[Heat-sensitive moxibustion combined with tropisetron hydrochloride for chemotherapy-induced nausea and vomiting: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of heat-sensitive moxibustion combined with tropisetron hydrochloride and tropisetron hydrochloride alone in the treatment of chemotherapy-induced nausea and vomiting (CINV). METHODS: Sixty CINV patients were randomly divided into an observation group and a control group, 30 cases in each group.The control group was treated with tropisetron hydrochloride. On the basis of the treatment in the control group, heat-sensitive acupoints were explored at Zhongwan (CV 12), Shenque (CV 8), Qihai (CV 6), Guanyuan (CV 4), Shangwan (CV 13), Xiawan (CV 10), Jianli (CV 11) and bilateral Zusanli (ST 36), Neiguan (PC 6), Tianshu (ST 25), Liangmen (ST 21) areas in the observation group，and heat-sensitive moxibustion was applied at heat-sensitive acupoints. The treatment started from the day of chemotherapy in both groups, once a day for 7 days. The occurrence and severity of nausea and vomiting after chemotherapy were recorded after each treatment on the 1st to 7th days of chemotherapy in the two groups, the complete remission rate was evaluated. The KPS score, quality of life scale score before and after treatment and incidence of myelosuppression were compared between the two groups. RESULTS: On the 2nd to 4th days of chemotherapy, the incidence and severity of nausea and vomiting in the observation group were lower than those in the control group (P<0.05), the complete remission rates of nausea and vomiting were higher than those in the control group (P<0.05). After treatment, the KPS score in the observation group was higher than those before treatment and in the control group (P<0.05). After treatment, the scores of emotional function and overall health status in the observation group were higher than those before treatment and in the control group (P<0.05), the scores of fatigue, pain, insomnia, loss of appetite and diarrhea were lower than those before treatment and in the control group (P<0.05). The incidence of myelosuppression in the observation group was 20.0% (6/30), which was lower than 46.7% (14/30) in the control group (P<0.05). CONCLUSION: Heat-sensitive moxibustion combined with tropisetron hydrochloride can effectively reduce nausea and vomiting after chemotherapy in patients with malignant tumor, improve the quality of life, relieve the myelosuppression caused by chemotherapy drugs.

Evaluation of the effects of different photosensitizers used in antimicrobial photodynamic therapy on tooth discoloration: spectrophotometric analysis.

BACKGROUND: Tooth discoloration is a common concern in antimicrobial photodynamic therapy (aPDT) using various photosensitizers (PS). Toluidine Blue (TB), Methylene Blue (MB), Phthalocyanine (Pc), and 2-mercaptopyridine-substituted zinc phthalocyanine (TM-ZnPc) are among those studied, but their relative impacts on tooth discoloration remain unclear. AIM: This study aimed to compare the effects of TB, MB, Pc, and TM-ZnPc in aPDT on tooth discoloration, utilizing a controlled experimental setup. MATERIALS AND METHODS: The study comprised seventy-five single-rooted incisors with root canals. Following meticulous preparation, a standardized area on the crown surface was designated for examination, and precise measurements of the initial tooth colors were recorded. Samples were randomly divided into five groups: Negative control, MB, TM, Pc, and TM-ZnPc. Photoactivation was performed using LED light, and color measurements were taken at multiple time points up to 90 days. Data were converted to Lab* color values of the CIE Lab* color system (International Commission on Illumination, Vienna, Austria), and ΔE values were calculated. Statistical analysis was performed using Two-way ANOVA and Post-Hoc Tukey tests (p < 0.05). RESULTS: At day 7 and 30, TM-ZnPc and Pc caused less discoloration compared to MB and TB. TM-ZnPc caused more tooth discoloration compared to Pc (p < 0.05). Compared to baseline, MB and TM-ZnPc caused more tooth discoloration at 30 days and TB caused more tooth discoloration at 90 days (p < 0.05). No significant difference was observed in terms of tooth discoloration at all periods evaluated after Pc application (p > 0.05). All photosensitizers tested in the study caused tooth coloration. CONCLUSION: All PS induced clinically detectable tooth discoloration, with TB and MB causing more significant discoloration compared to Pc and TM-ZnPc at certain time points. TM-ZnPc and Pc demonstrated more stable coloration levels over time, suggesting their potential reliability in aPDT applications. This study highlights the importance of selecting appropriate PS to minimize tooth discoloration in aPDT, with Pc showing promise in this regard.

A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer.

BACKGROUND: Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer. METHODS: Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25. RESULTS: Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks. CONCLUSIONS: The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT02393755.

The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study.

