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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Seven case reports of carboplatin treatment during the second and third trimesters with no untoward effects were reported (Mir et al., 2008). Carboplatin was embryotoxic and teratogenic in one rat study of offspring of rats exposed to carboplatin during embryogenesis; fetal weight was reduced, but there were no congenital anomalies (Manufacturer Product information; Kai et al., 1988).
Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Tabata et al. reported on the use of carboplatin as a single agent for four cycles, with delivery of a normal infant at 33 weeks, who demonstrated normal development at 1 year (54). Another child exhibited normal development at 18 months following two cycles of single-agent carboplatin in the treatment of stage III ovarian cancer diagnosed at 22 weeks of gestation (55). Carboplatin has also been combined with paclitaxel, resulting in normal development at 6 months of a child following three cycles of the combination prior to delivery (56). Mir et al. reviewed more than three dozen reports on the use of cisplatin or carboplatin, alone or in combination, to treat malignancies in the second and third trimesters (57). They report no fetal malformations in any patient treated with either compound when started after the first trimester, with the exception of one case of ventriculomegaly, diagnosed in a fetus in close proximity to chemotherapy administration.
Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Carboplatin is used for the treatment of numerous malignant solid tumours such as neuroblastoma, nephroblastoma, germ cell tumours, brain tumours, and retinoblastoma. It is administered either at conventional doses of 300 to 800 mg/m2 for several days in combination with other anticancer agents, or at high doses before haematopoietic stem cell transplantation. Unlike cisplatin, carboplatin does not require hyperhydration. When the dose is being calculated as a function of the glomerular filtration rate, the AUC target is, in general, 4 to 6 mg/min/ml in combination at conventional doses and in the order of 20 mg/min/ml during the administration of high doses. More recently, a weekly administration schedule has been developed for the treatment of brain tumours in young children.
Is the TCH-P regimen active in early or locally advanced HER2-positive breast cancer? Results of a retrospective study
Published in Acta Oncologica, 2022
Raffaele Longo, Victoire Thiebaut, Pierre-Olivier Legros, Marco Campitiello, Francesca Plastino, Christophe Goetz, Bogdan Margineanu, Julie Pujois, Michel Gunther, Julie Egea, Chloé Wendel
Study drugs were administered on a 3-weekly schedule. Intravenous or subcutaneous trastuzumab was administered according to patient’s preference. Intravenous trastuzumab was given at a loading dose of 8 mg/kg over 90 min (min), followed by a maintenance dose of 6 mg/kg over 30–90 min; subcutaneous trastuzumab was administered at the standard dose of 600 mg; pertuzumab was given intravenously at an initial dose of 840 mg over 60 min, followed by 420 mg over 30–60 min. Carboplatin was administered at a dose of AUC (area under the plasma concentration-time curve) 6 mg/ml x min and docetaxel at 75 mg/m.2 Docetaxel dose reductions to 60 mg/m2 then to 50 mg/m2 were allowed; after which docetaxel was discontinued; re-escalation was not permitted. For carboplatin, the first dose reduction was to an AUC of 5 mg/mL × min then to 4 mg/mL × min, after which carboplatin was discontinued; re-escalation was not permitted. Dose delays were permitted for selected hematological and/or non-hematological toxicity. Peg-filgrastim, a pegylated form of the recombinant human granulocyte colony-stimulating factor (G-CSF) analog filgrastim, was administered 24–72 h after every cycle of treatment. Patients received a total of six cycles. Between 3 and 6 weeks after the last dose, patients underwent definitive BC surgery. Following surgery, patients continued trastuzumab to complete 1 year of treatment in the case of a pCR. After the publication of the Katherine study [15], if a non-pCR was found, T-DM1 was administered for 14 cycles. Adjuvant radiotherapy and hormonotherapy were given as clinically indicated.
Protective effect of chrysin, a flavonoid, on the genotoxic activity of carboplatin in mice
Published in Drug and Chemical Toxicology, 2022
Basit L. Jan, Ajaz Ahmad, Altaf Khan, Muneeb U. Rehman, Khalid M. Alkharfy
Genotoxic effects of chemotherapeutic drugs like carboplatin can have secondary ramifications in normal cells, typically due to the formation of a large number of free radicals and reactive oxygen species (ROS), resulting in oxidative stress (Wakabayashi et al. 2014). The accumulation of free radicals is dangerous to the genetic material and other biomolecules and multiple studies have shown that use of carboplatin increases the levels of free radicals in the host, which leads to genotoxicity and secondary malignancies (Fong 2016). Oxidative stress alters lipids, nucleic acids and proteins by the generation of oxidized purines and pyrimidines, single-strand breaks and alkali-labile sites resulting in direct damage to the DNA (Reuter et al. 2010). In an effort to prevent these dangerous side-effects, anticancer drugs are combined with known antioxidant compounds to decrease their toxicity. The natural ability of flavonoids to decrease the ability of free-radicals to react in chemically stable molecules can be used in combination with anticancer drugs to reduce oxidative stress and therefore help in preventing the oxidative damage to DNA and other cellular molecules (Treml and Smejkal 2016). The mechanism of action of carboplatin in chemotherapy is its capacity to integrate with genomic DNA. Even though carboplatin has been a highly successful drug, it has several limitations and critical side-effects, usually related with the fluctuating mechanisms of DNA repair and off the mark effects on various other cellular constituents.
Perspectives on PARP inhibitors as pharmacotherapeutic strategies for breast cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Sun Young Oh, Shafia Rahman, Joseph A. Sparano
I-SPY2, a phase 2, adaptively randomized trial predicted 88% probability of success in a phase 3 trial when veliparib and carboplatin were added to standard therapy in patients with stage 2 or 3 breast cancer [107]. Seventy two patients with TNBC were randomly assigned to receive veliparib–carboplatin, and 44 patients with TNBC were assigned to receive control therapy. The estimated rates of pCR in the TNBC population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib–carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The rate of grade 3 or 4 hematologic toxic effects were higher in the veliparib–carboplatin group than in the control group: neutropenia (71% vs 2%), febrile neutropenia (1% vs 0%), thrombocytopenia (21% vs 0%), and anemia (28% vs 0%). The AE was also higher during doxorubicin/cyclophosphamide (AC) treatment among patients who had received veliparib–carboplatin than among those who had received control therapy: febrile neutropenia (12 vs 5%), and rates of neutropenia, thrombocytopenia, and anemia were also higher in the veliparib–carboplatin group. Dose reductions of paclitaxel occurred in 23 patients (32%) in the veliparib–carboplatin group and none in the control group. Dose reductions of carboplatin occurred in 34 patients (47%). During paclitaxel treatment, 13 patients (18%) in the veliparib–carboplatin group, as compared with 2 patients (5%) in the control group, discontinued therapy early.