Both PFS and OS for patients with HPV-positive tumors were superior to PFS and OS in patients with HPV-negative tumors (P=

Both PFS and OS for patients with HPV-positive tumors were superior to PFS and OS in patients with HPV-negative tumors (P= .012 and .046, respectively, log-rank test). either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis. == Results == After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P= .012) and OS (P= .046). == Conclusion == ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis. == INTRODUCTION == A majority of patients with squamous cell carcinoma of the head and neck (SCCHN) present with stage III or IV M0 disease, and a main therapeutic aim is locoregional disease control. However, risk of distant metastases tends to correlate with site and the extent of nodal involvement at presentation. As highly effective concomitant chemoradiotherapy programs improve local control, there may be a relative increase to as high as 30% to 40% in the risk of distant disease recurrence, especially among patients with N2/3 staging.14 Induction chemotherapy (ICT) as a component of primary treatment has been shown in several studies and meta-analyses5,6to decrease the emergence of metastatic disease. Moreover, the addition of a taxane to platinum and fluorouracil ICT has recently been reported to be superior to platinum and fluorouracil in randomized phase III studies, with increased tumor responses7and overall survival (OS)8,9observed for the three-drug schedule. The efficacy of ICT, followed by Cynarin radiotherapy with concomitant chemotherapy, is currently under study in prospective randomized trials.10 Prior study of paclitaxel and carboplatin administered in a 6-week course before chemoradiotherapy demonstrated that this regimen is feasible and resulted in a high complete response rate (CR) of 35% and overall response rate of 87% before subsequent chemoradiotherapy, with an OS rate of 70% at 3 years.11The addition of epidermal growth factor receptor (EGFR) targeted therapy with cetuximab seems to augment local tumor control and OS in patients treated with radiotherapy12and OS in patients with recurrent or metastatic disease receiving platinum-fluorouracil chemotherapy.13 We hypothesized that the addition of cetuximab to the weekly paclitaxel-carboplatin ICT regimen (PCC) would be an effective and well-tolerated regimen for the treatment of CRLF2 previously untreated patients with multiple cervical nodal metastases at risk for distant metastases. The study was also designed for risk-based variation with respect to the intensity of definitive locoregional treatment in an attempt to achieve local and regional tumor control with acceptable long-term adverse Cynarin effects. == PATIENTS AND METHODS == == Eligibility Cynarin Criteria and Baseline Staging == From February 2005 to December 2005, previously untreated patients with histologically proven, stage IVA or IVB SCCHN and nodal staging of N2b/c or N3 (oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx) were entered. Patients have been observed through August 2008. Normal hematopoietic, hepatic, and renal functions were required. Patients rendered disease free by initial surgical resection were not eligible. Staging procedures consisted of physical examination, panendoscopy, and head and neck computed tomography scan. The protocol and the informed consent were approved by The University of Texas M. D. Anderson Cancer Center Institutional Review Board. == Treatment == On the basis of the presentation at diagnosis, the protocol Cynarin guideline was for patients to receive PCC and then proceed to definitive local therapy with radiation as a single modality if T1-2, concomitant chemotherapy and radiation if T3-4, or surgery if an oral cavity was the primary site (Fig 1). The definitive treatment assignment was not to be determined by the response to ICT, but flexibility was permitted, dependent on chemotherapy-associated toxicity and physician judgment. For example, if a patient presented with a large T2 base of tongue primary tumor with an endophytic growth pattern, the attending physician had an option.