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Background: Cost-utility analyses (CUAs) increasingly use models to predict long-term outcomes and translate trial data to real-world settings. Model structure uncertainty affects these predictions. This study compares pharmacometric against traditional pharmacoeconomic model evaluations for CUAs of sunitinib in gastrointestinal stromal tumors (GIST). Methods: A two-arm trial comparing sunitinib 37.5 mg daily with no treatment was simulated using a pharmacometric-based pharmacoeconomic model framework. Overall, four existing models [time-to-event (TTE) and Markov models] were re-estimated to the survival data and linked to logistic regression models describing the toxicity data [neutropenia, thrombocytopenia, hypertension, fatigue, and hand-foot syndrome (HFS)] to create traditional pharmacoeconomic model frameworks. All five frameworks were used to simulate clinical outcomes and sunitinib treatment costs, including a therapeutic drug monitoring (TDM) scenario. Results: The pharmacometric model framework predicted that sunitinib treatment costs an additional 142,756 euros per quality adjusted life year (QALY) compared with no treatment, with deviations − 21.2% (discrete Markov), − 15.1% (continuous Markov), + 7.2% (TTE Weibull), and + 39.6% (TTE exponential) from the traditional model frameworks. The pharmacometric framework captured the change in toxicity over treatment cycles (e.g., increased HFS incidence until cycle 4 with a decrease thereafter), a pattern not observed in the pharmacoeconomic frameworks (e.g., stable HFS incidence over all treatment cycles). Furthermore, the pharmacoeconomic frameworks excessively forecasted the percentage of patients encountering subtherapeutic concentrations of sunitinib over the course of time (pharmacoeconomic: 24.6% at cycle 2 to 98.7% at cycle 16, versus pharmacometric: 13.7% at cycle 2 to 34.1% at cycle 16). Conclusions: Model structure significantly influences CUA predictions. The pharmacometric-based model framework more closely represented real-world toxicity trends and drug exposure changes. The relevance of these findings depends on the specific question a CUA seeks to address. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Targeted therapy has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients carrying common EGFR mutations, but the standard care for patients with rare mutations has not been well established. Here, we report a 65-year-old female diagnosed with stage IIIC lung adenocarcinoma located in the right inferior lobe, harboring uncommon EGFR L858M/L861R mutations. Remarkably, 24 days post-treatment of afatinib and anlotinib, chest CT scans demonstrated significant shrinkage of primary lesion, indicating a partial response. Except for mild hand-foot syndrome and diarrhea, no other severe adverse symptoms were observed throughout treatment. The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths globally. Patients are often diagnosed with advanced disease, in which systemic and locoregional therapies are commonly used as first-line treatment. Such treatments can cause adverse events (AEs) that negatively affect quality of life (QoL), which is particularly undesirable where prognosis is poor. The aim of the present study was to evaluate the impact of common AEs on QoL in patients with HCC. Methods: Data from the SARAH randomized controlled trial (RCT) were analyzed. Given the large number of distinct AEs that occurred in the trial, AEs were grouped as in the SARAH trial and prioritized using principal component analysis (PCA). Linear mixed-effects models were then applied with age, ECOG status, and AEs as predictors of the QoL change as measured with the EORTC Core Quality of Life Questionnaire (QLQ-C30). Results: The PCA resulted in the selection of 28 AEs for inclusion in the linear mixed-effects models. Of the 28 AEs, diarrhea, decreased appetite, abdominal pain, and palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome) were significant drivers of reductions in QoL as measured using the QLQ-C30 global health status scale. Diarrhea, abdominal pain, and hand-foot syndrome were also significant drivers of reduced QoL outcomes. Conclusion: The present analysis showed that diarrhea, decreased appetite, abdominal pain, and palmar-plantar erythrodysesthesia were significantly associated with reduced QoL in patients with unresectable HCC. Reducing the incidence and/or severity of these AEs should therefore be a key focus when selecting the optimal treatments for these patients. Plain English summary: Patients with advanced liver cancer can have a poor prognosis, and preservation of quality of life is an important consideration when choosing appropriate treatments. The SARAH clinical study looked at two treatment options for primary liver cancer — sorafenib and selective internal radiation therapy or SIRT — and collected data on quality of life and how often patients experienced adverse events. Our study used these data to understand which adverse events may have had the largest effect on quality of life. We found that, no matter how severe, gastrointestinal disorders (such as diarrhea, vomiting, nausea, and anorexia) were associated with significant reductions in patient quality of life. We also found that severe constitutional symptoms (such as fever, fatigue, and weight loss) significantly reduced quality of life. The findings may be used to inform choices of treatments or to better prioritize the management of adverse events that cause the greatest reductions in quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of advanced HepatoCellular Carcinoma (HCC) is based on first-line (L1) combination of atezolizumab and high-dose (HD) bevacizumab while second-line (L2) refers one antiangiogenic protein kinase inhibitors (aaPKI). This prolonged antiangiogenic pressure let us to observe an increasing occurrence of Hand-Foot Syndromes (HFS) in patients receiving aaPKI after HD bevacizumab combination. This study reports observations and discussions about the evidence and hypothesis that could be made. Methods: Patients who received the L1 combination from September 1st 2020 to December 31st 2022 to identify L2 aaPKI. Demographic, biological, oncological data and occurrence of HFS were collected. In addition were collected the number of L1 combination cycles, type of aaPKI, and delay between last L1 cycle and L2 initiation. This study had a purely exploratory purpose, so no statistical analysis was planned. Results: 17 patients received an aaPKI after the L1 HD bevacizumab combination with a median time of 26 days from last L1 cycle to L2 start. Five patients experienced HFS including grade 3 (n = 2) with sorafenib and cabozantinib. The HFS occurred with a median delay of 23 days (IQR: 21–28) from aaPKI start. Three patients experienced aaPKI-related dose-limiting toxicity. Conclusions: Proportion of patients experienced HFS in our cohort did not differ from pivotal trials data and the sample size do not allow to conclude. Hypotheses include timing of aaPKI start in HCC treatment, vascular toxicity at aaPKI start after HD bevacizumab discontinuation instead combination, patient-related outcome for a better understanding of these aaPKI-related HFS post HD bevacizumab. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the clinical impact of hand–foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a large group of patients with advanced thyroid cancer. Moreover, we looked for possible associations between HFS occurrence and clinical and pathological features. Methods: We retrospectively evaluated 239 patients with advanced thyroid cancer: 165 treated with lenvatinib and 74 with sorafenib. Statistical analyses were performed to verify which features could be correlated with HFS development. Results: HFS was observed in 35/74 (47.4%) and in 43/165 (26.7%) patients treated with sorafenib or lenvatinib, respectively. The median latency from the drug beginning and HFS appearance was 27 days for sorafenib and 2.9 months for lenvatinib. G3/G4 toxicity was observed in 16/35 (45.7%) patients treated with sorafenib and only in 3/43 (7%) treated with lenvatinib. Drug dose reduction due to HFS was required in 19/74 (25.7%) and 3/165 (1.8%) patients treated with sorafenib and lenvatinib, respectively. HFS occurrence was significantly associated with a longer duration of therapy in both groups. Conclusion: HFS was a frequent adverse event during both lenvatinib and sorafenib therapy, with a higher frequency and toxicity grade during sorafenib treatment. HFS was the most frequent reason for drug reduction or discontinuation in patient treated with sorafenib. Early diagnosis of HFS is important to allow early intervention, possibly in a multidisciplinary setting, and to avoid treatment discontinuation, which is highly relevant to obtain the maximum effectiveness of systemic therapy.

