1 Hacettepe University, Faculty of Medicine, Radiation Oncology, Ankara, Turkey
*E-mail: mcengiz@hacettepe.edu.tr
We read with great interest the article by Oh et al. recently published in Annals of Oncology addressing neoadjuvant chemotherapy and concomitant chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma [1]. Briefly, authors reported the results of 27 patients treated between 1990 and 1999 by neoadjuvant chemotherapy composed of cisplatin, 5-fluorouracil (5-FU), leucovorin, interferon- and followed by concomitant chemoradiotherapy with 5-FU, hydroxyurea and 70 Gy radiotherapy during weeks 1, 3, 5, 7, 9, 11 and 13. The authors concluded that their results are encouraging and deserve further research in a randomized setting. We wish to register our concern regarding their conclusion.
Intergroup study was the most important study until recently as it is the only randomized trial to show overall survival benefit with chemoradiotherapy [2]. However, its applicability to other nasopharyngeal cancer (NPC) patients has been criticized for differences in racial composition, high rate of differentiated squamous cell carcinoma histology, unexpected inferior results in the radiotherapy alone arm and, finally, a relatively low number of patients were registered during the long study period (193 patients randomized by various centers from RTOG, SWOG and ECOG in 6 years). Their data have similar problems to the Intergroup study.
We would like to mention three important points regarding their data. First, a careful inspection of their data reveals that in their study population 37% of the patients are differentiated squamous cell carcinoma which is similar to the findings of the Intergroup study (24.5% of 147 patients). Secondly, the design of their concomitant chemoradiotherapy regimen causes unnecessary prolongation of the overall treatment time of radiotherapy which is at least 13 weeks. It is well known that prolongation of the overall treatment time of radiotherapy is correlated with increased local regional failures. The authors used split course radiotherapy in their small group of patients which is not appropriate for treatment of head and neck cancers. Thirdly, we would like to mention the use of non-standard chemotherapeutic agents, namely 5-FU and hydroxyurea, during the concomitant phase of the treatment. Cisplatinum is accepted to be the golden standard for concurrent chemoradiotherapy regimens for treatment of head and neck malignancies [3]. Oh et al. used hydroxyurea and 5-FU combined with radiotherapy which is not the most effective regimen.
We think that the conclusion of this trial by Oh et al. is inappropriate because of the small patient size, inappropriate radiotherapy schedule and chemotherapy regimen. Based on their conclusion, we believe that further investigation of their intensified protocol in a randomized study will be only a waste of resources.
REFERENCES
1. Oh JL, Vokes EE, Kies MS et al. Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. Ann Oncol 2003; 14: 564569.
2. Al-Sarraf M, LeBlanc M, Giri PGS et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup Study 0099. J Clin Oncol 1998; 16: 13101317.[Abstract]
3. Ang KK, Garden AS. Radiotherapy for Head and Neck Cancers. Philadelphia, PA: Lippincott 2002.