care to a woman who presented to the emergency room with 20-cm chest wall mass. She was found to have inoperable stage IV triple-negative breast cancer with significantly poor prognosis. We describe her presentation, diagnosis, and treatment, identify the factors that contributed to her current condition, discuss the cancer health disparities and the associated risk factors, and reiterate what physicians should know to prevent similar unfortunate and unnecessary scenarios.
{"title":"Cancer health disparities and risk factors: lessons from a woman with a 20-cm chest wall mass, growing for 2 years","authors":"Janghee Woo, N. Palmisiano, G. Váradi","doi":"10.12788/j.cmonc.0027","DOIUrl":"https://doi.org/10.12788/j.cmonc.0027","url":null,"abstract":"The National Cancer Institute (NCI) has defined cancer health disparities as adverse differences in incidence, prevalence, mortality, survivorship, and burden of cancer or related health conditions that exist among specific populations in the United States. African Americans are more likely than members of any other racial or ethnic population to develop and die from cancer. African American women are more likely than are white women to die of breast cancer, although African American women have a lower incidence rate of this disease than white women. The most conspicuous factors that contribute to the observed disparities are associated with a lack of health care coverage, low socioeconomic status, and race/ethnicity. We recently provided care to a woman who presented to the emergency room with 20-cm chest wall mass. She was found to have inoperable stage IV triple-negative breast cancer with significantly poor prognosis. We describe her presentation, diagnosis, and treatment, identify the factors that contributed to her current condition, discuss the cancer health disparities and the associated risk factors, and reiterate what physicians should know to prevent similar unfortunate and unnecessary scenarios.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"154-158"},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) has dramatically changed the management of patients with CML. With continuous long-term TKI therapy, CML can be managed like a chronic condition, and most patients can expect to have a normal life expectancy. Given the prospect of lifelong therapy, however, issues related to adherence become particularly important and warrant greater attention since attainment of favorable long-term survival depends in large part on consistent, appropriate treatment administration over years, if not decades. As the multidisciplinary care team approach to cancer care has gained traction at academic centers and community practices, midlevel providers, including nurse practitioners and physician assistants, have taken on greater patient-related responsibilities. Midlevel providers have the potential to foster and maintain meaningful provider-patient relationships that may span years, and are well positioned to recognize and manage problems that patients may have with adherence. Here we discuss the importance of achieving and maintaining responses to TKI therapy, describe the clinical consequences of poor adherence to TKI therapy in CML, and outline factors behind poor adherence. We also share strategies that we use at our center to improve adherence to long-term TKI therapy for CML.
{"title":"Ensuring optimal adherence to BCR-ABL1 tyrosine kinase inhibitor therapy for chronic myeloid leukemia","authors":"M. Welch, Elizabeth S Kaled","doi":"10.12788/J.CMONC.0029","DOIUrl":"https://doi.org/10.12788/J.CMONC.0029","url":null,"abstract":"The advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) has dramatically changed the management of patients with CML. With continuous long-term TKI therapy, CML can be managed like a chronic condition, and most patients can expect to have a normal life expectancy. Given the prospect of lifelong therapy, however, issues related to adherence become particularly important and warrant greater attention since attainment of favorable long-term survival depends in large part on consistent, appropriate treatment administration over years, if not decades. As the multidisciplinary care team approach to cancer care has gained traction at academic centers and community practices, midlevel providers, including nurse practitioners and physician assistants, have taken on greater patient-related responsibilities. Midlevel providers have the potential to foster and maintain meaningful provider-patient relationships that may span years, and are well positioned to recognize and manage problems that patients may have with adherence. Here we discuss the importance of achieving and maintaining responses to TKI therapy, describe the clinical consequences of poor adherence to TKI therapy in CML, and outline factors behind poor adherence. We also share strategies that we use at our center to improve adherence to long-term TKI therapy for CML.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"138-146"},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Many professional entities endorse the need to deliver cancer genetics risk assessment (CGRA) services through a multidisciplinary team that includes trained genetics professionals. However, market forces, a lack of regulation of genetic testing, patent laws, cost barriers, and a limited workforce in genetics have resulted in an increasing number of community practitioners who order and interpret genetic testing. In addition, varying state-level laws and licensure requirements for genetic counselors may contribute to the nonuniform delivery of CGRA services across the United States. Those who perform genetic testing without having adequate training or expertise may incur liability risks. Moreover, the patient might not enjoy the maximum benefit of testing at the hands of an inadequately trained individual. In the setting of a limited number of professional who are trained in CGRA and a dearth of education and training resources, it is a challenge to integrate genetic testing services into clinical care. With advances in genomics and the implementation of personalized medicine, the problem will only be magnified, and it is critical that there are more opportunities for high quality education and training in clinical cancer genetics free of commercial bias. Successful strategies for delivering comprehensive CGRA services include academic-community partnerships that focus on collaboration with nongenetics providers or the inclusion of a genetics professional in the community setting as part of multidisciplinary patient care. These approaches can leverage the expertise of genetics professionals while allowing patients to remain in their community and enjoy better access to resources for long-term follow-up care.