Background: Recent studies have highlighted that TACE in conjunction with Lenvatinib (TACE-L) offers a promising adjunct therapy for advanced HCC patients, outperforming TACE plus Sorafenib (TACE-S). However, there has been a lack of research comparing these two regimens for intermediate HCC. Aims: This study aims to address the research gap by evaluating the efficacy of TACE-L versus TACE-S in intermediate HCC patients. Methods: A retrospective analysis was conducted on a cohort of consecutive intermediate HCC patients who received either TACE-L or TACE-S from November 2018 to December 2022. Portal vein width was assessed using abdominal NMRI or Doppler ultrasonography, and inflammatory markers were derived from routine blood counts. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse drug reactions (ADRs). Results: The study included 117 patients, with 56 in the TACE-S group and 61 in the TACE-L group. The TACE-S group demonstrated superior OS (HR = 1.704, 95% CI: 1.012–2.870, p = 0.045) compared to the TACE-L group. No significant difference was observed in PFS (HR:1.512, 95% CI: 0.988–2.313, p = 0.057) between the two groups. Subgroup analyses revealed that male patients, those with cirrhosis, and those with more than four tumors had better OS and PFS in the TACE-S group than in the TACE-L group. Inflammatory markers were comparable between the groups. The TACE-S group experienced a higher incidence of palmar-plantar erythrodysesthesia syndrome (PPE) (14/56 [25%] vs. 5/61 [8.1%], p = 0.014) but a lower incidence of hypertension (3/56 [5.3%] vs. 11/61 [18%], p = 0.035) compared to the TACE-L group. Conclusions: In patients with intermediate HCC, TACE-S was found to be more effective in terms of OS than TACE-L. No significant disparity was noted in PFS between the two treatment groups. [ABSTRACT FROM AUTHOR]

