Advanced Squamous Cell Carcinoma Of Head And Neck Research Articles

Nimotuzumab with intensity-modulated radiation therapy in unresectable and platinum-ineligible locally advanced head-and-neck cancer.

Background:Outcomes with conventional treatment are poor in patients with squamous cell carcinoma of head and neck (SCCHN). Treatment options are further limited for patients ineligible to receive platinum-based chemotherapy due to various factors such as geriatric age, comorbidity, and organ dysfunctions. The present study retrospectively evaluated the effectiveness of nimotuzumab when added to radiation therapy in unresectable, locally advanced SCCHN patients who were ineligible for platinum-based chemotherapy.Materials and Methods:The medical records of 21 patients with unresectable, locally advanced head-and-neck cancer and histologically confirmed squamous cell carcinoma who were ineligible for platinum-based chemotherapy treated with nimotuzumab and intensity-modulated radiation therapy (IMRT) from 2012 to 2017 were retrospectively analyzed. The tumor response rate and overall survival (OS) were analyzed. Patients were assessed for toxicity and adverse events (AEs) as per CTCAE version 4. Statistical analysis was performed using SPSS software.Results:The median number of doses of nimotuzumab received was 6, and median dose of radiotherapy was 60 Gy. The tumor response rate was calculated at 24 weeks after the completion of radiotherapy and was as follows: 76.2% (16) of patients showed complete response, 9.5% (2) of patients showed partial response, 4.8% (1) of patients showed stable disease, and 9.5% (2) of patients showed progression of disease. Median OS was 21 months, whereas 1-year survival rate was 63.7%. No Grade 3 or Grade 4 AEs were observed.Conclusion:Nimotuzumab with IMRT has achieved promising clinical outcomes in unresectable locally advanced SCCHN patients who are ineligible for platinum-based chemotherapy, without accumulation of toxicity.

1069P - Phase II study of biweekly TPFL induction chemotherapy for locally advanced squamous cell carcinoma of head and neck

Background: The induction chemotherapy (ICT) with triweekly TPF had been considered as an effective treatment in locally advance squamous cell carcinoma of head and neck (SCCHN). However, the treatment needs inpatient care and may have more toxicities for Asian patients. We conducted a phase 2 study of alternative biweekly TPFL as induction chemotherapy and evaluated the outcome and toxicities. Methods: Patients with locally advanced SCCHN were enrolled in the study. Induction chemotherapy with Docetaxel 50mg/m2, cisplatin 50mg/m2, 5-fluorouracil 2500 mg/m2 and leucovorin 250 mg/m2 was administered biweekly for six cycles, followed by local treatment including concurrent chemoradiotherapy, bio-radiotherapy or surgery plus adjuvant RT. Our primary endpoint is response rate after ICT. Results: Total 58 patients were enrolled in the study from June 2014 to September 2015. The median age is 53 years (from 28 to 69 y/o). The patients’ characteristics was mentioned as: primary site of oral cavity/oropharynx/hypopharynx: 18/25/15; stage IVa/IVb: 35/23; male /female: 54/4; performance status ECOG 0-1/2:57/1. In the oropharyngeal cancer patients neither p16 nor HPV16 status was not studied. Of those 58 patients, 56 patients received at least 4 cycles of chemotherapy. The overall response rate after ICT was 89.6 % (CR: 31% PR: 58.6%). Two patients escaped during induction chemotherapy. Grade 3/4 neutropenia was 25/9%; grade 3/4 mucositis was 1.7%; grade 3/4 diarrhea was 1.7%. Infection rate was 19%. The response rate after following treatment was 75 % (CR: 66.0%, PR: 9.0 %) The median follow-up time was 31.8 months. The overall 3 years PFS/OS was 34.3 %/56.1%. Local recurrence rate was 29.3% and distant metastasis rate was 10.3%. Six patients had second primary tumor. (10.3%) The 3 years PFS of patients with CR/PR were 59.3%/25.5%. The 3 years OS of patients with CR/PR were 81.7%/49.1%. Conclusions: Biweekly TPFL induction chemotherapy has excellent response rate in locally advanced SCCHN. In addition, the grade 3/4 adverse event was acceptable. The patients achieved CR after induction chemotherapy had very good outcomes. Clinical trial identification: CMUH103-REC2-038. Legal entity responsible for the study: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital. Funding: Sanofi, Taiwan branch. Disclosure: All authors have declared no conflicts of interest.

