Chemotherapy in pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
The use of cytotoxic chemotherapy in pregnancy has been reported for a number of different tumor types. While most of these studies have a limited number of patients, the data would suggest that many of these agents are quite safe in pregnancy, particularly in the second and third trimesters. In breast cancer, the use of a combination of 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide was found to be without complication to the fetus or infant when given in the second or third trimester (12). Taxanes have been used to treat patients with breast cancer. However, published studies at this time are limited to a small number of case reports (13,14). Other drugs used to treat breast cancer include vinorelbine, capecitabine, gemcitabine, trastuzumab, and tamoxifen, many of which are discussed subsequently.
Heterocyclic Drugs from Plants
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
Docetaxel better recognizes as Taxotere, is a heterocyclic plant-derived anticancer drug that is frequently used to treat cancers like stomach, lung (NSCLC) breast, brain, prostate, and others (General Cancer Information, 2016). Docetaxel is a semi-synthetic product of taxol (paclitaxel), separated from the bark of Pacific yew (Taxus brevifolia) giving insight as to its brand name taxotere. Taxol (paclitaxel) is commonly extracted from Taxus brevifolia and is required to treat ovarian, breast, and NSCLC. Paclitaxel can also treat AIDS-related Kaposi sarcoma (Paclitaxel, 2018). Both docetaxel and paclitaxel belong to ‘taxanes’ which is a diterpene class having a taxadiene core (Zhao et al., 2012). Taxanes are very efficient anticancer drugs. In contrast, diterpenes belong to a class called ‘terpenoids.’ Docetaxel is a frontline anticancer chemotherapeutic agent in this era (Choi et al., 2015).
Principles of Chemotherapy
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
There is still debate as to whether induction chemotherapy followed by concurrent chemoradiotherapy is more beneficial than concurrent chemoradiotherapy alone. Some large trials have shown no benefit10 while others have shown some.11 Interest was rekindled in induction chemotherapy when two trials, one European and one from North America, ‘TAX 323’ and ‘TAX 324’ showed benefit by including a taxane, such as docetaxel or paclitaxel in the induction chemotherapy regime in addition to cisplatin and 5-FU.12, 13 Response rates and survival outcomes were higher with taxane-containing regimens but toxicity was considerably higher and chemotherapy-related deaths were also increased with these regimens. Such sequential regimens are offered to patients with good performance status and fewer comorbidities, and those with bulky nodal disease, stage N2b and above, and where surgery is not appropriate.
Comparative Analysis of the Chemotherapy-Related Cognitive Impairments in Patients with Breast Cancer: A Community-Based Research
Published in Cancer Investigation, 2022
Maryam Owrangi, Mohammad Javad Gholamzadeh, Maryam Vasaghi Gharamaleki, Seyedeh Zahra Mousavi, Ali-Mohammad Kamali, Mehdi Dehghani, Prasun Chakrabarti, Mohammad Nami
In conclusion, although this study has confirmed the CRCI concept similar to previous literature and revealed potential worse neurotoxic effects of the AC-T regimen on attention, working memory, and language domains compared with the other commonly prescribed regimen, the exact mechanism behind the CRCI has not been fully identified and further research is needed. Since the emergence of the CRCI concept, different mechanisms have been proposed for this phenomenon. Neurotoxicity is a well-known side effect of taxanes in such a way that they can cause peripheral neuropathy, ataxia, cognitive decline, etc. Paclitaxel and docetaxel, which are parts of the AC-T and TAC regimens respectively, are the most commonly used taxanes. The mechanisms suggested for their neurotoxic impacts despite limited crossing of the blood-brain barrier (BBB) include negative effects on microtubule dynamics and synaptic plasticity, neuronal apoptosis, decreased hippocampal cell proliferation, cytokine dysregulation, and consequently neuroinflammation (41). In addition, as most of the BC chemotherapeutics with the exception of cyclophosphamide and fluorouracil can’t easily cross the BBB, oxidative stress and cytokine dysregulation seem to play an important role in developing CRCI (42).
Docetaxel-induced acute myositis: a case report with review of literature
Published in Journal of Chemotherapy, 2021
Sariya Wongsaengsak, Miguel Quirch, Somedeb Ball, Anita Sultan, Nusrat Jahan, Mohamed Elmassry, Shabnam Rehman
While the exact pathophysiology of docetaxel related myositis remains unclear, a few potential hypotheses have been proposed. First, taxanes induce an increase in the level of cytokines which have a cytotoxic effect on tumor cells leading to the release of tumor-derived antigens. These antigens and their secondary immune then induced an infiltration of monocytes and B cells.26 Several reports have suggested that taxanes are capable of inducing cytokine expression in various human tissues, including tumor cells and leukocytes.27–29 A study done by Tsavaris et al. on thirty patients with advanced breast cancer treated with single agent docetaxel or paclitaxel showed a significant increase in serum concentrations of IFN-ˠ, IL-2, IL-6, compared to pretreatment state and healthy controls. This effect was significantly more pronounced in patients treated with docetaxel than paclitaxel.26 An increase in levels of IL8, IL6, and IL10 was also noted following therapy with paclitaxel (in comparison with other cytotoxic regimens) in another similar report. The change in these cytokines significantly correlated with the onset of musculoskeletal adverse effects, such as fatigue and generalized myalgia.30 The other hypothesis is possible direct toxic effect of taxane on muscle tissue, as suggested by an increase in the acid phosphatase staining (indicative of accumulation of lysosomes) on muscle biopsy of patients exposed to these medications.1
Atezolizumab in the treatment of metastatic triple-negative breast cancer
Published in Expert Opinion on Biological Therapy, 2020
José Pérez-García, Jesús Soberino, Fabricio Racca, María Gion, Agostina Stradella, Javier Cortés
Taxanes inhibit cellular division via microtubule stabilization and induce mitotic catastrophe, a tumor-suppressive mechanism triggered during or after defective mitosis, culminating in senescence or cell death [44]. Recent data indicate that cancer cells escaping mitotic catastrophe efficiently promote the secretion of type I interferon (IFN), following the detection of cytosolic double-stranded DNA by pattern-recognition receptor cyclic GMP-AMP synthase, potentially resulting in their elimination by immunological mechanisms [45,46]. In addition to microtubule stabilization, taxanes have been reported to exert multiple immunomodulatory actions, promoting macrophage activation, differentiation and maturation of dendritic cells, inducing T cell proliferation and natural killer cells-mediated tumor cell lysis, and production of immunoenhancing cytokines such as interleukin 12, IFNγ, tumor necrosis factor α, and granulocyte-macrophage colony-stimulating factor, all which may increase the antitumor activity of immunotherapies ([40,41] and references therein).
Related Knowledge Centers
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