{"title":"Practical considerations in the delivery of genetic counseling and testing services for inherited cancer predisposition","authors":"T. Pal, C. Radford, S. Vadaparampil, A. Prince","doi":"10.12788/J.CMONC.0010","DOIUrl":"https://doi.org/10.12788/J.CMONC.0010","url":null,"abstract":"Many professional entities endorse the need to deliver cancer genetics risk assessment (CGRA) services through a multidisciplinary team that includes trained genetics professionals. However, market forces, a lack of regulation of genetic testing, patent laws, cost barriers, and a limited workforce in genetics have resulted in an increasing number of community practitioners who order and interpret genetic testing. In addition, varying state-level laws and licensure requirements for genetic counselors may contribute to the nonuniform delivery of CGRA services across the United States. Those who perform genetic testing without having adequate training or expertise may incur liability risks. Moreover, the patient might not enjoy the maximum benefit of testing at the hands of an inadequately trained individual. In the setting of a limited number of professional who are trained in CGRA and a dearth of education and training resources, it is a challenge to integrate genetic testing services into clinical care. With advances in genomics and the implementation of personalized medicine, the problem will only be magnified, and it is critical that there are more opportunities for high quality education and training in clinical cancer genetics free of commercial bias. Successful strategies for delivering comprehensive CGRA services include academic-community partnerships that focus on collaboration with nongenetics providers or the inclusion of a genetics professional in the community setting as part of multidisciplinary patient care. These approaches can leverage the expertise of genetics professionals while allowing patients to remain in their community and enjoy better access to resources for long-term follow-up care.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"147-153"},"PeriodicalIF":0.0,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benign metastasizing leiomyoma (BML) is a rare entity, of which a small number of cases, about 75 to 120, have been described in the literature since the condition was first described in 1939. It usually affects women of reproductive age with a history of uterine leiomyomatosis who have undergone a hysterectomy. The lung is the most common site of involvement. The pathologic features of this entity are described as having originated from the metastasis of the histologically benign uterine leiomyoma and are an uncommon lesion characterized by the presence of multiple smooth-muscle nodules that are often located in the lung, lymph nodes, or abdomen. Although these lesions are slow growing and asymptomatic and are usually incidentally diagnosed, they may rarely cause debilitating symptoms. Optimal treatment is controversial, but careful follow-up of these patients is recommended because the lesions show a lowgrade clinical malignant behavior although their appearance is benign. We describe here a rare case of pulmonary BML.
