Metastatic Squamous Cell Head Research Articles

Outcome of patients with recurrent/metastatic squamous cell head and neck cancer treated with platinum-based chemotherapy with or without cetuximab in real-world practice.

Patients with recurrent or metastatic squamous cell head and neck cancer (R/M SCHNC) exhibit a poor prognosis with a median overall survival (OS) time of <1 year. Platinum-based chemotherapy with or without cetuximab has been the standard of care in the last decade. The aim of the current retrospective study was to evaluate the outcome and tolerability of treatment in patients with R/M SCHNC receiving platinum/5-fluorouracil/cetuximab (PFE) chemotherapy compared with platinum/5-fluorouracil (PF) chemotherapy in daily clinical practice. A retrospective analysis was performed using the data of patients treated at the Institute of Oncology Ljubljana between April 2008 and May 2018. Progression-free survival (PFS) and OS were calculated with the Kaplan-Meier method and compared with the log-rank test. Multivariate regression Cox analysis was used to determine independent prognostic factors. A total of 67 patients were treated at the aforementioned Institute: 34 patients received the PF and 33 the PFE regimen. The mean age of patients was 54.6 years and 91% of patients were male. Median PFS time was 6.6 vs. 7.1 months for the PF vs. PFE groups, respectively (P=0.852). Median OS time was 9.6 vs. 11.5 months for the PF vs. PFE groups, respectively (P=0.029). The prognostic factor for PFS was partial remission [hazard ratio (HR), 0.32; 95% CI, 0.15-0.70; P=0.004]. Prognostic factors for OS were partial remission (HR, 0.15; 95% CI, 0.06-0.38; P<0.001) or stable disease (HR, 0.28; 95% CI, 0.13-0.64; P=0.002), and a subsequent line of treatment upon progression (HR, 0.28; 95% CI, 0.15-0.52; P<0.001). In the PFE group, 15.4% of patients had a grade >2 infusion reaction to cetuximab and 27.3% had grade 3 skin rash. There were no differences in diarrhoea, hypomagnesaemia, infections and febrile neutropenia; however, the mortality on active treatment was high (13.4%). In conclusion, patients treated with PFE had similar PFS, but improved OS compared with patients treated with the PF protocol. The proportion of patients who died under treatment due to disease progression and toxicity was high in both treatment arms. A thorough selection of patients for this treatment is crucial.

Systemic Therapy in Recurrent or Metastatic Squamous Cell Head and Neck Cancer

Systemic Therapy in Recurrent or Metastatic Squamous Cell Head and Neck Cancer

The emergence of long-term survivors in recurrent and metastatic squamous cell head and neck cancer.

The systemic therapies available in recurrent and metastatic head and neck squamous cell carcinoma to date are palliative-intent treatments in most cases. However, a small subgroup of patients derives unconventional benefit and become long-term survivors, achieving cure in some cases. This review focusses on this group of patients, discusses recent literature and suggests plausible molecular hypothesis. Human papillomavirus-related disease is known to confer a better prognosis in metastatic patients, probably because of its greater sensitivity to systemic therapies. This group of patients seems to have a greater immune activation, which could partly explain this fact. Moreover, the use of antiepidermal growth factor receptor therapies in the metastatic setting has doubled the prevalence of long-term survivors. One of the most plausible explanations is the immune-modulatory effect of cetuximab mediated by antibody-dependent cell-mediated cytotoxicity.These facts, along with the recent encouraging results of checkpoint inhibitors in this disease, give hope that these therapies will not only improve survival but also increase the prevalence of long-term survivors. Long-term survivors merit our utmost attention as an in-depth study of these patients could help us to better understand the tumour biology and allow us to develop robust biomarkers and effective targeted therapies, which could in turn lead to a true paradigm shift.

The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab

FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5.5 vs 4.1 months, P=0.02; median overall survival: 10.2 vs 7.2 months, P=0.04). In multivariate analysis, the FCGR2A and 3A genotypes as well as the time between initial diagnosis and relapse of disease not amenable to curative therapy remained the only independent prognostic factors for PFS. The results are in line with previous reports in colorectal cancer patients and confirm the possible value of genetic polymorphisms of immunocompetent cells for the success of cetuximab treatment.

Association between standardized uptake value and survival in patients with locally advanced or metastatic squamous cell head and neck cancer

Abstract Introduction and objective The present study aimed to evaluate the association between tumor Standard Uptake Value (SUVmax) values obtained by PET/CT, and survival in patients with locally advanced or metastatic squamous cell head and neck cancer. Method The present study included 38 patients with locally advanced or metastatic squamous cell head and neck cancer, who were staged using PET/CT at diagnosis. PET/CT imaging findings were evaluated retrospectively. The effect of SUVmax value by PET/CT on overall survival was analyzed. Results The most common tumor localization was laryngeal cancer among 38 patients included in the study (n = 25, 65.8%). The study group consisted of mostly male patients (n = 33, 86.8%), and the median age was 58 (range: 24–77). The median SUVmax value was 11 (range: 3–58). Median survival was 32.7 months in patients with SUVmax ≤11 compared to 16.5 months in patients with SUVmax >11 (p = 0.019).

