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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Paclitaxel (Taxol) is a taxoid, extracted from the bark of the Pacific yew tree, acts as an antimicrotubule agent through prevention depolymerization, thus, halting mitosis. Paclitaxel is approved to treat ovarian and breast cancers, and is used to treat endometrial and non-small-cell lung cancer. No studies of paclitaxel in pregnant women have been published.
Benign Disorders of Leukocytes
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Gene L. Gulati, Zoran Gatalica, Bong H. Hyun
Pelger-Huet anomaly is a benign autosomal dominant anomaly affecting primarily granulocytes, which are characterized by either bilobed nuclei (heterozygous form) or rounded nuclei (homozygous form) with coarsely clumped chromatin. The heterozygous form occurs in 1 in 6000 births, while the homozygous form is rare. The appearance of nuclei in neutrophils is classically described as “pince-nez” (a form of spectacles without ear pieces, very popular in Europe in the 1920s and 1930s). The more modern description compares them with the bikini tops (no straps). Nuclear chromatin is clumped in essentially all nucleated cells of the blood and bone marrow. In the heterozygous form, approximately 80% of neutrophils have classical bilobed nuclei, while a minor proportion has oblong, dumbbell, or peanut-shaped nuclei. A few neutrophils may have three-lobed nuclei, but it is rare, if not almost impossible, to find a four-lobed neutrophil. Pelger-Huet neutrophils are sometimes mistakenly identified as left shift, leading to unnecessary treatment. These cells function and survive normally. Affected individuals have normal resistance to infection. Acquired or pseudo-Pelger-Huet anomaly is more common and is associated with myelodysplastic syndromes, acute and chronic myeloid leukemias, HIV infection, and with the use of sulfonamides, colchicine, taxoid, etc. This acquired nuclear aberration is usually seen in minority of granulocytes and is a transient finding.
Current trends in the use of human serum albumin for drug delivery in cancer
Published in Expert Opinion on Drug Delivery, 2022
Milan Paul, Asif Mohd Itoo, Balaram Ghosh, Swati Biswas
Docetaxel is a taxoid, used clinically to treat various cancers, including breast, head, and neck, prostate, stomach, and non-small cell lung cancers. The conventional injectable formulation of DTX (Taxotere®) was approved by US-FDA in 1996 and formulated as a 40 mg/mL solution in Tween-80 (polyoxyethylene sorbitan monooleate, polysorbate 80), which further gets diluted with ethanol: water (13:87) and finally gets diluted with the infusion fluid. The formulation is accompanied by side effects, including acute hypersensitivity reactions and peripheral neuropathy. Hemolysis is also a common side effect. Moreover, Tween-80 inhibits the binding of taxanes to the transporter protein albumin, retarding their systemic transport. A phase II clinical trial of DTX-loaded albumin NPs was terminated in 2014 [72]. The toxicity could be one major issue, necessitating the development of an alternate strategy to prepare DTX-loaded albumin NPs.
Development and characterization of octreotide-modified curcumin plus docetaxel micelles for potential treatment of non-small-cell lung cancer
Published in Pharmaceutical Development and Technology, 2019
Quan An, Chen-Xiao Shi, Hao Guo, Shi-Min Xie, Ying-Ying Yang, Ying-Nan Liu, Zi-Hao Liu, Chang-Zheng Zhou, Feng-Ju Niu
Docetaxel is a taxoid antitumor agent used to treat several malignancies, including NSCLC (Chen et al. 2018). The antitumor mechanism of docetaxel is to suppress microtubular disassembly and prevent microtubular aggregation. Application of docetaxel as a free drug is limited because of its hydrophobicity and adverse effects such as hair loss, low blood cell counts, and vomiting. Micelles are promising drug carriers and can improve hydrophobic drug solubility. Polymeric micelles are formed from amphiphilic block polymers and can self-assemble in aqueous solution (Wang, Liu, Pu, et al. 2018; Rahdar et al. 2019). The graft copolymer, Soluplus (polyvinyl caprolactam polyvinyl acetate polyethylene glycol), is a newly developed double-affinity polymer compound with a low minimum micellar concentration (7.6 × 10−4% w/v), which enhances the solubility of some poorly water soluble drugs (Jin et al. 2015; Varela-Garcia et al. 2018).
Seek and destroy: improving PK/PD profiles of anticancer agents with nanoparticles
Published in Expert Review of Clinical Pharmacology, 2018
Anne Rodallec, Raphaelle Fanciullino, Bruno Lacarelle, Joseph Ciccolini
Because they are expected to spare healthy tissue, nanoparticles encapsulating cytotoxics should reduce the severe toxicities frequently observed with cytotoxics. Liposomal doxorubicin was primarily developed to reduce the cumulative cardio-toxic risk in breast cancer patients, rather than improving efficacy. Risks of developing cardiotoxicity with doxorubicin when compared to liposomal doxorubicin were significantly higher (i.e. p < 0.001) [70]. With liposomal vincristine (Marqibo®), accumulation in specific tissue such as lymph node allowed high doses (e.g. 2.25 mg/m2 QW, standard vincristine being used at 1.4 mg/m2) to be administered in ALL patients without triggering severe toxicities [71]. Similarly, a redox-responsive prodrug of docetaxel encapsulated into liposomes proved to be more effective and better tolerated and standard docetaxel in prostatic and lung cancer xenograft models, despite prolonged circulation time and higher exposure levels [32]. Non-clinical studies with nab-paclitaxel showed that DL50 could be increased by 70% in mice (i.e. 50 vs. 30 mg/kg), thus suggesting that nab-paclitaxel is better tolerated and can be administered with greater safety compared to conventional paclitaxel, most probably because toxic excipients used to solubilize taxoid drugs are not required anymore [61]. With other conjugated such as ADCs, specific payload release at the intracellular level ensures theoretically a much better tolerance. For instance, in rodents MTD of free emtansine was 0.2 mg/kg, but was 40 mg/kg, i.e. 200-fold higher, when conjugated to trastuzumab [72,73]. However, both on-target and off-target toxicities can still show with ADCs, potentially leading to halt early clinical development stages [74]. Indeed, in addition to target-mediated cell uptake, endocytosis, mannose receptors, FcRn and FcγR receptors can all lead to off-target toxicities and trigger unexpected side effects, even in tissue not presenting the target. For instance, thrombocytopenia is a common dose-limiting toxicity with TDM-1, despite lack of HER2 expression in platelets [75].