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A somatostatin analogue (SMS 201-995) alters the toxicity of 5-fluorouracil in Swiss mice.

The somatostatin analogue 201-995 (SMS), given in a short treatment schedule, 1 microgram/mouse, days 1-4, increased the lethal toxicity of a single, day 2, low lethal dose of 5-fluorouracil (FU), 400-500 mg/kg, in Swiss mice. The analogue did not change the time course of toxic deaths and produced neither autopsy evidence of increased gastrointestinal nor of increased bone marrow toxicity. Paradoxically, the analogue protected the peripheral white blood cell count (WBC). The nadir was only half as severe in the animals treated with SMS in addition to FU. The mechanism responsible for more frequent deaths due to combining SMS with FU is unknown. That brief administration of SMS in combination with marginally lethal, intensive therapy can produce unexpected increase in animal deaths bears consideration because these drugs are sometimes given simultaneously to patients, either fortuitously or in trials designed to limit the gastrointestinal side effects of FU.