The coexistence of malignant tumour and pregnancy is a state of simultaneous occurrence of two completely contradictory philosophical and biological phenomena – the development of a new life and a life-threatening terminal illness. Finally, a physician – in fact the whole team of doctors – is facing the fight for two lives: of the mother and her unborn child.The incidence of malignant disease in pregnancy is 0.05 to 0.1%. This condition is a major challenge for physicians because there are no randomised studies that could be the basis to choose the therapeutic methods – the medical knowledge merely comes from case reports, registries, and observational studies.The following cancers most often coexist with pregnancy: gynaecological neoplasm (especially cervical and ovarian cancer), breast cancer, lymphatic system neoplasm, and melanoma.Formerly, the diagnosis was clearly the necessity of abortion. Today – although unskilled doctors still propose the only therapeutic option – termination of pregnancy is not the only solution.The past few years have seen the updating of reports and guidelines for the management of pregnant women with cancer. This paper is a review and summary of the information from these publications.
Purpose Pamiparib is an investigational, selective, oral poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor that has demonstrated PARP–DNA complex trapping and CNS penetration in preclinical models, as well as preliminary anti-tumor activity in early-phase clinical studies. We investigated whether the single-dose pharmacokinetic (PK) profile of pamiparib is altered by coadministration of a strong CYP3A inducer (rifampin) or a strong CYP3A inhibitor (itraconazole) in patients with solid tumors. Methods In this open-label, phase 1 study, adults with advanced solid tumors received either oral pamiparib 60 mg (days 1 and 10) and once-daily oral rifampin 600 mg (days 3–11) or oral pamiparib 20 mg (days 1 and 7) and once-daily oral itraconazole 200 mg (days 3–8). Primary endpoints included pamiparib maximum observed concentration (Cmax), and area under the plasma concentration–time curve from zero to last quantifiable concentration (AUC0–tlast) and infinity (AUC0–inf). Secondary endpoints included safety and tolerability. Results Rifampin coadministration did not affect pamiparib Cmax (geometric least-squares [GLS] mean ratio 0.94; 90% confidence interval 0.83–1.06), but reduced its AUC0–tlast (0.62 [0.54–0.70]) and AUC0–inf (0.57 [0.48–0.69]). Itraconazole coadministration did not affect pamiparib Cmax (1.05 [0.95–1.15]), AUC0–tlast (0.99 [0.91–1.09]), or AUC0–inf (0.99 [0.90–1.09]). There were no serious treatment-related adverse events. Conclusions Pamiparib plasma exposure was reduced 38–43% with rifampin coadministration but was unaffected by itraconazole coadministration. Pamiparib dose modifications are not considered necessary when coadministered with CYP3A inhibitors. Clinical safety and efficacy data will be used with these results to recommend dose modifications when pamiparib is coadministered with CYP3A inducers.
U ciężarnych nowotwory złośliwe rozpoznaje się rzadko, jednak coraz późniejszy wiek kobiet zachodzących w ciążę przyczynia się do wzrostu częstości występowania chorób nowotworowych w tym okresie. Obok raka piersi do najczęściej diagnozowanych w omawianej grupie należy rak szyjki macicy. Współwystępowanie ciąży i raka wpływa na decyzje dotyczące diagnostyki, leczenia, sposobu porodu, przebiegu połogu i opieki nad noworodkiem. Postępowanie na każdym etapie wymaga konsensusu -opracowanego przez zespół multidyscyplinarny, w którego skład powinni wchodzić specjaliści z kilku dziedzin: ginekologii onkologicznej, położnictwa, neonatologii i onkologii. Wybór postępowania zależy także od decyzji pacjentki odnośnie do kontynuacji ciąży. W większości doniesień nie stwierdza się różnicy w przeżywalności między kobietami, u których raka szyjki macicy rozpoznano w czasie ciąży, a pozostałymi chorymi. Potwierdzono, że ciąża nie wpływa na czas przeżycia kobiet z rakiem inwazyjnym. Coraz większa wiedza na temat farmakokinetyki cytostatyków podawanych w trakcie ciąży i nowych metod onkologicznych oraz poprawa opieki nad leczoną matką i płodem sprawiają, że zmienia się postępowanie diagnostyczno-terapeutyczne. W wyższych stopniach zaawansowania klinicznego ostatnie rekomendacje zalecają wykonanie limfadenektomii, pozwalającej określić wysokie ryzyko choroby. W wybranych przypadkach stosuje się również