Concomitant chemoradiotherapy (CT/RT) vs neoadjuvant chemotherapy with docetaxel/cispaltin/5-fluorouracil (TPF) followed by CT/RT in locally advanced head and neck cancer. Final results of a phase II randomized study

6000 Background: Concomitant CT/RT is the standard treatment for locally advanced head and neck squamous cell carcinoma. This trial explores the efficacy of induction chemotherapy with TPF before concomitant CT/RT and concomitant CT/RT alone in locally advanced unresectable disease. Patients and Methods: From January 2003 to January 2006, 101 patients (pts) with stage III- IV M0, PS 0–1, were randomized to 2 cycles of cisplatin (P) 20mg/sqm days 1–4, 5FU (F) 800 mg/sqm 96-hour CI wks 1 and 6 during RT (66–70 Gy) (Arm A) or 3 cycles TPF (docetaxel 75 mg/sqm and P 80 mg/sqm on day 1, F 800 mg/sqm 96 hours CI) every 3 weeks followed by the same CT/RT (Arm B). Neck dissection was planned for pts with stage N2-N3 and pathological complete response (CR) at the primary tumor. A minimum accrual of 96 pts was required to detect a difference in radiological CR (primary endpoint) of at least 15% in favor of arm B. Results: Pts/tumor characteristics were well balanced in the two arms. During TPF, G3–4 neutropenia was the main hematological toxicity (52%) while nonhematological toxicities were mild. CR rate after TPF was 6.5%. During concomitant CT/RT, hematological and nonhematological toxicities were not increased in the experimental arm B and the feasibility of CT/RT was not compromised. Grade 3–4 toxicities in arms A and B, respectively, were mucositis 38% and 25%, dysphagia 21% and 16%, skin reaction 13% and 15%, weight loss 2% and 4%. Radiological evaluation (CT or MRI scan) of responses 6–8 weeks from the end of CT/RT showed a CR of 21.2% (CI: 64–89) in arm A and 50.0% (CI: 34–65) in arm B. Radiological CRs at 8 months for unresected pts were 40.0% in Arm A and 57.1% in Arm B. Median OS and 1-yr OS were respectively 33.3 months and 77.6% in Arm A, while median OS was not reached in arm B and 1-yr OS was 86.0%. Conclusions: Neoadjuvant TPF is feasible and does not compromise subsequent concomitant CT/RT. Compared with CT/RT, induction TPF plus CT/RT significantly improves clinical CR evaluated at 8 weeks and 8 months after the end of the treatment. A trend for improved OS was also observed. The phase III part of the study with survival as the primary end-point is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis