PLASMA CHROMOGRANIN-A - A MARKER OF SEROTONIN RELEASE AND OF EMESIS ASSOCIATED WITH CISPLATIN CHEMOTHERAPY

Purpose: Emesis is a common side effect of cancer chemotherapy. Seroto nin released from gastrointestinal enterochromaffin cells (ECC) may me diate chemotherapy-induced emesis. Since chromogranin A (CgA) is coloc alized in ECC storage granules with serotonin, we tested the hypothesi s that plasma CgA could mark emesis and serotonin release from ECC. Pa tients and Methods: The relationships between plasma CgA, serotonin re lease, and the development of vomiting following the first course of c isplatin chemotherapy were evaluated in 60 patients. Results: CgA leve ls increased in 59 of 60 patients (245% +/- 18% increase above baselin e levels, P < .001). The time course of the increase in plasma CSA mat ched that of emesis and of urinary 5-hydroxyindoleacetic acid (5-HIAA) . Significant (P < .001) positive correlations were found between the dose of cisplatin and the increases in plasma CgA, and between the cha nges in plasma CgA and urinary 5-HIAA after cisplatin (r = .54, n = 39 , P < .001). The increase in plasma CgA after cisplatin did not correl ate with changes in serum lactic dehydrogenase (LDH) activity, a marke r of cell toxicity or lysis. Conclusion: Plasma CgA marks emesis and s erotonin release induced by cisplatin. Since both CgA and serotonin ar e costored in ECC granules, we suggest that the source of release of e ach may be the ECC. Increases in plasma CgA are not explained by drug cytotoxicity. Exocytosis appears as the main mechanism by which cispla tin releases serotonin. This work further supports the role of seroton in as a mediator of emesis associated with cisplatin and suggests that plasma CgA level is a valuable tool in studies of chemotherapy-induce d emesis. (C) 1995 by American Society of Clinical Oncology.