Therapeutic Dilemma of Chemotherapy Dosing in Morbidly Obese Patient with AML: A Case Report and a Review of the Literature.

Obesity is a common and increasing problem affecting the developed world. There is no consensus on a standard approach to chemotherapy dosing has been adopted in obese patients. We present a 25 year old white male with worsening fatigue, dyspnea and recurrent cellulites. Physical examination was significant for morbid obesity of 616 lb (BMI 86.4 and BSA 3.43m²). Initial laboratory values were WBC 0.870/ml (3400–9200/ml), Hb 6.5g/dL (11.5–15.4g/dl), platelet count of 35,000/mm³ (130000–400000/mm³), MCV 91 mm³ (80–100mm³). Basic metabolic and coagulation panel was normal except elevated D-dimer and LDH. Peripheral smear consistent with hypochromic normocytic RBC, occasional schistocytes, premature myeloid cells, myeloid blasts 26% with granularity of cytoplasm and a few Auer rods were evident. Bone marrow biopsy was consistent with acute myeloid leukemia. Flowcytometry was positive for CD33, CD 38 and myeloperoxidase. Lymphoid antigens were negative. Cytogenetic analysis revealed normal karyotype and negative for t (15; 17). Patient was treated with standard induction regimen with cytarabine 243mg (100mg/m²) and daunorubicin 109mg (45mg/m²). Chemotherapy dosing was done according to the adjusted body weight (BSA 2.43 m²). Day 14 bone marrow was consistent with significant disease. Reinduction with high dose cytarabine 14000mg (3000mg/m²) had no response. Patient was then received gemtuzumab ozagomycin 22mg (9mg/m²) on day 1 and 14. Bone marrow analysis 30 days after the treatment was consistent with remission. Interestingly patient developed little adverse effect from the initial induction chemotherapy. Hospital course was complicated with Clostridium difficile colitis and neutropenic fever which was treated with antibiotics and voricanazole. Voricanazole dosing was done according to the actual body weight (1000mg IV twice daily). The peak and trough levels were within normal range. Failed response to initial induction treatment could be due to refractory disease or inadequate dosing of chemotherapy in this patient. BSA has been used to calculate the dose in anticancer therapy since 1950s. Experimental studies have demonstrated BSA based dosing failed to standardize the variation in pharmacokinetics of cytotoxic drugs. In obese cancer patients, the pharmacokinetics of the drug demonstrated a prolonged elimination time for several agents. Risk of both under dosing and overdosing can have detrimental affect outcome in obese patients. Prospective studies of chemotherapy pharmacokinetics are needed to address the issue of optimal chemotherapy dosing in obese population.