Background: Anlotinib, an oral multitarget tyrosine kinase inhibitor, has shown the ability to inhibit tumor angiogenesis. This study aimed to assess the effectiveness and safety of anlotinib plus docetaxel, epirubicin, and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen for locally advanced TNBC. Methods: Locally advanced TNBC patients who had received no prior systemic treatment were eligible for this study. The enrolled patients were scheduled to undergo six cycles of anlotinib (12 mg, d1-14, q3w) plus docetaxel (75 mg/m2, d1, q3w), epirubicin (75 mg/m2, d1, q3w) and cyclophosphamide (600 mg/m2, d1, q3w) prior to surgery, unless there was disease progression or severe toxicity. The primary objective of this study was the safety of this therapeutic regimen, and the secondary objective was the tumor response. The safety of this regimen was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the efficacy of this treatment was measured using the Response Evaluation Criteria in Solid Tumors version 1.1. Results: A total of 18 patients were included in this study. Participants completed an average of 5.56 neoadjuvant treatment cycles. The objective response rate (ORR) was 83.33%, and the disease control rate was 100%, respectively. The pCR was 55.6%. No patients discontinued therapy because of Adverse effects (AEs). Grade 3 or 4 AEs were observed in 5 cases (27.8%), with neutropenia and palmar-plantar erythrodysesthesia syndrome being the most common. Conclusions: Anlotinib combined with TEC as neoadjuvant therapy demonstrated manageable toxicity and promising antitumor activity for locally advanced TNBC. Further investigation of this combination regimen is warranted. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical efficacy and the safety of pegylated liposomal doxorubicin (PLD) in patients with advanced breast cancer who had previously used anthracyclines. Methods: The clinical data of 79 patients with advanced breast cancer treated with PLD-contained regimen in our hospital from May 2019 to January 2021 were retrospectively analyzed. The clinical efficacy, influencing factors and adverse reactions were evaluated between the group of PDL re-use and initial use. Results: Among 79 patients, 65 patients could be evaluated for efficacy, of which the objective response rate (ORR) was 13.85%, and the disease control rate (DCR) was 63.08%. In HER-2 positive advanced breast cancer, the ORR was 20.00%, the DCR was 75.00%, and the median progression free survival (PFS) was 3.23 months. The most common adverse reactions are bone marrow suppression, hand foot syndrome, and oral mucositis. Conclusion: The adjuvant chemotherapy with doxorubicin liposomes can achieve good efficacy in the treatment of advanced breast cancer, and the anti HER-2 treatment combined with doxorubicin liposomes has better efficacy and safety in the treatment of HER-2 positive advanced breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist Binterin and the Wnt-antagonist Winhibin. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs. Materials and Methods: This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to 9 weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR. Results: Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance. Conclusion: Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common adverse events (AEs) that occurred in response to targeted therapy for hepatocellular carcinoma were appetite loss (adverse event grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). Among these, appetite loss and general fatigue negatively affect overall survival (OS) and progression-free survival (PFS). Increasing AE grades of hypertension, proteinuria, and hypothyroidism were associated with better OS, whereas hypertension, HFS, and hypothyroidism were associated with better PFS. To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. [ABSTRACT FROM AUTHOR]

