Difference in decline in renal function due to cisplatin after a short or long hydration scheme in non-small-cell lung cancer: A retrospective cohort study (HYCIS-XL).

WHAT IS KNOWN AND OBJECTIVE: Nephrotoxicity is a frequently occurring side effect of cisplatin, which may be reduced by applying ample hydration. The aim of this study was to determine whether there is a difference in decline in renal function due to cisplatin between a short hydration (SH) and long hydration scheme (LH). METHODS: A retrospective, observational, cohort study was conducted in two hospitals. Patients in one hospital received an SH scheme (SH group), whereas patients in the other hospital received an LH scheme (LH group). Other aspects of treatment and hydration were comparable between both patient groups. Consecutive patients (≥18 years) treated for non-small-cell lung cancer with cisplatin-pemetrexed with ≥1 cisplatin dose were included. Patients were excluded when serum creatinine at baseline was <40 µmol/L. Primary outcome was the difference in estimated glomerular filtration rate (eGFR) between baseline and after the last cisplatin cycle for the SH and LH patients, regardless of the number of administered cisplatin courses. RESULTS: Fifty patients were included in the SH and LH group. There were no significant differences in baseline characteristics between the two groups. None of the patients had renal failure at baseline. After two cisplatin cycles, the median differences between the baseline eGFR and the eGFR after the last cisplatin dose were 1 (-6 to 5) and -9 (-22 to -2) mL/min/1.73 m2 (interquartile range) for the SH and LH group, respectively (P = .000). Less patients completed the four cycles in the LH group (16%) compared to the SH group (64%), mainly because more LH patients were switched to another treatment and due to nephrotoxicity. However, the difference in eGFR remained statistically significant (P = .027). WHAT IS NEW AND CONCLUSION: In this retrospective study, the SH scheme resulted in less decrease in renal function compared with the LH scheme, with a significant and clinically relevant difference. Additionally, more LH patients had to stop this effective treatment prematurely due to nephrotoxicity. Therefore, a short hydration scheme provides adequate and safe hydration, with a lower risk of nephrotoxic side effects and therefore better outcomes for patients and a reduction of healthcare costs.

Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia.

PURPOSE: To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Fifty-eight patients were randomly assigned to etoposide at 50 mg/m(2)/d with once- versus twice-daily doses for 22 days. On day 8, vincristine, asparaginase, and dexamethasone were started. Etoposide pharmacokinetics and pharmacodynamics were studied for 47, 28, and 26 patients on day 1, 8, and 22, respectively, of remission reinduction therapy. RESULTS: Of 48 patients with pharmacokinetic data, 42 (87.5%) achieved complete remission, three (6.3%) failed to achieve remission, and three (6.3%) died during induction. Median etoposide day 8 area under concentration-time curve (AUC) and cumulative AUC tended to be greater (P =.06 and P =.07, respectively) in patients (n = 23) who achieved complete remission (24 and 522 micro mol/L x h, respectively) than in patients (n = 3) who did not (14 and 303 micro mol/L x h, respectively). Three of eight patients with plasma concentrations exceeding 1.7 micro M (1 micro g/mL) for more than 8 hours daily, compared with one of 20 patients with concentrations exceeding 1.7 micro M for