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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Carmustine (BCNU) is an alkylating agent, FDA-approved for chemotherapy of a variety of neoplasms including multiple myeloma, lymphomas, and brain tumors. In a case report, one patient took carmustine throughout pregnancy and delivered a normal neonate (Schapira and Chudley, 1984). Carmustine must be suspected of being teratogenic because of its biochemical action (an alkylating agent) on substrates such as nucleotides. Rodents exposed to carmustine at several times the usual human dose during embryogenesis had increased frequency of birth defects (Wong and Wells, 1989). Otherwise, little information is published about the use of this agent during pregnancy in humans or animals.
Central nervous system neoplasms
Published in Ibrahim Natalwala, Ammar Natalwala, E Glucksman, MCQs in Neurology and Neurosurgery for Medical Students, 2022
Ibrahim Natalwala, Ammar Natalwala, E Glucksman
A 79-year-old man is brought to the A&E department because of a prolonged seizure. An MRI scan of his head shows a mass in the right cerebral hemisphere and a biopsy shows pleomorphic tumour cells bordering a central area of necrosis. The tumour cells stain positive for glial fibrillary acid protein. The patient undergoes a tumour debulking procedure where carmustine wafers are inserted into the tumour cavity. What is the mechanism of action of the class of drugs that includes carmustine? An alkylating agent that cross-links DNAAn antibiotic that intercalates DNAAn anti-metabolite that decreases DNA synthesisA vinca alkaloid that inhibits microtubule formationA monoclonal antibody directed against a specific tumour cell receptor
Carmustine
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Carmustine is a nonspecific nitrosurea derivative and alkylating antineoplastic agent. It alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. This agent also carbamoylates proteins, including DNA repair enzymes, resulting in an enhanced cytotoxic effect. Carmustine is indicated for the treatment of brain tumors, multiple myeloma, Hodgkin’s disease and non-Hodgkin’s lymphomas. It may also be administered topically in the treatment of cutaneous T-cell lymphoma (1).
Current therapeutic options for glioblastoma and future perspectives
Published in Expert Opinion on Pharmacotherapy, 2022
Elisa Aquilanti, Patrick Y. Wen
Nitrosoureas are alkylating agents that have adequate blood–brain barrier penetration. Examples of nitrosoureas are lomustine (CCNU), nimustine (ACNU), carmustine (BCNU), and fotemustine. Lomustine is the most used in the United States, and it is generally preferred over carmustine because of its oral administration. Lomustine is dosed at 90–130 mg/m2 every 6 weeks. Fotemustine is frequently used in some European countries. In randomized phase III trials that used lomustine as a control arm, the lomustine-only group showed response rates of ~10% or less, progression-free survival at 6 months of ~20% and overall survival of 6–9 months [28,40–42]. Lomustine was studied in combination regimens with procarbazine and vincristine (PCV) in older clinical trials, which showed response rates of ~3–11%, progression-free survival of ~3 months and overall survival of ~8 months [43,44].
Loco-regional drug delivery in oncology: current clinical applications and future translational opportunities
Published in Expert Opinion on Drug Delivery, 2021
Seona M. Rossi, Timothy Murray, Liam McDonough, Helena Kelly
Gliadel® wafers have been shown to release carmustine in vivo over a period of approximately 5 days with complete degradation of the wafer occurring over a period of 6–8 weeks. Release of the drug is characterized by two distinct phases, the diffusion-driven induction period in the first 10 h, followed by an erosion period where release is driven by the copolymer erosion with release facilitated by the increasing porosity of the wafer over time. Both in vitro and in vivo data shows that the release of carmustine from Gliadel® occurs over a period of approximately 5 days [52,53]. In vivo studies in rats and non-human primates show high dose delivery of carmustine at the tissue/polymer interface resulting in high tissue concentrations close to the implant site but dropping off rapidly (within 3 mm) highlighting one of the challenges of loco-regional delivery in terms of achieving adequate coverage at the tumor site. In non-human primate studies significant drug concentrations were also observed at greater distances from the implant site, upto 2 cm, possibly due to convective flows from postsurgical edema or through cerebrospinal fluid flow [54–56].
A novel strategy to the formulation of carmustine and bioactive nanoparticles co-loaded PLGA biocomposite spheres for targeting drug delivery to glioma treatment and nursing care
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Shufeng Yi, Fan Yang, Cunle Jie, Guiqin Zhang
Carmustine was recently used as a drug for treating glioma [13–15]. However, its usage was restricted due to the side effects such as bone marrow suppression [16] and pulmonary fibrosis [17]. To limit its toxicity, carmustine was impregnated with gliadel wafers [18]. These gliadel wafers were not successful as they do not show effective therapeutic efficacy due to poor penetration, inability to prevent tumor recurrence, lack of synergetic action with other chemotherapeutic drugs and/or radiotherapy [18,19]. To overcome these problems, different drug delivery vehicles were developed recently. These include liposomes, nanoshells, dendrimers, polymeric micelles, carbon nanotubes, polyglycolic acid (PGA) nanoparticles, polylactic acid (PLA) nanoparticles, and poly (D, L-lactic-coglycolides) acid (PLGA) nanoparticles [20,21]. In the present study, we hypothesize that carmustine and gold-loaded PLGA will be an effective treatment strategy for targeting glioma or brain tumors. The carmustine-gold-loaded PLGA will be target-specific, enhance therapeutic efficacy, bioavailability, and stability, and also minimizes the side effects. Hence, this paper discusses the preparation of carmustine-gold loaded PLGA-PSPE nanoparticles and their efficacy in treating brain tumors in vitro.