Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial.

BACKGROUND: The purpose of this study was to assess the efficacy, safety, and pharmacokinetics of cisplatin-based chemotherapy plus cetuximab as first-line treatment in Chinese and Korean patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients (n = 68) received cetuximab weekly plus 3-week cycles of cisplatin/5-fluorouracil (5-FU) chemotherapy for up to 6 cycles. The primary endpoint was overall response rate. RESULTS: The overall response rate was 55.9%, including 2 complete responses (CRs). Median overall survival (OS) was 12.6 months and median progression-free survival (PFS) was 6.6 months. Grade 3/4 adverse events (AEs) were reported in 41 (60.3%) patients. The safety profile was in line with previous clinical experience. The pharmacokinetic profile was in line with that observed with cetuximab in white and Japanese patients. CONCLUSION: The efficacy, safety, and pharmacokinetic findings from this study support the use of first-line platinum-based chemotherapy plus cetuximab in Chinese and Korean patients with recurrent and/or metastatic SCCHN (ClinicalTrials.gov NCT01177956).

Combined high-dose radiation therapy and systemic chemotherapy improves survival in patients with newly diagnosed metastatic nasopharyngeal cancer.

OBJECTIVES: To investigate the efficacy of high-dose radiation therapy (RT) to the primary and regional disease in combination with systemic chemotherapy and local treatment to metastatic foci in patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC). METHODS: One hundred and five consecutive patients with pathologically confirmed NPC with distant metastasis at diagnosis seen between 1995 and 2002 were reviewed. All were offered cisplatin-based chemotherapy, high-dose RT (>30 Gy) to the head and neck region, and active treatment to the metastatic foci. RESULTS: Patients' median age was 46 years, and all had a Karnofsky Performance Score of ≥70. Eighty-nine patients (85%) had metastases confined to 1 organ. Ninety-six patients (91%) received at least 1 cycle of chemotherapy and 71 (68%) received greater than 65 Gy of radiation to the head and neck region. With a median follow-up time of 22 months (range: 2 to 142 mo), 90 patients had deceased, and the median survival time of the entire group was 25 months. The 2 and 5-year estimated overall survival rates were 50% and 17%, respectively. Radiation dose of greater than 65 Gy to the primary region (P = 0.05) and number of organs with metastases (single vs. multiple) (P = 0.002) were independent predictive factors for overall survival on log-rank tests. Only moderately severe acute toxicities, such as Radiation Therapy Oncology Group grade 3 mucositis, skin desquamation, and leukocytopenia were observed. No patient experienced grade 4 acute toxicities. CONCLUSIONS: High-dose RT is indicated for local disease control in patients with metastatic NPC, and may improve survival when actively used with systemic chemotherapy and local treatment for metastatic foci. Patients with single-organ metastases have a better prognosis as compared with those with more widespread metastases.

Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: experience of 370 consecutive cases.

INTRODUCTION: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy. METHODS: Between August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well. RESULTS: With a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (< or = 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications. CONCLUSION: IMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.