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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Ifosfamide (Ifex) is a prodrug (requires metabolic activation by microsomal liver enzymes to active drug) chemotherapeutic that is a synthetic analog, chemically related to nitrogen mustards. As is the typical mechanism of action for alkylating agents, ifosfamide action is mediated by formation of DNA adducts. Ifosfamide is particularly toxic to the urinary epithelium and must be given with mesna (Mesnex, Uromitexan). It is a third-line chemotherapy of germ cell testicular cancer. Ifosfamide is also used to treat acute leukemias and lung, pancreas, breast, cervix, and endometrium cancers, as well as Ewing’s sarcomas, lymphomas, osteosarcoma, soft tissue sarcoma, and ovarian cancer.
Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
There have been several detailing the use of ifosfamide in the second and third trimesters, most commonly in multiagent combinations (46–48). No fetal anomalies have been noted and the infants appeared to be developing normally. One report, however, described the development of fetal growth restriction and anhydramnios after the first cycle of combination chemotherapy including ifosfamide, which was initiated in the second trimester for a maternal diagnosis of rhabdomyosarcoma of the face (49). The effects of ifosfamide given to humans during the first trimester are unknown. However, animal studies have demonstrated increased resorption and lethal anomalies when the drug has been given at high doses early in the pregnancy.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Ifosfamide is used to treat a number of solid tumors such as testicular, lung, ovarian, bone, cervical, breast, and soft-tissue sarcomas, and also both Hodgkin’s and non-Hodgkin’s lymphoma. It is administered rapidly by the intravenous route, in some cases in as little as one hour.
Trabectedin-irinotecan, a potentially promising combination in relapsed desmoplastic small round cell tumor: report of two cases
Published in Journal of Chemotherapy, 2023
Andrea Ferrari, Stefano Chiaravalli, Luca Bergamaschi, Olga Nigro, Virginia Livellara, Giovanna Sironi, Patrizia Gasparini, Sandro Pasquali, Nadia Zaffaroni, Silvia Stacchiotti, Carlo Morosi, Maura Massimino, Michela Casanova
The first patient received 6 courses of trabectedin and irinotecan. Radiological examination after 3 cycles showed a mixed response, with tumor shrinkage of the patient’s pulmonary and peritoneal lesions (from 17 mm and 32 mm at baseline, to 14 mm and 25 mm, respectively) and progression of his liver metastases (from 15 mm and 17 mm, to 38 mm and 20 mm, respectively) (Figure 1). According to RECIST criteria, this was considered a stable disease (19.7% increase, not sufficient to qualify for progressive disease). Also for the absence of valid alternative therapeutic options, 3 further cycles of trabectedin and irinotecan were administered. The new assessment after 6 courses revealed tumor progression at all disease sites, so the treatment was discontinued. After further treatment (prolonged 14-day continuous infusion of high-dose ifosfamide) achieved no response, the patient died of his tumor, 58 months after it was first diagnosed.
Neurokinin-1 receptor antagonists: review of their role for the prevention of chemotherapy-induced nausea and vomiting in adults
Published in Expert Review of Clinical Pharmacology, 2019
Meinolf Karthaus, Xaver Schiel, Christina H. Ruhlmann, Luigi Celio
Aprepitant is a substrate as well as a weak/moderate inhibitor and inducer of the cytochrome P450 (CYP) 3A4 enzyme [61,62]. Dexamethasone is also metabolized by CYP3A4 and its dosage must be reduced when administered concomitantly with aprepitant [39,40]. In pharmacokinetic studies, no clinically significant interactions were observed for aprepitant and several CYP3A4-metabolized chemotherapy agents or 5-HT3RAs [39,63]. Nevertheless, several case studies have reported a suspected interaction between aprepitant and ifosfamide, leading to an increased risk of encephalopathy [64,65]. The effect on CYP3A4 inhibition might be weaker with fosaprepitant due to the lack of intestinal exposure and reduced inhibition of the first-pass effect. However, the oral dexamethasone dose should also be reduced on days 1 and 2 when coadministered with fosaprepitant [66]. As a mild inducer of CYP2C9, a decrease in warfarin plasma concentration and in prothrombin time have been described when aprepitant and warfarin are coadministered [67]. Despite being a substrate of the P-glycoprotein (P-gp) transporter, aprepitant does not affect the pharmacokinetics of other P-gp substrates, including digoxin [68] and melphalan [69].
Standard treatment and emerging drugs for managing synovial sarcoma: adult’s and pediatric oncologist perspective
Published in Expert Opinion on Emerging Drugs, 2019
Giacomo G. Baldi, Daniel Orbach, Rossella Bertulli, Chiara Magni, Giovanna Sironi, Michela Casanova, Andrea Ferrari
A stronger cooperation between adult and pediatric oncologists in recent years has led to a more shared strategy. Though a global consensus is lacking, many oncologists now tend to recommend neo-adjuvant chemotherapy for adult SS [63], acknowledging its peculiarities vis-à-vis other STS (younger age at diagnosis, higher metastatic risk, and greater chemosensitivity). The reasoning is that systemic treatment with a combination of doxorubicin and ifosfamide could reduce the risk of distant metastasis, and that preoperative chemotherapy might enable conservative resections in locally advanced case, while the role of postoperative chemotherapy remains unclear. Of course, the risks of chemotherapy need to be considered, as well as the potential benefits: combinations of full-dose ifosfamide and doxorubicin are highly myelotoxic and carry a risk of infertility and cardiac and renal toxicity, especially in the pediatric population.