title: Nephrotoxicity as a Dose-Limiting Factor in a High-Dose Cisplatin-Based Chemoradiotherapy Regimen for Head and Neck Carcinomas.
abstract: OBJECTIVE
  Loco-regional control and organ preservation are significantly improved with concomitant cisplatin/radiotherapy and are compromised with less than 5% grade 3 nephrotoxicity (creatinine clearance 15-29 mL/min). However, although clinically important, in none of the randomized trials is grade 2 nephrotoxicity (defined as creatinine clearance 59-30 mL/min) mentioned. In this study, we assessed nephrotoxicity in daily practice among patients treated with high-dose cisplatin (100 mg/m² on days 1, 22, and 43), concurrently with chemoradiotherapy (CCRT) and the impact on treatment modifications.
  
  
  METHODS
  208 patients with advanced-stage malignancies of the head and neck region were evaluated. All patients were treated with high-dose cisplatin CCRT. The main outcome parameters were nephrotoxicity (defined as creatinine clearance grade 2 or more) and cumulative doses of cisplatin and radiation.
  
  
  RESULTS
  133 patients (64%) completed all pre-planned courses of cisplatin. Nephrotoxicity was the main reason to discontinue the chemotherapy. Grade 3 nephrotoxicity was seen in 16 patients (8%) while grade 2 nephrotoxicity was seen in 53 patients (25%). Thirty six patients (17%) could not complete the pre-planned chemotherapy due to nephrotoxicity.
  
  
  CONCLUSIONS
  In head and neck cancer patients, nephrotoxicity grade 2 is under-reported but is the major factor for discontinuing cisplatin during CCRT.
authors.affiliation: Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. j.hoek@nki.nl.
authors.forename: Jantien
authors.initials: J
authors.lastname: Hoek
authors.affiliation: Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. karenbloemendal@hotmail.com.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Bloemendal
authors.affiliation: Department of Otolaryngology and Head &amp; Neck Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. l.a.van_der_velden@lumc.nl.
authors.forename: Lilly-Ann A
authors.initials: LA
authors.lastname: van der Velden
authors.affiliation: Department of Radiotherapy, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. j.v.diessen@nki.nl.
authors.forename: Judi N A
authors.initials: JN
authors.lastname: van Diessen
authors.affiliation: Department of Biometrics, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. e.v.werkhoven@nki.nl.
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.affiliation: Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. m.klop@nki.nl.
authors.forename: Willem M C
authors.initials: WM
authors.lastname: Klop
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. m.tesselaar@nki.nl.
authors.forename: Margot E T
authors.initials: ME
authors.lastname: Tesselaar
keywords: chemoradiotherapy; cisplatin; head and neck cancer; nephrotoxicity