Science and Research

Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer

OBJECTIVES: To assess the effect of long-term pemetrexed maintenance therapy on patients' renal function. METHODS: In the PARAMOUNT phase III trial (NCT 00789373), pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function. RESULTS: Creatinine clearance >/=45 mL/min was required before the start of any cycle. Patients on pemetrexed maintenance had a significantly higher percentage maximum increase in sCr over baseline versus placebo for the range of >/=10% to >/=90% increase (p < .05). The risk of experiencing renal events leading to dose delays and discontinuations was higher with higher increases in sCr but reversible in most patients. sCr increases of >/=30% and >/=40% were associated with gender (female), age (<70 years) and longer exposure to pemetrexed compared with placebo. Sixteen (4%) pemetrexed patients and 1 (1%) placebo patient discontinued treatment due to drug-related renal events; 13/16 (81%) of those pemetrexed patients had sCr increases >/=30% and 7/13 (54%) had pre-existing conditions and/or were receiving nephrotoxic drugs. CONCLUSIONS: The appearance of renal events leading to dose delays and/or treatment discontinuations was associated with sCr increase of at least 30%. However, it was difficult to identify patients at a higher risk of treatment discontinuation due to a drug-related renal event based only on changes in pre-maintenance laboratory values.

  • Middleton, G.
  • Gridelli, C.
  • De Marinis, F.
  • Pujol, J. L.
  • Reck, M.
  • Ramlau, R.
  • Parente, B.
  • Pieters, T.
  • Visseren-Grul, C. M.
  • San Antonio, B.
  • John, W. J.
  • Zimmermann, A. H.
  • Chouaki, N.
  • Paz-Ares, L.

Keywords

  • Creatinine clearance
  • maintenance therapy
  • non-small-cell-lung cancer
  • pemetrexed
  • renal toxicity
  • serum creatinine
Publication details
DOI: 10.1080/03007995.2018.1439462
Journal: Current medical research and opinion
Pages: 865-871 
Number: 5
Work Type: Original
Location: ARCN
Disease Area: LC
Partner / Member: Ghd
Access-Number: 29424248
See publication on PubMed

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