The combination of chemotherapy and radiotherapy is emerging as the new standard modality for the treatment of locally advanced head and neck cancer, due to the inherent functional and cosmetic sequelae associated with its surgical management. Combination chemotherapy with 5-fluorouracil and cisplatin (FP) is one of the most active regimens for the head and neck cancer. Furthermore, both agents are known to act as radiosensitizer. This study was conducted to determine the efficacy, feasibility, and the toxicities of concurrent FP chemotherapy with radiotherapy. MATERIALS AND METHODS: Patients with histologically proven locally advanced head and neck cancer (T3-4 or node positive) were enrolled in the study. Patients received 5-fluorouracil, 1,000 mg/m2/day, continuously for 4 days, and cisplatin, 75 mg/m2, on day 1. This regimen was given every four weeks. The radiotherapy (45 Gy) was started on day 1 of the first cycle, and administered in 25 fractions. Following a three-week interval, the radiotherapy was resumed on day 1 of the third cycle of chemotherapy, and administered in 15 fractions (27 Gy). RESULTS: Of the 31 eligible patients included, 28 were able to be evaluated for the tumor response. The response rate for the 28 patients was 93% (16 complete responses, 10 partial responses). Disease free survival for the 16 complete responders was 37 months (median, 1 ~41 months), with a median follow-up time of 31 months. The 1-, 2-, and 3-year survival rates were 82%, 69%, and 63%, respectively. Regarding the feasibility of this treatments, only nineteen patients (61%) received the complete courses of scheduled treatments. The median duration of admission for all patients was 39 days. Grade 3 or 4 stomatitis were observed in 25 patients (83%) and appeared as the dose limiting toxicity of this regimen CONCLUSION: Although FP chemotherapy with concurrent radiotherapy is toxic, it is an effective and relatively feasible treatment for locally advanced head and neck cancer. The majority of patients experienced severe stomatitis, which appeared as the dose limiting toxicity of this regimen.
Chemoradiotherapy ; Cisplatin* ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination ; Fluorouracil* ; Follow-Up Studies ; Head and Neck Neoplasms* ; Head* ; Humans ; Radiotherapy* ; Stomatitis ; Survival Rate

PURPOSE: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. MATERIALS AND METHODS: Twenty-four ICR mice were divided into three groups? the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days 1~5. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. RESULTS: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. CONCLUSION: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.
Animals ; Body Weight ; Cisplatin* ; Eating ; Epidermal Growth Factor* ; Head ; Humans* ; Inflammation ; Mice* ; Mice, Inbred ICR ; Mouth Mucosa ; Mucositis ; Mucous Membrane ; Neck ; Radiotherapy* ; Stomatitis*