High incidence of symptomatic methemoglobinemia (metHb) in Asian patients (pts) treated with 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, triapine) and gemcitabine (GEM) in a second-line phase II trial of metastatic non-small cell lung cancer
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 18207
© 2007 American Society of Clinical Oncology
B. Ma, E. H. Tan, T. Mok, K. C. Lam, R. Soo, S. S. Leong, L. Z. Wang, F. Mo, A. T. Chan and B. C. Goh
Chinese University of Hong Kong, Hong Kong, China; National Cancer Center, Singapore; National University Hospital, Singapore, Singapore
18207
Background: Triapine (Vion Pharmaceuticals) is an inhibitor of ribonucleotide reductase that can enhance GEM uptake in GEM- resistant cell lines. Clinically significant metHb has been rarely reported with triapine & G6PD-deficient pts maybe more susceptible. This multicenter study evaluated the activity & safety of combined triapine-GEM in pts with metastatic NSCLC who had progressed despite prior response or disease stabilization to 1st line platinum-GEM regimen.
Methods: Eligible pts were treated with triapine (105mg/m2) as 4-hr IV infusion, followed by GEM (1g/m2) over 30-min on days 1, 8 & 15, repeating every 28 days for 6 cycles. G6PD-deficient pts were excluded.
Results: 6 males & 6 female Asian pts (median age: 65 yrs) received a median no. of 2 cycles (range 1–6 cycles). At a median follow-up of 4.6 mos, no response was seen. 4 pts had stable disease. Median time to progression was 3 mos (95% CI: 1.7–9.1 mos). Gr 3–4 toxicities included neutropenia (gr 3, 2 pts), hypoxia (gr 3, 3 pts) & dyspnea (gr 3, 1 pt). There were no treatment-related deaths & all pts remained alive at analysis. 4 pts developed symptomatic metHb during, or 4 hrs of stopping triapine. This was manifested as dyspnea &/or hypoxia, associated with an oxygen saturation of 90% at room air. Arterial metHb assay performed during the hypoxic episode showed a metHb level of up to 15% of total concentration of hemoglobin ([Hb]), which fell to < 5% of [Hb] within 4–6 hrs of stopping triapine. All pts recovered with conservative treatment & none required reversal with methylene blue. 3 out of the 4 pts were able to continue treatment after dose-reduction of triapine.
Conclusions: The cause of the relatively high incidence of triapine-related symptomatic metHb was unclear in this Asian cohort. This study was terminated prematurely due to lack of response.
No significant financial relationships to disclose.