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paclitaxel (PNP, Dabur / DO/NDR/02 / PNP, Dabur)

✓ Approved

Fresenius Kabi · TUBB · 小分子

什么是 paclitaxel？

paclitaxel 是一种小分子，由Fresenius Kabi研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

商品名PNP, Dabur, DO/NDR/02, PNP, Dabur
公司Fresenius Kabi
药物类别小分子
分子靶点TUBB
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Fresenius Kabi

作用机制

分子靶点

paclitaxel 作用于 1 个分子靶点：

TUBBtubulin beta class I (TUBB1, CSCSC1)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

paclitaxel 针对 4 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancer✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Non-small cell lung cancer stage IV✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Ovarian cancer✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Non-small cell lung cancer metastatic✓ Approved

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A Successful Multimodal Treatment for High-Grade Serous Ovarian Cancer with BRCA2 Heterozygous Deletion with Multiple Recurrences: A Case Report.

Chu Hsiao-Han HH, Liu Feng-Yuan FY, Wang Chun-Chieh CC, Lin Mei-Chun MC et al.

Management of recurrent high-grade serous ovarian cancer (HGSOC) remains a challenge. This case presents a successful multimodal treatment plan in a BRCA-mutated patient with repeated recurrences. A 60-year-old woman diagnosed with FIGO stage III HGSOC received initial debulking surgery followed by chemotherapy at another hospital in December 2017. The patient presented to our institution in March 2019 for further management because of a suboptimal response to 2nd-line chemotherapy. A disseminated disease extent was identified. She progressed (new bone metastasis) during the 3rd- to 5th-line platinum-based chemotherapy, but achieved complete remission after changing to pembrolizumab and weekly paclitaxel. She had a 3rd relapse at the anterior mediastinum (proven by thoracoscopic resection in April 2020, and the tumor was found to harbor a BRCA2 heterozygous deletion), which was controlled by adjuvant radiotherapy combined with nivolumab and nab-paclitaxel, followed by maintenance therapy nivolumab plus olaparib, and eventually olaparib monotherapy. A 4th recurrence at the perigastric lymph nodes was found through periodic positron emission tomography surveillance with normal CA-125 in September 2021. Resection of metastasis and hyperthermic intraperitoneal chemotherapy (HIPEC) were performed, and maintenance therapy was again with olaparib. She has maintained remission since then. A durable remission is possible by multimodality management, including the strategic use of chemo-immunotherapy, localized resection plus HIPEC/adjuvant radiotherapy, and poly (ADP-ribose) polymerase (PARP) inhibitor maintenance, in BRCAm-HGSOC with multiple recurrences.

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Leucoseptoside A reverses multidrug resistance in breast cancer cells by targeting P-glycoprotein (P-gp/ABCB1) transporter.

Zhang Haoxue H, Li Xiaohan X, Xie Bingling B, Wu Fangyun F et al.

The overexpression of P-glycoprotein (P-gp) in tumor cells and its mediated drug efflux represent key mechanisms of cancer multidrug resistance (MDR). Natural compounds are attractive candidates for reversing MDR due to their multi-target activity and hypotoxicity. This study evaluated the ability of leucoseptoside A (LeuA) to reverse P-gp-mediated MDR in MCF-7/ADR cells.The MDR reversal activity of LeuA was assessed based on changes in drug sensitivity measured using the MTT assay. P-gp expression was measured by Western blotting. The intracellular accumulation of rhodamine 123 (Rh123) and adriamycin (ADR) was determined using confocal laser scanning microscopy and flow cytometry, and P-gp ATPase activity was assessed using the Pgp-Glo™ system. The binding mode and affinity of LeuA for P-gp were predicted by molecular docking.LeuA markedly enhanced the sensitivity of MCF-7/ADR cells to ADR and paclitaxel (PTX). This mechanism was achieved by inhibiting P-gp efflux rather than altering its protein expression levels. Molecular docking analysis further revealed that LeuA competitively binds to the drug-binding pocket of P-gp with a higher binding affinity than verapamil (VRP).LeuA is a potent reversal agent for P-gp-mediated MDR, promising as a natural inhibitor for cancer therapy.