{"title":"Benign metastasizing leiomyoma: 'a sheep in wolf's clothing'","authors":"R. Sehgal, A. Maghrabi","doi":"10.12788/J.CMONC.0006","DOIUrl":"https://doi.org/10.12788/J.CMONC.0006","url":null,"abstract":"Benign metastasizing leiomyoma (BML) is a rare entity, of which a small number of cases, about 75 to 120, have been described in the literature since the condition was first described in 1939. It usually affects women of reproductive age with a history of uterine leiomyomatosis who have undergone a hysterectomy. The lung is the most common site of involvement. The pathologic features of this entity are described as having originated from the metastasis of the histologically benign uterine leiomyoma and are an uncommon lesion characterized by the presence of multiple smooth-muscle nodules that are often located in the lung, lymph nodes, or abdomen. Although these lesions are slow growing and asymptomatic and are usually incidentally diagnosed, they may rarely cause debilitating symptoms. Optimal treatment is controversial, but careful follow-up of these patients is recommended because the lesions show a lowgrade clinical malignant behavior although their appearance is benign. We describe here a rare case of pulmonary BML.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"122-125"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. L. Kleynberg, Y. Kabir, Punprapai Boriboonsomsin, Jeffrey M. Miller
A58-year-old man was admitted to hospital with gross hematuria and a history of a prostate nodule that had been unchanged in size over a period of 3 years. A digital rectal examination revealed a nodule, confirmed by pelvic computed tomography and magnetic resonance imaging scans. Microscopic findings from a transrectal ultrasound-guided biopsy of the prostate revealed phyllodes tumor of the prostate and seminal vesicle, with well-differentiated fibrosarcoma and undifferentiated sarcoma. An initial prostate-specific antigen (PSA) value was 2 ng/mL (normal, 4 ng/dL). Over time, the mass grew in size and caused abdominal bloating, bladder outlet obstruction, and kidney failure. A radical prostatectomy was performed and the patient had an uneventful postoperative course. Thereafter, the patient received adjuvant radiation therapy. A few months after surgery, the symptoms worsened and imaging revealed a recurrence and metastasis to his lungs. The patient is currently receiving palliative chemotherapy.
{"title":"Malignant phyllodes tumor of the prostate and seminal vesicle: an unusual presentation","authors":"R. L. Kleynberg, Y. Kabir, Punprapai Boriboonsomsin, Jeffrey M. Miller","doi":"10.12788/J.CMONC.0007","DOIUrl":"https://doi.org/10.12788/J.CMONC.0007","url":null,"abstract":"A58-year-old man was admitted to hospital with gross hematuria and a history of a prostate nodule that had been unchanged in size over a period of 3 years. A digital rectal examination revealed a nodule, confirmed by pelvic computed tomography and magnetic resonance imaging scans. Microscopic findings from a transrectal ultrasound-guided biopsy of the prostate revealed phyllodes tumor of the prostate and seminal vesicle, with well-differentiated fibrosarcoma and undifferentiated sarcoma. An initial prostate-specific antigen (PSA) value was 2 ng/mL (normal, 4 ng/dL). Over time, the mass grew in size and caused abdominal bloating, bladder outlet obstruction, and kidney failure. A radical prostatectomy was performed and the patient had an uneventful postoperative course. Thereafter, the patient received adjuvant radiation therapy. A few months after surgery, the symptoms worsened and imaging revealed a recurrence and metastasis to his lungs. The patient is currently receiving palliative chemotherapy.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"21 1","pages":"126-127"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung cancer is the leading cause of cancer-related mortality among men and women in the United States. Non–small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Most patients with NSCLC present with advanced disease and median overall survival in this incurable setting remain dismal. Accumulating evidence suggests that both histology and molecular signature have prognostic and predictive value for NSCLC. Recent advances in the molecular characterization of NSCLC tumors have made individualized treatment approaches feasible. Personalized chemotherapy and targeted biological therapy based on a tumor’s individual biologic and molecular profile can optimize efficacy while minimizing toxicity. Molecular testing for activating mutations in the epidermal growth factor receptor (EGFR) domain and EML4-ALK translocation are routinely used to guide therapeutic decisions. Several new treatments that irreversibly target EGFR family members are in development for patients with NSCLC. Novel EML4-ALK inhibitors such as LDK378 are promising agents with encouraging early efficacy data. KRAS mutations are the most common mutation in adenocarcinomas. Although no agents for this subset of NSCLC have been approved, there are several agents in clinical development, including selumetinib, an MEK inhibitor, that seem promising. A growing body of evidence suggests that NSCLC is subject to immune surveillance. Immunotherapeutic interventions, including vaccine therapy and antigen-independent immunomodulatory strategies, may improve outcomes in NSCLC. In this review, we summarize recent advances in non–small-cell lung cancer, with an emphasis on investigational strategies for individualized treatment.
