Paclitaxel-Induced Sickle Cell Crisis

Nicole M. Wilson, PharmD; Janet L. Espirito, PharmD, BCOP; Vicente Valero, MD; Lajos Pusztai, MD, PhD

Disclosures

Am J Health Syst Pharm. 2008;65(14):1333-1336. 

In This Article

Case Report

A 55-year-old postmenopausal African-American woman had stage IIB (T2, N1, M0) invasive ductal carcinoma of the left breast. A diagnostic needle biopsy indicated that her tumor was negative for both estrogen and progesterone receptors and the human epidermal growth factor receptor type 2 gene amplification. Her medical history was normal. She was not taking any medications and did not report a family history of cancer or other diseases. At the time of diagnosis, she weighed 86 kg. She had mild microcytic anemia, with a hemoglobin of 10.5 g/dL (normal range, 12-16 g/dL) and a mean corpuscular volume of 71 fL (normal range, 82-98 fL). Her total bilirubin and lactate dehydrogenase concentrations were slightly elevated at 1.2 mg/dL (normal range, 0-1 mg/dL) and 673 IU/L (normal range, 313-618 IU/L), respectively. Her other blood counts and liver function test values were normal. Systemic staging with a bone scan and computed tomography scans of her chest and abdomen did not reveal any metastatic disease.

The patient underwent segmental mastectomy of her left breast and axillary lymph node dissection that revealed a 4-cm invasive cancer, with 1 of 10 axillary lymph nodes positive for metastatic disease. Her treatment plan included adjuvant chemotherapy with weekly paclitaxel 80 mg/m2i.v. for 12 weeks, followed by four cycles of i.v. fluorouracil, epirubicin, and cyclophosphamide followed by radiation. The patient's baseline hemoglobin concentration before the initiation of paclitaxel was 10.8 g/dL. Dexamethasone was administered as a pretreatment. The first cycle of paclitaxel was well tolerated until seven days after administration, when the patient reported being awakened in the middle of the night with a sudden onset of excruciating lower back pain and muscle spasms that radiated to her buttocks. She was seen in the emergency department and given hydromorphone and cyclobenzaprine for pain control, but she was unable to walk due to muscle spasms and lower extremity weakness and was admitted for further tests. Computed tomography and magnetic resonance imaging of the thoracic and lumbar spine showed no evidence of cord compression, metastatic disease, disk rupture, or other cause for her symptoms. The results of a lumbar puncture were also negative. Laboratory analysis revealed a hemoglobin concentration of 7.3 g/dL, bilirubin concentration of 2.0 mg/dL, and lactate dehydrogenase concentration of 704 IU/L. Her white blood cell count was normal; however, a shift to the left was noted. Her electrolytes and renal and other liver function test values were within normal limits. The patient also had a low-grade fever and hypoxia. Arterial blood gas showed a partial pressure of oxygen of 57 mm Hg (lower limit of normal = 75 mm Hg), which improved with oxygen supplementation through nasal cannula. Results of blood and urine cultures were negative. A computed tomography angiogram of her chest and chest radiograph showed no evidence of pulmonary emboli or infarct but did show areas of consolidation, indicating possible pneumonia. The patient received one unit of packed red blood cells, empirical antibiotics, high doses of opioid analgesics, and muscle relaxants.

The hematology department was consulted. A review of systems confirmed fatigue, back pain, left-sided rib pain, and shortness of breath that worsened on deep inspiration (pleuritic type). On direct questioning about her history of blood disorders, the patient recalled being told that she had sickle cell trait, but denied ever having a sickle cell crisis. Laboratory tests revealed the following concentrations: hemoglobin, 8.7 g/dL; mean corpuscular volume, 76 fL; reticulocyte count, 8.8% (normal range, 0.5-1.5%); bilirubin, 2.9 mg/dL (direct, 0.5 mg/dL; indirect, 2.4 mg/dL); and lactate dehydrogenase, 1716 IU/L. Her iron values were consistent with microcytic anemia, not caused by iron deficiency. Laboratory tests during her 13-day hospitalization were consistent with hemolysis ( Table 1 ). Hemoglobin electrophoresis was performed, which identified the presence of hemoglobin S and hemoglobin C. The patient was diagnosed with hemoglobin SC disease and later discharged from the hospital with as-needed, low-dose oxycodone and baclofen, antibiotics, and folic acid.

Paclitaxel was discontinued and the patient received i.v. fluorouracil, epirubicin, and cyclophosphamide. Laboratory tests before starting this chemotherapy regimen revealed a hemoglobin concentration of 10.5 g/dL, bilirubin concentration of 1.2 mg/dL, and lactate dehydrogenase concentration of 476 IU/L. The patient received prechemotherapy hydration with 1 L of 0.9% sodium chloride injection over two hours, as well as standard pretreatment with dexamethasone, ondansetron, and lorazepam. Darbepoetin was added with each cycle of chemotherapy. Although the patient's bilirubin value was slightly elevated, likely because of hemolysis rather than liver dysfunction, the dosage of epirubicin was reduced by 25% for the first two cycles to ensure tolerability before advancing to the full dosage. The first cycle was well tolerated, with no complaints other than grade 1 fatigue and grade 1 nausea. The patient complained of back and shoulder pain approximately one week after chemotherapy, but this was adequately controlled with a nonprescription nonsteroidal antiinflammatory drug. Follow-up laboratory tests one week after chemotherapy revealed a hemoglobin concentration of 10.4 g/dL, bilirubin concentration of 0.9 mg/dL, and lactate dehydrogenase concentration of 363 IU/L. Laboratory tests before cycles 2 and 3 of chemotherapy included hemoglobin concentrations of 10.7 and 10.4 g/dL, bilirubin concentrations of 1.6 and 1.4 mg/dL, and lactate dehydrogenase concentrations within normal limits, respectively. The second cycle was also well tolerated, with the exception of some grade 1 myalgias and grade 1 paresthesias. The patient received full-dosage epirubicin for her third cycle of chemotherapy. Eight days later, the patient developed grade 2-3 myalgias and generalized muscle aches requiring a visit to the emergency department. Laboratory tests conducted in the emergency department revealed a hemoglobin concentration of 9.4 g/dL, bilirubin concentration of 1.5 mg/dL (direct, 0.0 mg/dL; indirect, 1.5 mg/dL), and lactate dehydrogenase concentration of 540 IU/L. The pain was controlled with as-needed, low-dose hydromorphone, and the patient was able to return home without hospitalization. The patient chose not to receive any further adjuvant chemotherapy and instead decided to proceed with radiation.

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