China
Africa
Explore chapters and articles related to this topic
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
A further application of precision medicine technologies is to attempt to predict any unacceptable toxic effects of chemotherapeutic agents in individual patients so that doses can be reduced, or the agents avoided. For example, irinotecan (CamptoTM or CamptosarTM) is metabolized to the active agent SN-38, a potent topoisomerase I inhibitor which is approximately 200- to 2,000-fold more cytotoxic than irinotecan itself. SN-38 is inactivated through glucuronidation by the enzyme UGT1A1 (Uridine Diphosphate Glucoronosyltransferase 1A1), and approximately 10% of Caucasians have variants of the UGT1A1 gene, thus expressing lower level of UGT1A1 enzymes in their liver and leading to serious side effects from irinotecan treatment. Therefore, patients identified as carrying the variant UGT1A1 gene can be started on a lower dose of irinotecan, or an alternative agent prescribed. This use of biomarkers to guide treatment is discussed in Section 11.6.6.
Treatment of Cancer
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Two subtypes of lung cancer include non-small cell lung cancer and small cell lung cancer. The small cell lung cancer is the most aggressive form of lung cancer and is initially treated with a platinum-based combination regimen that includes cisplatin and irinotecan. Patients who fail the platinum-based therapy can be treated with topoisomerase I inhibitor topotecan. With early diagnosis, it may be curable using the combination of chemotherapy and radiation therapy.
The Genus Peganum
Published in Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen, Harmal, 2017
Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen
Jing Lu Liang and coworkers at Yeungnam University, Korea, found aerial parts of P. nigellastrum to contain a possible species-unique set of anticancer phytochemicals that they refer to as luotonins A, B, C, D, and E (pyrroloquinazolino-quinoline alkaloids, canthin-6-one alkaloids, and a 4(3H)-quinazolinone alkaloid) that are all cytotoxic to P-388 human leukemia cells, with luotonin A the most deadly owing to its modulation of topoisomerase I-dependent DNA-cleavage in the leukemic cells (Liang et al. 2011). The mechanism for this effect is related to the fact that luotonin A “stabilizes the human DNA topoisomerase I-DNA covalent binary complex, affording the same pattern of cleavage as the structurally related topoisomerase I inhibitor camptothecin” (Cagir et al. 2003). Luotonin A also mediated topoisomerase I-dependent cytotoxicity toward Saccharomyces cerevisiae lacking yeast topoisomerase I, but possessing a plasmid with the human topoisomerase I gene under the aegis of a galactose promoter (Figures 2.26 through 2.30).
Optimizing the storage of chemotherapeutics for ophthalmic oncology: stability of topotecan solution for intravitreal injection
Published in Ophthalmic Genetics, 2020
F. Bossacoma, M. Cuadrado-Vilanova, J. Vinent, M.G. Correa, D. Gavrus, H. Castillo-Ecija, J. Catala-Mora, J. Mora, P. Schaiquevich, G.L. Chantada, A. M. Carcaboso
Intravitreal administration of topotecan, a topoisomerase I inhibitor, has also been reported (4). Even though it also shows potent antitumor activity and its pharmacokinetics and ocular side effects have been described in detail, there is less experience in its use (5). The main degradation product of topotecan in aqueous solutions is produced by the pH-dependent hydrolysis of topotecan lactone ring to the open (inactive) topotecan carboxylate (6). To maintain the lactone form stable, topotecan formulations are acidified with tartaric acid (7). Topotecan aqueous solutions keep the pH below 4 and the lactone form is stable up to 24 h at room temperature and up to 7 days at 5°C, diluted at a concentration of 0.025 mg/mL in 5% dextrose or 0.9% sodium chloride, in PVC and polyolefin infusion bags and glass bottles (8). However, the stability of the topotecan concentration used for intravitreal injection (20 µg topotecan dose in 100 µL vehicle 0.9% sodium chloride; i.e., 0.2 mg/mL) remains not characterized, and the optimal conditions to conserve such solution should be defined. The aim of this study was to address the stability of this clinical formulation stored frozen or at RT for different times.
