Locally Advanced Squamous Cell Carcinoma Of Head And Neck Research Articles

854MO Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Final analysis of randomized phase III GORTEC 2017-01 REACH trial

854MO Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Final analysis of randomized phase III GORTEC 2017-01 REACH trial

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial

To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN). Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20. Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n= 66) and pembrolizumab-RT (n= 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P= 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P= 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P= 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P= 0.006), mainly due to mucositis, radiodermatitis, and rash. Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Induction Chemotherapy with Cisplatin, Paclitaxel, and Capecitabine (PTC) in Locally Advanced (LA) Squamous Cell Carcinoma of Head and Neck (SCCHN)

<h3>Purpose/Objective(s)</h3> In Guatemala's Roosevelt Hospital, most patients consult with locally advanced stages of SCCHN. Cisplatin, Docetaxel, and 5FU regimen has shown superiority over Cisplatin plus 5FU during the induction of LA cases, with afew reports supporting the substitution of 5FU with capecitabine for LA SCCHN. During the COVID-19 pandemic, we performed induction therapy with PTC in patients with LA SCCHN to reduce inpatient treatment. <h3>Materials/Methods</h3> We performed a retrospective analysis of patients with LA SCCHN with preserved swallowing function treated with Cisplatin 75mg/m², Paclitaxel 175mg/m², and Capecitabine 1000mg/m² twice a day for 14 days. RECIST and CTCAE were used to measure response and adverse events. <h3>Results</h3> A total of 16 LA SCCHN patients were treated with PTC induction. Treated patients were mostly men, smokers, and considered not candidates for surgical resection (Table 1). The mean of cycles administered was 3.5 (SD = 0.97). Regarding the response to the PTC regimen, 93.6% of patients achieved disease control. Only 6.2% of patients stopped capecitabine, whereas 37.5% required dose reduction. The main adverse events were nausea, vomiting, and diarrhea. <h3>Conclusion</h3> The PTC regimen worked as induction therapy for patients with LA SCCHN. The substitution of 5FU for Capecitabine requires prospective validation.

LBA35 Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Randomized phase III GORTEC-REACH trial

Based on a potential synergistic effect of anti–PD-L1 avelumab plus cetuximab and radiotherapy (RT), this combination was tested in a randomized phase III trial against 2 standards of care (SOC) in LA-SCCHN.

Comparative study on hemato- and nephrotoxicity profile of weekly versus every 3-weekly cisplatin dosage during induction chemotherapy in locally advanced head neck squamous cell carcinoma

BackgroundCisplatin is a frontline anticancer drug routinely used as part of concurrent chemoradiation administered at 3-weekly (100 mg/m2) dose. However, its role as fractionated weekly dose has achieved favorable outcome in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN) during induction chemotherapy (IC). We therefore sought to compare the toxicity outcomes of patients with LA-SCCHN treated with platinum-based IC at a single institution study using split-dose cisplatin chemotherapy. We compared the hematological and renal toxicity profile between the weekly cisplatin (30 mg/m2) (group A) versus 3-weekly (100 mg/m2) (group B) dosage schedule in this setting.ResultsThe median age of the patients in groups A and B were 49.1 years and 48.27 years respectively with male:female ratio of 4:1. Most of the patients were of oropharyngeal cancers. Group A patients showed greater neutropenia (40.2%) than group B (20.6%). There was statistically significant fall in Hb% level in group A (13.9%) than in group B (11.9%). Renal profile showed greater rise in serum urea and serum creatinine (52.7%) in group B than in group A (52.29%) with statistically significant difference.ConclusionsSince toxicities induced by high-dose cisplatin are irreversible and reduce quality of life in patients, the weekly regimen may be preferred owing to less renal toxicity, lesser hospitalization and more feasible in situations with high patient load and limited resources.

Cetuximab Concurrent with Radiotherapy in Unresectable, Locally Advanced Squamous Cell Carcinoma of Head and Neck: Real-World Evidence from a Tertiary Care Hospital.