Environmental conditions, such as temperature and water vapor pressure (WVP), affect skin function. We prospectively determined the association between the patients’ living environment and docetaxel-induced hand-foot syndrome (HFS). This study included patients with breast or lung cancer, who were treated with docetaxel at our institution from September 2017 to March 2019. The patient’s skin condition and the temperature and WVP of their living rooms were recorded during two cycles of docetaxel-based chemotherapy. The association between the room temperature, WVP of the patient’s living rooms, and the occurrence of HFS was considered. We reported four cases in which HFS occurred. The room temperature and WVP of the living rooms of patients were 18.8 ℃ / 9.0 hPa, 19.4 ℃ / 10.5 hPa, 19.9℃ / 8.8 hPa, 22.4℃ / 10.3 hPa. In general, sweating is rare at room temperatures of 20°C-22°C and humidity of 40%-50%. This environment is calculated as WVP 9.4 hPa-13.2 hPa. In skin with reduced water contents of stratum corneum, the barrier function is impaired and inflammatory mediators are increased. The four patients with HFS were thought to have decreased water contents of stratum corneum due to suppressed sweating and insensible perspiration in the living environment. It was suggested that the patient's living environment may have influenced the onset of HFS. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) are linked with various cutaneous side effects ranging from mild to life-threatening. Herein, we present a unique case of palmar-plantar erythrodysesthesia (PPE) in a patient treated with atezolizumab. Case report: A 72-year-old white man was diagnosed with Tumor, node, metastasis (TNM) stage IIIA lung adenocarcinoma in November 2022. He underwent right lower lobectomy and mediastinal lymphadenectomy followed by adjuvant cisplatin-pemetrexed. As of May 2023, he did not have any evidence of relapse. He then started switch maintenance therapy with atezolizumab. At 24 weeks, the patient developed erythematous palmar skin lesions, followed by blisters and peeling of both palms, which were associated with swelling and pain, consistent with grade 2 PPE. Management and outcome: Causality assessment between nivolumab and PPE via adverse drug reaction probability scale revealed a score of 5. Atezolizumab was continued, and he started on a cream consisting of trolamine and 75% water to palms twice daily. A follow-up visit 6 weeks later showed significant improvement in symptoms and appearance of palmar lesions. Discussion: Cutaneous side effects are commonly seen with ICIs. PPE is a common dermatologic toxicity of certain tyrosine kinase inhibitors (TKIs). This effect has been previously reported with combination therapies consisting of an ICI plus a TKIs, but not with ICI monotherapy. Awareness of this potential side effect of ICIs would prevent unnecessary work-up, and lead to its prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective Hand-foot syndrome is a dose-limiting toxicity of capecitabine. At present, there is no unified gold standard for the establishment of hand-foot syndrome model. To induce hand-foot syndrome and provide a reference for the establishment of hand-foot syndrome model by administering capecitabine in ICR mice. Methods 42 male ICR mice were randomly divided into control group (6 mice) and experimental group (36 mice). The experimental group was given capecitabine (275 mg/kg, twice/d) by intragastric administration for two weeks, and the control group was given 0.5% CMC-Na (4 ml/kg, twice/d), to evaluate whether the animal model of hand-foot syndrome was successfully constructed through H&E staining of mouse foot skin samples and observe morphological changes and the characteristic appearance of mouse foot skin. After the experiment, the mice were sacrificed, and plasma was collected to quantify the concentrations of capecitabine and metabolites. Results Control mice did not showed symptoms of hand-foot syndrome. The skin of the feet of 19 mice in the experimental group showed symptoms such as erythema and swelling, and H&E staining results showed that the plantar skin angular epidermis was thickened, and part of the keratin was exfoliated and damaged, which was considered to be hand-foot syndrome. There were no significant differences in the concentrations of capecitabine and its metabolites between mice with and without hand-foot syndrome. Conclusion The model of hand-foot syndrome induced by capecitabine in mice was successfully established. Differences in exposure levels of capecitabine and metabolites may not be the cause of hand-foot syndrome. [ABSTRACT FROM AUTHOR]

Copyright of African Journal of Reproductive Health is the property of Women's Health & Action Research Centre and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Napkin rashes represent different varieties of cutaneous lesions that affect the napkin area and cause a burden on infants and their parents. Objective: To evaluate different diaper rashes in pediatric patients less than 3 years old. Patients and methods: All 300 pediatric patients with napkin lesions were included in the study. Every patient's personal and medical history as well as photographs were compiled and recorded in data sheets. Results: The most common rashes affecting the napkin area were contacted napkin dermatitis (29%) and napkin candidiasis (28%) followed by hand-foot mouth disease (12%). There was a statistically significant relation between the rate of daily napkin changing and the occurrence of contact napkin dermatitis. Conclusion: Different types of cutaneous rashes could affect the napkin area other than contact napkin dermatitis and candidiasis, which should be taken into consideration during the evaluation of napkin lesions. [ABSTRACT FROM AUTHOR]

