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E. Aalbersberg

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    P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P1.03-011 - Standard Pre-Hydration May Compromise Treatment Outcome of CRT with Low-Dose Cisplatin (ID 392)

      09:30 - 17:00  |  Author(s): E. Aalbersberg

      • Abstract
      • Slides

      Cisplatin-based chemoradiation is the standard treatment for many types of cancer, including NSCLC. A main drawback of cisplatin is the high nephrotoxicity rate, that can be reduced by a stringent hydration regimen before, during, and/or after cisplatin administration. Standard pre-hydration with all cisplatin administrations is mandatory for high-dose cisplatin, and can be considered for low-dose cisplatin. However, it has recently been shown that pre-hydration not only reduces nephrotoxicity, but also reduces esophageal toxicity in lung cancer patients treated with concurrent daily low-dose cisplatin. This suggested that pre-hydration might systemically lower cisplatin dose in tissues, including in the tumor, and may therefore adversely affect treatment outcome. Aim: The aim of this study was to determine (1) if pre-hydration lowers cisplatin concentrations in tumor tissue in a mouse model, and (2) if the introduction of standard pre-hydration for low-dose cisplatin has adversely affected treatment outcome in lung cancer patients.

      Tumor-bearing Balb/c nude mice with cisplatin sensitive tumors were either pre-hydrated with saline, dehydrated, or had no intervention (control) before a single administration of cisplatin 6mg/kg or 3mg/kg. Renal function was assessed with MAG3 scintigraphy at 1, 24, 72, or 168h after treatment, and mice were subsequently sacrificed to determine tumor platinum concentrations. For the patient study, all stage III NSCLC patients who received daily concurrent low-dose cisplatin and radiotherapy in the NKI-AVL between 01-2007 and 06-2014 were evaluated for PFS. Patients treated in 2007-2010 (n=224) started pre-hydration with 1L saline only after renal function loss was detected, while patients treated in 2011-2014 (n=216) received standard pre-hydration from treatment day 1.

      Pre-hydration protected mice from nephrotoxicity caused by cisplatin and dehydration worsened nephrotoxicity, confirming the validity of the mouse model. Pre-hydration significantly reduced tumor platinum concentrations (down to 50% of control mice at 1h after treatment, and comparable to mice treated with only half the dose of cisplatin), and dehydration increased tumor platinum concentrations. In patients the pre-hydration cohort demonstrated a shorter PFS (median 14 vs. 11 months, log-rank p=0.06), against the trend of gradually improving treatment outcome over the past decades.

      Pre-hydration reduces tumor platinum levels in mice, comparable to giving only half a dose of cisplatin. Patients treated with standard pre-hydration show a tendency to a lower PFS compared to patients with pre-hydration on indication. Further research is needed to elucidate this phenomenon. Meanwhile the application of standard pre-hydration in low-dose cisplatin regimens may be reconsidered.

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