Sequential Chemoradiotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil in Patients With Locally Advanced Head and Neck Cancer

Abstract

The purpose of this phase II trial was to evaluate the toxicity of a sequential chemoradiotherapy approach using docetaxel, cisplatin, and 5-fluorouracil (5-FU) (DCF) with granulocyte colony-stimulating factor support in previously untreated patients with locally advanced head and neck cancer (HNC). Secondary endpoints included preliminary assessment of response. Patients with locally advanced HNC, a World Health Organization performance status 0 to 2, and no prior history of chemotherapy or radiotherapy were included. Treatment consisted of docetaxel 80 mg/m2 (1-hour infusion) on day 1, cisplatin 40 mg/m2 (1-hour infusion) on days 2 and 3, and 5-fluorouracil 1,000 mg/m2 (24-hour continuous infusion), on days 1 to 3, repeated every 28 days for a maximum of 4 cycles per patient. All patients received granulocyte colony stimulating factors subcutaneously between days 4 and 9. Radiation therapy (RT) to the primary tumor site and neck lymph nodes was planned within 5 weeks of the last cycle of chemotherapy. The primary tumor site received 60 to 70 Gy. Twenty patients (median age 56 years, range: 40-72 years) received a total of 60 cycles of DCF. The median number of cycles was 3 (range: 1-4 cycles). All patients were evaluable for toxicity and response. The most common acute nonhematologic toxicities from DCF induction chemotherapy included alopecia, mucositis, peripheral sensory neuropathy, onycholysis, and asthenia. Febrile neutropenia developed in two patients and grade IV diarrhea in one patient. There were no treatment-related deaths. The overall response rate (RR) after DCF induction chemotherapy was 90% (95% confidence interval [CI]: 76.8-103.1%). After the completion of RT, the overall RR was 95% with a complete response rate of 73% (95% CI: 49.9-90.1%). Organ preservation was achieved in eight patients with laryngeal cancer and one patient with base of tongue involvement. After a median follow-up of 36 months (range: 5-43 months) the median disease-free and overall survival have not been reached yet. The 1- and 2-year survival rates were 85% and 60%, respectively. Sequential chemoradiotherapy with DCF and growth factor support is feasible and very active, with durable responses in patients with locally advanced head and neck cancer. Further evaluation of this modality is justified in the context of a clinical trial.

Phase I and initial phase II results from a trial investigating weekly docetaxel and carboplatin given neoadjuvantly and then concurrently with concomitant boost radiotherapy for locally advanced squamous cell carcinoma of the head and neck

“…The utility of docetaxel for head and neck disease has been confirmed in the clinic. Docetaxel has demonstrated activity in the setting of advanced metastatic disease, [5][6][7] and is feasible in combination with concurrent daily radiotherapy. 8 -10 The current trial builds on these previous reports by using two complementary clinical strategies.…”

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

“…At a recent follow-up (median 24 months), the 2-year overall survival rate was 42% (Posner et al, 2001c). Janinis et al (2001) administered docetaxel 80 mg m À2 d1, cisplatin 40 mg m À2 d2 and d3 and continuous 5-FU 1000 mg m À2 day À1 d1 -3 every 4 weeks in chemonaïve patients with locally advanced SCCHN. All patients received G-CSF d4 -9.…”

Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future?

“…Several groups aimed to investigate the clinical benefit, if any, of adding taxane therapy to the IC regimen. A series of phase I and phase II trials used a high-and intermediate-dose docetaxel, cisplatin, and 5-FU (TPF)-based IC regimen for patients with advanced SCCHN [21][22][23][24].…”

“…Several groups aimed to investigate the clinical benefit, if any, of adding taxane therapy to the IC regimen. A series of phase I and phase II trials used a high-and intermediate-dose docetaxel, cisplatin, and 5-FU (TPF)-based IC regimen for patients with advanced SCCHN [21][22][23][24].Following phase II trials involving the addition of taxane therapy, three randomized phase III trials emerged to explore the benefit of induction TPF versus PF alone in terms of clinical outcomes (Table 2). In the European TAX-323 study, 358 patients with stage III or stage IV unresectable disease and no evidence of distant metastasis (80% of patients included had T3 or T4 lesions and 71% had N2 or N3 nodal disease) were randomized to TPF (docetaxel, 75 mg/m 2 on day 1; cisplatin, 75 mg/m 2 on day 1; 5-FU, 750 mg/m 2 by continuous infusion for 5 days) or PF therapy (cisplatin, 100 mg/m 2 ; 5-FU, 1,000 mg/m 2 by continuous infusion on days 1-5) for up to four cycles followed by RT in both treatment arms [4].…”