Objective: The current research aims to evaluate the efficacy and safety of anlotinib, an orally administered small-molecular tyrosine kinase inhibitor (TKI), in the treatment of recurrent epithelial ovarian cancer (EOC). Methods: Patients with recurrent EOC subjected to treatment with anlotinib in Fourth Hospital of Hebei Medical University from 2020 to 2022 were included. The evaluation involved a thorough review of medical records, focusing on parameters such as the objective response rate (ORR), disease control rate (DCR), survival outcomes, and safety profile. Results: This study recorded 51 patients, with 26 patients undergoing anlotinib monotherapy. The median progression-free survival (PFS) was 4.0 months, whereas the median overall survival (OS) was not reached. Seven cases underwent a combined treatment of anlotinib with chemotherapy. Among them, two patients achieved partial response (PR), two were categorized as stable disease (SD), and three were identified as having progressive disease (PD). The ORR and DCR were 28.5% (2/7) and 57.1% (4/7), respectively. Additionally, 18 cases received anlotinib maintenance therapy, and the median PFS and the median OS were 7.0 months and 25.5 months, respectively. The most prevalent adverse effects included fatigue (38.6%), hypertension (27.3%), nausea and vomiting (25.0%) and hand-foot syndrome (25.0%). Conclusion: Anlotinib demonstrated mild efficacy in the treatment of recurrent EOC, whether employed as monotherapy, chemotherapy-combined therapy, or maintenance therapy. The safety profile was proven manageable and well-tolerated, suggesting that anlotinib may emerge as a viable and novel treatment option for recurrent EOC. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the efficacy and safety of anlotinib targeted therapy for the treatment of patients with advanced digestive system neoplasms (DSNs). Methods: Clinical trials were extracted from PubMed, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and the Wanfang database up to October 2023. Outcome measures, including therapeutic efficacy, quality of life (QOL) and adverse events, were extracted and evaluated. Results: Twenty trials, including 1,613 advanced DSNs patients, were included. The results indicated that, compared with conventional treatment alone, the combination of anlotinib targeted therapy with conventional treatment significantly improved the patients' 6-months overall survival (OS, OR=1.76, CI=1.53 to 2.02, P<0.00001), overall response (ORR, OR=1.76, CI=1.53 to 2.02, P<0.00001) and disease control rate (DCR, OR=1.51, 95% CI=1.25 to 1.84, P<0.0001). Moreover, the group that received the combined therapy had higher rates of hypertension (P<0.00001), proteinuria (P<0.00001), fatigue (P<0.00001), diarrhea (P<0.00001), hypertriglyceridemia (P=0.02), alanine aminotransfease (ALT)increased (P=0.004), aspartate transaminase (AST) increased (P=0.006), anorexia (P<0.00001), weight loss (P=0.002), abdominal pain (P=0.0006), hypothyroidism (P=0.02), prolonged QT interval (P=0.04). Analyses of other adverse events, such as gastrointestinal reaction, leukopenia, and neutropenia, did not reveal significant differences (P>0.05). Conclusion: The combination of anlotinib targeted therapy and conventional treatment is more effective for DSNs treatment than conventional treatment alone. However, this combined treatment could lead to greater rates of hypertension, albuminuria and hand-foot syndrome. Therefore, the benefits and risks should be considered before treatment. [ABSTRACT FROM AUTHOR]

Aim: Lenvatinib mesylate (LEN) is an oral tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events. This study was aimed at investigating the incidence of LEN‐induced palmar‐planter erythrodysesthesia syndrome (PPES) and its relationship with patient demographics by analyzing clinical laboratory data of LEN‐treated patients with HCC. Methods: This was a single‐centre, retrospective study of patients with HCC who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration. Results: Overall, 75 patients with HCC were enrolled. LEN‐induced PPES was found in 48.0% (36/75 patients). In these patients, alkaline phosphatase (ALP), γ‐Glutamyl transpeptidase (γ‐GTP) and monocytes (MONO) were significantly high (ALP: p = 1.32 × 10−3, γ‐GTP: p = 4.25 × 10−3 and MONO: p = 0.013). The cut off values of ALP, γ‐GTP and MONO for LEN‐induced PPES were estimated at 573 U/L, 89 U/L, and 310 counts/μL, respectively. In the multivariate analysis, γ‐GTP and MONO were independent risk factors for LEN‐induced PPES. Conclusions: High γ‐GTP and high MONO were risk factors for LEN‐induced PPES. [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. Methods: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. Results: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07–11.27) and 13.17 months (95% CI 2.78–23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. Conclusions: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment. [ABSTRACT FROM AUTHOR]

Introduction Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. Methods Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). Results Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. Conclusions The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting. [ABSTRACT FROM AUTHOR]

Capecitabine is a widely used and effective oral chemotherapeutic agent for metastatic breast cancer and colorectal cancer; however, it is associated with several adverse effects. Of these effects, hand–foot syndrome (HFS) or palmar–plantar erythrodysesthesia, characterized by chronic inflammation, particularly of the hands and feet, is most notable. Chronic inflammation increases the risk of squamous cell cancers. We present a unique case of a patient with metastatic breast cancer whose disease was controlled with capecitabine for over a decade. She experienced chronic grade 1–2 HFS and subsequently developed squamous cell skin cancer on the palms and soles. To the best of our knowledge, squamous cell cancer associated with capecitabine exposure has not been previously reported. This case report aims to shed light on this association, thereby expanding the existing literature on the topic.

Abstract Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents the other docetaxel-induced adverse inflammatory effects in a dose-dependent manner. This study aimed to evaluate the dose-dependent efficacy of systemic DEX in attenuating HFS in patients with breast cancer receiving docetaxel. Patients with breast cancer receiving docetaxel (75 mg/m2)-containing regimens (n = 111) were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2–4, and analyzed retrospectively. Development of all-grade HFS in all treatment cycles was significantly lower in the 8 mg group (50.0%) than in the 4 mg group (73.0%, P = 0.03), with primary endpoint accomplishment. Moreover, its development in the first cycle was also lower in the 8 mg group than in the 4 mg group. These results were confirmed in a propensity score-matched population. Logistic regression analysis suggested higher DEX dosage as an independent preventive factor (adjusted odds ratio 0.35; 95% confidence interval 0.14–0.86, P = 0.02 for all cycles; 0.26, 0.11–0.63, P = 0.003 for the first cycle). Our study suggests that systemic DEX prevents the occurrence of docetaxel-induced HFS in patients with breast cancer in a dose-dependent manner in a real-world setting.

