Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: The optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m(2)/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m(2)/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m(2)/d1-5 + 29-33; n = 74). RESULTS: At least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. CONCLUSION: Two courses of fractionated cisplatin (20 mg/m(2)/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity.

Effect of post-exposure administration of keratinocyte growth factor (Palifermin) on radiation effects in oral mucosa in mice.

Oral mucositis is a severe component of the acute radiation syndrome. The present study was initiated to determine the potential of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) to ameliorate oral mucositis in a mouse model after a single radiation exposure. A 3 x 3 mm(2 )area in the center of the lower tongue surface of C3H/Neu mice was irradiated with graded single doses of 25 kV X-rays. Acute mucosal ulceration was used as the quantal end-point for dose-response analyses. Palifermin was applied at a dose of 15 mg/kg on days 0, 1, 2, 3, 4 or 5. For comparison, three injections of 5 or 15 mg/kg on days 1-3 were administered. The ED(50) (dose at which ulceration is expected in 50% of the animals) for irradiation alone was 11.6 +/- 1.2 Gy. Mean latent time was 9.4 +/- 0.2 days; mean ulcer duration was 2.8 +/- 0.2 days. Single injections of rHuKGF did not result in a significant increase in isoeffective radiation doses at any of the administration days. However, the latent time to ulceration was significantly shortened by 1-2 days in all protocols. Repeated administration of rHuKGF (15 mg/kg) resulted a significant increase in ED50 to 16.8 +/- 4.0 Gy (P = 0.0047); the mean latent time was 4.4 +/- 0.9 days. Three injections of 5 mg/kg of Palifermin on days 1-3 yielded an ED50 of 19.4 +/- 1.7 Gy. In this protocol, mean latent time was 6.6 +/- 0.6 days. In conclusion, Palifermin has a potential to reduce the mucositis burden in patients after a single radiation exposure. Repeated injections are required. For three injections, a negative dose-effect of rHuKGF was observed. The optimum dose, number and timing of the administration require further investigation.