MiR-1275 promotes cell migration, invasion and proliferation in squamous cell carcinoma of head and neck via up-regulating IGF-1R and CCR7

PurposemiRNAs can play vital role in migration, invasion and proliferation in Squamous cell carcinoma of head and neck (SCCHN). In our study, we attempted to validate the expression and function of miR-1275 in SCCHN, and we also identified the mechanism by which miR-1275 affects migration, invasion and proliferation of SCCHN. MethodsReal-time polymerase chain reaction (RT-PCR) was employed to evaluate the expression of miR-1275 in both SCCHN tissues and cell lines. The role of miR-1275 in SCCHN cells was verified by cell function experiments upon transfection with miR-1275 mimics and inhibitor. Western blot analysis was employed to test the target gene expression of miR-1275. Survival analysis was made with the information of SCCHN patients expressed miR-1275 from The Cancer Genome Atlas (TCGA) database. ResultsmiR-1275 expression was up-regulated in SCCHN tissues and advanced metastatic SCCHN cells. Increasing miR-1275 expression in SCCHN could promote cell migration, invasion and proliferation probably by upregulating Insulin-like growth factor 1 receptor (IGF-1R) and C-C chemokine receptor type 7(CCR7) protein levels, whereas inhibition of miR-1275 could lead the opposite effects, although others have already demonstrated that IGF-1R is a direct target of miR-1275. Survival analysis suggested that patients with lower miR-1275 expression may have a better outcome. ConclusionsHerein we report for the first time that miR-1275 could act as a tumor-promoter in SCCHN possibly by regulating its target gene via novel miRNA mechanisms. MiR-1275 plays an important role in promoting SCCHN progression. The miR-1275 may be a potential therapeutic target for SCCHN treatment in the future.

Enumeration and molecular characterization of circulating tumor cell using an in vivo capture system in squamous cell carcinoma of head and neck.

ObjectiveDetection rate and isolation yield of circulating tumor cell (CTC) are low in squamous cell carcinoma of head and neck (SCCHN) with in vitro approaches due to limited sample volumes. In this study, we applied the CellCollector to capture CTC in vivo from peripheral blood. MethodsIn total, the study included 22 cases with 37 times of detection. All of the patients were newly diagnosed with locally advanced or metastatic SCCHN, including laryngocarcinoma (40.9%, 9/22) and hypopharyngeal carcinoma (59.1%, 13/22). All patients received CTC analysis before treatment. Three patients received induction chemotherapy. Sixteen patients received surgical therapy, of which 13 patients received postoperative detection. Two patients received both induction chemotherapy and surgery treatment. Patients underwent two successive CellCollector applications 24 h before and 7 d after surgical therapy. Nine healthy volunteers were enrolled as the control group. Epidermal growth factor receptor variant type III (EGFRVIII) expression was analyzed with fluorescent dye labeled antibody.ResultsWith CellCollector isolation, 72.7% (16/22) of the patients were positive for ≥1 CTC (CTC; range, 1–17 cells) before treatments and 46.7% (7/15) of patients were CTC positive for ≥1 CTC (CTC; range, 1–29 cells) after surgical therapy. Moreover, the detection rate of CellCollector (82.4%, 14/17; CTC count range, 0–17) in advanced SCCHN (stage III–IV) was much higher than that in early stages (stage I–II, 40.0%, 2/5; CTC count range, 0–2) (P<0.05). EGFRVIII expression of CTC was also analyzed with fluorescence staining. One CTCEGFRVIII-positive patient was detected from six CTC-positive patients, and the positive expression of EGFRVIII was also found in the tumor tissue of this patient. ConclusionsIn vivo detection of CTCs had high sensitivity in SCCHN, which might improve CTC application in clinic.

Analysis of chemotherapy selection for locally advanced squamous cell carcinoma of head and neck (SCCHN) in a commercially insured population in the United States.

