The nephroprotective effect of short hydration during cisplatin treatment in head and neck cancer patients.

Cisplatin based chemotherapy remains the main treatment for head and neck
cancer patients. Although highly effective cisplatin efficacy is often limited
by toxicity. Cisplatin induced nephrotoxicity (CIN) remains the main dose
limiting toxicity despite numerous preventive interventions. Extensive
hydration prior- and post cisplatin infusion is one of the interventions to
prevent nephrotoxicity. Its efficacy in reducing CIN is well established. The
optimal duration of hydration is however still debated.
During the last decades numerous publications have reported about the
feasibility of a short hydration scheme during cisplatin chemotherapy. Some
publications have even shown that short hydration during cisplatin chemotherapy
might even be more effective in preventing nephrotoxicity than long hydration.
Most of these publications are however limited by their design as they consist
of non-randomized single arm studies, retrospective studies or prospective
studies with historical controls. Data from randomized controlled clinical
trials are still lacking.
Besides possible better nephroprotective effects, short hydration has other
clear benefits over long hydration as well. Short hydration would enable
outpatient treatment and reduced treatment burden for patients, optimizing
quality of life and reducing healthcare costs.
Therefore we shall conduct a prospective randomized controlled trial to examine
superiority of a short hydration (SH) scheme versus and long hydration (LH)
scheme during Cisplatin treatment in head and neck cancer patients with regard
to the incidence of CIN expressed as the clinically significant endpoint Acute
Kidney Injury.

To evaluate the incidence of CIN during cisplatin 40mg/m2 Q1W chemotherapy in
patients with head and neck cancer and establish whether SH is superior to LH
during cisplatin chemotherapy in reducing the incidence of AKI grade>=1.
Secondary objectives are to determine differences in average relative dose
intensity and the difference in the incidence of acute kidney injury grade 1,
grade 2, grade 3, grade 4 and grade 5 as per Common Terminology Criteria for
Adverse Events; CTCAE v4.0, incidence of hospitalization due toxicity.

A prospective, unblinded, single center, randomized controlled clinical trial
in which the superiority of short hydration versus long hydration is examined
regarding the incidence of Acute Kidney Injury grade >=1

Patients will receive standard care cisplatin chemo radiation therapy. Prior to
treatment, patients will be randomized over an arm in which the cisplatin is
administered using a long hydration regime or an experimental arm in which
patients are given cisplatin using a short hydration regimen.

We see the risk and burden as negligible. Patients do not have to bear
additional burdens compared to their standard care treatment.

For future analysis, an extra bloodsample (10 ml) and a portion of urine will
be taken per study visit. In addition, patients in the study will be required
to attend one additional follow-up visit 3 months after the last treatment with
cisplatin. During this follow-up visit, one extra blood sample (10 ml) and a
portion of urine will also be taken for future analysis.

The risk, although we do not expect this, is that more nephrotoxicity will
occur in the short hydration arm. We will address this risk with an interim
analysis.