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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
A semisynthetic derivative of podophyllotoxin, etoposide (VePesid, VP-16VPP), inhibits DNA synthesis. The closely related molecule, podophyllum, has been used to treat condylomas, but is avoided because of its toxicity. It is approved to treat testicular and small-cell lung cancer, acute leukemia, lymphomas, gestational trophoblastic tumors, and a variety of carcinomas. One infant whose mother was treated with etoposide polytherapy during pregnancy was normal at birth (Rodriguez and Haggag, 1995). In another case report, one infant was born with cerebral atrophy following first trimester exposure to etoposide (Elit et al., 1999), but 16 infants in another case report had no congenital anomalies. Etoposide was given in one of 13 pregnancies in the second and third trimesters, the infant was alive and normal at birth (Song et al., 2019).
Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Unlike the topoisomerase I inhibitors, there are dozens of published reports detailing the use of etoposide in pregnancy. Many of these patients have been diagnosed with endodermal sinus tumors, although a variety of other tumors have also been treated with this agent in pregnancy (76). Animal studies have demonstrated multiple fetal abnormalities when the drug is administered during organogenesis, including fetal loss, exencephaly, encephalocele, hydrocephalus, gastroschisis, microphthalmia or anophthalmia, dextrocardia, and axial skeleton defects (77). Etoposide is most frequently given with other agents such as bleomycin and cisplatin (BEP), and the reports occurring in the pregnant patients are no exception. One fetus developed ventriculomegaly and the child now has cerebral atrophy following a single course of BEP (78). Another patient had two cycles of BEP starting at 18 weeks and delivered a normal infant during laparotomy for metastatic disease at 31 weeks. Yet another patient, diagnosed at 26 weeks of gestation with Burkitt’s lymphoma, was treated with cyclophosphamide, vincristine, doxorubicin, cytarabine, etoposide, ifosfamide, mesna, and intrathecal cytarabine and delivered a healthy baby at 32 weeks (46). Another patient was treated with BEP at 26 weeks for a metastatic tumor of unknown primary. She developed septicemia and delivered prematurely. The infant has moderate sensor-ineural hearing loss (79). Several other reports describe the delivery of normal, healthy infants following etoposide administration.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Side effects of etoposide include GI symptoms (e.g., nausea, vomiting, constipation, diarrhea, mucositis, abdominal pain, and decreased appetite), blood disorders (e.g., myelosuppression, thrombocytopenia, anemia, and leucopenia), susceptibility to infection, alopecia, arrhythmia, hypertension, asthenia, hepatotoxicity, malaise, myocardial infarction, and skin reactions.
Combination of chemotherapy and immune checkpoint therapy by the immunoconjugates-based nanocomplexes synergistically improves therapeutic efficacy in SCLC
Published in Drug Delivery, 2022
Zhang Tao, Xingwang Kuai, Guangwei Wang, Sanfeng Liu, Kai Liu, Heng Zhang, Shujing Xia, Hua Zhu
In the present study, to ensure the conjugated carboplatin can completely release from TPP1NP-EP, the carboplatin was conjugated with PCL polymer by the pH-sensitive hydrazone bond. In this case, the release behavior of TPP1NP-EP was respectively investigated in pH 6.0 and pH 7.4. As shown in Figure 2(D), negligible signal of carboplatin was detected in the release medium of pH 7.4. However, burst release behavior was obtained in the medium of pH 6.0 with more than 95% of carboplatin released from TPP1NP-EP within 6 h. Furthermore, the release behavior of etoposide was evaluated as well. It was revealed that similar cumulative etoposide release was obtained in the medium of pH 6.0 than the pH 7.4 (Figure 2(E)). Besides, controlled-release behavior of etoposide was observed in both of pH 6.0 and pH 7.4.
Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review
Published in Hematology, 2019
Shuoshan Wang, Jingguo Wu, Xiaoli Jing, Yongwei Zhang, Hao Tang, Junlin Wu
Moreover, treatment guidelines for HLH during pregnancy have not been established elsewhere due to the side effects on fetus. Now, the safest treatment is corticosteroids and IVIG with treatment of the underlying cause. Among the 11 related cases summarized in Table 1, only three patients were effective with steroids or IVIG regimen alone [8,9,14]. Wang et al. have reported that etoposide can be bravely considered as an alternative drug especially for pregnancy-related HLH who had no response to corticosteroids/IVIG therapy. But, suitable dosages and toxic and side effects require further clinical observation [24]. Among the 11 patients, six were treated with etoposide on the basis of steroids or IVIG regimen, and only two patients survived [10,15]. Obviously, some patients even had no effective responses to the traditional treatment regimen. Therefore, finding a target and effective drug therapy for HLH during pregnancy remains a huge challenge in clinical settings.
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
Etoposide is a chemotherapy used in the United States for over 30 years to treat lymphoma, leukemia, neuroblastoma, and sarcomas, as well as ovarian, testicular, and lung cancer. The drug is associated with multiple side effects including bone marrow suppression and hypotension. As a topoisomerase II inhibitor, etoposide works by complexing with DNA to induce double strand breaks and prevent rejoining of the strands by the topoisomerase II enzyme to eventually block DNA synthesis. Few cases of pulmonary toxicity have been reported in relation to the use of etoposide [77,78]. For example, a case report indicates the development of bilateral diffuse interstitial and alveolar infiltrates including fibrosis and respiratory failure in lung cancer patients [78]. Due to the limited cases of etoposide-induced lung toxicity, no mechanistic insights have been provided in the literature about how etoposide may affect the lung tissue. However, its significant inhibition on DNA synthesis, cell division, and survival may cause collateral damage to normal resident lung cells including alveolar epithelial cells.