{"title":"Recent advances in the management of advanced non–small-cell lung cancer","authors":"C. Aggarwal, C. Langer","doi":"10.12788/j.cmonc.0005","DOIUrl":"https://doi.org/10.12788/j.cmonc.0005","url":null,"abstract":"Lung cancer is the leading cause of cancer-related mortality among men and women in the United States. Non–small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Most patients with NSCLC present with advanced disease and median overall survival in this incurable setting remain dismal. Accumulating evidence suggests that both histology and molecular signature have prognostic and predictive value for NSCLC. Recent advances in the molecular characterization of NSCLC tumors have made individualized treatment approaches feasible. Personalized chemotherapy and targeted biological therapy based on a tumor’s individual biologic and molecular profile can optimize efficacy while minimizing toxicity. Molecular testing for activating mutations in the epidermal growth factor receptor (EGFR) domain and EML4-ALK translocation are routinely used to guide therapeutic decisions. Several new treatments that irreversibly target EGFR family members are in development for patients with NSCLC. Novel EML4-ALK inhibitors such as LDK378 are promising agents with encouraging early efficacy data. KRAS mutations are the most common mutation in adenocarcinomas. Although no agents for this subset of NSCLC have been approved, there are several agents in clinical development, including selumetinib, an MEK inhibitor, that seem promising. A growing body of evidence suggests that NSCLC is subject to immune surveillance. Immunotherapeutic interventions, including vaccine therapy and antigen-independent immunomodulatory strategies, may improve outcomes in NSCLC. In this review, we summarize recent advances in non–small-cell lung cancer, with an emphasis on investigational strategies for individualized treatment.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"109-114"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66797708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Applied molecular profiling is a method for helping clinicians select the most appropriate therapy for a patient with cancer by determining the level of gene and/or protein expression within the cancer and comparing that expression pattern with the expression profiles of cancers with known outcomes. This approach facilitates the development and selection of tumor-specific therapies based on the identification of biomarkers within a tumor. Molecular characterization techniques such as immunohistochemistry, microarray analysis, and fluorescence in situ hybridization have facilitated identification and validation of a number of important solid tumor biomarkers, including HER2/neu, EGFR, EML4/ALK, and KIT, and can also be used to identify biomarkers (eg, BCR-ABL, CD20, CD30) in various hematologic malignancies. It is of note that molecular profiling can be used to identify targets in tumors for which a therapeutic agent may already be available, thus avoiding the administration of an unproven investigational agent. As the field of molecular profiling continues to evolve and next-generation techniques such as exome sequencing – sequencing 1% of the genome – and whole gene sequencing gain currency, biomarker identification and analysis will become less expensive and more efficient, and possibly allow for a pathway-oriented approach to treatment selection. Wider acceptance and use of molecular profiling should therefore help practicing physicians and oncology researchers keep pace with advances in the understanding of oncogenic expression in various malignancies and encourage the use of molecular profiling in earlier stages of cancer rather than as an option of last resort.
