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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Antineoplastic drugs most commonly used to treat chronic leukemia include antimetabolites (methotrexate, thioguanine, mercaptopurine, and cytarabine), anthracycline antibiotics (daunorubicin and doxorubicin), and plant alkaloids (vincristine). Alkylating agents are also used as antileukemic drugs. Notably, all of these drugs are cytostatic, although mechanisms differ (cytotoxicity, DNA, and protein synthesis suppression). Therefore, all antineoplastics have a very high potential for causing birth defects with exposure during embryogenesis because this period is characterized by the highest rate of cell division (hyperplasia) and increase in size (hypertrophy) during human life.
Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Alkylating agents include the subclass of nitrogen mustards, of which the compounds in most common use today include cyclophosphamide, ifosfamide, and melphalan, and chlorambucil. To exhibit their antineoplastic properties, many of these agents, such as cyclophosphamide, must be converted to an active metabolite in the liver. The compounds then attach to the alkyl groups in DNA, causing cross-linking between double-helix strands and preventing the uncoiling of DNA that is necessary for replication. Alkylating agents are used in several different tumor types including, but not limited to, breast cancer, NHL, chronic lymphocytic leukemia, ovarian cancer, bone and soft-tissue sarcomas, and rhabdomyosarcomas.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The alkylating agents (a term often used to encompass both methylating and cross-linking agents) are still among the most widely used drugs in cancer chemotherapy. They exert their biological effect by interacting covalently with DNA, thus interfering directly with cell replication. In addition to the side effects common to many cytotoxic agents, there are two further problems associated with prolonged use. First, gametogenesis can be severely affected, thus leading to infertility, and, second, when combined with extensive irradiation, these agents cause a significant increase in the incidence of acute nonlymphocytic leukemia later in life.
Nivolumab plus ipilimumab in metastatic uveal melanoma: a real-life, retrospective cohort of 47 patients
Published in OncoImmunology, 2022
Hélène Salaün, Leanne de Koning, Mathilde Saint-Ghislain, Vincent Servois, Toulsie Ramtohul, Agathe Garcia, Alexandre Matet, Nathalie Cassoux, Pascale Mariani, Sophie Piperno-Neumann, Manuel Rodrigues
Uveal melanoma (UM) is the most frequent primary intraocular malignancy in adults. Metastases occur in one-third to half of UM patients, predominantly in the liver.1 Once metastatic, UM is associated with poor prognosis, with a median overall survival (OS) of 12–16 months.2,3 Alkylating agents have been the main therapeutic option for the last decades. More recently, immune checkpoint inhibitors (ICI) such as nivolumab or pembrolizumab have been used, but overall response rate (ORR) is usually less than 5%, and no benefit on survival has been reported.4,5 Very recently, tebentafusp, a bispecific T-cell engager that redirects the cells toward gp100-positive melanocytes, has become the standard of care for HLA-A02:01-positive metastatic patients where available.2 However, there is currently no standard of care neither for HLA-A02:01-positive patients who progress on tebentafusp nor for HLA-A02:01-negative metastatic patient in first line.
Treatment of classical Hodgkin’s lymphoma in children and adolescents
Published in Expert Opinion on Pharmacotherapy, 2019
David Gómez-Almaguer, Oscar González-Llano, Valentine Jiménez-Antolinez, Andrés Gómez-De León
Another important side effect of treatment is infertility, the use of alkylating agents is related to gonadal dysfunction including azoospermia in male patients and premature ovarian failure in women [59]. A study of GHSG assessing fertility in female patients after being treated with trials HD7 to HD9, showed that at 3.2 years of follow up, 51% of patients receiving eight cycles of dose-escalated BEACOPP present amenorrhea [60]. When comparing ABVD and BEACOPP in female fertility, amenorrhea is more common in the latter; despite this fact a recent single-center study showed that there is no significant difference between females treated with ABVD or BEACOPP in achieving pregnancy [61]. The American Society of Clinical Oncology updated in 2018 the guidelines for fertility preservation in children and adults with cancer. For postpubertal children options include semen or oocyte cryopreservation but for prepubertal children ovarian or testicular cryopreservation are still in investigation [62].
Anticancer therapy and lung injury: molecular mechanisms
Published in Expert Review of Anticancer Therapy, 2018
Li Li, Henry Mok, Pavan Jhaveri, Mark D Bonnen, Andrew G Sikora, N. Tony Eissa, Ritsuko U Komaki, Yohannes T Ghebre
Alkylating antineoplastic agents are a class of chemotherapeutic drugs that recognize and directly interact with DNA by transferring their alkyl group to the DNA base. Alkylating agents are very effective in treating several cancer types including hematologic malignancies, breast cancer, and lung cancer. Examples of alkylating antineoplastic agents include nitrogen mustards (e.g. cyclophosphamide, chlorambucil), nitrosureas (e.g. carmustine, streptozocin), hydrazines (procarbazine, temozolomide), alkyl sulfonates (e.g. busulfan), and metal salts (cisplatin, carboplatin). Preclinical studies and case reports indicate that these agents have significant adverse effects including causing lung toxicity that extends from acute pneumonitis to late-onset pneumonitis that progresses into fibrosis [17].