A study of the impact of palliative chemotherapy and the effect of age on the quality of life of patients with recurrent or metastatic squamous cell head and neck cancer

A study of the impact of palliative chemotherapy and the effect of age on the quality of life of patients with recurrent or metastatic squamous cell head and neck cancer

Approval Summary: Cetuximab in Combination With Cisplatin or Carboplatin and 5-Fluorouracil for the First-Line Treatment of Patients With Recurrent Locoregional or Metastatic Squamous Cell Head and Neck Cancer

On November 7, 2011, the U.S. Food and Drug Administration approved cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil for the first-line treatment of patients with recurrent locoregional or metastatic squamous cell head and neck cancer. Approval was based on a randomized study of 442 patients conducted outside the U.S. Cisplatin (100 mg/m2 intravenously) or carboplatin (area under the curve 5 intravenously) on day 1 with 5-fluorouracil (1,000 mg/m2/day continuous intravenous infusion days 1-4) were administered every 3 weeks. Cetuximab, 400 mg/m2 intravenously, was administered initially followed by cetuximab, 250 mg/m2 intravenously weekly. After completion of six planned treatment courses, cetuximab patients without progression continued cetuximab 250 mg/m2 weekly. The study used European Union (EU)-approved cetuximab rather than U.S.-approved cetuximab. U.S.-approved cetuximab provides approximately 28% higher exposure relative to EU-approved cetuximab in a pharmacokinetic comparability study in monkeys. Overall survival, the primary efficacy endpoint, was significantly improved in cetuximab-treated patients (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.64-0.98; p = .034, stratified log-rank test). Median survival times were 10.1 and 7.4 months, respectively. Progression-free survival (PFS) was also significantly improved in patients receiving cetuximab (HR: 0.57; 95% CI: 0.46-0.72; p < .0001). Median PFS times were 5.5 and 3.3 months, respectively. Response rates were 35.6% and 19.5% (odds ratio: 2.33; 95% CI: 1.50-3.60; p = .0001). Adverse reactions (≥25%) from cetuximab plus chemotherapy treatment included nausea, anemia, vomiting, neutropenia, rash, asthenia, diarrhea, and anorexia. Conjunctivitis occurred in 10% of cetuximab patients. Other adverse reactions, sometimes severe, included infusion reactions, hypomagnesemia, hypocalcemia, and hypokalemia.

1053 - The Usefulness of G8 Evaluation in Therapeutic Decision and Prediction of Tolerance in Locally Advanced or Metastatic Squamous Cell Head and Neck Cancer (SCCHN) Patients Older Than 65 Years

ABSTRACT Background 2/3 of HN age, TNM, histology, nutritional status, ACE -27 index, toxicity of treatment. Results We studied 21 patients: 9 pts (42%) less than 70, 4 pts (19%) between 70 -75 and 7 pts (33%) over 75, mostly locally advanced, squamous histological type; denutrition in 9 pts (42%) 2 over 75 years; 33% had swallowing problems and 25% loss weight superior of 10% in the last 3 months before treatment. ACE 27 index was over 2 for 18 (85%) patients.We found a G8 score Conclusions this preliminary prospective study demonstrates that G8 score identify frailty in 42% of elderly SCCHN patients older than 65 years. An adapted tool for geriatric asessement in SCCHN patients seems necessary. Disclosure All authors have declared no conflicts of interest.

Role of EGF inhibitors in the treatment of recurrent or metastatic squamous cell head and neck cancer

Role of EGF inhibitors in the treatment of recurrent or metastatic squamous cell head and neck cancer Jochen H LorchDana Farber Cancer institute, Boston, MA, USAAbstract: Squamous cell cancer of the head and neck (SCCHN) is a major contributor to morbidity and mortality worldwide. In recent years, inhibition of the epidermal growth factor receptor has become an established treatment strategy in SCCHN both in the up-front treatment and in the recurrent and metastatic setting. This review summarizes the most important developments of the recent past and provides an overview of newer developments. Keywords: squamous cell cancer, head, neck, epidermal growth factor receptor

Role of EGF inhibitors in the treatment of recurrent or metastatic squamous cell head and neck cancer

Squamous cell cancer of the head and neck (SCCHN) is a major contributor to morbidity and mortality worldwide. In recent years, inhibition of the epidermal growth factor receptor has become an established treatment strategy in SCCHN both in the up-front treatment and in the recurrent and metastatic setting. This review summarizes the most important developments of the recent past and provides an overview of newer developments.