Background: This phase Ib study was performed to determine the safety of combination capecitabine with alpleisib (phosphatidylinositol 3-kinase catalytic subunit p110a blockade) and determine the maximal tolerated dose (MTD) and recommended phase ll dose (RP2D) of this combination regimen in patients with advanced solid tumors refractory to standard therapy. The synergistic anti-tumor activity and pharmacokinetics (PK) were investigated. Methods: Dose escalation phases were conducted in patients with advanced solid cancers who were refractory to standard therapy regardless of PIK3CA mutation. Patients were administered orally once daily alpelisib (200mg and 300mg) and twice daily capecitabine (850mg, 1000mg, 1250mg orally, days 1-14) every 3 weeks. Standard "3 + 3" dose escalation was used to define the MTD. The effect of alpelisib on the PK of capecitabine was assessed. Results: Patients with 6 colorectal cancer (three PIK3CA mutation) and 6 breast cancer (all PIK3CA mutation) were enrolled. The first three patients in dose level 0 (alpelisib 200mg daily, capecitabine 1,000 mg/m² twice daily) had no doselimiting toxicities (DLTs). In dose level 1 (alpelisib increased to 300 mg daily, capecitabine 1,000mg twice daily), one of six patients had DLT (grade (Gr) 3 hyperglycemia). When dose level 2 (alpelisib 300mg daily, capecitabine 1,250 mg/m² twice daily) was expanded to 3 patients, no patients had DLTs. The combination of alpelisib 300mg daily and capecitabine 1,250 mg/m² twice daily was declared as the MTD/RP2D in patients with advanced solid tumors. The most common AEs were Gr 1-3 hyperglycemia (75.0%). Frequent all-grade, treatmentrelated AEs included Gr 2-3 nausea (75.0%), Gr 1-2 diarrhea (50.0%), Gr 1-2 hand-foot syndrome (41.7%), Gr 1-2 anorexia (41.7%), Gr 2 mucositis (33.3%). Antitumor activity was observed in patients with PIK3CA mutant breast cancer (3 partial response and 3 stable disease of total 6 patients). Alpelisib exposure (Cmax and AUC0-12) was unaffected by concomitant capecitabine. There were no clinically relevant drug-drug interactions observed between alpelisib and capecitabine. Conclusions: The combination of alpelisib and capecitabine is generally tolerated, without pharmacokinetic interactions, and shows antitumor activity in patients with PIK3CA mutant advanced cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Many cancer treatments, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy, can cause skin side effects. These are called 'dermatologic toxicities' or 'skin toxicities'. There are many different types of skin toxicities, some of which can not only affect the quality of life but also lead to cancer treatment being stopped or slowed down. This paper gives an overview of 12 of the most common skin toxicities experienced by people receiving cancer treatment. These include rashes, dry skin, skin irritation, hair loss, changes in skin colouring, and itching. We have provided Australia/New Zealand-specific recommendations on how skin toxicities can be prevented and managed, including the role of dermocosmetic solutions. Cancer systemic therapeutics and radiotherapy are often associated with dermatological toxicities that may reduce patients' quality of life and impact their course of cancer treatment. These toxicities cover a wide range of conditions that can be complex to manage with increasing severity. This review provides details on twelve common dermatological toxicities encountered during cancer treatment and offers measures for their prevention and management, particularly in the Australian/New Zealand context where skincare requirements may differ to other regions due to higher cumulative sun damage caused by high ambient ultraviolet (UV) light exposure. Given the frequency of these dermatological toxicities, a proactive phase is envisaged where patients can actively try to prevent skin toxicities. [ABSTRACT FROM AUTHOR]

Purpose: Standard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC. Patients and methods: In 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires. Results: 54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32–3.98, P = 0.003; OR = 4.36, 95% CI = 0.95–19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08–3.55, P = 0.024; OR = 1.86, 95% CI = 1.1–3.14, P = 0.02; OR = 2.34, 95% CI = 1.29–4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001). Conclusions: This study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence. [ABSTRACT FROM AUTHOR]

This article explores a rare skin condition called cryptococcoid Sweet syndrome, which can be triggered by infection, cancer, or certain medications. The case discussed involves a patient who had previously used hydralazine and had a history of cocaine use. The article emphasizes the connection between hydralazine use and autoimmune disorders like Sweet syndrome. It also stresses the importance of distinguishing between true cryptococcosis and cryptococcoid Sweet syndrome, and calls for more research on this condition and its potential causes. [Extracted from the article]

