Pulmonary reactions to chemotherapeutic agents: the ‘chemotherapy lung’
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Paclitaxel and docetaxel are chemotherapeutic agents used in the treatment of breast, ovarian and lung cancers. There are well-documented cases of pulmonary toxicity induced by paclitaxel in the literature, although the exact incidence remains elusive. Patients typically experience the onset of dry cough, dyspnoea and chest tightness within a few minutes of administration of the drug, suggesting a type 1 hypersensitivity reaction.62–64 IgE antibodies directed against paclitaxel or maybe its vehicle, Cremophor EL, are thought to be responsible. This reaction may occur in as many as 30 per cent of patients, and may be somewhat preventable by premedication with steroids. Lung auscultation may reveal significant wheezing, suggesting bronchospasm. Radiographic findings are non-specific, typically consisting of transient interstitial infiltrates, suggesting a hypersensitivity mechanism. Cases of non-cardiogenic pulmonary oedema have been described. Rare cases of interstitial pneumonitis presumably induced by docetaxel have also been reported. The combination of docetaxel and gemcitabine may be particularly harmful.
An Introduction to the Ethnopharmacology of Wild Plants
Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa in Ethnopharmacology of Wild Plants, 2021
The first agents to advance into clinical use were the isolation of the vinca alkaloids, vinblastine, and vincristine from Catharanthus roseus, for the treatment of cancer followed by the discovery of paclitaxel from Taxus brevifolia (Kinghorn 1994, Kaur et al. 2011). Various parts of the Taxus have been used for the treatment of some noncancerous cases (Crag and Newmann 2005). Taxus baccata was also reported for the treatment of cancer. Paclitaxel is significantly active against ovarian cancer, advanced breast cancer, and lung cancer. Topotecan is used for ovarian and lung cancer from Xi shu tree [Camptotheca acuminata] (Steenhuysen 2007). Camptothecin, isolated from Camptotheca acuminate, is used for the treatment of ovarian and small cell lung cancers, and colorectal cancers (Kinghorn 1994, Creemer et al. 1996, Bertino 1997). Irinotecan is used for colon cancer treatment from Xishu tree [Camptotheca acuminate] (Online Medical Dictionary 2007). Epipodophyllotoxin was isolated as the active antitumor agent from the roots of Podophyllum species, Podophyllum peltatum and Podophyllum emodi, used in the treatment of lymphomas and bronchial and testicular cancers (Harvey 1999). The Podophyllum peltatum and P. emodii are used for the skin cancers.
Small-Molecule Targeted Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The agent has been investigated in clinical trials for the treatment of progeria, a rare genetic disorder in which symptoms of aging occur prematurely. A Phase II clinical trial was completed in 2012, which demonstrated that a combination of lonafarnib and two other agents met clinical efficacy endpoints. In another clinical study in patients with metastatic NSCLC who had failed previous taxane regimens, lonafarnib was found to have some antitumor activity in the 29 patients studied, with 3 achieving partial responses, an overall 16-week average disease-free progression survival time and an average overall survival of 39 weeks. However, these results were insufficient for further progression of lonafarnib. Minimal side effects were observed with this combination of paclitaxel and lonafarnib, with fatigue, diarrhea, and dyspnea being the most frequent side effects. Only one patient had a significant reduction in white blood cell count and reports of more serious side effects such as respiratory insufficiency and acute respiratory failure were infrequent.
Functional paclitaxel plus honokiol micelles destroying tumour metastasis in treatment of non-small-cell lung cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Xin Wang, Lan Cheng, Hong-Jun Xie, Rui-Jun Ju, Yao Xiao, Min Fu, Jing-Jing Liu, Xue-Tao Li
Dequalinium (DQA) is a quaternary ammonium cation. As a kind of mitochondrial-targeted drug, DQA can selectively accumulated in the mitochondria of cancer cells. Some previous studies had demonstrated that the modification of DQA on the liposomal surface could increase the cellular uptake by electrostatic interactions [14,15]. Honokiol is an active natural extract of traditional Chinese herb Magnolia offcinalis, and it is widely used as a supplementary functional drug in treatment of cancer for the various biological properties such as inhibiting the VM channels, suppressing the invasion of cancer cells and reducing the adhesion rate between cancer cells and body environment [16,17]. Paclitaxel is one of the most effective chemotherapy drugs for treating various kinds of cancer. The underlying mechanism for the cytotoxicity of paclitaxel is mainly from binding tubulin and stabilizing microtubules. These stable microtubules inhibit the division of cancer cells at the G2/M phase of cell cycle [18,19]. Therefore, the combination of paclitaxel plus honokiol was considered for the preparation of micelles. In this way, the proliferation of lung cancer cells was restricted by paclitaxel, and cellular metastases and VM channels were suppressed by honokiol in the meanwhile. This combination fundamentally solved the problem of tumor metastasis which was inevitable for traditional chemotherapy when killing cancer cells.
The development of peptide-drug conjugates (PDCs) strategies for paclitaxel
Published in Expert Opinion on Drug Delivery, 2022
Longkun Wang, Hongyuan Chen, Fengshan Wang, Xinke Zhang
Paclitaxel is a first-line anti-cancer drug for ovarian and breast cancer, as well as other types of solid tumors. However, it is also faced with various challenges especially for its poor water solubility, low selectivity for the target, and resistance. Peptide-drug conjugates are a unique class of molecules that integrate peptides and small-molecule drugs to achieve increased therapeutic outcomes and enhanced therapeutic index. Currently, various peptide-paclitaxel conjugates have been synthesized to increase water solubility, alter cellular mechanisms, and target-specific tissues. Taking advantage of tumor-targeting peptide, paclitaxel can be delivered and internalized into specific tumor cells with minimizing exposure to healthy cells, and conjugates can rapidly liberate the paclitaxel to restore its activity under the stimulation of the tumor microenvironment. With the aid of cell-penetrating peptides, the conjugates can not only improve the water solubility and penetrability of paclitaxel in the form of nanoparticles but also combat drug resistance by changing the way of drug entering cells.
Paclitaxel-loaded nanoparticles decorated with bivalent fragment HAb18 F(ab’)2 and cell penetrating peptide for improved therapeutic effect on hepatocellular carcinoma
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Cheng Jin, Ling Bai, Lemin Lin, Shuangquan Wang, Xiaolong Yin
Paclitaxel is a highly potent anticancer drug for different cancers, especially cervical, breast, lung and ovarian cancers [9]. There are many reports in the literature regarding the activity of paclitaxel against HCC in vitro and in vivo [10–12]. Due to poor water solubility, paclitaxel is traditionally intravenously administered with cremophor EL® [polyethoxylated castor oil and ethanol (1:1, v/v)] as a solvent. However, cremophor EL may cause serious undesired side-effects and lead to hypersensitivity reactions in many patients. Recently, an albumin-bound paclitaxel NPs (Abraxane™) is the first Cremophor EL-free paclitaxel agent which was approved for clinical application by the Food and Drug Administration [13]. Our previous study suggested the selective therapeutic effect of targeted paclitaxel loaded NPs on liver cancer stem cells [14].
Related Knowledge Centers
- Chemotherapy
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- Pancreatic Cancer
- Intravenous Therapy
- Protein-Bound Paclitaxel