Used to treat advanced melanoma, vemurafenib has been shown to increase serum creatinine; but neither the prevalence nor the mechanism for the increase is known, say researchers from Assistance-Publique-Hôpitaux de Paris. Their study suggests 2 mechanisms are at work.
In their retrospective study of 70 patients, the researchers found that 97% had an immediate—but stable—increase in their creatinine level after starting vemurafenib. At the first visit, 1 month after starting the drug, 68 patients had a significant increase in serum creatinine levels, with a median variation of 22.8%. However, in 44 of 52 patients who discontinued the drug, because the melanoma had progressed, creatinine levels returned to baseline.
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Serum cystatin C levels also rose, although less than that of serum creatinine. Researchers say the increase showed that the creatinine increase was partly a result of renal function impairment. Moreover, renal explorations showed that vemurafenib led to inhibition of creatinine tubular secretion.
According to the researchers, the dual mechanism of both inhibition of creatinine tubular secretion and slight renal function impairment makes interpreting creatinine variations difficult. They offer a decision tree to help clinicians manage creatinine elevations due to the drug. The researchers suggest testing for serum creatinine and cystatin C before beginning the treatment and during monthly follow-ups.
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The collected data are reassuring. Apart from rare cases of serious adverse events, such as severe acute renal failure, an increase in serum creatinine below 50% and/or moderate signs of tubular dysfunction should not lead to discontinuing treatment if it is otherwise effective.
Source:
Hurabielle C, Pillebout E, Stehlé T, et al. PLoS ONE. 2016;11(3):e0149873. doi:10.1371/journal.pone.0149873.