3-aminopyridine-2-carboxaldehyde-thiosemicarbazone and Carcinoma--Renal-Cell

Triapine is a novel small molecule ribonucleotide reductase inhibitor that showed activity in renal cell carcinoma (RCC) cell lines. Evaluating new agents with novel mechanisms remains of interest for patients with incurable RCC. This was a single-arm, multicentre phase II trial where Triapine was given at a schedule of 96 mg/m2 2-h infusion daily x 4 repeated every 2 weeks in patients with recurrent RCC. A median of four cycles of Triapine was administered to 19 eligible patients. One response was seen (7%.) Median time to progression was 3.6 months. Common adverse events (AEs) were grade 1-2, with fatigue in 74%, nausea in 68% and vomiting in 58%. However grade 3/4 neutropenia was seen in 79% and acute reactions of hypoxia, hypotension, methemoglobinemia were seen. Dose reductions/delays due to AEs were common with only 47% of patients receiving > 90% of planned dose intensity. The study closed, at the end of stage 1 as it did not meet the minimal efficacy criteria to proceed. Further evaluation of Triapine at this dose and schedule in patients with advanced kidney cancer is not recommended.

Topics: Aged; Antineoplastic Agents; Canada; Carcinoma, Renal Cell; Clinical Trials as Topic; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Pyridines; Ribonucleotide Reductases; Thiosemicarbazones; Treatment Outcome

We report occurrence of severe methemoglobinemia in a patient on novel experimental anti-cancer drug, Triapine. Treatment with methylene blue led to massive hemolysis due to concomitant G6PD deficiency. We recommend that G6PD screening be done in high-risk populations prior to commencement of Triapine therapy.

Topics: Antineoplastic Agents; Carcinoma, Renal Cell; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Methemoglobinemia; Middle Aged; Pyridines; Thiosemicarbazones