The use of trastuzumab emtansine (T‐DM1) has revealed significant efficacy in HER2‐positive metastatic breast cancer (MBC). However, optimal therapeutic strategies following T‐DM1 failure remain a subject of debate in clinical practice. In this multicenter, retrospective, real‐world study, we sought to examine the effectiveness and safety of tyrosine kinase inhibitors (TKIs) as a therapeutic strategy in HER2‐positive MBC who developed T‐DM1 resistance. Between September 2018 and December 2022, 66 patients were enrolled. The median progression‐free survival of TKIs‐based therapy was 10.1 months (95% CI, 4.7–15.6). Objective response rate and clinical benefit rate were 18.2 and 66.7%, respectively. TKIs‐based therapy demonstrated better effectiveness in patients who had previously derived benefit from T‐DM1 and featured acquired resistance to trastuzumab. The most common adverse events were diarrhea (36, 54.5%), hand‐foot syndrome (31, 47.0%), and leucopenia (30, 45.5%). In conclusion, TKIs‐based therapy showed promising effectiveness and safety in HER2‐positive MBC patients after T‐DM1 failure. [ABSTRACT FROM AUTHOR]

Purpose: The skin and mucous membrane of cancer patients can be directly or indirectly impaired during the treatment of cancers, bringing about not physical but also psychological damages to cancer patients. A practical guideline is of great significance to improve the quality of life for patients suffered from cutaneous adverse events. Methods: This guideline was generated based on up-to-date evidence and the consensus of experts specialized in dermatology. Results: The current guideline include the baseline screening of skin and mucosal membranes, the manifestations of injuries on skin, mucosa and appendages, along with the treatment of them. The causal anti-tumor management include chemotherapy, radiotherapy, immune therapy and surgery. Conclusion: This guideline can be helpful to reduce the risk of cutaneous adverse events during anti-cancer treatment and improve the quality of life of patients suffered from these adverse events. [ABSTRACT FROM AUTHOR]

This article provides a radiologic analysis of the musculoskeletal manifestations of Maffucci syndrome, a rare nonhereditary disorder characterized by the coexistence of enchondromas and hemangiomas. The study focuses on a 42-year-old woman with Maffucci syndrome and examines the distinct radiographic features found in the hands, feet, and shoulders. The results reveal multiple scattered enchondromas distributed diffusely across these areas, with small well-circumscribed lucent lesions predominantly metaphyseal in location. The findings contribute valuable insights for clinicians, radiologists, and orthopaedic specialists, aiding in early diagnosis and personalized management strategies. [Extracted from the article]

Introduction: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. Methods: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS). Results: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient's or investigator's decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study. Conclusion: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection. [ABSTRACT FROM AUTHOR]

Introduction: Hand-foot syndrome (HFS) significantly impacts quality of life in cancer patients undergoing capecitabine treatment. This study assessed capecitabine-associated HFS prevalence, its impacts on chemotherapy treatment, and identified risk factors in multiracial Malaysian patients. Methods: We included adult cancer patients receiving capecitabine at Sarawak General Hospital for at least two cycles from April 1, 2021 to June 30, 2022. HFS rates, time to HFS, and proportions of HFS-related treatment modifications were determined. Characteristics between patients with and without HFS were compared and multivariable logistic regression was used to identify risk factors for all-grade HFS and grade ≥2. Results: Among 369 patients, 185 (50.1%) developed HFS, with 14.6% experiencing grade ≥2 and 21.6% (40/185) underwent treatment modifications. Risk factors for all-grade HFS include older age (OR 1.03 95%CI 1.01, 1.06), prior chemotherapy (OR 2.09 95%CI 1.22, 3.58), higher capecitabine dose (OR 2.96 95%CI 1.62, 5.38), prolonged treatment (OR 1.36 95%CI 1.21, 1.51), folic acid intake (OR 3.27 95%CI 1.45, 7.35) and lower neutrophil count (OR 0.77 95%CI 0.66, 0.89). For HFS grade ≥2, older age (OR 1.04 95%CI 1.01, 1.08), female sex (OR 2.10 95%CI 1.05, 4.18), Chinese race (OR 2.10 95%CI 1.06, 4.18), and higher capecitabine dose (OR 2.62 95%CI 1.28, 5.35) are significant risk factors. Use of calcium channel blockers were associated with reduced risks of all-grade HFS (OR 0.27, 95%CI 0.12, 0.60) and grade ≥2 (OR 0.21 95%CI 0.06, 0.78). Conclusion: This study provides real-world data on capecitabine-induced HFS in Malaysian patients and identifies risk factors that may offer insights into its understanding and management. [ABSTRACT FROM AUTHOR]

