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