Reply Response to the comments on ‘‘Acute toxicity of three versus two courses of cisplatin for radiochemotherapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN): A matched pair analysis” First of all, we would like to thank Dr. Bossi and colleagues for their comments regarding our article ‘‘Acute toxicity of three versus two courses of cisplatin for radiochemotherapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN): A matched pair analysis”. We would like to reply to these comments: 1. A dose reduction by more than 25% is the criterion for a dose limiting toxicity (DLT) found in many phase I trials. Therefore, we selected this cut-off point. Because there are no standards regarding such cut-off points, one may argue or speculate which one would be the best. The term of dose intensity (DI) is used to define the drug dose delivered per time unit and is expressed as mg/m 2 per week. However, if the total dose is reduced by more than 25% the DI is also lower. 2. We agree with Bossi et al. that there is no strong rationale for choosing the cut-off point regarding age as we did. However, there are no standards regarding age groups. Therefore, we do not con- sider this a disadvantage of our study. More important is that we have included eight potential prognostic factors for matching the patients. These are more factors than generally used for stratifica- tion in randomised trials, which considerably reduced the risk of selection bias in our study. 3. Bossi et al. state that their own study in cooperation with the Princess Margaret Hospital Toronto, Canada demonstrated a better disease-free survival if a cumulative dose of 300 mg/m 2 cisplatin has been administered concurrently with radiotherapy. 1 However, in their study only patients who had received cisplatin and full dose of radiotherapy (!) were included. Thus, their study suffers from a relevant selection bias, because both interruptions and discontinuation of radiotherapy significantly impair the prognosis of SCCHN patients. 2 The most common cause for such interruptions or discontinuation is chemotherapy-related acute toxicity. In our present study, 90% of patients of the higher dose group experienced at least one grade P3 toxicity compared to 20% in the lower dose group. 3 We agree that patients who can receive the full dose of 300 mg/m 2 are likely to have a better prognosis than other patients. However, such patients usually have a better performance status and less co-morbidity than those patients who were unable to receive the complete planned chemotherapy dose. So it may be questioned whether the improved prognosis is a result of a higher chemotherapy dose or of the presence more favourable prognostic factors before treatment. Therefore, the findings of the study of Granata et al. are not in contradiction to our matched pair analysis, as their results cannot be compared to our results. 1 4. Bossi et al. state that the use of EGFR-antibodies plus cis- platin given concurrently with radiotherapy may be too toxic. We agree that caution is mandatory if novel combinations of anti- cancer treatment are used. However, in the study of Pfister et al. 4 which has been cited by Bossi et al. in this context, cisplatin and cetuximab were combined with a more intensive radiation regimen compared to conventionally fractionated radiotherapy. Thus, it is likely that such an intensive regimen is associated with relatively high acute toxicity. On the other hand, this intensive regimen resulted in encouraging outcomes. Further studies are required to better define the optimal regimen for the treatment of locally advanced SCCHN taking into account both toxicity and efficacy. 5. Bossi et al. are right regarding the groups A and B in the Patients and Methods section of our paper. 3 The 10 group A patients had received three courses of fractionated cisplatin, and the 30 group B patients has received two courses of fractionated cisplatin. We would like to excuse for this mistake. In summary, concurrent radiochemotherapy with a cumula- tive dose of 300 mg/m 2 is a very toxic regimen. Patients may benefit if they can receive the complete planned chemotherapy dose. However, in order to achieve the best treatment results, interruptions and discontinuation of radiotherapy due to che- motherapy-related toxicity are best avoided. Therefore, three courses of cisplatin appear a good option only for selected patients with a very good performance status and very little co-morbidity. Sincerely, Dirk Rades and Steven E. Schild (on behalf of the authors). References 1. Granata R, Pond G, Kim J, et al. Cisplatin dose intensity correlates with out come in patients with locally advanced head and neck squamous cell carcinoma receiving concurrent cisplatin based chemoradiation: a multi-institutional experience. EJC Suppl 2009;7:472. 2. Rades D, Stoehr M, Kazic N, et al. Locally advanced stage IV squamous cell carcinoma of the head and neck: impact of pre-radiotherapy hemoglobin level and interruptions during radiotherapy. Int J Radiat Oncol Biol Phys 2008;70:1108–14. 3. Rades D, Kronemann S, Meyners T, et al. Acute toxicity of three versus two courses of cisplatin for radiochemotherapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN): a matched pair analysis. Oral Oncol 2010;46:549–52. 4. Pfister DG, Su YB, Kraus DH, et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. J Clin Oncol 2006;24:1072–8. 1368-8375/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2010.10.005 Oral Oncology 46 (2010) 889–890 Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology