ESMO 2011 Report – How safe is chemotherapy during pregnancy?

by Dr Sunil Upadhyay – The overall incidence of cancer is known to increase with age. However, there is hardly any age group that can be spared from the risk of developing cancer and the resulting necessary treatment. Its incidence in young women is enormous and remains an important cause of death in women of child bearing age. It is estimated that approximately 1 in 1000 pregnant women will have cancer. In Europe, up to 5000 women are thought to be diagnosed with cancer during pregnancy every year. It is expected that the incidence will increase because more women delay pregnancy by the time the risk of cancer starts rising. The majority of these women are diagnosed with this life-threatening disease during pregnancy but a small number, despite taking precautions, get pregnant whilst undergoing treatment for their malignancy. Most oncologists do come across this traumatic situation during their lifetime of practice. This situation presents an ethical dilemma to all concerned. It puts immense stress on the mother, their families and clinicians.

There is good amount of experience on the safe management of pregnant women with surgery and/or radiotherapy. Unfortunately, there is paucity of reliable data on the management of pregnant women with chemotherapy using cytotoxic and emerging molecular agents. Cytotoxic drugs are known to be potent teratogenic agents. It is believed that chemotherapy during pregnancy can cause birth defects. Therefore, most of the time, termination of early pregnancy or early delivery of the viable foetus by caesarean section at around 32 weeks of pregnancy are the difficult options to choose from for the majority of women and their physicians. There are limited studies on the effects of chemotherapy on foetus and most of the information is based on case reports, review of records or small uncontrolled studies. Because chemotherapeutic agents damage rapidly dividing cells, studies conducted in animals have been found to show similar effects on the foetal tissue leading to high risk of spontaneous abortions or malformations.

Frederic Amant from Katholieke Universiteit in Leuven, Belgium presented the results of a small study during the presidential session at EMCC 2011 in Stockholm and reassured the audience that children who were exposed to chemotherapy in utero during the second and/or third trimester of pregnancy did not appear to suffer from any detrimental effects related to their general well being, neurological and cardiac functioning. However, 47 of the 70 children born from 68 pregnancies were delivered preterm and it was found that prematurity, but not chemotherapy, did affect these children’s cognitive development significantly. In this study, children from Belgium, Netherlands and Czech Republic, exposed to chemotherapy before birth were examined between the age of 18 months and 18 years for potential negative effects of the chemotherapy. The recruitment started in 2005 and included children born between 1991 and 2010. They were examined at birth (post 2005) and at the age of 18 months, 5-6, 8-9, 11-12, 15-16 and 18 years. During pregnancy, the mothers were treated with chemotherapy either alone or adjuvant to surgery, radiotherapy or both. The most common cancer was breast (35), followed by haematological cancers like leukaemia & lymphoma (18), ovarian (6), cervical cancer (4) and others. The children were assessed for their general health, school performance, sporting activity, and their social and family situations by means of a questionnaire completed by the parents at each visit. The development of their mental process was assessed by evaluating intelligence, verbal and non-verbal memory, attention, working memory and executive functions. Parents also completed a questionnaire on behavioural and emotional problems. Cardiac function was assessed by ECG and echocardiography. The average gestational age at birth was 35.7 weeks but seven children were born early at between 28-32 weeks, nine were born early at between 32-34 weeks, 31 were born preterm, 34-37 weeks, and 23 were born at term, 37 weeks or more, with two twin pregnancies.

The data presented showed that the incidence and type of congenital malformations were similar to the general population, as was growth, general health and development but no heart abnormality. Cognitive development was in the normal range for the majority but those that fell below the normal IQ range were mainly those that had been born early. Prenatal exposure to chemotherapy for leukaemia as one of the possible causes could not be ruled out in one set of twins born at 32.5 weeks who were found to have significant neuro-developmental delay.

These results provide evidence to support the view that prenatal exposure to chemotherapy is safe after the first trimester of pregnancy. The chemotherapy should be continued till the baby is mature because the baby has smaller risk from chemotherapy than from premature delivery. The researchers estimate that the baby loses 2.5 IQ points for each week that he or she is delivered early. Dr Amant concluded that the fear of foetal exposure to chemotherapy should no longer be an indication to terminate a pregnancy and it should no longer be a reason to delay maternal treatment which may have negative impact on prognosis. Longer follow-up data is required on more children particularly for the detection of any late onset toxicity, fertility and germ cell mutagenesis in the children, their future offspring and the final negative impact on their average life expectancy. (Abstract 12 LBA)