O1-12-1CAN EARLY MEASUREMENT OF URINARY N-ACETYL-β-GLUCOSAMINIDASE HELP PREDICT TOXICITY OF CISPLATIN-BASED CHEMOTHERAPY?

Abstract Background: Although cisplatin is a widely used anticancer drug to treat various types of cancers, its clinical application is limited by severe systemic toxicities, such as nephrotoxicity, hematological toxicity, and gastrointestinal toxicity. There is no reliable and validated biomarker to predict toxicity caused by cisplatin. Methods: Sixty-six patients who underwent cisplatin-based first line chemotherapy between June 2010 and November 2013 were retrospectively analyzed. Patients who had received adjuvant oral chemotherapy can be included. Urinary N-Acetyl- β-Glucosaminidase (uNAG) levels measured 2 or 3 days after administration of cisplatin were collected, and adverse events for 2 cycles of chemotherapy were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Results: Patients characteristics were as follows: male/female 59/7, median age 65 (range 36 to 78), esophageal/gastric/ other cancer 59/5/2, chemotherapy regimen docetaxel-cisplatin-fluorouracil/fluorouracil-cisplatin/S-1-cisplatin 54/4/8, cisplatin dose (mg/m2) 80/70/60 7/43/2. A significant increase of the uNAG (>30 U/gCr) was observed in 4 patients (6.1%). Grade 3/4 toxicity was observed in leukopenia (50%), neutropenia (61%), hyponatremia (29%), increased creatinine (1.5%). All 4 patients with increased uNAG developed grade 3/4 hyponatremia. Patients with 30 U/gCr or higher uNAG developed statistically lower minimum serum sodium level (median 121.0 vs. 133.5 mEq/L, p = 0.0024, Mann-Whitney U test), while patients with severe hyponatremia (19 patients) did not necessarily showed high uNAG. There was no apparent correlation between uNAG and other toxicities. Conclusion: The early significant increase in uNAG may predict the occurrence of subsequent sever hyponatremia in cisplatin-based chemotherapy.