Cetuximab (EGFR-targeted IgG1 monoclonal antibody) has shown to improve the treatment outcomes in head and neck cancer. The evidence on the beneficial outcomes of cetuximab with radiotherapy (RT) in unresectable patients of locally advanced squamous cell carcinoma of head and neck (LA-SCCHN) is limited in real-life practice. The present study evaluated the treatment outcomes of cetuximab concurrent with RT in Indian patients with unresectable LA-SCCHN. We retrospectively reviewed fifty-one patients with unresectable LA-SCCHN between January 2013 and December 2017, who were treated with cetuximab concurrently with RT. Tumor response and disease-free survival (DFS) were estimated. Tumor response using RECIST (1.1) criteria reported complete response in 66.7%, partial response in 31.4% and progressive disease in 1.9% of the patients. The overall response rate was 98%. The 1-year and 2-year DFS was 85% and 69% respectively. The median DFS was significantly better in stage 3 than stage 4. The most common toxicity observed was mucositis and skin reactions (grade 3). Cetuximab concurrent with RT was effective in Indian patients with unresectable, LA-SCCHN and had an acceptable toxicity profile in real-life practice. The real-life beneficial evidence of the combination is consistent with the results documented in the randomized controlled trials.

1118PD - Avelumab-cetuximab-radiotherapy versus standards of care (SoC) in patients (pts) with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Safety phase of randomized trial GORTEC 2017-01 (REACH)

BackgroundBased on the hypothesis of a synergistic effect of the anti-PDL1 avelumab when combined with cetuximab (cetux) and RT, this new combination is tested in a large scale randomized trial against two well established SoC in LA-SCCHN pts. MethodsThis randomized multicenter phase III trial comprises two cohorts of pts deemed fit (Cohort 1) to receive high dose cisplatin (CDDP 100mg/m², Q3W) or unfit (Cohort 2) to receive CDDP. The SoC is IMRT (69.96Gy, 33 fractions) combined with CDDP in Cohort 1 (arm A) and with cetux (arm D) in Cohort 2 (400mg/m² Day-7 and 250mg/m² weekly). In both cohorts, experimental (exp) arms are IMRT concomitant with cetux (same schedule as in SoC) and avelumab (10mg/kg Day-7 and every 2 weeks) followed by avelumab 10mg/kg bi-monthly for 12 months (arms B and C). The primary objective is to test whether exp arm is superior to SoC for progression-free survival in each cohort, with 400 and 268 pts to be randomized to Cohort 1 and 2 respectively. Monitoring of grade ≥4 acute adverse events (AE) in both exp arms was planned with null and alternative hypotheses of 15% and 35%, 1-sided α error = 0.10, Lan-DeMets α spending function, power 95%. This safety phase was approved by the Independent Data and Safety Monitoring Committee (IDSMC) and planned to be run on the first 41 pts randomized in exp arms, in 3 steps, after 8 weeks follow-up of 14, 27 and 41 pts. ResultsBetween September 2017 and August 2018, 82 pts with LA-SCCHN were randomized including 41 in the exp arms. All pts of exp arms received the entire RT, except one in arm C with early stop after 55Gy. In exp arms, 36 pts (88%) and 31 pts (76%) received the expected number of avelumab and cetux administrations during RT. In the exp arms, the most common grade ≥3 AE were radiation dermatitis, mucositis and dysphagia. Grade ≥4 AEs occurred in 5/41 (12%) pts in the exp arms (all in arm C), in 3/21 (14%) pts in arm A and 2/20 (10%) in arm D. Only one grade 5 AE occurred in arm A. ConclusionsThe combination of avelumab, cetuximab and RT is tolerable for pts with LA-SCCHN in the safety phase of this ongoing phase 3 trial and an approval to continue the trial was given by IDSMC. Clinical trial identificationNCT02999087. Legal entity responsible for the studyGORTEC. FundingMerck Serono. DisclosureY. Tao: Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Research grant / Funding (institution): Debiopharma; Research grant / Funding (institution): Pfizer. J. Thariat: Advisory / Consultancy: BMS; Advisory / Consultancy: Nanobiotix. J. Guigay: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Innate pharma; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono. J. Bourhis: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD. All other authors have declared no conflicts of interest.

Is prophylactic percutaneous endoscopic gastrostomy necessary for chemoradiotherapy after total laryngectomy?

Abstract Background Post-operative concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) for locally advanced squamous cell carcinoma of head and neck (LASCCHN) frequently induces severe oral mucositis and dysphagia, which lead to insufficient oral intake and negative impact on treatment outcomes. Therefore, prophylactic percutaneous endoscopic gastrostomy (PEG) has been widely performed. However, PEG placement often causes some complications such as bleeding or abscess. The aim of this study is to evaluate necessity of prophylactic PEG in adjuvant CCRT for high-risk patients with LASCCHN who underwent total laryngectomy. Methods This study retrospectively analyzed 117 LASCCHN patients who underwent either total laryngectomy or other surgery followed by adjuvant CCRT with CDDP at Shizuoka Cancer Center between April 2008 and December 2018. We evaluated the rate of patients unable to obtain sufficient nutrition via oral intake from initiation of CCRT until one year after completion of CCRT, and nutrition-support-free survival. The risk factors for inability of oral intake were determined by using the Cox proportional hazards model. Results Of 117 patients, 25 patients received total laryngectomy and 92 patients received other surgery. The rate of patients unable to obtain sufficient nutrition via oral intake was significantly lower in the total laryngectomy group (16% vs 57%, P Conclusion Prophylactic PEG for adjuvant CCRT may not be necessarily required for the LASCCHN patients who underwent total laryngectomy because of high feasibility of oral intake.

