CHEMOTHERAPY

Predicting Reprisal of Solid Cancer Treatment and 60-Month Survival after Medical Intensive Care: A Single-Centre Cohort Study
Ferrari V, Morand L, Hyvernat H, Schiappa R, Dellamonica J and Martis N
Our study aimed to identify relevant features associated with the reprisal of antineoplastic treatment in patients with solid cancers after unplanned admittance to the intensive care unit (ICU) and to assess 60th-month survival in patients with solid neoplasms admitted to the ICU.
Importance of Sex-Dependent Differences for Dosing Selection and Optimization of Chemotherapeutic Drugs
Seydoux C, Briki M, Wagner AD, Choong E, Guidi M, Carrara S, Thoma Y, Livio F, Girardin FR, Marzolini C, Buclin T and Decosterd LA
Despite major advances in cancer treatment in the past years, there is a need to optimize chemotherapeutic drug dosing strategies to reduce toxicities, suboptimal responses, and the risk of relapse. Most cancer drugs have a narrow therapeutic index with substantial pharmacokinetics variability. Yet, current dosing approaches do not fully account for the complex pathophysiological characteristics of the patients. In this regard, the effect of sex on anticancer chemotherapeutic drugs' disposition is still underexplored. In this article, we review sex differences in chemotherapeutic drug pharmacokinetics; we suggest a novel approach that integrates sex into the traditional a priori body surface area (BSA) dosing selection model, and finally, we provide an overview of the potential benefits of a broader use of therapeutic drug monitoring (TDM) in oncology.
Phase I Clinical Study of a Multi-Kinase Inhibitor TG02 Capsule for the Treatment of Recurrent High-Grade Gliomas with Failed Temozolomide Treatment in Chinese Patients
Guo CC, Yang QY, Xi SY, Zhou J, Zhou ZH, Cao X, Liao YX, Li BX, Dai XR, Wong M, Li YJ, Yu XH and Chen ZP
We report the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of a multi-kinase inhibitor (TG02 capsule) as a new therapy for patients with recurrent high-grade gliomas in China.
Primary Squamous Cell Carcinoma of the Duodenum: A Case Report and Literature Review
Hui Y, Ke F, Lu W, Qiu W, Zheng X and Cheng H
Duodenal squamous cell carcinoma is an exceedingly rare occurrence among gastrointestinal malignancies, and its diagnosis and treatment are not well understood.
Meta-Analysis of the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced Gastric Cancer and Gastroesophageal Junction Cancer
Yang J, Luo W, Ma X, Cui Y, Xie J, Pan C, Chen Z and Yang S
Pembrolizumab has been approved for the first-line treatment of patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced GC/GEJ still needs to be precisely determined.
Therapeutic Drug Monitoring: A Driver to Precision Medicine for Patients with Hematological Malignancies
Stemler J, Brüggemann RM and de Jonge NA
Targeted therapies have revolutionized the treatment of hematological malignancies, offering improved efficacy with fewer off-target effects compared to traditional chemotherapy. However, significant pharmacokinetic (PK) and pharmacodynamic (PD) variability exists among patients receiving these therapies.
The Impacts of Active and Inactive Ghrelin on Cachexia and Immune Checkpoint Inhibitor Monotherapy in Patients with Non-Small Cell Lung Cancer
Murata D, Azuma K, Nishii Y, Murotani K, Matama G, Kawahara A, Tokito T, Sasada T, Hoshino T and Azuma K
Identifying the underlying mechanisms of immune checkpoint inhibitor resistance in patients with cachexia is a current challenge. Ghrelin is a peptide hormone that plays an important role in the metabolism of patients with cancer cachexia. Despite the importance of ghrelin in cancer cachexia, most previous studies on the subject have not distinguished between the forms of ghrelin.
Disseminated Infection Caused by Nocardia cyriacigeorgica in Immunocompromised Patient Confirmed by Whole Genome Sequencing
Varda Brkić D, Babel J, Budimir A, Butić I, Gužvinec M, Jurić D, Ferenčak I, Bošnjak S and Mareković I
Nocardia spp. is an opportunistic pathogen capable of causing localized and disseminated infections in immunocompromised hosts. It is critical for serious infections to have an early and accurate identification of this pathogen in order to enable timely and focused combination antimicrobial treatment.
