自引率: 1.6%
被引量: 4549
通过率: 暂无数据
审稿周期: 2
版面费用: 暂无数据
国人发稿量: 8
投稿须知/期刊简介:
The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist toxicologist pharmacist pharmacologist biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents. Each issue contains original articles dealing with anticancer drug development. Other sections are devoted to invited review articles and letters to the editor. The journal also affords the opportunity to publish the proceedings of special workshops and symposia devoted to the development of new anticancer agents. Provided they add to the understanding of the investigational agents the journal is not adverse to publishing clinical trials with negative results. Investigational New Drugs cuts across all the usual lines or subdisciplines providing a locus for the presentation of relevant investigations and the discussion of critical questions appropriate to the entire field of new anticancer drug development.
期刊描述简介:
The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist toxicologist pharmacist pharmacologist biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents. Each issue contains original articles dealing with anticancer drug development. Other sections are devoted to invited review articles and letters to the editor. The journal also affords the opportunity to publish the proceedings of special workshops and symposia devoted to the development of new anticancer agents. Provided they add to the understanding of the investigational agents the journal is not adverse to publishing clinical trials with negative results. Investigational New Drugs cuts across all the usual lines or subdisciplines providing a locus for the presentation of relevant investigations and the discussion of critical questions appropriate to the entire field of new anticancer drug development.
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Neoadjuvant immunochemotherapy in locally advanced laryngeal cancer and hypopharyngeal cancer: higher objective response rate and organ-preservation rate.
This study retrospectively analyzed the curative effect of neoadjuvant PD-1 inhibitors combined with chemotherapy of locally advanced laryngeal and hypopharyngeal cancer and compared with chemotherapy plus EGFR inhibitors and chemotherapy alone. From January 1 2018 to October 1 2023, a total of 113 patients in Beijing Tongren Hospital, who were diagnosed with locally advanced laryngeal cancer and hypopharyngeal cancer and received neoadjuvant immunochemotherapy, were enrolled. The primary outcome measures included objective response rate, organ-preservation rate, downstaging rate, and overall survival. Of 113 patients, including 34 patients were given immunochemotherapy, 38 patients chemotherapy plus EGFR inhibitor, and 41 patients chemotherapy. Most were male, and the median follow-up time in the immunochemotherapy group was 12 months. Neoadjuvant immunochemotherapy could improve the objective response rate (88.2%, p < 0.05), downstaging rate (79.41%, p < 0.05), and organ-preservation rate (97.1%, p < 0.05). However, compared with chemotherapy and chemotherapy plus EGFR inhibitors, immunochemotherapy did not significantly improve patients' 1-year and 2-year survival rates. Neoadjuvant PD-1 inhibitor combined with chemotherapy could improve the objective response rate, downstaging rate, and organ-preservation rate in patients with locally advanced laryngeal and hypopharyngeal cancer. Our study showed that this treatment regimen could more effectively protect the laryngeal function of patients. It provided a new treatment mode for patients with a strong desire to preserve the larynx. Further prospective studies are needed to confirm this conclusion.
被引量：- 发表：1970
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Predictive value of ZFHX4 mutation for the efficacy of immune checkpoint inhibitors in non-small cell lung cancer and melanoma.
Studies have shown that the Zinc finger homeobox 4 (ZFHX4) might be a factor in the prognosis of malignancies. However, little is known about the association between the ZFHX4 mutation and the effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and melanoma. Three public ICIs-treated NSCLC cohorts were divided into discovery cohort (n=75) and validation cohort (n=62), which were used to evaluate the relationship between ZFHX4 mutation and ICIs effectiveness in NSCLC. Seven ICIs-treated melanoma cohorts (n = 418) were used to analyze the relationship between ZFHX4 mutation and immunotherapy efficacy in melanoma. NSCLC and skin cutaneous melanoma (SKCM) cohorts from The Cancer Genome Atlas (TCGA) were used to investigate underlying mechanism. Patients with ZFHX4 mutant-type (ZFHX4-Mut) showed a superior objective response rate (ORR) (P < 0.01) and longer progression-free survival (PFS) (P < 0.05) than patients with ZFHX4 wild-type (ZFHX4-WT) in NSCLC cohorts. In the melanoma cohorts, patients carrying ZFHX4-Mut had a higher ORR (P = 0.042) and longer overall survival (OS) (P = 0.011). Besides, patients with NSCLC and melanoma harboring ZFHX4-Mut had a higher tumor mutation burden (TMB) (P<0.001) and tumor neoantigen burden (TNB) (P<0.001) than those harboring ZFHX4-WT. ZFHX4 mutation was associated with higher levels of plasma B cells, activated CD4+ memory T cells, and CD8+ T cells. Seven DNA damage repair pathways were significantly enriched in the ZFHX4-Mut group. ZFHX4 mutation could serve as a predicter for the efficacy of ICIs therapy in NSCLC and melanoma.
被引量：- 发表：1970
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Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.
Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.
被引量：- 发表：1970
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Phase II trial of multi-kinase inhibitor ESK981 in patients with metastatic castration-resistant prostate cancer.
ESK981 is a potent tyrosine kinase and PIKfyve lipid kinase inhibitor. This phase II trial evaluated the efficacy of ESK981 as a single agent in patients with androgen receptor-positive (AR +) metastatic castration-resistant prostate cancer (mCRPC). Eligible patients had mCRPC with progression on AR-targeted agents and without prior chemotherapy treatment. Each patient received 160 mg ESK981 once daily for 5 days per week for 4 weeks per cycle (except for an adverse event (AE) occurrence). The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included the time and the duration of PSA response, PSA progression rates, PSA progression free survival (PFS) and overall survival (OS). Exploratory investigations included whole exome sequencing in patients before treatment, and morphological evaluation of biopsy samples pre- and post-treatment. PSA was evaluated in 13 patients. Only one patient (7.7% two-sided 95% Wilson CI (0.4%, 33.3%)) experienced a reduction in their PSA levels by 50% or more. The most common grade 3 treatment-related AEs were cardiac disorders, diarrhea, hypertension, alanine transaminase and aspartate transaminase elevations. No grade 4-5 events occurred. Median PFS was 1.8 months, and median OS was 12.1 months. Peripheral immune cells showed increased T cell activation and cytokine production in two patients who received 12-weeks of ESK981. Although relatively well tolerated, ESK981 alone showed no anti-tumor activity in patients with AR + mCRPC and its further evaluation as a single agent in AR + mCRPC is not warranted. (Trial registration: ClinicalTrials.gov, NCT03456804. Registration date: March 7, 2018).
被引量：1 发表：1970
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Broad-spectrum anti-cancer activity of fused human arginase variants.
The rapid increase in cancer cases worldwide necessitates the development of novel therapeutic approaches. Therapies targeting cancer's altered metabolism, especially those that deplete critical amino acids, have emerged as promising ones, some of which are already being used in clinical practice and many others are under development. This study reports the anti-cancer activity of two novel fused human arginase I (FHA) variants, FHA-3 and FHA-12, assessed using the NCI-60 human tumor cell line panel. Both variants have demonstrated a range of potencies in a single-dose assay (10 µM), but FHA-3 was found to be more potent with significant growth inhibition in most tested cell lines. To calculate 50% growth inhibition (GI50), FHA-3 was further evaluated in a five-dose assay, where notable anti-cancer activity was observed across the nine cancer types of the NCI-60 panel. Our results demonstrated the broad-spectrum anti-cancer activity of novel FHA variants, with FHA-3 being the most potent. Further studies elucidating its efficacy in animal models will help explore its therapeutic potential.
被引量：- 发表：1970
