scholarly journals Modern combined targeted and immunotherapy of metastatic skin melanoma

2020 ◽  
pp. 54-61
Author(s):  
S. A. Protsenko ◽  
E. N. Imyanitov ◽  
A. I. Semenova ◽  
D. Kh. Latipova ◽  
A. V. Novik ◽  
...  
Keyword(s):  
Treatment Options ◽  
Survival Rates ◽  
New Drugs ◽  
Phase Iii ◽  
Immune Checkpoints ◽  
Malignant Neoplasms ◽  
Skin Melanoma ◽  
Clinical Prognosis ◽  
New Treatment

Melanoma of the skin is one of the most aggressive malignant neoplasms. Metastatic skin melanoma has an extremely poor clinical prognosis with a high mortality rate, accounting for 80% of all deaths from skin malignancies. The approaches to the treatment of metastatic skin melanoma have been dynamically developing over the past decade. New drugs and their combinations are becoming more affordable. In connection with the advances in molecular genetics and the development of new targeted drugs, treatment outcomes have significantly improved: first of all, overall survival and the time to progression of the disease, which has set new challenges for continuing research in this area. The development of new treatment options for patients with inoperable and/or metastatic melanoma with a mutation in the BRAFV600 gene is still in high demand. Emerging data from clinical and preclinical studies suggest that synergies can be observed between inhibitors of immune checkpoints and inhibitors of BRAF and MEK. Despite the fact that inhibitors of the BRAF signaling pathway have a high frequency of objective responses, in most cases their duration is short. Inhibitors of immune checkpoints provide a longer lasting effect, but the response rate is relatively low. Combining the two types of therapy can improve survival rates over the long term. This review demonstrates the results of phase III randomized trials that have allowed to determine the current standards in the treatment of metastatic skin melanoma. We also demonstrated our own experience of using a triple combination of targeted therapy with BRAF/MEK inhibitors in combination with PD-1 inhibitors.

scholarly journals The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast Cancer: A Review

2021 ◽  
Author(s):  
Panneerselvam Theivendren ◽  
Selvaraj Kunjiappan ◽  
Yashoda Mariappa Hegde ◽  
Kaveena Ravi ◽  
Sivakumar Vellaichamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Survival Rates ◽  
Drug Repurposing ◽  
Current Treatment ◽  
New Drugs ◽  
Health Concern ◽  
Drug Resistant ◽  
The Future ◽  
New Treatment

Breast cancer is a major health concern as it is the second leading cause of death from cancer. There are several well-known risk factors that contribute to breast cancer. Despite the various treatment options available, complete cure is still difficult due to heterogenicity of BC subtypes. As a result, identifying BC subtypes is critical for determining the optimal treatment approach. Over the last several years, new drugs targeting particular therapeutic targets have resulted in significant advances in the treatment of breast cancer. Nonetheless, resistance to treatment is the “major” issue, and a significant increase in survival rates has been the main focus for researchers. The purpose of this review article is to provide a broad overview of the molecular basis of drug resistance in breast cancer, as well as a detailed assessment of current treatment options, potential new treatment methods for drug-resistant breast cancer and repurposed drugs used for treatment. The possibility of non-cancer drugs being studied for breast cancer in the future, as well as the obstacles and bottlenecks of drug repurposing, is also highlighted. Finally, we go through present problems and future prospects in drug-resistant breast cancer therapy.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

scholarly journals Risk of developing second malignant neoplasms in patients with neuroblastoma: a population study of the US SEER database

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Hongnan Zhen ◽  
Hui Guan ◽  
Jiabin Ma ◽  
Wenhui Wang ◽  
Shen Jing ◽  
...  
Keyword(s):  
Risk Factor ◽  
Digestive System ◽  
Survival Rates ◽  
Endocrine System ◽  
Malignant Neoplasms ◽  
Seer Database ◽  
The Us ◽  
Second Malignant Neoplasms ◽  
Risk Patients

Abstract Background Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs). Methods The SEER 18 Regs (1973–2015) and SEER 9 Regs (1973–2015) data of the surveillance, epidemiology, and end results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis. Results The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR = 4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR = 7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR = 2.138, 95% CI = 1.634–2.797, p < 0.001) was the only independent risk factor for developing SMNs. Conclusion This study identifies the risk factor for developing SMNs in patients with neuroblastoma, which could facilitate individualized screening for high-risk patients, to allow early diagnosis and treatment of SMNs.

scholarly journals Use of immuno-oncology in melanoma

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
M.G. Smylie
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Treatment Options ◽  
Survival Rates ◽  
Interleukin 2 ◽  
Immune Checkpoints ◽  
Immune Detection ◽  
The U.S ◽  
Made In

Treatment options for patients with metastatic melanoma have expanded rapidly since the approval of ipilimumab by the U.S. Food and Drug Administration in 2011. Cytokines such as interferon and interleukin-2 were approved in 1995 and 1998 respectively. However, the effect on survival was marginal, and the toxicity, substantial. Multiple vaccine studies likewise failed to show improvements in survival. The “Holy Grail” came with the discovery of immune checkpoints, and the first metastatic melanoma trial to show an improvement in overall survival involved the use of an immune checkpoint inhibitor against ctla-4: ipilimumab. Since then, the field of immuno-oncology has exploded, with approvals for PD-1 inhibitors and discovery, in clinical trials, of several novel checkpoints such as tim-3, lag-3, and others. In fact more than 950 novel immunotherapy drugs are currently being trialled. Recently, combinations of ctla-4 and PD-1 inhibitors have been associated with 1-year survival rates exceeding 80% and 4-year survival rates greater than 50%. In no tumour has as much progress been made in the last 5 years as in melanoma, and the efforts to unravel and exploit mechanisms used by the tumour to avoid immune detection are just beginning.

