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Integrative hyperthermia treatments for different types of cancer
Published in Clifford L. K. Pang, Kaiman Lee, Hyperthermia in Oncology, 2015
Clifford L. K. Pang, Kaiman Lee
It is applied for endocrine-refractory metastatic prostate cancer patients to delay cancer growth and prolong the lives of patients. Studies have confirmed that docetaxel can effectively prolong the survival time of endocrine-refractory metastatic prostate cancer patients, whereas cabazitaxel can further extend the survival time of patients failed by the treatment of docetaxel. Many clinical trials are studying new drugs and drug combinations, aiming to find treatment means with more effectiveness and less adverse reactions.
Therapeutic Options for Prostate Cancer: A Contemporary Update
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sakthivel Muniyan, Jawed A. Siddiqui, Surinder K. Batra
Historically, advanced PCa is frequently managed with chemotherapies whenever the patients exhaust other AR-targeting approaches. Taxol-based chemotherapeutic agents were shown to be significantly associated with the beneficial effects of PCa management; for the same reason FDA approved it for CRPCa [22, 24]. Docetaxel is a microtubule stabilizing agent, which will lead to cell cycle arrest at G2/M phase eventually resulting in apoptosis [51, 52]. Microtubules are intracellular filaments that take part in cytoskeleton structural maintenance, vesicular transport, cellular trafficking, and mitochondrial functioning. Taxanes may promote apoptosis by inhibiting the anti-apoptotic function of BCL2 family of proteins [51] and tumor suppressor protein p53 function [52], up-regulating cyclin-dependent kinase inhibitor A (p21, Cip1) [53]. Recently, it has also been proposed that the docetaxel may inhibit AR vesicular transport apart from microtubule formation and thereby induces apoptosis [54, 55]. Cabazitaxel is a next-generation semisynthetic taxane derived from a precursor extracted from yew tree needles. The primary mechanism of action of cabazitaxel is similar to docetaxel in binding and inhibiting β-tubulin, thereby resulting in cell death through G2/M arrest. However, in clinics, it has a limitation of crossing the blood-brain barrier and reduced p-glycoprotein (pgp) binding affinity [56]. In vitro, it shows higher efficacy than docetaxel in PCa cells [57]. Mitoxantrone hydrochloride is another chemotherapeutic agent used in the treatment of CR PCa patents along with prednisone, which exhausted all other therapeutic options. Mitoxantrone is a type II topoisomerase inhibitor, which will inhibit cell proliferation by disrupting DNA synthesis and DNA repair by intercalation between the DNA bases [58, 59]. Today, there are various chemotherapeutic agents available but are palliative for CR PCa patients who has exhausted all other therapeutic options.
Urological Anti-cancer Agents
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Bernadett Szabados, Thomas Powles
Castration-resistant metastatic prostate cancer treated with previous docetaxel.Six cycles of Cabazitaxel every three weeks.
Advances in paclitaxel combinations for treating cervical cancer
Published in Expert Opinion on Pharmacotherapy, 2020
Luigi Della Corte, Fabio Barra, Virginia Foreste, Pierluigi Giampaolino, Giulio Evangelisti, Simone Ferrero, Giuseppe Bifulco
The remarkable clinical development of nab-paclitaxel has ensured investigators and various other nano-formulations and taxane conjugates have been researched. However, only a small part of the nano-formulations has reached the experimental clinical status. Poly(l-glutamic acid)-paclitaxel (PG-TXL) belongs to the few formulations reaching phase III clinical trials in oncology; unfortunately, the development of PG-TXL stopped in 2016 due to the inability to show significant improvement over current standard care; paclitaxel bound to DHA (a natural fatty acid) has advanced to phase III trials for metastatic melanoma; cabazitaxel, a semisynthetic derivative of docetaxel, obtained a notable antitumor activity in preclinical and clinical studies in docetaxel-refractory clinical settings. In contrast to the first-generation taxanes, this compound is a poor substrate for P-glycoprotein. Cabazitaxel was approved by the FDA in 2010 for the treatment of hormone-refractory prostate cancer. New studies on derivative of conventional taxanes for cervical cancer are demanding [105].
PARP inhibitors for homologous recombination-deficient prostate cancer
Published in Expert Opinion on Emerging Drugs, 2018
Eric S. Christenson, Emmanuel S. Antonarakis
Cabazitaxel is newer microtubule inhibitor that is approved for use in patients with prostate adenocarcinoma after progression on docetaxel therapy or who are intolerant. This is based on the results of the TROPIC trial, which showed an improvement in progression-free survival (2.8 versus 1.4 months) and overall survival (15.1 versus 12.7 months) of cabazitaxel over mitoxantrone when used in combination with prednisone after prior receipt of docetaxel therapy [24]. A recent first-line chemotherapy trial (FIRSTANA) comparing docetaxel versus cabazitaxel in chemotherapy-untreated CRPC patients failed to show superiority of cabazitaxel in this setting, while a second study suggested that patients who don’t achieve an adequate initial PSA response to docetaxel might fare better if they are immediately switched to cabazitaxel [25,26]. Thus, cabazitaxel generally remains a second-line chemotherapy option for CRPC at present, while docetaxel is the preferred first-line treatment. In addition, docetaxel added to androgen deprivation has been shown to improve survival in men with metastatic hormone-sensitive prostate cancer with higher initial disease burden, representing a reasonable standard of care for newly diagnosed metastatic patients who are chemo-fit [27–29].
Emerging cell cycle inhibitors for treating metastatic castration-resistant prostate cancer
Published in Expert Opinion on Emerging Drugs, 2018
Cabazitaxel is a semisynthetic taxane derivative approved for second-line mCRPC for patients having cancer progression despite docetaxel. In the phase III TROPIC trial, the hazard ratio for death in men treated with cabazitaxel (25 mg/m2 every three weeks) compared with those taking mitoxantrone (12 mg/m2 every three weeks) was 0.70 (95% CI 0.59–0.83; p < 0.0001) [33]. The most common clinically significant grade 3 or higher adverse events observed with cabazitaxel were neutropenia (82%) and diarrhea (6%). Twenty-eight (8%) patients in the cabazitaxel group and five (1%) in the mitoxantrone group had febrile neutropenia. Contraindications to the use of cabazitaxel include underlying hepatic dysfunction or compromised bone marrow function.