6066Background: Multiple standard of care options exist for locally advanced SCCHN. We analyzed treatment plans submitted for commercially insured patients by practicing medical oncologists for pre...

Treatment of Locally Recurrent and Metastatic Squamous Cell Carcinoma of Head &amp; Neck

The survival rate at 3 years after potentially curative surgical or radiation treatment for locally advanced squamous cell carcinoma of head and neck (SCCHN) remains quite poor at 30 to 50%. Over 50% of these patients relapse locally or at distant sites and with a median survival of 6-9 months. This review focuses on the established and experimental strategies seeking to improve this outcome. Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody engineered specifically to compete with the natural ligand for EGFR binding sites on the external surface of the cell membrane. This antibody have demonstrated significant disease control rate of over 45% as single agent in the locally recurrent/metastatic disease setting. The combination of cetuximab with platinum-based and taxane-based chemotherapy regimens has resulted in disease control rate of up to 80%. Studies are currently ongoing to assess the activity of immunotherapeutic agents like CTLA-4, PD-1, and PD-L1 inhibitors in the treatment of advanced SCCHN both in biomarker selected and unselected patient population with encouraging preliminary results. Moreover, the combination of these agents with standard chemotherapy regimens, and with cetuximab in the treatment of SCCHN is also being explored.

A meta-analysis comparing cisplatin-based to carboplatin-based chemotherapy in moderate to advanced squamous cell carcinoma of head and neck (SCCHN).

6036 Background: The cisplatin (CDDP)-based CT is considered as the standard regimen for the treatment of moderate to advanced SCCHN. Recently, an alteration is made to carboplatin (CBDCA) because ...

Retrospective review of capecitabine as adjuvant therapy in high risk or recurrent squamous cell carcinoma of head and neck (SCCHN).

e17043 Background:For patients with recurrent SCCHN there are currently no evidence- based, approved adjuvant treatment options (following surgery and/or chemoradiotherapy for recurrent disease). Roughly 40-75% of these high-risk patients recur after treatment, with median survival rates up to 10 months. Capecitabine, an oral 5FU pro-drug, has documented efficacy in the treatment of metastatic and locally advanced SCCHN. In this retrospective analysis, we hypothesize that prolonged exposure to capecitabine may offer benefit to patients with recurrent/high disease when given adjunctively. Methods: We identified 17 patients with either locally advanced SCCHN with multiple high-risk features or recurrent SCCHN that were treated with adjuvant capecitabine post chemo-radiation or surgery for 1 year. The data was extracted from a database of patients treated for SCCHN at the University of Michigan Comprehensive Cancer Center from 2003 through 2015 and matched with 17 control patients by age, sex, and clinical s...

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.

A randomized phase II study of docetaxel with or without vandetanib in recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN)

There are limited chemotherapeutic options for advanced recurrent or metastatic SCCHN. The efficacy and toxicity of docetaxel with or without vandetanib was investigated in these patients. Patients with pathologically confirmed, recurrent or metastatic SCCHN who had progressed on platinum based therapy given as definitive or palliative treatment, were randomized in this open label, multicenter phase II study of docetaxel (75 mg/m2 IV Q3 weeks) with or without vandetanib (100 mg PO daily). The primary objective was response rate (RR) and secondary objectives were progression free survival (PFS), overall survival (OS), disease control rate (DCR) and duration of response (DOR). 29 analyzable patients were enrolled, 14 in docetaxel arm and 15 in combined arm. PR was achieved in 1 patient in the docetaxel arm and 2 patients in the combined arm. The objective RR was 7% (1/14) (95% CI 0.2-33.8%) in the single and 13% (2/15) (95% CI 1.6-40.4%) combined arm. The median PFS was 3.21 (95% CI 3.0-22.0) and 9 (95% CI (5.86-18.1) weeks; median OS was 26.8(95% CI 17.7-100.7+) and 24.1 (95% CI, 16.4-171.1+) weeks. Most common adverse events were fatigue, dysphagia, diarrhea or constipation, cytopenias and alopecia. Although an initial benefit in response was noted and statistical criteria met there was only a minor trend towards improved PFS for the combined arm. The study was designed with low threshold for activity in each arm and results were deemed not to be of enough clinical significance in this group of patients to continue accrual.