scholarly journals How I treat relapsed acute lymphoblastic leukemia in the pediatric population

Blood ◽  
2020 ◽  
Vol 136 (16) ◽  
pp. 1803-1812 ◽  
Author(s):  
Stephen P. Hunger ◽  
Elizabeth A. Raetz
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Survival Rates ◽  
Treatment Decision ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
The Past

Abstract Relapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children, with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only ∼50% of children with first relapse of ALL survive long term, and outcomes are much worse with second or later relapses. Recurrences that occur within 3 years of diagnosis and any T-ALL relapses are particularly difficult to salvage. Until recently, treatment options were limited to intensive cytotoxic chemotherapy with or without site-directed radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). In the past decade, several promising immunotherapeutics have been developed, changing the treatment landscape for children with relapsed ALL. Current research in this field is focusing on how to best incorporate immunotherapeutics into salvage regimens and investigate long-term survival and side effects, and when these might replace HSCT. As more knowledge is gained about the biology of relapse through comprehensive genomic profiling, incorporation of molecularly targeted therapies is another area of active investigation. These advances in treatment offer real promise for less toxic and more effective therapy for children with relapsed ALL, and we present several cases highlighting contemporary treatment decision-making.

A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA5002-LBA5002 ◽  
Author(s):  
Howard M. Sandler ◽  
Chen Hu ◽  
Seth A. Rosenthal ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Current Standard ◽  
T Stage

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.

scholarly journals New Treatment Options for Chronic Constipation: Mechanisms, Efficacy and Safety

2011 ◽  
Vol 25 (suppl b) ◽  
pp. 29B-35B ◽  
Author(s):  
Michael Camilleri
Keyword(s):  
Bile Acid ◽  
Serotonin Receptor ◽  
Treatment Options ◽  
Chloride Ion ◽  
New Drugs ◽  
Receptor Subtype ◽  
Efficacy And Safety ◽  
Guanylate Cyclase C ◽  
Patient Responsiveness ◽  
New Treatment

The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes.

Immunotherapy of multiple sclerosis

2009 ◽  
Vol 21 (S2) ◽  
pp. 27-34 ◽  
Author(s):  
Sven G. Meuth ◽  
Stefan Bittner ◽  
Heinz Wiendl
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Evidence ◽  
Treatment Options ◽  
Phase Iii ◽  
The Past ◽  
Phase Iii Clinical Trials ◽  
New Treatment ◽  
System Disorder ◽  
Immunomodulatory Therapies ◽  
Ms Therapy

Abstract:Multiple sclerosis (MS) is regarded as a prototypic inflammatory autoimmune central nervous system disorder causing neurological disability in young adults. Recommended basic immunomodulatory therapies of MS are currently interferon beta and glatiramer acetate. Both have proven to be clinically and paraclinically effective and clinical evidence suggests that treatment should be initiated as early as possible.However, despite the fact that therapeutic options for MS have significantly been widened over the past decade there is still tremendous activity in the search for new treatment options for MS.One important development in the field is reflected by the substantial number of promising results for oral therapies. Various phase III clinical trials are currently being initiated or are already underway evaluating the efficacy of a variety of orally administered agents, including cladribine, teriflunomide, laquinimod, fingolimod and fumaric acid. It is hoped that these oral therapies for MS further broaden our armament for MS therapy.

New advances in the diagnosis and management of hepatocellular carcinoma

BMJ ◽  
2020 ◽  
pp. m3544 ◽  
Author(s):  
Ju Dong Yang ◽  
Julie K Heimbach
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Early Stage ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Long Term Outcomes ◽  
Stage Disease

ABSTRACT Hepatocellular carcinoma is one of the leading causes of cancer related death in the world. Biannual surveillance for the disease in patients with cirrhosis and in high risk carriers of hepatitis B virus allows early stage cancer detection and treatment with good long term outcomes. Liver ultrasonography and serum α fetoprotein are the most commonly used surveillance tests. If suspicious results are found on the surveillance test, multiphasic computed tomography or magnetic resonance imaging should be undertaken to confirm the diagnosis of hepatocellular carcinoma. If radiologic tests show inconclusive results, liver biopsy or repeat imaging could be considered for confirmation of hepatocellular carcinoma. Management of the disease is complex. Patients should be evaluated by a multidisciplinary team, and the selection of treatment should consider factors such as tumor burden, severity of liver dysfunction, medical comorbidities, local expertise, and preference of patients. Early stage hepatocellular carcinoma is best managed by curative treatment, which includes resection, ablation, or transplantation. Patients with intermediate stage disease often receive locoregional treatment. Systemic treatment is reserved for patients with advanced disease. Several positive, phase III, randomized controlled trials have expanded the systemic treatment options for advanced hepatocellular carcinoma with promising long term outcomes, especially trials using combination treatments, which could also have eventual implications for the treatment of earlier stage disease.

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