Background: The combination of dual‐targeted human epidermal growth factor receptor 2 (HER2) therapy and chemotherapy is the standard first‐line regimen for recurrent/metastatic breast cancer (mBC). However, the toxicity of such combination therapy can lead to some patients being unable to tolerate adverse events or bear treatment costs. As a novel irreversible pan‐ErbB receptor TKI (pyrotinib), can the dual oral administration of pyrotinib plus capetabine (PyroC) provide first‐line survival benefits and serve as a more affordable treatment option? Methods: This real‐world retrospective study included patients diagnosed with HER2‐positive mBC who received PyroC as a first‐line treatment at West China Hospital between May 2018 and July 2023. The survival data and toxicity profiles were reported in this study. Results: A total of 64 patients received PyroC as first‐line therapy. The median progression‐free survival (PFS) was 19.6 months (95% CI 15.0–27.2), while overall survival (OS) has not yet been reached. Kaplan–Meier analysis indicated that age (≥60, p = 0.03) and metastasis sites (p = 0.004) were related to poor efficacy of PyroC, while there was no relationship between effectiveness and menstrual status, hormone receptor (HR) status or previous treatment with anti‐HER2 therapy. Furthermore, the objective response rate (ORR) and disease control rate (DCR) were 79.7% and 98.4%, respectively. Of the patients, 78.1% reported treatment‐related adverse events (TRAEs). The predominant adverse events were diarrhea (n = 46, 71.9%) and hand‐foot syndrome (n = 10, 15.6%). Conclusion: The dual oral administration regimen (PyroC) has a promising ORR or PFS in HER2‐positive mBC patients, with an acceptable safety profile and convenience. [ABSTRACT FROM AUTHOR]

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity. [ABSTRACT FROM AUTHOR]

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication. [ABSTRACT FROM AUTHOR]

Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine. Case presentation: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution. Conclusions: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a significant global health burden, with high morbidity and mortality rates. It is often diagnosed at middle to advanced stage, affecting approximately 35% of patients at the time of diagnosis. Currently, chemotherapy has been used to improve patient prognosis and increase overall survival. However, chemotherapy can also have cytotoxic effects and lead to adverse reactions, such as inhibiting bone marrow hematopoiesis, causing digestive dysfunction, hand-foot syndrome, and even life-threatening conditions. In response to these adverse effects, researchers have proposed using Traditional Chinese Medicine (TCM) as an option to treat cancer. TCM research focuses on prescriptions, herbs, and components, which form essential components of the current research in Chinese medicine. The study and implementation of TCM prescriptions and herbs demonstrate its distinctive holistic approach to therapy, characterized by applying multi-component and multi-target treatment. TMC components have advantages in developing new drugs as they consist of single ingredients, require smaller medication dosages, have a precise measure of pharmacodynamic effects, and have a clear mechanism of action compared to TCM prescriptions and herbs. However, further research is still needed to determine whether TMC components can fully substitute the therapeutic efficacy of TCM prescriptions. This paper presents a comprehensive analysis of the research advancements made in TCM prescriptions, herbs, and components. The findings of this study can serve as a theoretical basis for researchers who are interested in exploring the potential of TCM for the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months. [ABSTRACT FROM AUTHOR]

Objective To investigate the correlation between plasma inflammatory factors [IL-1β, IL-6, IL-10, IL-12, IL17, IL-23, TNF-α, TGF-β, IFN-γ, C-reactive protein (CPR) CCL-5] and hand-foot syndrome in colorectal cancer patients after taking capecitabine. Methods 35 colorectal cancer patients treated with capecitabine were collected and the degree of severity was divided according to the hand-foot syndrome grading diagnostic criteria. The concentrations of inflammatory factors in plasma were determined by ELISA kits. Results The standard curve of all inflammatory cytokines were linear (r>0.9900), and plasma concentrations of inflammatory cytokines in patients with colorectal cancer were determined. The concentration of TNF-α changed obviously, which had reference value. Conclusion The concentrations of different inflammatory factors were different and the concentration of TNF-α was closely correlated with the severity of hand-foot syndrome. [ABSTRACT FROM AUTHOR]

Objective: It has been observed that the prognosis of patients with HER2‐positive metastatic breast cancer has improved significantly with HER2‐targeted agents. However, there is still a lack of evidence regarding first‐line anti‐HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti‐HER2 treatment in these patients. Methods: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer were enrolled. Pyrotinib plus albumin‐bound paclitaxel were used as first‐line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. Results: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow‐up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand‐foot syndrome (3.7%). Toll‐like receptor 3 (TLR3) and Proto‐oncogene tyrosine‐protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. Conclusions: This study demonstrates that pyrotinib plus albumin‐bound paclitaxel as a first‐line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients. [ABSTRACT FROM AUTHOR]