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High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy
- Source :
- Cancer Management and Research, Vol 2014, Iss default, Pp 261-265 (2014)
- Publication Year :
- 2014
- Publisher :
- Dove Medical Press, 2014.
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Abstract
- Vikram Gota,1 Krunal Kavathiya,1 Kartik Doshi,1 Murari Gurjar,1 Solai E Damodaran,1 Vanita Noronha,2 Amit Joshi,2 Kumar Prabhash2 1Department of Clinical Pharmacology, Advanced Centre for Treatment Research and Education in Cancer, 2Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India Background: Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC). While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Methods: Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Results: Sixteen of 46 patients (35%) had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively). Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively). Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Conclusion: Higher exposure to pemetrexed is associated with grade ≥3 hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in Indian patients needs further investigation. Keywords: non small cell lung carcinoma, platinum compounds, pharmacokinetics, pharmacogenetics
Details
- Language :
- English
- ISSN :
- 11791322
- Volume :
- 2014
- Database :
- OpenAIRE
- Journal :
- Cancer Management and Research
- Accession number :
- edsair.doajarticles..8cb719cd5916cf6b810c7f99c6226ba6