Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients.

OBJECTIVE: For most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety. METHODS: We reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0-2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety. RESULTS: We identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8-55.8), and disease control rate was 65% (95% CI, 52.9-77.1). With a median follow-up of 35.7 months (IQR 28.6-48.8), median PFS was 5.8 months (95% CI, 4.5-7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0-1 patients, median OS was 14.8 months (95% CI, 12.2-21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III-IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders. CONCLUSION: The weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.

Interest to consider re-challenging by cetuximab and platinum containing regimen in recurrent Head and Neck Cancer.

BACKGROUND: The EXTREME protocol is the standard of care for recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) in first line. Beyond the first-line except immunotherapy, poor efficacy was reported by second-line chemotherapy. Re-challenge strategies based on a repetition of the first line with platinum and cetuximab regimens might have been an option to consider. METHODS: We performed a retrospective study in order to assess the efficacy of the cetuximab plus platinum doublet-based chemotherapy regimen in patients with R/M HNSCC progressing after at least 3 months of cetuximab maintenance (EXTREME protocol). We complete a retrospective review of all medical records from R/M HNSCC patients treated after 16 weeks with the EXTREME regimen and treated with a re-challenge strategy between January 2010 and December 2014 in our institution (Centre Paul Strauss, Strasbourg, France). RESULTS: 33 patients were identified. The re-challenged strategy provided an ORR in 33.3% of cases and a DCR of 69.6% of cases. The median OS and PFS observed from the second line were 11.2 months and 6.5 months for the subset re-challenged by EXTREME or PCC regimens respectively. The response rate between patients with a platin free interval within 3 and 6 months and greater than 6 months were equal. Drugs dose intensity were better with the PCC protocol than the EXTREME regimen used as a rechallenge. CONCLUSIONS: This study suggest re-challenging strategy by these regimens could be considered beyond the first line as an option when the platin free interval is greater than 3 months.

Cetuximab-Carboplatin-5-Fluorouracil Regimen in Elderly Patients with Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A French Retrospective Survey.

BACKGROUND: The cetuximab plus platinum-based chemotherapy regimen is a standard of care in the treatment of recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The feasibility in the elderly population is currently unknown. METHODS: We performed a retrospective study in order to assess the efficacy and safety of the cetuximab plus platinum-based chemotherapy regimen in patients >65 years with recurrent or metastatic HNSCC. We performed a retrospective review of all medical records from recurrent or metastatic HNSCC patients >65 years treated with the cetuximab plus platinum-based chemotherapy regimen between September 2008 and December 2013 in our institution (Centre Paul Strauss, Strasbourg, France). RESULTS: A total of 59 patients were identified. Carboplatin in combination with 5-fluorouracil (FU) was the only cetuximab-associated chemotherapy regimen used for treating elderly patients. The median progression-free survival was 4 months (95% confidence interval [CI]: 2.9-4.7), and the median overall survival was 9.1 months (95% CI: 6.5-13.1). Grade 3 or 4 toxicity adverse events occurred in 52% (n = 31) of the patients (mostly hematologic toxicities and infections). CONCLUSIONS: This retrospective study suggests that the cetuximab plus carboplatin-5FU chemotherapy is an effective treatment option for elderly patients with recurrent or metastatic HNSCC.

Prognostic factors of survival in head and neck cancer patients treated with surgery and postoperative radiation therapy.

CONCLUSIONS: Given that radiation therapy (RT) is currently initiated as soon as possible after surgery, our results indicate that the main prognostic factors of survival are pT and pN stages in patients treated with surgery and postoperative RT for locally advanced head and neck squamous cell carcinoma (HNSCC). OBJECTIVES: To determine the prognostic factors for survival in patients treated with surgery and postoperative RT for locally advanced HNSCC. PATIENTS AND METHODS: A retrospective study was performed on 308 consecutive patients treated from 1990 to 1998 with surgery and postoperative RT. In addition to histological factors, time-related factors were considered. RESULTS: The median age of the whole cohort was 56 years (range 35-83). Median follow-up was 98 months. Median interval from surgery to the start of RT was 44 days (range 18-157), while median RT duration was 52 days (range 22-115). From univariate analysis of overall survival, statistically significant prognostic factors were pT stage (p<0.0001), pN stage (p=0.008), RT duration (p=0.01) and total treatment time (p=0.02). Perineural invasion, perivascular invasion, extranodal spread and positive resection margins did not appear to be related to survival. From multivariate analysis, the only statistically independent prognostic factors appeared to be pT and pN stages.

Prognostic indicators for survival in head and neck squamous cell carcinomas: analysis of a series of 621 cases.

BACKGROUND: We sought to study the influence of pT classification, pN status, tumor volume, and number of lymph nodes invaded on survival of patients with head and neck cancers to improve therapeutic indications. METHODS: This was a retrospective study of 621 consecutive patients treated from 1990 to 1997 by a single team. RESULTS: In univariate analysis, pT classification (p < .0001), pN status (p < .0001), capsule rupture (p < .0001), the number of lymph nodes invaded (0, 1-3, 4-9, > or =10) (p < .0001), and the tumor volume (p < .0001) were significantly associated with overall survival. A Cox model identified as independent prognostic indicators age (p < .0001), pT classification (p < .0001), and pN status (p < .0001). CONCLUSIONS: Not only pT classification and pN status but also the number of the lymph nodes invaded and the tumor volume should be considered as essential prognostic indicators, and any clinical trial developed should stratify accordingly.