Induction chemotherapy (ICh) followed by concurrent chemoradiotherapy (ChR) in locally advanced squamous cell carcinoma of head and neck (SCCHN): Experience in a Mexican institute.

e17031 Background: ICh has taken an important role in the treatment of locally advanced disease, but it has not been recognized in which patients (pts) may be the best option ICh followed by ChR or just ChR. We present our experience with ICh followed by ChR regimen in the National Cancer Institute of Mexico (INCan). Methods: We identified 69 patients (pts) diagnosed with locally and/or regionally advanced non-metastatic squamous cell cancer of head and neck, who were attended at the INCan from 2008-2012, in whom, the original treatment was ICh with two cycles of Paclitaxel (P), cisplatin (C) and 5Fluorouracil (5FU) scheme, followed by concurrent ChR with C. But only 35 pts of the original group accomplished the treatment. Results: 13 pts were women (37%) and 22 were men (63%).The median age at diagnosis was 59 years old. In stages III (28%), IVa (46%), and IVb (26%); AJCC, 2002. The subsites per pts. studied were: oral cavity 9 (25.7%), larynx 9 (25.7%), hypopharynx 7 (20%), paranasal sinuses 7 (20%) and oropharynx 3 (8.6%). The rate response was observed in 83%: complete objective rate response (CR) in13 pts (37%), partial response rate in 16 pts (46%) and progression rate in 6 pts. (17%). The mean survival was of 18.3 months (mth) (CI-95: 0.32-0.68).Median survival was not achieved in pts with CR with a median follow up of 2 yrs, pts with PR had a median survival of 15 mth (CI-95: 0.27-0.75) and the median progression was 11 mth (CI-95: 0.11-0.80). We have not got any CR with ICh only, but 13 patients obtained CR at the end of the ChR. Neither age, sex nor subsites were crucial to the clinical response. Conclusions: Our results cannot distinguish patients who might benefit from ICH. In the intention-to-treat population, more than a half of pts did not complete the proposed scheme. Recently, we reported a study using an alternative scheme: Cisplatin and gemcitabine concurrent with radiotherapy to treat pts with advanced SCCHN, and we found that this scheme of treatment is effective and well tolerated, with a 5 yr progression-free survival rate of 27.8 (CI-95: 0–61.5). Yet further studies are needed to compare ICh followed by RCh vs RCh to assess what the best treatment may be.

Low-dose fractionated radiation with induction chemotherapy for locally advanced head and neck cancer: 5 year results of a prospective phase II trial.

This study aims to report the long-term outcomes of a novel treatment approach utilizing induction low-dose fractionated radiation therapy (LDFRT) and chemotherapy for locally advanced squamous cell carcinoma of head and neck (SCCHN). We prospectively enrolled 40 patients with locally advanced SCCHN (77 % stage IV) on a phase II clinical trial and treated with induction paclitaxel (225 mg/m2), carboplatin (AUC 6), and LDFRT (80 cGy BID on days 1 and 2) every 21 days for two cycles. Forty patients enrolled; 39 were evaluable. The acute toxicity and response data have been previously reported; overall response rate (RR) was 82 %. After induction, definitive therapy was concurrent chemoradiation (CRT) in 51 %, XRT alone in 39 %, surgery in 5 %, and surgery and XRT in 5 %. The long-term outcomes are now reported with a median follow-up of 83 months. Locoregional control (LRC) is 80 % and distant control (DC) is 77 %. Five-year overall survival (OS), disease-specific survival, and progression-free survival (PFS) are 62 %, 66 %, and 58 %, respectively. Induction chemotherapy with LDFRT has a high initial RR, comparable toxicity to two-drug induction regimens, but adds a third novel and effective agent, LDFRT. Five-year follow-up shows favorable outcomes compared to historical controls and excellent compliance with definitive therapy. This novel treatment approach is now planned for phase 3 trial evaluation.