BACKGROUND: Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy. METHODS: A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR). RESULTS: The median follow-up period was 28.6 months (range: 2.3-54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2-7.4 months), and the median OS was 17.1 months (95% CI 12.0-22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1-2, and no increase in adverse events was observed compared to monotherapy. CONCLUSION: Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.

Antifibrotic treatment adherence, efficacy and outcomes for patients with idiopathic pulmonary fibrosis in Spain: a real-world evidence study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood. METHODS: An observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected. RESULTS: 232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity. CONCLUSIONS: in this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.

Efficacies of anlotinib monotherapy versus gemcitabine-based chemotherapy for patients with advanced soft tissue sarcoma after the failure of anthracycline-based chemotherapy.

OBJECTIVE: The purpose of this study was to compare the antitumor efficacy of anlotinib with gemcitabine-based chemotherapy as subsequent treatment regimens in patients with advanced non-specific soft tissue sarcoma (STS) after the failure of anthracycline-based chemotherapy. METHODS: Patients diagnosed with advanced STS who were treated with either anlotinib or gemcitabine-based chemotherapy between May 2009 and May 2023 in our center were eligible. All patients experienced disease progression or recurrence after the anthracycline-based chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were disease control rate (DCR), overall survival (OS) and safety. RESULTS: We included 49 patients receiving anlotinib and 45 patients receiving gemcitabine-based chemotherapy. The median follow-up time was 76.9 weeks (range 2.9-678.9 weeks). The DCR (65.3% vs. 57.8%; p = 0.610), PFS (24.0 weeks vs. 18.6 weeks; p = 0.669) and OS (79.4 weeks vs. 87.0 weeks; p = 0.471) of anlotinib and gemcitabine-based chemotherapy indicated similar clinical efficacy. Moreover, exploratory subgroup analyses showed that patients with STS originating from limbs and trunk were inclined to benefit from anlotinib treatment (median PFS: 31.3 weeks vs. 12.4 weeks; p = 0.045). ECOG PS was an independent predictor of the PFS [Hazard Ratio (HR) 0.31; 95% confidence interval (CI) 0.11-0.85; p = 0.023] and OS (HR 0.26, 95%CI 0.10-0.70; p = 0.008) in the anlotinib group. While neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic factor of the PFS (HR 0.33, 95%CI 0.11-0.98; p = 0.045) in the gemcitabine-based chemotherapy group. The incidence of grade 3 or higher related AEs in anlotinib and gemcitabine-based chemotherapy was 20.4% (n = 10) and 20.0% (n = 9), respectively. CONCLUSION: Our research suggested that anlotinib and gemcitabine-based chemotherapy showed similar clinical efficacy and safety in the subsequent treatment of advanced STS after the failure of anthracycline-based chemotherapy.

Safety and efficacy of Rucaparib in the treatment of ovarian cancer and patients with BRCA mutation: a systematic review and meta-analysis of phase III randomized clinical trials.

INTRODUCTION: Our systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of Rucaparib, a PARP inhibitor (PARPi), in patients with ovarian cancer and BRCA mutation. METHODS: Online databases were comprehensively searched for all phase III Randomized trials that used Rucaparib therapy for ovarian cancer patients and patients having BRCA mutation. Efficacy results are progression-free survival and overall response rate in addition to addressing its safety concerns. RESULTS: After pooling data from 4 clinical trials, the analysis showed a significant improvement in PFS among ovarian cancer patients and for the maintenance therapy with a hazard ratio (HR) of 0.49 (95% CI 0.34-0.73, p = 0.0003) and 0.42 (95% CI 0.29-0.62, p < 0.0001), respectively. For patients with BRCA mutations, the PFS showed significant improvement with a (HR) of 0.42 (95% CI 0.25-0.71, p < 0.001). A difference was observed in the risk of grade ≥ 3 TEAEs between the two groups (RR = 2.48; 95% CI 1.40-4.37). CONCLUSION: Rucaparib demonstrated significant efficacy in improving PFS and ORR in ovarian cancer patients, particularly those having BRCA mutations. However, they should be closely monitored due to the greater risk of various adverse effects.

Phase Ib study of anlotinib in combination with anti-PD-L1 antibody (TQB2450) in patients with advanced acral melanoma.