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Diffuse hepatic hemangiomatosis (DHH) in adults is a rare benign vascular tumor of the liver that histologically resembles a hepatic hemangioma but is characterized by an infiltrative growth pattern despite the absence of cytologic atypia typical of hepatic angiosarcoma. Although generally indolent, its clinical course is variable, and rapidly progressive or fatal cases have been reported. Due to its rarity and overlapping radiological and histopathological features with those of other vascular lesions, its diagnosis can be challenging. We present the case of a 51-year-old female with multiple hepatic lesions, initially suspected to be hepatic hemangiomas. Six months later, the lesions had progressed rapidly. A percutaneous liver biopsy revealed dilated sinusoids lined with endothelial cells without marked atypia, thus suggesting a benign vascular lesion. However, the rapid clinical course raised concerns regarding hepatic angiosarcoma, and the patient received weekly paclitaxel followed by durvalumab. No therapeutic response was observed, and the patient died of tumor rupture. Autopsy revealed diffuse replacement of the hepatic parenchyma with multiloculated cystic vascular spaces lined with pleomorphic endothelial cells. No histological heterogeneity or extrahepatic lesions are observed. These findings supported the diagnosis of DHH. This case report contributes to the current knowledge of the clinical and pathological features of this rare entity. In addition, pleomorphic endothelial cells observed during autopsy may be attributable to treatment-related artifacts.

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Pulmonary Artery Intimal Sarcoma Successfully Treated With Surgery and Adjuvant Chemotherapy: A Case Report.

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We report a case of pulmonary artery intimal sarcoma successfully treated with surgical resection followed by weekly paclitaxel. The tumor harbored a tumor protein p53 mutation, amplifications of epidermal growth factor receptor, platelet-derived growth factor receptor alpha, and KIT, and focal positivity for mouse double minute 2.

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Hematological immune-related adverse events associated with immune checkpoint inhibitors (ICIs) are rare, and autoimmune hemolytic anemia (AIHA) is particularly uncommon. A 71-year-old woman with stage IIA triple-negative breast cancer received perioperative pembrolizumab with carboplatin and paclitaxel. During the first treatment cycle, she developed acute severe anemia with laboratory findings consistent with hemolysis. Despite a negative direct antiglobulin test (DAT), major alternative causes of hemolysis were considered unlikely, leading to a clinical diagnosis of suspected ICI-associated AIHA. Oral prednisolone (1 mg/kg) promptly resolved hemolysis without recurrence. Pembrolizumab was discontinued; however, imaging demonstrated a clinical complete response, and subsequent surgery confirmed a pathological complete response (pCR). This case demonstrates that AIHA during ICI therapy may occur despite a negative DAT and underscores the importance of prompt recognition and corticosteroid therapy. Favorable oncologic outcomes, including pCR, may still be achieved despite early discontinuation of ICI therapy.

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Performance of a sirolimus-eluting balloon with phospholipid nanocarriers in the treatment of long de novo coronary artery disease: the prospective GINGER trial.

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Sirolimus-coated balloons (SCB) may offer improved antiproliferative efficacy over paclitaxel-coated balloons; however, data regarding their performance in de novo coronary lesions are limited. The GINGER study aimed to evaluate the angiographic efficacy and clinical safety of a SCB (Magic Touch®) in the treatment of long (≥ 25 mm) de novo coronary artery lesions. This observational, prospective, multicenter, single-arm cohort study enrolled patients with at least one long de novo lesion treated with SCB. Co-primary endpoints were late lumen loss (LLL) and net lumen gain at 9 months. Secondary endpoints included: procedural success, periprocedural myocardial infarction, binary restenosis and a device-oriented composite endpoint (DOCE), defined as the composite of cardiac death, target vessel myocardial infarction (TV-MI) and clinically-driven target lesion revascularization (CD-TLR). The study was registered at ClinicalTrials.gov (NCT05471245). A total of 104 patients was enrolled at 8 centers. Mean lesion length was 28.9 ± 16.0 mm and reference vessel diameter was 2.3 ± 0.6 mm. Procedural success was achieved in all cases. At 9-month angiographic follow-up, LLL was 0.28 ± 0.68 mm, net lumen gain 0.62 ± 0.63 mm, and binary restenosis was observed in 33.3% of lesions. Clinical events at 12-month included DOCE in 6.7% of patients, cardiac death in 1.0%, TV-MI in 4.8% and CD-TLR in 3.8%. No lesion thrombosis was reported. In a real-world cohort of patients with long de novo coronary lesions, the Magic Touch SCB was associated with a LLL of 0.28 mm, which should be interpreted in light of the high complexity of treated lesions. Future randomized trials are warranted to evaluate its clinical efficacy in comparison with new-generation drug-eluting stents.

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