¹University of Manitoba, Winnipeg, MB, Canada

Abstract

Background: Since amantadine acetylation occurs only by spermine-spermidine acetyltransferase, and the enzyme is induced in tumor tissue, we hypothesized that amantadine acetylation would serve as a biomarker for malignancy.

Methods: We conducted a phase 2 clinical trial to test the hypothesis. We recruited 109 patient volunteers diagnosed with cancer, and at various stages of treatment, who presented to our outpatient clinics. Age ranged from 30-83 yr (median 62 yr) and the majority were male 64M:45F. One hundred patients completed the protocol. Two hr after supper, patients ingested 200 mg of amantadine HCl and urine was collected for the next 12 hr. Seven patients with head and neck cancer also provided a sputum sample 2 hr after amantadine ingestion. Blinded samples were analyzed for amantadine and its acetyl metabolite.

Results: All specimens contained amantadine, and 9 urine samples contained acetylamantadine, as did 2 sputum samples. Positive sputum samples were not concordant with respective urine samples. Diagnoses for patients positive for acetylamantadine included lung cancer, 4/43, head and neck cancer, 4/12, multiple myeloma, 1/1, pancreatic cancer, 1/2, and a neuroendocrine tumor, 1/1.

Conclusions: Initial findings support our hypothesis. Positive sputum samples suggest that timing of specimen collections may be critical, and that sputum may represent a more convenient biological specimen to investigate this metabolic association more critically.