{"title":"Applied molecular profiling: evidence-based decision-making for anticancer therapy","authors":"G. Weiss","doi":"10.12788/J.CMONC.0004","DOIUrl":"https://doi.org/10.12788/J.CMONC.0004","url":null,"abstract":"Applied molecular profiling is a method for helping clinicians select the most appropriate therapy for a patient with cancer by determining the level of gene and/or protein expression within the cancer and comparing that expression pattern with the expression profiles of cancers with known outcomes. This approach facilitates the development and selection of tumor-specific therapies based on the identification of biomarkers within a tumor. Molecular characterization techniques such as immunohistochemistry, microarray analysis, and fluorescence in situ hybridization have facilitated identification and validation of a number of important solid tumor biomarkers, including HER2/neu, EGFR, EML4/ALK, and KIT, and can also be used to identify biomarkers (eg, BCR-ABL, CD20, CD30) in various hematologic malignancies. It is of note that molecular profiling can be used to identify targets in tumors for which a therapeutic agent may already be available, thus avoiding the administration of an unproven investigational agent. As the field of molecular profiling continues to evolve and next-generation techniques such as exome sequencing – sequencing 1% of the genome – and whole gene sequencing gain currency, biomarker identification and analysis will become less expensive and more efficient, and possibly allow for a pathway-oriented approach to treatment selection. Wider acceptance and use of molecular profiling should therefore help practicing physicians and oncology researchers keep pace with advances in the understanding of oncogenic expression in various malignancies and encourage the use of molecular profiling in earlier stages of cancer rather than as an option of last resort.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"115-121"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66796966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bosutinib finds its place in the CML treatment paradigm","authors":"M. Deininger","doi":"10.12788/J.CMONC.0002","DOIUrl":"https://doi.org/10.12788/J.CMONC.0002","url":null,"abstract":"","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"103-104"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66796846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bosutinib was recently approved for the treatment of chronic phase (CP), accelerated phase (AP), or blast phase (BP) Philadelphia chromosomepositive (Ph ) chronic myeloid leukemia (CML) in adult patients with resistance or intolerance to prior therapy. The approval was based on findings in a combined phase 1/2 single-arm trial. The recently reported phase 3 BELA trial compared bosutinib and imatinib as first-line treatments in patients with CP CML and reported no difference in complete cytogenetic response (CCyR) rates at 1 year, but improved major molecular response (MMR) rate and time to response, as well as a distinct safety profile. Bosutinib is an oral dual SRC/ABL kinase inhibitor that is active against many BCR-ABL mutations associated with imatinib resistance (with the exception of T315I and V299L) and that has reduced activity against nonspecific molecular targets (eg, c-KIT and plateletderived growth factor receptor) associated with toxicities reported for other second-generation tyrosine kinase inhibitors (TKIs). CML is characterized by a constitutively active BCR-ABL fusion protein, and SRC-family kinases have a critical role in cell adhesion, invasion, proliferation, survival, and angiogenesis. Bosutinib has been found to inhibit growth of experimental tumors that express several imatinib-resistant forms of BCR-ABL.
{"title":"Bosutinib in previously treated CML and in first-line comparison with imatinib","authors":"J. Abraham","doi":"10.12788/j.cmonc.0003","DOIUrl":"https://doi.org/10.12788/j.cmonc.0003","url":null,"abstract":"Bosutinib was recently approved for the treatment of chronic phase (CP), accelerated phase (AP), or blast phase (BP) Philadelphia chromosomepositive (Ph ) chronic myeloid leukemia (CML) in adult patients with resistance or intolerance to prior therapy. The approval was based on findings in a combined phase 1/2 single-arm trial. The recently reported phase 3 BELA trial compared bosutinib and imatinib as first-line treatments in patients with CP CML and reported no difference in complete cytogenetic response (CCyR) rates at 1 year, but improved major molecular response (MMR) rate and time to response, as well as a distinct safety profile. Bosutinib is an oral dual SRC/ABL kinase inhibitor that is active against many BCR-ABL mutations associated with imatinib resistance (with the exception of T315I and V299L) and that has reduced activity against nonspecific molecular targets (eg, c-KIT and plateletderived growth factor receptor) associated with toxicities reported for other second-generation tyrosine kinase inhibitors (TKIs). CML is characterized by a constitutively active BCR-ABL fusion protein, and SRC-family kinases have a critical role in cell adhesion, invasion, proliferation, survival, and angiogenesis. Bosutinib has been found to inhibit growth of experimental tumors that express several imatinib-resistant forms of BCR-ABL.","PeriodicalId":72649,"journal":{"name":"Community oncology","volume":"10 1","pages":"105-108"},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66796885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：