Targeted therapy in head/neck and gastric cancers

The epidermal growth factor receptor (EGFR/HER1) is a member of the erbB family of receptor tyrosine kinase proteins, which also includes HER2, HER3, and HER4. EGFR is almost universally expressed in squamous cell carcinoma of head and neck (SCCHN), and high levels of expression have been correlated with a poor clinical prognosis [1]. Cetuximab, an IgG1 monoclonal antibody against EGFR, has demonstrated improved survival and disease control when used in combination with radiation therapy for the treatment of locally advanced SCCHN, and in combination with platinum-based chemotherapy in recurrent or metastatic SCCHN [2-4]. Additionally, single-agent cetuximab is active and provides good disease control rate and duration in platinum-refractory SCCHN [5]. Comparison of cetuximab versus cisplatin concurrently with radiotherapy is under investigation in patients with human papillomavirus-associated oropharyngeal cancer, who have better prognosis and may benefit from less toxic treatment [6]. Overexpression of HER2 in gastric cancer results in aggressive clinical course and poor prognosis [7]. Trastuzumab, a monoclonal antibody against HER2, exhibits antitumor activity in HER2 overexpressed gastric cancer cells, and enhances effects of chemotherapy in gastric cancer xenograft overexpressing HER2 [8]. The ToGA study screened about 3,800 patients with advanced gastric cancer from 24 countries, and HER2 overexpression was detected in 22% [9]. Higher rates of HER2 overexpression occurred in intestinal and proximal or gastroesophageal junction cancers than in diffuse or distal gastric cancers. In TOGA study, 584 patients with HER2 overexpression were randomized to receive fluoropyrimidine and cisplatin treatment with or without trastuzumab. Patients who received trastuzumab plus chemotherapy achieved longer overall survival (13.8 months vs. 11.1 months, P= 0.0046), longer progression-free survival (6.7 months vs. 5.5 months, P=0.0002), and higher response rates (47% vs. 35%, P=0.0017) than those who received chemotherapy alone. Complete response was noted in 5.4% of patients receiving trastuzumab plus chemotherapy vs. 2.4% in chemotherapy alone. There were no significant differences in the toxicities between these two groups. This study has established a new paradigm using trastuzumab in combination with chemotherapy in patients with advanced gastric cancer overexpressing HER2. Neoadjuvant treatment is a standard of care for locally advanced esophageal and gastric cancer. We have previously reported a case of pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in HER2-overexpressing gastric cancer [10]. Incorporating trastuzumab as a part of neoadjuvant therapy in esophageal and gastric adenocarcinoma overexpressing HER2 is currently under active investigation. Radiation Therapy Oncology Group is conducting a phase III neoadjuvant study in patients with HER2-overexpressing esophageal adenocarcinoma to determine if trastuzumab increases disease-free survival when added to chemoradiotherapy [11]. Other studies conducted in Europe are adding trastuzumab to oxaliplatin-based regimen as perioperative chemotherapy for HER2-overexpressing esophagogastric or gastric adenocarcinoma, and looking for improvement of pathological complete response and disease-free survival [12,13]. Pertuzumab is a monoclonal antibody interfering with HER2 dimerization with other HER receptors such as EGFR, HER3 and HER4. Pertuzumab and trastuzumab bind to HER2 at different sites, and combination of both antibodies leads to stronger inhibition of erbB signaling and greater therapeutic efficacy when combined with docetaxel in breast cancer [14]. Combination of pertuzumab and trastuzumab with platinum-based chemotherapy is currently studied in HER2-overexpressing gastric cancer [15].

Antiepidermal Growth Factor Receptor Therapy in Squamous Cell Carcinoma of the Head and Neck

Squamous cell carcinoma of head and neck (SCCHN) is the most common neoplasm of the upper aerodigestive tract. In this paper, we attempt to summarize the role and applications of the epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (moAbs) and tyrosine kinase inhibitors (TKIs) locally advanced as well as metastatic SCCHN. Targeted therapy in SCCHN is now incorporated in the first-line regimes for advanced disease. Novel targeted agents, including the EGFR antibody, cetuximab, have been approved for use as single agents or in combination with radiation therapy or chemotherapy in treatment of recurrent metastatic or locally advanced SCCHN. Refractory mechanisms that bypass the pathway of EGFR inhibitors activity are identified explaining resistance to targeted therapy. Strategies of cotargeting EGFR and other pathways are under investigation. Examples of targeted therapy being used include mammalian target of rapamycin (mtor) inhibitors, antivascular endothelial growth factor (VEGF) moAb, and other inhibitors. We will be focusing our paper on the preclinical and clinical aspects of EGFR inhibition in SCCHN and touch upon other targeted therapies in application.