BACKGROUND: Acral melanoma, the most common subtype of melanoma in Asians, is often diagnosed at an advanced stage and responds poorly to current programmed cell death protein 1 (PD-1) inhibitors. OBJECTIVES: To evaluate the safety and efficacy of TQB2450 and anlotinib in patients with advanced acral melanoma in a phase Ib study (NCT03991975). METHODS: Patients received TQB2450 (1200 mg every 3 weeks) and anlotinib (10 mg or 12 mg once daily, 2-week on/1-week off) in the dose-escalation and dose-expansion phases. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and objective response rate (ORR). RESULTS: Nineteen patients were enrolled between June 2019 and June 2022. The majority of patients (16 of 19 patients) received anlotinib and TQB2450 as first-line treatment. No DLTs were observed, and MTD was not reached. Eighteen (94.7%) out of 19 patients experienced treatment-related adverse events (TRAEs), but most were grade 1 or 2. Grade 3 or greater TRAEs occurred in seven patients (36.8%). The ORR was 26.3% (two complete responses and three partial responses). The disease control rate was 73.7%. The median duration of response was 30.3 months [95% confidence interval (CI): 5.8-NA]. The median progression-free survival (PFS) was 5.5 months (95% CI: 2.8-NA), and median overall survival was 20.3 months (95% CI: 14.8-NA). Whole-exome sequencing suggested that acquired drug resistance might be attributed to activation of the MAPK signalling pathway and transformation to an immunosuppressive tumour environment. CONCLUSIONS: TQB2450 combined with anlotinib showed favourable tolerance and promising anti-tumour activity with a prolonged PFS compared with anti-PD1 monotherapy in patients with advanced acral melanoma.

Evaluation of the efficacy and safety of either or both mirabegron and silodosin, as a medical expulsive therapy for distal ureteric stones.

OBJECTIVE: To evaluate efficacy and safety of either or both silodosin and mirabegron as MET for distal ureteric stones ≤ 10 mm. PATIENTS AND METHODS: This study enrolled a total of 105 patients, aged between 20 and 56 years, diagnosed by single radiopaque distal ureteral stone measuring ≤ 10 mm. The recruitment period spanned from May 2020 to December 2021. The patients were randomly divided into three groups, with each group consisting of 35 participants. Group A received a once-daily dose of 8 mg of silodosin, group B received a once-daily dose of 50 mg of mirabegron, and group C received a combination of both medications. Treatment was administered to all patients until the stone was expelled or for a maximum duration of four weeks. The stone-free rate was determined by analyzing KUB films with or without ultrasonography. RESULTS: The rate of stone expulsion was significantly higher in group C compared to groups A and B (P = 0.04 and P = 0.004, respectively). The mean (standard deviation) time for stone expulsion in groups A, B, and C was 14 ± 2.3 days, 11 ± 3.1 days, and 7 ± 2.2 days, respectively. Group C demonstrated a significantly shorter stone expulsion time compared to groups A and B (P = 0.001 and P = 0.04, respectively). The frequency of renal colic in group C was significantly lower than that in groups A and B, resulting in a reduced requirement for analgesics (P < 0.05). Anejaculation occurred at a significantly higher rate in the silodosin group (73.9%) and combination group (84%) compared to the mirabegron group (P < 0.05). CONCLUSIONS: The findings of this study suggest that both silodosin and mirabegron are effective treatments for the expulsion of lower ureteric stones. Furthermore, the combination of these medications leads to an increased rate of stone expulsion and a reduced duration of expulsion.

Cebranopadol for the Treatment of Chronic Pain.

PURPOSE OF REVIEW: Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. RECENT FINDINGS: In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects.

OBJECTIVE: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects. METHODS: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them. RESULTS: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN. CONCLUSION: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

A real-world disproportionality analysis of Rucaparib: Post-marketing Pharmacovigilance Data.

BACKGROUND: Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the long-term safety of rucaparib in large sample population was unknown. The presented study aimed to evaluate rucaparib-associated adverse events (AEs) according to the real-world pharmacovigilance database. METHODS: Disproportionality analysis was conducted to assess the association between rucaparib and its AEs. Data were collected from the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS) between January 2017 and June 2022. The characteristics of rucaparib-related AEs, and the onset time were further analyzed. RESULTS: A total of 9,296,694 AE reports were recorded in the FAERS during the study period, among which 7,087 reports were associated with rucaparib. About 135 rucaparib-related AE signals in 15 system organ class (SOCs) were identified. The most common AEs included anaemia, thrombocytopenia, nausea, vomiting, fatigue, blood creatinine increase, alanine aminotransferase increase, and aspartate aminotransferase increase, which were listed in the label for rucaparib. Of note, 21 new and unexpected significant AEs that off-label were also found in our study, such as preferred term (PTs) of intestinal obstruction, gastrooesophageal reflux disease, blood iron decreased, dehydration, and hypersomnia. The median onset time of rucaparib-related AEs was 12 days (interquartile range [IQR] 1-62 days), and had early failure types. CONCLUSION: Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.

