Major combined electrolyte deficiency during therapy with low-dose Cisplatin, 5-Fluorouracil and Interferon alpha: report on several cases and review of the literature [ISRCTN62866759]

A patient with resected adenocarcinoma of the pancreas was treated with adjuvant radio-chemo-immunotherapy using a combination of low-dose Cisplatin, 5-Fluorouracil and Interferon alpha together with external beam radiation. Severe hypocalcaemia without signs of acute renal failure or electrolyte disturbance occurred within 2 days at the 4th week of treatment and required intensive care treatment.Combination of biological and cytotoxic therapies may increase the incidence of severe hypocalcaemia in pancreatic cancer. Oncologists should remain attentive of this problem as more highly active regimes become available.Hypocalcaemia is a known side-effect in high-dose Cisplatin chemotherapy of solid tumors [1,2]. In the classic case, hypocalcaemia is caused by excessive urinary loss and decreased renal up-take during high-dose Cisplatin treatment. Proximal tubular damage leads to decreased reabsorption of cations. Acute nephrotoxicity presents with increased creatinine and persistent protein and electrolyte losses. Chronic nephrotoxicity is characterized by a decrease of glomerular filtration rate and a slightly elevated but persistent magnesium, potassium and calcium excretion [3]. Hypomagnaesemic induced hypocalcaemia is caused by inhibition of parathyroid hormone secretion, impaired calcium release from the bones and low tissue responses to PTH due to low magnesium levels. Cisplatin associated hypocalcaemia and hypercalciuria can not be influenced by calcium supplementation. Correction of magnesium blood levels usually should improve the hypocalcaemia [4]. Hypocalcaemia may be associated with tetany, depression, carpopedal spasm, neuromuscular excitability, cardiac arrythmias with prolonged Q-T interval and sudden death, making it a true oncological emergency [5].Outside cytotoxic therapy hypocalcaemia has been observed after thyroid and parathyroid surgery, chronic renal failure, acute rhabdomyolysis and pancreatitis [6-9]. Cisplatin is often used in combinations wit