Concurrent chemoradiotherapy with weekly platinum for patients with unresectable/locally advanced SCCHN and comorbidities.

e16024 Background: Concurrent chemoradiotherapy (CRT) with cisplatin 100mg/m2, given every 3 wks, is a standard treatment option for unresectable/locally advanced squamous cell carcinoma of head and neck (SCCHN). However, many pts are unable to tolerate the toxicity of standard dose Cisplatin. We are presenting the two year follow up data of our previously reported study where we evaluated the efficacy and feasibility of concurrent weekly dose platinum with RT in patients who have a poor performance status (PS) and multiple comorbidities. Methods: We retrospectively identified pts treated with weekly platinum and RT for locally advanced SCCHN. Treatment response was evaluated by clinical exam, PET and CT scans. Results: 33 pt charts were identified from 2003-2007. 28 pts had upfront CRT and 5 had CRT for recurrent disease. Carboplatin AUC 2(n=11) or cisplatin 35mg/m2 (n=20) or both used alternately (n=2) were given weekly, concurrently with RT. Median duration of therapy was 6 wks. Primary disease sites: oral cavity (n=6), oropharynx (n=20), hypopharynx (n=4), and occult primary with neck disease (n=3). Stages: III (n = 4), IVA (n = 24), and IVB (n=5). PS: KPS 60% (n=13),70% (n=10), 80%(n=5), 90%(n=5). 10 pts had significant comorbidities limiting therapy with standard dose platinum. 28 pts had CRT only and 5 had surgery followed by CRT. 23 pts (73%) had CR, 3 (9%) had PR and 6 (18%) had progressive disease at the first follow-up imaging. Med. duration of follow up: 33+ mo (range 5- 71 mo). DFS at 1 yr: 86.4% (95% CI: 63.3%-95.4%) DFS at 2 yrs: 67.9% (95% CI: 44.2%-83.2%). OS at 1 yr: 92.6% (95% CI: 73.8%-98.1%) OS at 2 yrs: 66.7% (95% CI: 45.8% - 81.0%). Conclusions: The results of the two year follow up of concurrent weekly platinum and RT for unresectable/ locally advanced SCCHN are provocative. The two year DFS and OS rates are comparable with those previously reported in good PS, study eligible pts as in RTOG 91-11, and by Adelstein et al (JCO 2003 Jan 1;21(1):92-8) and Bonner et al (NEJM 2006 Feb 9;354(6):567-78). In addition to comparable and sustained survival rates in pts with poor PS and comorbidities, it is a regimen with excellent tolerability and may be considered as a reasonable option in this group of pts. No significant financial relationships to disclose.

An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): Four-year survival results from a phase IIb study.