A phase I study of two administration schedules of the Polo-like kinase 1 inhibitor BI 2536 in patients with advanced solid tumors

3069 Background: BI 2536 is a novel highly potent and selective inhibitor of the serine-threonine Polo-like kinase 1 (Plk1), a key regulator of cell cycle progression. Objectives of this trial were the assessment of the maximum tolerated dose (MTD), overall safety, pharmacokinetics and preliminary efficacy of BI 2536 given intravenously. Methods: Sequential cohorts of 3–6 patients (pat) with advanced or metastatic solid tumors received infusions of BI 2536 following a toxicity guided dose escalation design. In the first part of the trial, a single administration was given every 21 days (d1). After completion of accrual BI 2536 was administered on three consecutive days (d1–3) in a dose intensified schedule in additional patient cohorts. Further treatment courses were given in the absence of disease progression and after recovery of toxicity after a 3-week observation period. Results: Of the 52 entered patients a total of 40 pts were treated at doses of 25 (n=3), 50 (n=3), 100 (n=3), 200 (n=25) and 250 mg (n=6) in the d1 schedule. The MTD for the d1 schedule was defined at 200 mg. Dose limiting toxicity (DLT) consisted of neutropenic infection and occurred in 2/6 patients at 250 mg. Reversible CTCAE grade ≥ 3 neutropenia represented the main drug related toxicity with an incidence of 13/25 in the 200 mg and 5/6 in the 250 mg dose cohorts. Alopecia was reported in 20% of pat. Further common drug related adverse events (AE’s) consisted of nausea (38%), anorexia (25%) fatigue (18%), vomiting (18%) and mucositis (12%) and were mostly of mild to moderate intensity (CTCAE grade ≤ 2). PK analysis showed dose proportionality of Cmax and AUC0-∞ with a high clearance (∼ 1400 mL/min) and a high volume of distribution (∼ 1200 L). A correlation between exposure and neutropenia was observed. Patients were treated for up to 10 courses without evidence of accumulating toxicity. One partial response was observed in a patient with metastatic squamous cell head and neck cancer treated at 250 mg. The DLT was determined at 3x70 mg in the dose intensified schedule with the MTD still pending. Conclusion: In summary BI 2536 is a Plk1 inhibitor with a favorable safety and PK profile. Neutropenia as a mechanism-related toxicity indicates target inhibition in vivo. First signs of antitumor activity were observed. [Table: see text]

Phase II study of rhizoxin in squamous cell head and neck cancer

To test the anti-tumour activity of rhizoxin in recurrent and/or metastatic squamous cell head and neck cancer, we performed a phase II study. Eligibility required histologically proven squamous cell head and neck cancer. Patients could only have received one prior chemotherapy. Patients were entered if WHO PS was < or = 2 and organ functions were normal. Treatment consisted of rhizoxin 1.5-2.0 mg m-2 i.v. bolus injection once every 3 weeks. Thirty-two patients entered the study. All were eligible, 31 were evaluable for toxicity and 25 for response. Toxicity mainly consisted of pain at the tumour site and leucocytopenia. Mild asthenia and stomatitis were also observed. Two objective partial responses, lasting 7.5 and 3.5 months, were seen. Rhizoxin at this dose and schedule has minor activity in recurrent and/or metastatic squamous cell head and neck cancer.

Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma with a combination of vinorelbine, cisplatin, and 5-fluorouracil: A multicenter phase II trial

Vinorelbine has been demonstrated to be active against squamous cell carcinomas of the head/neck (SCHNC) and lung. This multicenter phase II trial was carried out to evaluate the activity and tolerability of the combination of vinorelbine, cisplatin, and 5-fluorouracil given on an outpatient schedule in a series of 80 patients with recurrent SCHNC. Eighty patients with recurrent and/or metastatic SCHNC were treated with a combination of CDDP 80 mg/m2on day 1, 5-FU 600 mg/m2 as a 4-hour infusion on days 2-5, and vinorelbine 25 mg/m2 on days 2 + 8. This cycle was repeated every 28 days. Most patients had oral cavity, larynx, or oropharynx carcinoma (88%). Forty-seven had previously received surgery alone, two radiotherapy alone, and 31 surgery plus radiotherapy. Seventy-two patients had locoregional recurrency, and eight had distant metastases. According to an intent-to-treat analysis, complete response (CR) of a mean duration of 12.7+ months was achieved in 13% of cases (95% CI 5%-21%), and partial response of 8.3+ months in 45% of patients (95% CI 33%-56%), for an overall response rate of 55% (95% CI 43%-65%). Nine patients (11%) showed no change, and 22 (28%) progressed. Five patients were not evaluable for response and toxicity. CR were seen more frequently in patients pretreated with only surgery than in those who had also received radiotherapy (15% vs. 9%; p = 0.7). No statistically significant differences in response rate according to site of primary tumor were found (p = 0.8, NS). The received dose intensities of 5-FU, CDDP, and VNR were 90%, 92%, and 82%, respectively. The overall survival of the series as a whole was 9.7+ months (range 4-27). Toxicity was generally acceptable. Grades 3 and 4 leukopenia were recorded in 11% and 5% of patients, respectively. Noteworthy was the occurrence of pain at the tumor site after vinorelbine administration in 5 patients. The combination regimen of CDDP, 5-FU and vinorelbine is quite active in the treatment of metastatic and/or recurrent SCHNC. This regimen should be tested as initial treatment in previously untreated patients and compared to a standard regimen in recurrent SCHNC.