Aerobic Exercise Alleviates Doxorubicin-Induced Cardiotoxicity via Inhibition of Ferroptosis
Liu H, Li H, Zhou N, Zhang Y, Gong L, Zhang E and Zhang Y
Doxorubicin (DOX), a potent anthracycline, is widely used in cancer therapy, but its effect is limited by doxorubicin-induced cardiotoxicity (DIC). Increasing evidence suggests that DIC is associated with ferroptosis, a cell death characterized by the iron-dependent accumulation of lipid peroxides. Although aerobic exercise is recommended for chemotherapy-related cardiac dysfunction, the extent to which its protective effects against DIC are mediated through the inhibition of ferroptosis remains largely unclear. The aim of this study was to elucidate the mechanism through which aerobic exercise attenuates DIC and provide theoretical support for promoting scientifically guided exercise in patients with DIC.
Cryoablation Combined with Programmed Cell Death Protein 1 Inhibitor Pembrolizumab for Advanced Non-Small Cell Lung Cancer
Wang L, Yang K, Xie X, Wei H, Wang P, Wang S and Wang P
This study aims to evaluate the efficacy and safety of cryoablation combined with pembrolizumab treatment versus cryoablation alone in patients with advanced non-small cell lung cancer (NSCLC).
Carnitine Levels Decrease during Oxaliplatin Infusion: A Pilot Study
van Geffen LPW, Mols F, Geurts VCM and Vreugdenhil G

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of chemotherapy. Low carnitine levels might negatively affect the development of CIPN. However, little is known of the course of carnitine levels during and directly after chemotherapy administration. Intervention studies using carnitine to prevent CIPN were contradictory, possibly due to different timing and route of carnitine supplementation. Better understanding of carnitine courses might improve future studies. This study aimed to investigate whether oxaliplatin-based chemotherapy administration affects blood and urinary levels of carnitine. We hypothesized that oxaliplatin increases renal excretion of carnitine, thereby causing a carnitine deficiency, which might contribute to the development of CIPN.

Endoplasmic Reticulum Stress Modulates Therapeutic Responses in Hepatocellular Carcinoma
Chen YL, Chou CW, Liu IH, Wu YH and Chen CY
Hepatocellular carcinoma (HCC) is one of the primary types of liver cancer, and the mortality trend of HCC patients is estimated to continue rising in the future. Chemotherapy drugs or targeted therapies are considered primary treatment modalities for intermediate-stage or advanced-stage HCC. Although these drugs can extend the survival rate of HCC patients, prolonged treatment often raises concerns about drug resistance or cancer recurrence, leading to undesirable therapeutic outcomes. Drug treatments generally involve promoting cytotoxicity and inhibiting oncogenic signaling pathways, and the response of cancer cells to drug-induced stress situations may potentially impact the effectiveness of treatment. The unfolded protein response (UPR) acts as a cellular stress response mechanism, activating pathways such as DNA repair and autophagy to help cellular survival when cells are damaged. It has also been shown that under sustained or excessive stress, UPR can control cell fate toward programmed cell death, such as apoptosis. Previous studies have found that activation of UPR plays an essential role in cancer cell growth and drug resistance. Various molecules or signaling pathways regulated by the UPR assist cancer cells in responding to anticancer drugs, enabling their survival during treatment.
Role of a Therapeutic Drug Monitoring-Guided Strategy of Isavuconazole for Optimizing Efficacy/Safety Outcomes in Onco-Hematological Pediatric Patients: A Systematic Review
Gatti M, Cojutti PG and Pea F
Evidence concerning the implementation of a therapeutic drug monitoring (TDM)-guided approach for optimizing isavuconazole exposure in onco-hematological pediatric patients is limited. The aim of this systematic review was to summarize the current evidence about the role that a TDM-guided strategy of isavuconazole may have in optimizing efficacy/safety outcomes of invasive fungal infection (IFI) treatment/prophylaxis among onco-hematological pediatric patients.
Gaza's First Polio Case in 25 Years: Is Health Infrastructure Collapse Threatening Resilience?
