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Japanese Journal of Clinical Oncology Mar 2020Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens... (Review)
Review
Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens are being developed based on the predicted sensitivity for specific breast cancer histological types. Systemic therapy is selected according to recurrence risk, with the treatment for low-risk patients being de-escalated, while high-risk patients receive aggressive systemic treatment with an adequate dose and duration. Neoadjuvant systemic therapy has a different aim. The efficacy of systemic therapies, based on the sensitivities to drugs, is supported by improvements in the rate of breast-conserving therapy. The response to neoadjuvant systemic therapy is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers unique to individual patients allow appropriate targeted therapy, which can achieve optimal efficacy.
Topics: Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Neoadjuvant Therapy
PubMed: 32147701
DOI: 10.1093/jjco/hyz213 -
Nature Reviews. Clinical Oncology Sep 2021The treatment goal for patients with early-stage lung cancer is cure. Multidisciplinary discussions of surgical resectability and medical operability determine the... (Review)
Review
The treatment goal for patients with early-stage lung cancer is cure. Multidisciplinary discussions of surgical resectability and medical operability determine the modality of definitive local treatment (surgery or radiotherapy) and the associated systemic therapies to further improve the likelihood of cure. Trial evidence supports cisplatin-based adjuvant therapy either after surgical resection or concurrently with radiotherapy. Consensus guidelines support neoadjuvant chemotherapy in lieu of adjuvant chemotherapy and carboplatin-based regimens for patients who are ineligible for cisplatin. The incorporation of newer agents, now standard for patients with stage IV lung cancer, into the curative therapy paradigm has lagged owing to inefficient trial designs, the lengthy follow-up needed to assess survival end points and a developmental focus on the advanced-stage disease setting. Surrogate end points, such as pathological response, are being studied and might shorten trial durations. In 2018, the anti-PD-L1 antibody durvalumab was approved for patients with stage III lung cancer after concurrent chemoradiotherapy. Since then, the study of targeted therapies and immunotherapies in patients with early-stage lung cancer has rapidly expanded. In this Review, we present the current considerations in the treatment of patients with early-stage lung cancer and explore the current and future state of clinical research to develop systemic therapies for non-metastatic lung cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Lung Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Therapies, Investigational
PubMed: 33911215
DOI: 10.1038/s41571-021-00501-4 -
Drug Design, Development and Therapy 2020Neoadjuvant chemotherapy is increasingly used in breast cancer, especially for downstaging the primary tumor in the breast and the metastatic axillary lymph node.... (Review)
Review
Neoadjuvant chemotherapy is increasingly used in breast cancer, especially for downstaging the primary tumor in the breast and the metastatic axillary lymph node. Accurate evaluations of the response to neoadjuvant chemotherapy provide important information on the impact of systemic therapies on breast cancer biology, prognosis, and guidance for further therapy. Moreover, pathologic complete response is a validated and valuable surrogate prognostic factor of survival after therapy. Evaluations of neoadjuvant chemotherapy response are very important in clinical work and basic research. In this review, we will elaborate on evaluations of the efficacy of neoadjuvant chemotherapy in breast cancer and provide a clinical evaluation procedure for neoadjuvant chemotherapy.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Neoadjuvant Therapy
PubMed: 32606609
DOI: 10.2147/DDDT.S253961 -
Cells Nov 2022As the most dangerous tumors, brain tumors are usually treated with surgical removal, radiation therapy, and chemotherapy. However, due to the aggressive growth of... (Review)
Review
As the most dangerous tumors, brain tumors are usually treated with surgical removal, radiation therapy, and chemotherapy. However, due to the aggressive growth of gliomas and their resistance to conventional chemoradiotherapy, it is difficult to cure brain tumors by conventional means. In addition, the higher dose requirement of chemotherapeutic drugs caused by the blood-brain barrier (BBB) and the untargeted nature of the drug inevitably leads to low efficacy and systemic toxicity of chemotherapy. In recent years, nanodrug carriers have attracted extensive attention because of their superior drug transport capacity and easy-to-control properties. This review systematically summarizes the major strategies of novel nano-drug delivery systems for the treatment of brain tumors in recent years that cross the BBB and enhance brain targeting, and compares the advantages and disadvantages of several strategies.
