PMID- 24940080
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140618
LR  - 20220316
IS  - 1179-1322 (Print)
IS  - 1179-1322 (Electronic)
IS  - 1179-1322 (Linking)
VI  - 6
DP  - 2014
TI  - High plasma exposure to pemetrexed leads to severe hyponatremia in patients with 
      advanced non small cell lung cancer receiving pemetrexed-platinum doublet 
      chemotherapy.
PG  - 261-5
LID - 10.2147/CMAR.S60177 [doi]
AB  - 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.
FAU - Gota, Vikram
AU  - Gota V
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment Research and 
      Education in Cancer, Mumbai, India.
FAU - Kavathiya, Krunal
AU  - Kavathiya K
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment Research and 
      Education in Cancer, Mumbai, India.
FAU - Doshi, Kartik
AU  - Doshi K
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment Research and 
      Education in Cancer, Mumbai, India.
FAU - Gurjar, Murari
AU  - Gurjar M
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment Research and 
      Education in Cancer, Mumbai, India.
FAU - Damodaran, Solai E
AU  - Damodaran SE
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment Research and 
      Education in Cancer, Mumbai, India.
FAU - Noronha, Vanita
AU  - Noronha V
AD  - Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
FAU - Joshi, Amit
AU  - Joshi A
AD  - Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
FAU - Prabhash, Kumar
AU  - Prabhash K
AD  - Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
LA  - eng
PT  - Journal Article
DEP - 20140604
PL  - New Zealand
TA  - Cancer Manag Res
JT  - Cancer management and research
JID - 101512700
PMC - PMC4051622
OTO - NOTNLM
OT  - non small cell lung carcinoma
OT  - pharmacogenetics
OT  - pharmacokinetics
OT  - platinum compounds
EDAT- 2014/06/19 06:00
MHDA- 2014/06/19 06:01
PMCR- 2014/06/04
CRDT- 2014/06/19 06:00
PHST- 2014/06/19 06:00 [entrez]
PHST- 2014/06/19 06:00 [pubmed]
PHST- 2014/06/19 06:01 [medline]
PHST- 2014/06/04 00:00 [pmc-release]
AID - cmar-6-261 [pii]
AID - 10.2147/CMAR.S60177 [doi]
PST - epublish
SO  - Cancer Manag Res. 2014 Jun 4;6:261-5. doi: 10.2147/CMAR.S60177. eCollection 2014.