Branda F, Ceccarelli G, Giovanetti M, Ciccozzi M and Scarpa F
Safety and Efficacy of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Pegfilgrastim in Japanese Patients with Advanced or Metastatic Urothelial Carcinoma
Harano T, Ikeda M, Hirano S, Shimura S, Toyoda M, Okuda S, Koguchi D, Tsumura H, Ishii D and Matsumoto K
Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) therapy is indicated as first-line or neoadjuvant chemotherapy (NAC) for patients with advanced or metastatic urothelial carcinoma (UC). However, no studies reported ddMVAC therapy with pegfilgrastim (3.6 mg) in Japanese patients. We investigated the safety and efficacy of ddMVAC therapy with pegfilgrastim in patients with advanced or metastatic UC.
Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite?
Eschalier C, Lafont T, Marsili S, Yakoubi M, Brice A, Thomas F, White-Koning M, Allal B and Chatelut E
Therapeutic drug monitoring of imatinib is widely performed to individualize imatinib dosage. While N-desmethyl imatinib is an active metabolite of imatinib, its concentrations are not routinely determined.
Therapeutic Drug Monitoring, Population Pharmacokinetics Models, and External Validation of High-Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia
Maximova N, Calabrò PF, Cangialosi A, Di Paolo A and Maximova N
High-dose methotrexate (MTX) is used to treat pediatric acute lymphoblastic leukemia (ALL). The drug has a low therapeutic index and a highly interindividual variability in systemic exposure. These characteristics necessitate dose adjustments and therapeutic drug monitoring protocols, while population pharmacokinetic (POP/PK) models may enable more precise drug dosing. Therefore, we assessed the performance of external POP/PK models in ALL children receiving high-dose MTX.
Downregulation of Rad51 Expression and Activity Potentiates the Cytotoxic Effect of Osimertinib in Human Non-Small Cell Lung Cancer Cells
Ko JC, Chen JC, Huang CH, Chen PJ, Chang QZ, Mu BC, Chen JJ, Tai TY, Suzuki K, Wang YX and Lin YW
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has shown significant clinical benefits in patients with EGFR-sensitizing mutations or the EGFR T790M mutation. The homologous recombination (HR) pathway is crucial for repairing DNA double-strand breaks (DSBs). Rad51 plays a central role in HR, facilitating the search for homology and promoting DNA strand exchange between homologous DNA molecules. Rad51 is overexpressed in numerous types of cancer cells. B02, a specific small molecule inhibitor of Rad51, inhibits the DNA strand exchange activity of Rad51. Previous studies have indicated that B02 disrupted Rad51 foci formation in response to DNA damage and inhibited DSBs repair in human cells and sensitized them to chemotherapeutic drugs in vitro and in vivo. However, the potential therapeutic effects of combining osimertinib with a Rad51 inhibitor are not well understood. The aim of this study was to elucidate whether the downregulation of Rad51 expression and activity can enhance the osimertinib-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells.
Time-Kill Curve Analysis of Fucoidan Combination with Conventional Antibiotics against Biofilms Formation of Methicillin-Resistant Staphylococcus aureus and Acinetobacter baumannii Clinical Isolates
Nazari M, Taheri M, Nouri F, Bahmanzadeh M and Alikhani MY
This study investigates the efficacy of fucoidan combination with antibiotics, against single-species biofilms and mixed-species, individual planktonic, and coculture planktonic conditions of Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii by time-kill curve analysis.
Successful Isavuconazole Treatment for Pulmonary Mucormycosis in a Patient Intolerant to Liposomal Amphotericin B with Pharmacokinetic Insights: A Case Report
Yasu T, Hoshino M, Sakamoto N and Kobayashi M
Mucormycosis presents a diagnostic challenge characterized by high morbidity and mortality rates due to its swift and pervasive nature, which leads to extensive tissue destruction and dissemination. Immunocompromised individuals, notably those with hematological malignancies, are at a heightened risk. First-line antifungal agents include liposomal amphotericin B (L-AMB), posaconazole, and isavuconazole (IVZ), which offer advantages, such as minimal drug interactions and a favorable safety profile. However, the necessity and efficacy of therapeutic drug monitoring (TDM) of IVZ remain unclear.
Novel Insights into Epiploic Appendagitis in a Breast Cancer Patient on Abemaciclib: A Case Report
Islam J, Hughes P, Lam F and DeSouza K
Epiploic appendagitis is an uncommon cause of acute abdominal pain, often mimicking surgical emergencies. This case highlights the diagnostic process for epiploic appendagitis in a breast cancer patient receiving abemaciclib, a CDK4/6 (cyclin-dependent kinase) inhibitor, and discusses potential associations with targeted therapies.