Nephrotoxicity as a Dose-Limiting Factor in a High-Dose Cisplatin-Based Chemoradiotherapy Regimen for Head and Neck Carcinomas.

Jantien Hoek,Karen M Bloemendal,Erik Van Werkhoven,Margot E T Tesselaar,Willem M C Klop,Lilly-Ann A Van Der Velden,Judi N A Van Diessen

doi:10.3390/cancers8020021

Abstract

Purpose: 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.

Highlights

Concurrent chemo-radiotherapy (CCRT) is the standard of care for unresectable locally advanced head and neck squamous cell cancer (HNSCC), organ preservation, positive surgical margins, and/or lymph node involvement with extra-capsular extension [1,2,3]
Cancers 2016, 8, 21 cisplatin regimen is associated with major toxic side effects
In cisplatin-based CCRT schedules, acute nephrotoxicity is commonly graded by an increase of serum creatinine levels, according to the Common Terminology Criteria for Adverse Events (CTCAE)

Summary

Introduction

Concurrent chemo-radiotherapy (CCRT) is the standard of care for unresectable locally advanced head and neck squamous cell cancer (HNSCC), organ preservation, positive surgical margins, and/or lymph node involvement with extra-capsular extension [1,2,3]. Cisplatin is standardly dosed in a three-weekly schedule of. 100 mg/m2 (total dose 300 mg/m2 ) combined with standard RT [3,6,7,9,10]. Cancers 2016, 8, 21 cisplatin regimen is associated with major toxic side effects (myelosuppression, neurotoxicity, ototoxicity, and nephrotoxicity). In cisplatin-based CCRT schedules, acute nephrotoxicity is commonly graded by an increase of serum creatinine levels, according to the Common Terminology Criteria for Adverse Events (CTCAE). Using these criteria nephrotoxicity ěgrade 3 occurs in only 4%–9% of patients [7,10,11]. Espeli et al [12], for instance used the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE)

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