The Precision Medicine Approach in Oncology
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Capecitabine (XelodaTM) and 5-fluorouracil are fluoropyrimidine antimetabolites (Figure 11.27) used in the treatment of breast and GI cancers including esophageal, gastric, and colorectal. For breast cancer they are often used in combination with docetaxel. Common side effects of agents of this type include diarrhea, vomiting, abdominal pain, fatigue, and rashes. Other less common but more serious side effects include myelosuppression, neurotoxicity, cardiac toxicities, blood clotting problems, allergic reactions, and hand-foot syndrome. Between 10–30% of patients have severe side effects from capecitabine and 5FU, and less than 1% die from their treatment. Structures of capecitabine (XelodaTM) and 5-Fluouracil.
Complications of Intravesical Therapy
Kevin R. Loughlin in Complications of Urologic Surgery and Practice, 2007
There has been only one Phase I clinical trial of intravesical docetaxel reported, but its novelty, activity, and tolerability deserve mention (96). In this dose-escalating trial, docetaxel was administered beginning at 5 mg in 40 cc saline, increasing to 75 mg in 100 cc over a total of six dose ranges once a week for 6 weeks. All patients were pretreated with oral dexamethasone to decrease the probability of a hypersensitivity reaction, estimated to occur with a frequency of 6.5% with systemic therapy (97). There was no systemic absorption noted in any patient. Three patients reported urinary frequency (grade I), four patients experienced dysuria (grade I), five had hematuria (2 grade I, 3 grade II), and three had transient facial flushing (grade I). These mild toxicities occurred at all dose levels without a clear indication of dose effect. All resolved without any clinical intervention. No dose-limiting toxic levels was reached. Five of these all pretreated BCG-failure patients are disease-free at 14 months of follow-up (98).
Management of Anaplastic Thyroid Cancer/Lymphoma
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
In the presence of metastatic ATC, life expectancy is poor and therefore maintaining a good quality of life for as long as possible is imperative. Short 1–2-week courses of radiation as described above may control local symptoms. Unfortunately, ATC is not a chemosensitive disease and the response rates to systemic therapy are generally poor and short-lived. Currently, of the available chemotherapeutic agents the taxanes (paclitaxel or docetaxel), doxorubicin and cisplatin have the greatest clinical effect. Docetaxel (60 mg/m2 i.v. every 3 weeks) can stabilize disease for a time and rarely results in a complete response.25 There are several small reports on the use of molecular targeted agents. Antimicrotubular agents and kinase inhibitors occasionally result in a partial response or stable disease but more research is required.2, 7, 32 Palliative radiation may be required for bone and lung metastases.33
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
Curcumin is difficult to use in drug development for several reasons, including water insolubility, chemical instability, low bioavailability, an absence of potency and selective target activity, and limited tissue distribution. However, curcumin can inhibit tumor metastasis in other ways. Docetaxel is a chemotherapeutic agent used to treat several cancers, including NSCLC, breast cancer, head and neck cancer, and stomach cancer. The application of docetaxel as an antitumor drug is limited because of its hydrophobicity and adverse effects. In this study, codelivery of curcumin and docetaxel in OCT-modified micelles simultaneously induced tumor cell apoptosis and inhibited tumor metastasis. The OCT-modified curcumin plus docetaxel micelles have several prominent physicochemical properties, including smooth spherical morphology (Figure 1B) and centralized particle size distribution (Figure 1C). High encapsulation efficiency, suitable particle size of the targeting micelles, and delayed release behavior would help prevent the rapid leakage during drug delivery and the accumulation in tumor tissues through the leaky vasculature (Li et al. 2013).
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.
An up-to-date evaluation of abiraterone for the treatment of prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Jason Shpilsky, Julia Stevens, Glenn Bubley
Abiraterone is an effective and well-tolerated addition to ADT in both mCSPC and mCRPC. In mCSPC, docetaxel has primarily demonstrated a benefit in high-volume disease whereas abiraterone has demonstrated a benefit in a general mCSPC population [30,40]. Furthermore, docetaxel is associated with fatigue, neuropathy, and cytopenias which may preclude use in an elderly population. Intravenous docetaxel is less convenient as compared to an oral therapy. When considering apalutamide or enzalutamide, providers must consider the risks for seizures, falls, and fatigue. Although there are no head-to-head studies comparing efficacy of abiraterone to the novel anti-androgens in this setting, sequencing data with abiraterone versus enzalutamide for mCRPC are instructive. The crossover trial by Khalaf and colleagues indicated that using abiraterone before enzalutamide may be beneficial due to low abiraterone response after enzalutamide failure [31]. These results could be extrapolated to use of abiraterone for mCSPC to allow subsequent use of enzalutamide for mCRPC.