Anhydramnios associated with administration of trastuzumab and paclitaxel for metastatic breast cancer during pregnancy

Abstract

A 38-year-old women in her second pregnancy presented with symptomatic metastatic spinal-cord compression 7 years after undergoing lumpectomy and axillary dissection for stage I primary breast cancer. Immunohistochemistry analysis of the tumour had shown that it was oestrogen-receptor negative, progesterone-receptor positive, and overexpressed ERBB2. The patient had received six cycles of cyclophosphamide, methotrexate, and fl uorouracil followed by radiotherapy and then tamoxifen, which she had taken for 5 years. 86 months after primary diagnosis the patient developed paresthesia and hypoesthesia of the left arm and pain in the cervical vertebrae. MRI showed diff use metastatic infi ltration of the corpus of the second cervical vertebra (fi gure 1) with spinal-cord compression. Additional lesions in the fourth thoracic vertebra and the left femur were also seen with bone scintigraphy, but no other signs of metastatic disease were identifi ed by clinical examination, chest radiograph, or abdominal ultrasound. At this time the patient was 17 weeks pregnant with normal fetal development. After counselling the patient decided to continue pregnancy and was started on hydromorphone hydrochloride. Palliative radiotherapy of 46 Gy given in 23 fractions was administered to the cervical vertebra, which resulted in clinically improved neurological symptoms and pain. Cervical radiotherapy was undertaken with lead shielding of the uterus to protect the fetus. At 25+6 weeks’ gestation the patient received trastuzumab (8 mg/kg loading dose) combined with 175 mg/m of paclitaxel, followed by another cycle at 28+5 weeks with the dose of trastuzumab reduced to 6 mg/kg and the dose of paclitaxel kept the same. Close fetal surveillance was undertaken. Between 26 weeks’ gestation and 32 weeks’ gestation, during two cycles of trastuzumab and paclitaxel, fetal abdominal circumference stopped increasing and the volume of amniotic fl uid decreased to almost anhydramnios (fi gure 2). The mother was of normal constitutional size with normal weight gain of 11 kg during pregnancy and no other risk factors for restriction of intrauterine growth. Tests for premature rupture of the membranes were negative. At 31+6 weeks the volume of both fetal kidneys was decreased below the fi fth percentile. Additionally, the urinary bladder was barely visible, suggesting reduced renal function, and doppler sonography showed increased resistance indices of both the renal arteries (fi gure 3). Doppler sonography of the fetal umbilical and maternal uterine arteries was normal, which suggested healthy placental function. Serial ultrasound measurements of femur length, biparietal diameter, and head circumference were all within normal limits. As a result of the evidence of fetal renal failure and cessation of abdominal growth, fetal lung maturation was induced with corticosteroids after two cycles of trastuzumab and paclitaxel, and a caesarean section was done at 32+1 weeks’ gestation. The male newborn infant weighed 1460 g (tenth percentile), had a body length of 39 cm, and had a head circumference of 29.5 cm. The pH value of the umbilical artery was 7.31. The placenta weighed 290 g and placental histology was normal. The newborn infant showed signs of bacterial sepsis with hypotension, transient renal failure, respiratory failure necessitating mechanical ventilation, and positive laboratory fi ndings (C-reactive protein 30 mg/dL). With antibiotic treatment blood pressure normalised after 2 days and mechanical ventilation was ended on day 6. Diuresis was adequate with serum creatinine slightly increased (1.6 mg/dL) until day 14. Ultrasonography of the fetal kidneys showed transient hyperechodensities in the renal parenchyma that resolved by day 28. These transient hyperechodensities are often noted in newborn infants with transient renal failure as a result of decreased renal perfusion. Echocardiography and cranial ultrasound examinations were normal. The infant was discharged at age 6 weeks weighing 2335 g and in healthy condition. Development at 12 weeks was normal. Lancet Oncol 2007; 8: 79–81