Nobukazu Fuwa, Yoshiyuki Ito, Takeshi Kodaira, Akira Matsumoto, Minoru Kamata, Kazuhisa Furutani, Hiroyuki Tatibana, Masahiro Sasaoka and Kozo Morita

Background: The present study was conducted to evaluate the therapeutic results of alternating chemoradiotherapy for locally advanced nasopharyngeal cancer (NPC).

Methods: The subjects consisted of six patients with stage III nasopharyngeal cancer and 26 patients with stage IV nasopharyngeal cancer. Using 6 MV photons, radiotherapy was performed at an exposure of 1.8–2.0 Gy five times per week. That is, a total absorbed dose of 36–40 Gy was irradiated between the base of the skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 26–30 Gy was additionally given thereafter. One course of chemotherapy consisted of the administration of 5-fluorouracil (5-FU) at a dose of 700 mg/m2/24 h for 5 days (days 1–5) and cisplatin (CDDP) at a dose of 50 mg/m2/24 h for 2 days (days 6–7) and a total of 2–3 courses of chemotherapy were performed. During the alternating chemoradiotherapy, chemotherapy was performed initially and 3–5 days after completing the chemotherapy, radiotherapy was performed for 3–4 weeks. Thereafter, chemotherapy and radiotherapy were performed alternately.

Results: The scheduled courses of alternating chemoradiotherapy were completed in 30 (94%) of 32 patients. Although one patient developed shock induced by metal allergy to CDDP, no severe adverse effects were noted in any other patients. In these 32 patients, the overall 5-year survival rate was 75% (95% confidence interval: 60–90%) and the progression-free survival rate was 63% (95% CI: 46–89%).

Conclusions: This method of alternating chemoradiotherapy yielded higher or at least similar survival rates and lower toxicities than concurrent chemoradiotherapy and is worth trying in a multi-institutional study.

Although the incidence of nasopharyngeal cancer is high in the southern part of China (1,2), its incidence in Japan is rather low and is similar to that in Western countries (3). Owing to its anatomical characteristics, the surgical treatment of nasopharyngeal cancer is very difficult to perform. In addition, most cases of nasopharyngeal cancer are histologically classified as undifferentiated carcinoma with relatively high radiosensitivity. Therefore, radiotherapy is the first choice of treatment modality for nasopharyngeal cancer (4–8). However, although nasopharyngeal cancer is more sensitive than other head and neck cancers to radiotherapy, the overall 5-year survival rate reported in a large series was 41% (9). Therefore, various combinations of radiotherapy and chemotherapy, such as concurrent chemoradiotherapy (10–12), neoadjuvant therapy (13–17), adjuvant therapy (18,19) and alternating therapy (20), have been attempted.

Although many phase II studies previously reported useful combinations of radiotherapy and chemotherapy (10,18,20–23), only four randomized phase III studies evaluated the anti-tumor effects of chemoradiotherapy in comparison with those of radiotherapy alone (24–27). Two of these four studies reported that the progression-free survival (PFS) rate was significantly more satisfactory in patients treated with chemoradiotherapy than in those treated with radiotherapy alone (24,27). In particular, very satisfactory therapeutic results were obtained in the Intergroup 0099, in which cisplatin (CDDP) was administered concurrently with radiotherapy and the combination of CDDP and 5-fluorouracil (5-FU) was subsequently administered after radiotherapy (24). Therefore, the above combination of chemotherapy and radiotherapy may become a standard treatment modality for nasopharyngeal cancer in the future.

In 1987, we initiated alternating chemoradiotherapy using CDDP and 5-FU. Although the number of subjects was limited, our previous non-randomized study showed therapeutic results similar to those of chemoradiotherapy demonstrated by the Intergroup 0099 trial. In the present study, we evaluated the therapeutic results of alternating chemoradiotherapy, together with its usefulness and controversial points.

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