China
Africa
Explore chapters and articles related to this topic
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.
Drug Delivery
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Gudrun Fleischhack, Martin Garnett, Kévin Beccaria
Alkylating agents are highly effective in the treatment of a broad spectrum of malignancies in childhood, including CNS tumors. These agents exert their cytotoxic effect by covalent binding to DNA or proteins on nucleophilic macromolecules. By the formation of these reactive intermediates they disturb the DNA replication and transcription in form of single- or double-strand breaks and cross-linking the nucleic acids or nucleic acids with proteins. Hydrophilic alkylating agents (e.g., oxazaphosphorines) require active transport into the cells and are cell cycle-dependent whereas lipophilic alkylating agents (e.g., nitrosoureas) diffuse into the cells and are independent of cell proliferation. Besides these differences their antineoplastic activity and toxicity profile vary considerably due to their pharmacokinetic profiles (metabolism, CNS penetration, elimination, and detoxification). Based on their steep dose–response curve characteristics they are often used in high-dose chemotherapy regimens where the severe myelosuppression can be overcome by autologous or allogeneic stem cell transplantation. All these agents can produce relevant acute toxicity (e.g., renal, gastrointestinal, cutaneous, and neurological) and long-term side effects (e.g., infertility and permanent impaired renal function—all agents, pulmonary fibrosis linked to nitrosoureas). Additionally, they are highly carcinogenic, mutagenic, and teratogenic.15
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.
Incidence of solid cancer in patients with follicular lymphoma
Published in Acta Oncologica, 2019
Marc Sorigue, Roosa E.I. Prusila, Jyrki Jauhiainen, Santiago Mercadal, Aleksi Postila, Petteri Salmi, Taru Tanhua, Susanna Tikkanen, Sakari Kakko, Hanne Kuitunen, Marjukka Pollari, Ilja Nystrand, Milla E.L. Kuusisto, Kaija Vasala, Esa Jantunen, Eija Korkeila, Peeter Karihtala, Juan-Manuel Sancho, Taina Turpeenniemi-Hujanen, Outi Kuittinen
Patients who received alkylator- or anthracycline-based regimens had a lower cumulative incidence of solid cancer (<3% at 5 years) than those treated with bendamustine-based, radiotherapy or other regimens. However, patients treated with alkylating agents had a markedly higher risk of death at 5 years. We then compared anthracycline and bendamustine-based strategies, because they are the most commonly used at present [11]. The use of anthracycline-based front-line regimens was associated with a lower cumulative incidence of solid cancer when compared with bendamustine (Supplementary figure 1). However, patients who received anthracycline-based regimens were younger (median [IQR] age at diagnosis: 58 [49–65] for anthracycline-treated patients vs. 65 [58–73] for bendamustine-treated patients). All other baseline variables were similar between the two groups. In a Cox proportional hazard regression, including age and use of bendamustine- vs. anthracycline-based treatment, the former correlated with the development of solid cancer (hazard ratio for age at diagnosis: 1.044 [95% CI 1.021–1.066], p = .0001), while the latter was of borderline significance (hazard ratio for bendamustine-based therapy 2.47 [95% CI 0.92–6.68], p = .07) (Supplementary data).
45 GyRBE for group III orbital embryonal rhabdomyosarcoma
Published in Acta Oncologica, 2019
Daniel J. Indelicato, Ronny L. Rotondo, Raymond B. Mailhot Vega, Haruka Uezono, Scott Bradfield, Vibhuti Agarwal, Marinka L. Hol, Julie A. Bradley
Over the past two decades, the high cure rate for embryonal rhabdomyosarcoma of the orbit has prompted international efforts to de-intensify treatment. This effort has taken two broad forms in cooperative group studies via (a) reducing exposure to alkylating chemotherapy and (b) reducing exposure to ionizing radiation through lower prescription doses and smaller radiotherapy target volumes. A recent report from the Children’s Oncology Group (COG) [1]; however, asserts that children with group III embryonal orbital rhabdomyosarcoma who receive lower cumulative doses of cyclophosphamide (4.8 g/m2) and a lower radiation dose (45 Gy) to the tumor plus a 1-cm margin are at an increased risk of local failure compared to the historic Intergroup Rhabdomyosarcoma Study (IRS)-IV patients who received 26.4 g/m2 cyclophosphamide and 50.4 to 59.4 Gy to the tumor plus a 2-cm margin [2,3]. Specifically, the 5-year local failure rate increased from 2% to 13%. Patients with tumors demonstrating a partial response to induction chemotherapy were shown to be at particular risk of failure—approaching 16%—following the de-intensified therapy regimen. These findings prompted many COG institutions to revert to a dose of 50.4 Gy for group III orbital rhabdomyosarcoma.