Effect of umifenovir (arbidol) versus standard care on clinical outcome in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to spread quickly throughout the world, mainly due to the lack of effective drug therapies and vaccines. The effectiveness of the antiviral drug umifenovir needs to be further clarified. METHODS: This retrospective cohort study included 1254 patients who were diagnosed with COVID-19 between February 19 and April 5, 2020 in Hubei Maternity and Child Health Hospital. They were divided into umifenovir group (n = 760, 60.60%) and control group (n = 496) without using umifenovir. The primary endpoint was a composite of intubation or death in a time-to-event analysis. The clinical outcomes were compared between the two groups using multivariable Cox analysis with inverse probability weighting according to the propensity score. RESULTS: A total of 760 (60.60%) patients received umifenovir, and 496 patients did not do so. Of the enrolled patients, 1049 (83.65%) had mild or moderate COVID-19, and the remaining 205 had severe or critical COVID-19. The mortality rate in the umifenovir group was 2.76% (21/760) versus 2.02% (10/494) in the control group. In terms of treatment outcomes, the discharge status of the patients in the umifenovir group was no better than that in the control group after propensity score matching (n = 485 in each group). In addition, the respiratory rate, a severe condition, or critical condition of the disease were the three main risk factors affecting the endpoint of death (p = 0.0028, p = 0.0009 and p < 0.0001, respectively). CONCLUSION: This retrospective cohort study showed that oral administration of umifenovir alone did not improve outcomes for patients with COVID-19.

Efficacy and Safety of Anlotinib in Overall and Disease-Specific Advanced Gynecological Cancer: A Real-World Study.

Purpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting. Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1-14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%). Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.

Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery.

iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.

Risk of Malnutrition in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease Treated With Nintedanib in the Randomized, Placebo-Controlled SENSCIS Trial.

OBJECTIVE: To assess adverse events (AEs) in relation to baseline body mass index (BMI) and the risk of malnutrition in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) treated with nintedanib. METHODS: Among patients with SSc-ILD randomized to receive nintedanib or placebo in the SENSCIS trial, we assessed AEs in subgroups by baseline BMI ≤20 kg/m2 and BMI >20 kg/m2 , and the risk of malnutrition using a modified version of the Malnutrition Universal Screening Tool (MUST), over 52 weeks. RESULTS: The AE profile of nintedanib was similar between subgroups with a baseline BMI ≤20 kg/m2 (n = 61) and a baseline BMI >20 kg/m2 (n = 515). In these subgroups, respectively, AEs led to treatment discontinuation in 16.7% and 15.9% of the nintedanib group and 13.5% and 8.0% of the placebo group, respectively. Based on the modified MUST, the proportions of patients who had a low risk of malnutrition at baseline and at their last assessment were 74.0% in the nintedanib group and 78.1% in the placebo group, while the proportions who were classified as at low risk at baseline but at high risk by their last assessment were 4.5% in the nintedanib group and 1.0% in the placebo group. CONCLUSION: In the SENSCIS trial, most patients with SSc-ILD remained at low risk of malnutrition over 52 weeks, but the proportion at high risk was higher in patients who received treatment with nintedanib compared to those who received placebo. Management of disease manifestations and AEs that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD.

Pan-cancer efficacy and safety of anlotinib plus PD-1 inhibitor in refractory solid tumor: A single-arm, open-label, phase II trial.

The combination of immunotherapy and antiangiogenic agents for the treatment of refractory solid tumor has not been well investigated. Thus, our study aimed to evaluate the efficacy and safety of a new regimen of anlotinib plus PD-1 inhibitor to treat refractory solid tumor. APICAL-RST is an investigator-initiated, open-label, single-arm, phase II trial in patients with heavily treated, refractory, metastatic solid tumor. Eligible patients experienced disease progression during prior therapy without further effective regimen. All patients received anlotinib and PD-1 inhibitor. The primary endpoints were objective response and disease control rates. The secondary endpoints included the ratio of progression-free survival 2 (PFS2)/PFS1, overall survival (OS) and safety. Forty-one patients were recruited in our study; 9 patients achieved a confirmed partial response and 21 patients had stable disease. Objective response rate and disease control rate were 22.0% and 73.2% in the intention-to-treat cohort, and 24.3% and 81.1% in the efficacy-evaluable cohort, respectively. A total of 63.4% (95% confidence interval [CI]: 46.9%-77.4%) of the patients (26/41) presented PFS2/PFS1 >1.3. The median OS was 16.8 months (range: 8.23-24.4), and the 12- and 36-month OS rates were 62.8% and 28.9%, respectively. No significant association was observed between concomitant mutation and efficacy. Thirty-one (75.6%) patients experienced at least one treatment-related adverse event. The most common adverse events were hypothyroidism, hand-foot syndrome and malaise. This phase II trial showed that anlotinib plus PD-1 inhibitor exhibits favorable efficacy and tolerability in patients with refractory solid tumor.