5530 Background: h-R3mAb (nimotuzumab) is a humanized monoclonal antibody targeting epidermal growth factor receptor (EGFR). EGFR is over-expressed in >90% squamous cell carcinoma of head and neck (SCCHN). Patients with advanced inoperable SCCHN have poor outcome to radiotherapy (RT) or chemoradiotherapy (CRT) treatment alone. Adding biologically active targeted therapies to RT/CRT might further improve therapeutic outcome with minimal morbidity. Methods: Total of 113 patients with (stage III or IVa), inoperable SCCHN were screened; 92 randomized in 1:1 ratio in two groups; group A received [RT Vs RT+h-R3mAb] and group B received [CRT vs. CRT+h-R3mAb]. Treatment included radiotherapy in total dose 60 -66Gy, h-R3mAb 200mg by I.V infusion over 60 min/ week for 6weeks and in group B, chemotherapy CDDP 50mg/week for 6weeks. Results: Seventy-six patients were evaluable; 36-groupA and 40-groupB. Locoregional response was 100% in CRT+h-R3mAb vs. 70% in CRT and 76% in RT+h-R3mAb vs. 37% in RT. At 48 months follow-up; Overall survival rate (ITT) was 47% in (CRT+h- R3mAb) vs. 21% (CRT)(p = 0.01) and 34% (RT+h-R3mAb)vs. 13%(RT)(NS), median overall survival was NR* for (CRT+h-R3mAb) vs. 21.9 months (CRT)(HR-0.35, P-0.01) and 14.3months (RT+h-R3mAb) vs. 12.7months (RT)(HR-0.74, P-0.42). The subjects alive in CRT+h-R3mAb arm had mean EGFR values of 67.5%. There was no statistically significant difference in mean EGFR % with respect to survival of alive and deceased in this population. Adding h-R3mAb to Chemoradiation resulted in significant reduction in risk of death by 65 % (HR 0.35, p-0.01). Conclusions: Concurrent use of h-R3mAb with RT/CRT is safe and efficacious; it enhanced locoregional control and survival on long term follow-up. This is the first randomized study demonstrating clinical benefit from EGFR-targeting mAb in the absence of the advanced toxicities due to its distinguished property of preferentially targeting the tumor. The encouraging efficacy data recommends further development of CRT+h-R3mAb paradigm in treatment of SCCHN. No significant financial relationships to disclose.

Phase II study of synchronous chemoradiotherapy with capecitabine in patients with locally advanced squamous cell carcinoma of the head and neck.

5570 Background: Cisplatin may be relatively non-discriminating in its radiosensitising action. We evaluated the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of head and neck (SCCHN). Methods: 50 patients with stage III/IV SCCHN were enrolled. Nineteen patients received 450-550 mg/m2capecitabine twice daily, for 28days as a part of phase I study and 31 received 500 mg/m2BD. Radiotherapy prescribed dose was 5,500cGy in 20 fractions over 4 weeks. Results: Median age was 55 (range 38-76) years, 72% had stage IV disease. Median duration of follow-up was 6 years. Forty one out of 50 (82%) patients completed the full course of capecitabine and 47/50 (94%) completed the initially prescribed radiotherapy. There were no treatment related deaths. There was no grade 3/4 haematological or renal toxicity. Five patients developed drug related grade 3 or 4 acute toxicity (cardiac, skin, bowel), 47 developed grade 3 (44) or 4 (3) mucositis from chemoradiotherapy. Twenty-two (44%) patients required tube feeding for acute mucositis with one (2%) being tube dependent at 1 year. Complete response rate at 3 months was achieved in 47/50 (94%) of patients. Relapse occurred in 14/50 (28%) patients at 5 years. The loco-regional control, overall survival and cancer specific survival at 3 and 5 years were 78% and 72%, 72% and 64% and 82% and 75% respectively. Conclusions: This schedule of capecitabine for locally advanced SCCHN is well tolerated. The local control in this series compares favourably with other synchronous chemoradiotherapy reports. Chronic dysphagia and tube dependence is uncommon with this approach. Capecitabine as targeted therapy given with each fraction of radiotherapy and administered orally may have significant advantages over intravenous, 3 weekly cisplatin. No significant financial relationships to disclose.

Management of unresectable head and neck cancers - a retrospective analysis at a rural medical college of India.

To study the natural course of disease in patients of advanced squamous cell carcinoma of head and neck (SCCHN) admitted in a rural tertiary hospital and to formulate an acceptable protocol of management and their prognosis. A 5-year retrospective analysis of patients of advanced SCCHN attended in the department of Radiotherapy and admitted at department of ENT at B. S. Medical College, Bankura, West Bengal were analyzed for the present study. B. S. Medical College, Bankura at West Bengal, which is a rural medical college and act as tertiary referral, center for three district of West Bengal namely Midnapur, Purulia, Bankura, part of Burdwan and adjoining area of Jharkhand state. We investigated 100 patients in our hospital who presented with advanced and in-operable stage of SCCHN. Biopsy proved cases of SCCHN in stage III, stage IVA and stage IVB which is surgically unresectable and without any past history of radiotherapy and chemotherapy were included in this study. KEY DEMOGRAPHIC FEATURES: Eighty-nine men and 11 female with advanced SCCHN were included in this study. Their median age was 48 years (36-78 years) with a median weight of 44 kg and median Karnofsky score 70. Different types of palliative surgical intervention like Ryles' tube insertion (16%), feeding jejunostomy (11%), tracheostomy (60%) and arterial ligation (2%) was done to relieve the symptoms. Forty-three patients received chemoradiation and 22 patients received only radiotherapy. Best supportive care was provided to 35 patients. Twenty-nine percent of patients had partial response in terms of disease control and none had complete response. Symptomatic relief of respiratory obstruction, dysphagia and pain constitute the mainstay of treatment in the present study. A short course of radiotherapy is found to be effective in control of symptoms and helps to improve the quality-of-life. Complete response to therapy in advanced head and neck squamous cell carcinoma with a poor nutritional status is very difficult to achieve.

