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BACKGROUND: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs). METHOD: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials. RESULT: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated. CONCLUSION: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.
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Ensayos Clínicos como Asunto , Desarrollo de Medicamentos , Inmunoconjugados , Neoplasias , Sistema de Registros , Humanos , Neoplasias/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Antineoplásicos/uso terapéuticoRESUMEN
AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.
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Trastorno Depresivo Mayor , Escitalopram , Humanos , Puntos de Acupuntura , Citalopram , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Resultado del TratamientoRESUMEN
Postoperative intestinal obstruction is one of the most common and challenging complications after patients receive pelvic or abdominal surgery. The effectiveness of conventional therapies is varied and they are associated with a high recurrence rate. Traditional Chinese Medicine can be beneficial in the treatment of intestinal obstruction. In this case, a 65-year-old woman had progressively increasing abdominal pain, distension, and constipation following total hip replacement surgery. The patient was diagnosed with partial intestinal obstruction and was treated for 6 days without success using conventional Western medicine, including Enema Glycerini and Sodium Phosphates Rectal Solution. We received a request from the surgical department for a Chinese medicine consultation. Two doses of modified Dachengqi Decoction herbal formula were prescribed for the patient. The patient had her first flatus and defecation within 2 hours after ingestion of the first dose of herbal medicine and subsequently all of the symptoms were relieved. The patient was soon discharged without any further complications; a 5-year follow-up indicated that the patient had no recurrence of intestinal obstruction. This case is the first to report the effect of a Chinese herbal decoction in achieving remission of intestinal obstruction with only 1 dose. Large scale randomized controlled trials are warranted to confirm our findings.
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Medicamentos Herbarios Chinos , Obstrucción Intestinal , Anciano , Estreñimiento/tratamiento farmacológico , Estreñimiento/etiología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Obstrucción Intestinal/tratamiento farmacológico , Medicina Tradicional China , Fitoterapia , Complicaciones Posoperatorias/tratamiento farmacológicoRESUMEN
Background: Previous studies in animals and humans indicated that transcutaneous vagus nerve stimulation (tVNS) and transcutaneous electrical acupoint stimulation (TEAS) on trigeminal nerve-innervated forehead acupoints can relief the symptoms of depression. However, due to the limited investigations on these two interventions, more research are needed to confirm their efficacy in depression. To improve the efficacy of the single treatment, we combined two treatments and created a novel non-invasive stimulation, transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). To assess the efficacy and safety of TECAS, we compare it with a selective serotonin reuptake inhibitor (SSRI), escitalopram, for the treatment of depression. Methods/Design: This is a multi-center, non-inferiority, randomized controlled trial that will involve 470 patients with mild to moderate depression. Patients will be randomly assigned to either the TECAS group or the escitalopram group in a 1:1 ratio. The TEAS group will receive two sessions of treatments per day for 8 consecutive weeks, and the escitalopram group will receive 8 weeks of oral escitalopram tablets prescribed by clinical psychiatrists as appropriate for their condition. The primary outcome is the clinical response as determined by Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 8, with -10% as the non-inferior margin. The secondary outcomes include the response rate determined by 17-item Hamilton Depression Rating Scale (HAMD-17), remission rate, changes from baseline in the scores on the MADRS, the HAMD-17, the Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Short Form 36 Health Survey (SF-36). Discussion: This will be the first randomized controlled trial to compare the efficacy of TECAS with escitalopram for depression. If effective, this novel intervention could have significant clinical and research implications for patients with depression. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03909217].
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The preparation and stability of oil-in-water emulsions stabilized by hydrophobically modified hydroxyethyl cellulose (HMHEC) were investigated. The rheological measurements of aqueous HMHEC were studied. It was found that HMHEC showed much better thickening ability than the parent (HEC) from which it was derived, which is caused by the association of the hydrophobic alkyl chains, which are absent in HEC. The oscillatory experimental results of the emulsions showed that at higher concentrations, HMHEC could form an elastic gel, which has good thixotropic properties. The stability and droplet size distribution were investigated by visual observation, photomicrograph and a laser-scattering particle size distribution analyzer. The adsorption of HMHEC at the oil-water interface and the surface of emulsion droplets due to the penetration of the alkyl chains in HMHEC into the oil phase were confirmed by visual observation, the interfacial tension method and an in situ environmental scanning electron microscope (ESEM). The stability of emulsions prepared using HMHEC is based on both an associative thickening mechanism caused by alkyl chains in HMHEC and the adsorption of HMHEC at the oil-water interface, which can form a solid film preventing coalescence of the droplets.