Weekly paclitaxel in escalating doses in a patient with anthracycline-resistant, triple-negative, metastatic breast cancer with severe liver dysfunction
The patient, a 54-year-old lady, was diagnosed with breast cancer 6 months back. She presented with an 8 cm lump in the right breast. A mobile axillary node 2 cm in size was also palpable. The metastatic work-up, including a chest radiograph (X-ray), ultrasound of the abdomen (USG) and a bone scan, was negative. She underwent modified radical mastectomy (MRM) along with axillary node dissection. The size of the tumor was 7 cm. Three of 13 axillary nodes contained tumor deposits. A diagnosis of pT3 N1 M0 infiltrating duct carcinoma, Grade 3 was made. Immunohistochemistry revealed the tumor to be triple negative (estrogen, progesterone receptor negative and her-2 neu negative).\nShe was then started on chemotherapy - FEC (fluorouracil 500 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2). After three cycles, she complained of appearance of nodules at the incision site as well as backache. Physical examination revealed local recurrence with the presence of multiple skin nodules at the MRM incision site. The contrast-enhanced computerized tomography of the abdomen revealed multiple liver metastases, one large metastases in the right lobe 8 cm in dimension as well as five lesions 1–2 cm in size. A magnetic resonance imaging of the spine and pelvis revealed multiple skeletal metastases in the lumbar, sacral and left illiac regions.\nShe was then referred to our center. HerPS was 3. Her liver functions (LFTs) were deranged [], and were as follows: serum bilirubin (S. bil) 2.2 mg% (normal range – 0.3–1.1 mg%), aspartate aminotransferase (AST) 375 IU/L (normal range – 0–25 IU/L), alanine aminotransferase (ALT) 369 IU/L (normal range – 0–35 IU/L) and alkaline phosphatase (ALP) 363 IU/L (normal range – 38–126 IU/L). The prothrombin time was mildly deranged, 17 (test)/12 (control) s. There was no history of preceding liver disease. Blood tests for presence of hepatitis B surface antigen and serology for hepatitis C, A and E were noncontributory.\nShe was started on weekly paclitaxel 20 mg/m2 and zoledronate 4 mg every 4 weekly.\nAfter the first dose of paclitaxel, LFTs showed mild deterioration. S.bil rose to 3.81 mg%, AST to 446 IU/L, ALT to 373 IU/L and ALP to 1338 IU/L. However, her PS improved to 2 and the skin lesions stopped progressing. The same dose was given for the next two cycles.\nHer skin lesions showed signs of resolution and the LFTs improved. The dose was subsequently increased to 30 mg/m2. Steady improvements in the clinical status and LFTs were noted and dose increments of 10 mg/ m2 were made with each successive dose. The 60 mg/ m2 dose was associated with asymptomatic worsening of the LFTs. Hence, the dose was modified to 40 mg/ m2 [].\nAt the end of the 10th week, her PS had improved to 1. The skin lesions had disappeared. Radiological evaluation revealed a partial response. The 8-cm liver lesion had reduced to 3.5 cm in size. All the five lesions 1–2 cm in size initially had become less than I cm in dimension. The patient had no bone pains. There was no toxicity except grade 1 anemia – hemoglobin (Hb) 9.5 gm% (normal range 12–15 g/dL). Alopecia owing to receipt of the previous FEC administration persisted. The LFTs also improved. The regimen was extremely well tolerated.\nThe week 12 dose could not be administered owing to thrombophlebitis. However, 5 days after the administration of the Week 13 dose (40 mg/m2), the skin lesions reappeared.\nUltrasound of the liver revealed that the lesion had increased in size from 3.5 cm to 4.5 cm. In view of progressive disease, paclitaxel was discontinued and the patient was placed on single-agent carboplatin.