Cost utility of docetaxel as induction chemotherapy followed by chemoradiation in locally advanced squamous cell carcinoma of the head and neck

Trial TAX 324 showed that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (TPF) compared with cisplatin and 5-fluorouracil (PF) followed by chemoradiation increases survival and time to progression in squamous cell carcinoma of head and neck (SCCHN). A Markov model was developed to estimate the cost-effectiveness of induction chemotherapy with docetaxel in the United Kingdom from the payer perspective. Health states were based on the WHO criteria for objective response to cancer treatments. Efficacy and safety data were obtained from the trial. Resource utilization, costs, and utility data were primarily derived from the literature. A patient on TPF gained 4.1 quality adjusted life years (QALYs) versus 2.0 QALYs for PF patient. Corresponding lifetime costs were pound 32,440 and pound 28,718. The cost per QALY gained for TPF versus PF was pound 1782. TPF is cost-effective as induction chemotherapy in locally advanced SCCHN compared with PF. Local treatment patterns may impact findings for other countries.

Concurrent chemoradiotherapy with weekly platinum for patients with unresectable/locally advanced SCCHN and comorbidities

17033 Background: Concomitant chemoradiotherapy (CRT) with cisplatin, given every three weeks, is a standard treatment option in the management of unresectable/ locally advanced squamous cell carcinoma of head and neck (SCCHN). Many patients are unable to tolerate the toxicity of standard dose cisplatin. The purpose of the present study was to evaluate the efficacy and feasibility of concurrent weekly dose platinum with RT in patients who have a poor performance status (PS) and multiple comorbidities. Methods: We retrospectively identified patients treated with weekly dosing of platinum and concomitant RT for locally advanced SCCHN. Carboplatin AUC 2 (n = 11) or Cisplatinum at 35 mg/m2 (n = 20) or both used alternately (n = 2) were given weekly, concurrently with RT. Median duration of treatment was 6 weeks. Treatment response was evaluated by clinical exam, PET and CT scans. Results: Thirty three patient charts were identified between 2003–2007. 28 patients had upfront treatment with CRT for their disease and 5 had recurrent disease. Primary sites of disease were: oral cavity (n = 6), oropharynx (n = 20), hypopharynx (n = 4) and occult primary with neck disease (n = 3). Stages: Stage III (n = 4), Stage IV A (n = 24) and Stage IV B (n = 5). 28 patients had CRT only and 5 had surgery followed by CRT. 23 patients (73%) had complete remission (CR), 3 (9%) had partial remission and 6 (18%) had progressive disease at the first follow-up imaging. Median duration of follow up was 14+ mo (range 5-45 mo) for all patients. 1 yr overall survival rate was 86% (n = 24/28) for upfront treatment and 60% (n = 3/5) for recurrent disease. Updated disease free survival at the median follow up will be available for the meeting. Conclusions: Concomitant weekly dose platinum and concomitant RT for unresectable/locally advanced SCCHN results in a high CR and survival rates in patients with poor PS and comorbidities. Although, the follow up of our series is short at this time, these results are comparable to those achieved with standard dose Cisplatinum 100 mg/m2 given every three weeks with RT. However, the weekly regimen is better tolerated in such patients. Prospective trials should be designed based on performance status scales to further validate the feasibility of this regimen. No significant financial relationships to disclose.