The development of malignant disease during pregnancy leads to an enormous emotional burden to the patient, her partner and the medical staff, accompanied by medical dilemmas. Surgery for malignant tumours seems to be safe, whereas the teratogenicity of cytotoxic agents depends on several factors, including their type, timing of exposure, dose and characteristics affecting placental transfer . The use of chemotherapy during the first trimester increases the risk of spontaneous abortion, foetal death and major malformation and is generally contraindicated in this period. Accumulating data suggests that at the time organogenesis is completed, the risk of intrauterine growth restriction and low birth-weight is low. In consequence, chemotherapy is a viable option in selected pregnant women. However, only a few studies have evaluated the long-term consequences for children exposed to chemotherapy while in utero [1–5]. Owing to the limited clinical experience and the unique taxane antineoplastic mode of action, generally the use of taxanes in pregnancy is not recommended . Until now, only a few cases of chemotherapy with taxanes, including paclitaxel alone or in combination with either cisplatin or carboplatin, applied during pregnancy, have been reported [1, 3, 4, 6–14]. In all cases but one, organogenesis had been completed by the time of treatment onset. Current experience includes five cases of EOC treated with 6, 5 (two cases), 4 and 3 cycles of paclitaxel-based chemotherapy, respectively, and one patient with FIGO III dysgerminoma administered 4 cycles of paclitaxel/carboplatin (Table 1) [6, 9–12, 14]. We presented another patient with advanced EOC, who received 2 cycles of TC chemotherapy during the second trimester of pregnancy. Therapy did not apparently affect the development of the infant during the first 6 years of observation. No teratogenic effects of 3 cycles of TC combination (with paclitaxel administered at 135 mg/m2/24 h) for EOC during pregnancy were reported by Sood et al.  in 2001. Similarly to our case, the patient’s outcome was fatal, whereas the growth and the development of the infant was normal at 29 months of age. No teratogenic effect was also shown within 20 months of the infant’s life in the dysgerminoma patient administered paclitaxel/carboplatin chemotherapy . In another case, the episode of respiratory insufficiency occurring immediately after the delivery in a newborn exposed to 3 cycles of TC chemotherapy due to mother’s lung cancer was considered to be related to neonatal prematurity rather than chemotherapy toxicity .
Overall, there have been so far about 52 reports of pregnant women managed with platinum-based chemotherapy, including 19 women treated for EOC with 2–6 cycles of single-agent or cisplatin/carboplatin-containing multidrug chemotherapy, starting at the second or third trimester of gestation [3–6, 10–17].
Our patient was administered cisplatin as it is preferred over carboplatin owing to the higher risk of thrombocytopenia . Additionally, in 2004 at the start of chemotherapy, the clinical experience on the use of carboplatin treatment in pregnant women was very limited.
The review of all studies (published in English from 1977 to March 2008) concerning platinum therapy showed 43 cases of pregnant women (cisplatin in 36, carboplatin in 6, and both agents in one patient) . In this group two foetal malformations were recorded, in both cases after therapy with cisplatin. However, causality related to in utero cisplatin exposure could not be proven. Acute respiratory distress (in three premature newborns), cytopenia, elevation of serum creatinine and hearing impairment were also observed. No foetal malformations and normal neonatal examinations were reported after therapy with carboplatin. It is believed that the administration of both platinum salts is feasible during the second and third trimester of pregnancy; however owing to the transplacental transfer of these drugs in late pregnancy, collecting further data on teratogenic effects remains highly relevant.
Until now, the longest reported follow-up of the children exposed to intra-uterine chemotherapy with cisplatin or paclitaxel, with no evidence of sequelae, has been 42 months and 40 months, respectively [6, 15]. We have reported another case of a child exposed to the TC combination with no evidence of sequelae after 73 months of follow-up.
The staging and treatment of cancer at pregnancy should preferentially follow the standard approach . Due to increased levels of Ca 125 in pregnancy and puerperium, the diagnostic value of this assay is limited . The typical management of ovarian carcinoma includes total hysterectomy. Pregnant women diagnosed with advanced EOC should undergo organ-saving surgery, with the removal of the reproductive organs only after the delivery . In our case, the surgery was restricted to a mere staging and this might have worsened treatment efficacy.
The prognosis of maternal ovarian cancers is similar to those in non-pregnant women in the reproductive age . Suboptimal therapy and initial advanced stage of disease as a result of delayed diagnosis in some pregnant women are associated with worse outcome. The presented case was diagnosed in an advanced stage, with no real chance for cure.
In conclusion, standard chemotherapy including paclitaxel for advanced EOC diagnosed during pregnancy seems to be safe; however, potential risks and benefits of this therapy still have to be cautiously weighted.