[Phase I study of capecitabine with concurrent radiotherapy in early-stage nasopharyngeal carcinoma].

OBJECTIVE

To evaluate the dose-limiting toxicity (DLT), efficacy and maximum tolerated dose (MTD) of capecitabine with concurrent radiotherapy in patients with node-positive stage II nasopharyngeal cancer.

METHODS

From August 2002 to June 2003, 30 patients with node-positive stage II T(2)N(1)M(0) nasopharyngeal cancer were retrospectively reviewed. Median age 43 years (range 32 - 63 years), ECOG performance status <or= 2. Radiotherapy of 68 - 72 Gy/34 - 36 fractions was delivered to the nasopharynx and 64 - 70 Gy/32 - 35 fractions to the node-positive area. Capecitabine was administered orally on day 1 of radiotherapy by an intermittent schedule (14 days treatment; 7-day rest) at 3 weekly intervals for two cycles. Patients were alloted into one of four escalating dose cohorts (500, 750, 1000 and 1250 mg/m(2), bid). Dose escalation was done after six patients had completed 2 cycles of chemotherapy at the previous dose level with DLT assessed.

RESULTS

Twenty-eight patients were evaluable for toxicity and efficacy: CR 12 (42.9%), PR 13 (46.4%), SD 3 (10.7%), the overall response rate (CR + PR) was 89.3%. The CR response rate of the node-positive area and of the nasopharynx were 50.0% (14/28) and 46.4% (13/28). No DLT was observed at the dosage group of 500 mg/m(2) and 750 mg/m(2). Three of 9 patients experienced DLT at 1000 mg/m(2) with grade III stomatitis; 4 of 6 at 1250 mg/m(2) with grade III stomatitis (4/6), grade III diarrhea with grade IV febrile neutropenia (1/6) and grade III thrombocytopenia (1/6). The toxicity of grade I and II was hand-foot syndrome (4/28), fatigue (14/28), nausea and vomiting (19/28), diarrhea (5/27), and weight loss (21/28).

CONCLUSION

A dose of 750 mg/m(2) of capecitabine might be recommended for combination with radiotherapy. This regimen is tolerable and valid for nasopharyngeal carcinoma. A randomised phase III comparison with 5-Fu is justified.