Topics: Humans; Nanoparticle Drug Delivery System; Antineoplastic Agents; Brain Neoplasms; Glioma; Blood-Brain Barrier
PubMed: 36497021
DOI: 10.3390/cells11233761 -
ESMO Open Aug 2021Primary diffuse large B-cell (DLBCL) lymphoma of the central nervous system (CNS) (PCNSL) is a new lymphoma entity, recognized by the 2017 WHO classification of... (Review)
Review
Primary diffuse large B-cell (DLBCL) lymphoma of the central nervous system (CNS) (PCNSL) is a new lymphoma entity, recognized by the 2017 WHO classification of hematopoietic and lymphoid tumors. Unlike systemic DLBCL, the use of anthracycline-based chemotherapy combinations is associated with disappointing outcomes, due to low CNS bioavailability of related drugs. Therefore, international researchers investigated alternative strategies, mostly including drugs able to cross the blood-brain-barrier at low or high doses, with a progressive improvement in survival. Some effective chemotherapy combinations of high-dose methotrexate (HD-MTX) with alkylating agents and rituximab with or without cytarabine have been tested in international randomized trials and represent the induction treatment in everyday practice, with some variations among different geographical areas. In patients aged 70 years or younger, MATRix (HD-MTX/cytarabine/thiotepa/rituximab) chemotherapy followed by consolidative high-dose chemotherapy plus autologous stem cell transplantation or whole-brain irradiation has been associated with a significant improvement in overall survival. Other treatment options, such as non-myeloablative high-dose chemotherapy, oral drug maintenance, and some targeted drugs like ibrutinib or lenalidomide, are being tested in high-level international trials. These steps toward further effective treatments are motivated by an incessant search for less neurotoxic options. Thanks to international cooperation, we can affirm that PCNSL is a potentially curable tumor, especially in young patients. However, several questions remain unanswered: the optimal treatment for elderly patients as well as the management of intraocular and meningeal disease require further scientific efforts. Beside treatments, advances on molecular and radiological diagnostic tools will increase our knowledge of this disease, allowing the possibility to anticipate diagnosis and to better categorize patients' responses. This article analyzes the available literature in this setting and provides evidence-based recommendations for the management of PCNSL patients.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Large B-Cell, Diffuse; Transplantation, Autologous
PubMed: 34271311
DOI: 10.1016/j.esmoop.2021.100213 -
Breast (Edinburgh, Scotland) Mar 2022The availability of HER2-targeted therapy has dramatically improved patient outcome in HER2-positive (HER2+) early breast cancer (EBC) as recently demonstrated by the... (Meta-Analysis)
Meta-Analysis
The availability of HER2-targeted therapy has dramatically improved patient outcome in HER2-positive (HER2+) early breast cancer (EBC) as recently demonstrated by the EBCTCTG metaanalysis on trastuzumab in HER2+ EBC: Adding trastuzumab to chemotherapy has reduced recurrence rates and breast-cancer related mortality by a third [1]. Today, neoadjuvant therapy has become standard of care for women with stage II or III tumors as pathological complete response (pCR) status after surgery can be used to individualize adjuvant systemic therapy. pCR is correlated with favorable patient outcome, particularly in hormone receptor (HR) negative HER2+ EBC, as demonstrated by the FDA meta-analysis. Moreover, for patients with non-pCR, 14 cycles of adjuvant T-DM1 have become a new adjuvant therapy standard based on the results of the KATHERINE trial. Primary surgery can be offered to patients with low tumor burden (cN0 cT1). For this low-risk subgroup, 12 weeks of adjuvant paclitaxel + trastuzumab for one year are correlated with excellent outcome based on the APT trial results. A multidisciplinary team is essential right from the beginning for optimal locoregional and systemic therapy in such a complex neoadjuvant - adjuvant continuum of care. Clinical trials in HER2+ EBC are currently evaluating further therapy de-escalation in low-risk disease or patients with pCR whereas for patients with non-pCR, escalation trials are also ongoing. Newly approved drugs for HER2+ MBC like tucatinib or trastuzumab-deruxtecan or even immunotherapy combinations are being evaluated to improve upon efficacy of T-DM1 alone in the non-pCR setting. Regarding de-escalation, the WSG ADAPT trial demonstrated feasibility of avoiding overtreatment and individualizing neoadjuvant therapy without compromising outcome. Further de-escalation trials (e.g. DECRESCENDO, COMPASS-HER2) are currently ongoing.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Neoadjuvant Therapy; Paclitaxel; Receptor, ErbB-2; Trastuzumab
PubMed: 35148934
DOI: 10.1016/j.breast.2022.01.006 -
Current Treatment Options in Oncology Dec 2022Improvements in systemic therapy in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have improved patient outcomes and reduced the... (Review)
Review
Improvements in systemic therapy in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have improved patient outcomes and reduced the incidence of CNS relapse. However, management of patients with CNS disease remains challenging, and relapses in the CNS can be difficult to salvage. In addition to treatment with CNS-penetrant systemic therapy (high-dose methotrexate and cytarabine), intrathecal prophylaxis is indicated in all patients with ALL, however is not uniformly administered in patients with AML without high-risk features. There is a limited role for radiation treatment in CNS prophylaxis; however, radiation should be considered for consolidative treatment in patients with CNS disease, or as an option for palliation of symptoms. Re-examining the role of established treatment paradigms and investigating the role of radiation as bridging therapy in the era of cellular therapy, particularly in chemotherapy refractory patients, is warranted.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Cytarabine; Methotrexate; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Myeloid, Acute; Central Nervous System; Central Nervous System Neoplasms
PubMed: 36510037
DOI: 10.1007/s11864-022-01032-5 -
International Journal of Molecular... Feb 2022In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth... (Review)
Review
In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.