An update on current pharmacotherapy for vulvar cancer
Published in Expert Opinion on Pharmacotherapy, 2023
Giorgio Bogani, Innocenza Palaia, Giorgia Perniola, Federica Tomao, Antonella Giancotti, Daniele Di Mascio, Giuseppe Capalbo, Ludovico Muzii, Pierluigi Benedetti Panici, Violante Di Donato
In 1977, Deppe et al. evaluated for the first time the role of chemotherapy (adriamycin 45 mg/m2 every 3 weeks) in four patients with advanced vulvar carcinoma. Three out of four patients achieved objective regression of the nodal and primary tumor [37]. The EORTC phase II trial 55985 evaluated the role of paclitaxel (every 3 weeks for up to 10 cycles) in 31 patients with locally advanced, recurrent, or metastatic vulvar cancer [38]. The overall response rate was 13.8% (4 out of 29 women evaluable for response), thus suggesting a moderate activity of paclitaxel in vulvar cancer. Cormio et al. tested the combination between cisplatin and vinorelbine in recurrent vulvar cancer patients naive for chemotherapy [39]. The objective response rate was 40% (6 out of 16 women), and the median overall survival was 19 months [39]. Boabang et al., in an in vitro study, evaluated the cytotoxic effect of various chemotherapeutic agents (including topotecan, cisplatin, etoposide, and paclitaxel) in four squamous cell lines of cancers of the lower genital tract [40]. Topotecan (a topoisomerase I inhibitor) showed a more significant anti-tumor activity than other chemotherapeutic agents. However, we have to consider that topotecan use, in clinical practice, correlates with a high risk of hematological toxicity [40]. To date, no effective standard of care still exists for patients with recurrent or metastatic vulvar carcinoma. Generally, patients are treated with the same schedule used for concurrent chemoradiation, including cisplatin, paclitaxel, 5-fluorouracil, bleomycin, and ifosfamide [9,10]. Further investigations testing targeted therapies and immune checkpoint inhibitors are warranted in order to identify the most appropriate treatment paradigm for patients with metastatic disease.
Optimizing adjuvant and post-neoadjuvant therapy in HER2-positive early breast cancer
Published in Expert Review of Anticancer Therapy, 2022
Shimoli V. Barot, Erin Roesch, Jame Abraham
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate comprised of a humanized monoclonal anti-HER2 antibody linked to a potent topoisomerase I inhibitor payload via a cleavable tetrapeptide-based linker. It selectively binds HER2 and is internalized by the cell, where lysosomal enzymes cleave the peptide linker. The released topoisomerase I inhibitor payload damages tumor cell DNA. The payload also has high cell membrane permeability enabling elimination of both target and surrounding tumor cells[51]. T-DXd has shown robust and promising results in HER2-positive mBC. The single-arm phase II DESTINY-Breast01 study demonstrated a high rate of durable response (objective response rate of 61.4% and median duration of response of 20.8 months) and an excellent 18-month OS of 74% with T-DXd in a heavily pretreated population of 184 patients with HER2-positive mBC. The rates of ≥grade 3 treatment-related adverse events and interstitial lung disease (ILD) were 61.4% and 15.2% (28 patients) respectively[52]. This trial led to the U.S. Food and Drug Administration (FDA) approval of T-Dxd in December 2019 for the treatment of patients with unresectable or metastatic HER2-positive BC who have received two or more prior anti-HER2-based regimens. Furthermore, in the landmark phase III DESTINY-Breast03 trial, T-DXd demonstrated a significant improvement in PFS (hazard ratio 0.2840, p = 7.8 x 10−22) as compared to T-DM1 at a median follow-up of 16 months in 524 patients previously treated with trastuzumab and taxane for HER2-positive mBC. The benefit was observed across all pre-specified subgroups, including patients with brain metastases (hazard ratio 0.3796). The estimated 12-month OS was 94.1% vs 85.9% (hazard ratio 0.56, p = 0.007172) but long-term follow-up is needed to see if it crosses the pre-specified boundary for significance. There was no difference in treatment-related adverse events. The incidence of drug-related ILD was overall higher with T-DXd than with T-DM1 (10.5% vs 1.9%)[53].