Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1), bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1 through 5, continuous infusion) followed by radiotherapy was given to the CT/RT group. All patients were treated in a uniform fashion by definitive-intent radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456 patients were entered onto the study, with 228 patients randomized to each treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group) were assessable. All 456 patients were included in survival analysis according to the intent-to-treat principle. The 5-year overall survival (OS) rates were 63% for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free survival (RFS) time was 50 months for the RT group and not reached for the CT/RT group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT group (P =.05). The 5-year freedom from local recurrence rate was 82% for the CT/RT group and 74% for the RT group (P =.04). There was no significant difference in freedom from distant metastasis between the two treatment groups (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study failed to demonstrate any significant survival benefit with the addition of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma should not be used outside of the context of a clinical trial.

Combination of angiogenesis inhibitor TNP-470 with cytotoxic drugs in experimental therapy of nasopharyngeal carcinoma.

This study was conducted to evaluate the effectiveness of angiogenesis inhibitor 6-O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470. AGM-1470) in the treatment of nasopharyngeal carcinoma (NPC) alone and in combination with cytotoxic agents. Forty-two male BALB/c nude mice bearing human NPC cell line CNE-2 were randomized into 6 groups: those treated with saline solution, TNP-470, cisplatin (DDP), fluorouracil (5-FU), TNP-470 + DDP, and TNP-470 + 5-FU, respectively. In every treatment group, tumor growth was suppressed significantly. The combination of 5-FU with TNP-470 showed significant enhancement in antitumor efficacy. TNP-470 also enhanced the inhibitory effect of DDP, although not to statistical significance. All animals gained in body weight, although treatment with 5-FU caused slight, reversible diarrhea of 2 to 3 days' duration. The results showed that TNP-470 suppressed the growth of the human NPC cell line and enhanced the antitumor effect of 5-FU without increasing its toxicity. The combination of angiogenesis inhibitors with conventional cytotoxic agents is promising in the treatment of NPC.

Primary study in experimental antiangiogenic therapy of nasopharyngeal carcinoma with AGM-1470 (TNP-470).

OBJECTIVE: To evaluate the efficacy of the angiogenesis inhibitor AGM-1470 for the experimental treatment of nasopharyngeal carcinoma (NPC). METHODS: A NPC human tumour model was built by tumour-bearing nude mice using the NPC cell line CNE-2. Twenty-one BALB/c nude mice bearing CNE-2 xenografts were randomized into a treatment group and a control group. In the treatment group, AGM-1470 was injected 30 mg/kg subcutaneously every other day; while the vehicle (three per cent ethanol solution in 0.9 per cent saline) was given to the mice in control group. Tumour volumes and animal weights were measured every third day. Autopsy was performed after 18 days of treatment. The tumour tissue as well as the murine tissues of heart, kidney, and liver in each mouse were removed for formalin fixation and routine HE staining. Pathological evaluation was performed in these tissues. RESULTS: There was a significant difference in tumour volume between the two groups at day 9 of treatment and this increased thereafter. At day 15 of treatment, the tumour volume was 4251 +/- 559 mm3 (n = 10) in the control group versus 3122 +/- 967 mm3 (n = 11) in the AGM-1470 treated group (p = 0.004); and T:C ratio (mean tumour volume of treated/mean tumour volume of control) was 0.73, resulting in a 27 per cent decrease in tumour growth. Central necrosis and consequential shrinkage of tumours occurred in both groups at the end of experiment. Physical toxicity and histological toxicity of heart, liver, and kidney did not result from AGM-1470 therapy. CONCLUSIONS: AGM-1470 suppresses the growth of the human NPC cell line CNE-2. Treatment by AGM-1470 has no physical nor histological toxicity. Angiogenesis inhibitors may be effective in the treatment of the local lesion of NPC.