Topics: Breast Neoplasms; Cell Proliferation; Female; Humans; Immunotherapy; Molecular Targeted Therapy; Receptors, Steroid
PubMed: 35216405
DOI: 10.3390/ijms23042288 -
Theranostics 2022Skin diseases are the fourth leading cause of nonfatal and chronic skin diseases, acting as a global burden and affecting the world economy. Skin diseases severely... (Review)
Review
Skin diseases are the fourth leading cause of nonfatal and chronic skin diseases, acting as a global burden and affecting the world economy. Skin diseases severely impact the patients' quality of life and have influenced their physical and mental state. Treatment of these skin disorders with conventional methods shows a lack of therapeutic efficacy, long treatment duration, recurrence of the condition, and systemic side effects due to improper drug delivery. However, these pitfalls can be overcome with the applications of advanced nanocarrier- and microneedle (MN)-based transdermal drug delivery strategies that provide efficient site-specific drug delivery at the target site. These advanced transdermal drug delivery strategies can be more effective than other drug administration routes by avoiding first-pass metabolism, enhancing the drug concentration in local skin lesions, and reducing systemic toxicity. Compared with traditional transdermal delivery methods, nanocarrier- or MN-based drug delivery systems are painless, noninvasive, or minimum-invasive and require no expensive equipment. More importantly, they can introduce more advanced functions, including increased skin penetration efficiency, controlled drug release rates, enhanced targeting abilities, and theranostic functions. Here, the emergence of versatile advanced transdermal drug delivery systems for the transdermal delivery of various drugs is reviewed, focusing on the design principles, advantages, and considerations of nanocarrier- and MN-based transdermal drug delivery strategies and their applications in treating diverse skin diseases, including psoriasis, dermatitis, melanoma, and other skin diseases. Moreover, the prospects and challenges of advanced transdermal delivery strategies for treating dermatological disorders are summarized.
Topics: Administration, Cutaneous; Drug Delivery Systems; Humans; Needles; Pharmaceutical Preparations; Quality of Life; Skin; Skin Diseases
PubMed: 35547773
DOI: 10.7150/thno.69999 -
Clinical Cancer Research : An Official... Jun 2020While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional...
PURPOSE
While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known.
EXPERIMENTAL DESIGN
PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. HRs, with 95% probability intervals (PI), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piece-wise exponential proportional hazards hierarchical models including pCR as predictor.
RESULTS
Overall, 52 of 3,209 publications met inclusion criteria, totaling 27,895 patients. Patients with a pCR after NAT had significantly better EFS (HR = 0.31; 95% PI, 0.24-0.39), particularly for triple-negative (HR = 0.18; 95% PI, 0.10-0.31) and HER2 (HR = 0.32; 95% PI, 0.21-0.47) disease. Similarly, pCR after NAT was also associated with improved survival (HR = 0.22; 95% PI, 0.15-0.30). The association of pCR with improved EFS was similar among patients who received subsequent adjuvant chemotherapy (HR = 0.36; 95% PI, 0.19-0.67) and those without adjuvant chemotherapy (HR = 0.36; 95% PI, 0.27-0.54), with no significant difference between the two groups ( = 0.60).
CONCLUSIONS
Achieving pCR following NAT is associated with significantly better EFS and OS, particularly for triple-negative and HER2 breast cancer. The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR likely reflects tumor biology and systemic clearance of micrometastatic disease, highlighting the potential of escalation/deescalation strategies in the adjuvant setting based on neoadjuvant response..
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local
PubMed: 32046998
DOI: 10.1158/1078-0432.CCR-19-3492