chemioterapię neoadiuwantową -do czasu uzyskania dojrzałości płodu. W pracy przedstawiono najnowsze doniesienia naukowe i zalecenia międzynarodowych grup ekspertów dotyczące leczenia raka szyjki macicy u kobiet w ciąży.Słowa kluczowe: rak szyjki macicy, ciąża, limfadenektomia, chemioterapia neoadiuwantowa, dysplazja szyjki macicy Malignancies are rarely diagnosed in pregnant women, yet the increasing age of women getting pregnant contributes to a higher incidence of cancers during this period. Apart from breast cancer, cervical cancer is the most frequently diagnosed malignancy in the said population. The co-occurrence of pregnancy and cancer affects decisions related to diagnostics, treatment, the manner of parturition, the course of the postpartum period and postnatal care. At each stage, the management requires consensus -developed by a multidisciplinary team composed of specialists of different fields: gynecologic oncology, obstetrics, neonatology and oncology. The choice of procedures is also dependent on the patient's decision regarding the continuation of pregnancy. The majority of reports do not point to any differences in the survival rate between women diagnosed with cervical carcinoma during pregnancy and other women affected by the disease. However, it has been confirmed that pregnancy does not have any effect on the survival time of women affected by invasive cancer. With a broader knowledge of pharmacokinetics of cytostatic drugs administered during pregnancy and new oncologic methods as well as Streszczenie
e12566 Background: This study discusses the analysis of the prospectively collected material on pregnant patients treated for breast cancer at the Department of Breast Cancer and Reconstructive Surgery of the Maria Skłodowska-Curie National Oncology Institute - National Research Institute (until 2020: Oncology Center - Institute) in Warsaw, in the years 1995 - 2020. 84 patients were included into the final analysis and 72 children were assessed simultaneously. Methods: The paper summarizes information on the diagnosis and treatment of breast cancer during pregnancy, the course of pregnancy and childbirth and the birth parameters of children i.e. weight, length and Apgar score, as well as the dependencies between them, mainly the impact of some breast cancer, diagnosis and treatment process features on the newborns. The patietnt’s survavial - DFS ( disease free survival) and OS ( overall survival) - was also analyzed. The course of breast cancer diagnosis and treatment data were obtained from the patients’ medical documentation (medical records) and from information provided by the mothers during follow-up visits and read in the children's health books. In order to answer the research questions, statistical analyzes were conducted using the IBM SPSS Statistics 26 package. Results: In the analyzed period, the disease recurrence was recognized in 34 (40.5%) patients, and 24 (28.6%) patients died. The median disease-free survival (DFS) was 12.3 years (147.5 months), and the median overall survival (OS) was not reached during the follow-up period. The estimated 5-year survival rates for DFS and OS were 57.9% and 74.5% respectively, and for 10-year survival - 51.4% and 64.5%. The study showed a statistically significant relationship between the baseline clinical advancement and DFS. It has been also analyzed how the diagnosis, treatment and method of pregnancy termination changed in two time periods (1995-2012 and 2013-2020). There were no statistically significant differences in survival - both DFS and OS - between the group of patients treated before and after 2012. In the assessment of the impact of some factors on the birth children parameters (weight and length), statistically significant results were obtained for: pregnancy advancement at diagnosis, breast cancer stage at diagnosis, pregnancy advancement at the start of chemotherapy, the chemotherapy regimen (classic or dose-dense), the number of cycles of chemotherapy given during pregnancy, and the number of drugs used in supportive treatment. Conclusions: The entire analysis has become not only an insightful characteristic of the studied group, but also these results may be important in everyday clinical practice and may help to optimize the management of an extremely complex and difficult situation, which is the coexistence of pregnancy with a malignant disease that threatens the mother’s life.
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