Safety and efficacy of nimotuzumab with concurrent chemoradiotherapy in unresectable locally advanced squamous cell carcinoma of head and neck: An Indian rural hospital experience.

Context:Nimotuzumab is the only anti-epidermal growth factor receptor monoclonal antibody which can be safely added to concurrent chemoradiotherapy (CRT) to improve efficacy in the management of unresectable, locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). However, the evidence available on this is limited.Aims:We retrospectively investigated efficacy and safety of nimotuzumab when combined with chemoradiation for LA-SCCHN.Settings and Design:Hospital records of 39 patients from January 2012 to December 2016 diagnosed with locally advanced (Stage III-IVb), unresectable SCCHN, and treated with concurrent CRT with weekly nimotuzumab were reviewed retrospectively after fulfilling the inclusion/exclusion criteria.Subjects and Methods:Tumor response was calculated as per response evaluation criteria in solid tumors criteria 1.1. Association of tumor response with independent variables was assessed. Overall survival (OS) and progression-free survival (PFS) were calculated. All patients were assessed for toxicity as per common terminology criteria for adverse events Common Terminology Criteria for Adverse Events v 4.0 (U.S. Department of health and human services, National Institutes of Health, National Cancer Institute).Results:At 6 months after completion of treatment, objective response rate was 97.44% with 26 (66.67%) patients attaining Complete response (CR), 12 (30.77%) patients with Partial response (PR), and one patient (2.56%) had stable disease. Subgroup analysis did not show a significant association of tumor response with independent factors. OS at 1 and 2-year was 100% and 72.9%, while PFS at 1 and 2-year was 87% and 54.40%. The incidence of Grade I, II, III, and IV toxicity was 30%, 18.18%, 41.82%, and 10%, respectively. No grade V toxicity was observed. Common adverse events observed were mucositis (33.64%), skin reaction (24.55%), neutropenia (20.91%), vomiting (18.18%), and diarrhea (2.73%).Conclusions:Nimotuzumab is an efficacious and safe option when added to concurrent CRT in unresectable, LA-SCCHN.

Efficacy of Carboplatin/Paclitaxel-Based Radiochemotherapy in Locally Advanced Squamous Cell Carcinoma of Head and Neck

Background: Cisplatin-based chemotherapy (CTX) is commonly used concurrently with radiotherapy for head and neck cancer. The value of CTX regimens other than cisplatin for locally advanced squamous cell carcinoma of head and neck (LASCCHN) has not been well established. Here we compare the outcome of patients treated with different platinum-based chemotherapy regimens. Methods: Medical records from 104 patients with LASCCHN treated with radiochemotherapy (RCTX) between February 2013 and August 2016 were analyzed. Results: All patients were treated with intensity-modulated radiation therapy (51 definitive, 53 postoperative). The median total dose was 66.6 Gy and the median fraction dose was 1.8 Gy. 81 (78%) patients were administered cisplatin CTX, 23 (22%) patients received carboplatin and paclitaxel (CarboTaxol). The rate of recurrence was 38% in patients treated with cisplatin and 30% in CarboTaxol-treated patients (p = 0.6). Regarding the CTX regimens, event-free survival (EFS) was 37 versus 30 months (p = 0.6) and overall survival (OS) was 35 versus 28 months (p = 0.5) in cisplatin group versus CarboTaxol group, respectively. Significantly higher grade 3/4 acute toxicity in terms of dysphagia was observed following cisplatin-based RCTX (p = 0.002). In multivariable analysis, females and patients with early primary tumors (T1-2) have longer EFS and OS, regardless the CTX regimen. Conclusions: Primary or adjuvant RCXT with CarboTaxol is a safe and effective treatment alternative for LASCCHN patients with contraindication to cisplatin-based RCTX.

Nimotuzumab with Concurrent Chemoradiation in Inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck: An Indian Experience

Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti EGFR humanized monoclonal antibody approved for treatment of LASCCHN, with concurrent chemoradiation. Objective: To assess the efficacy and safety of nimotuzumab with concurrent chemoradiation in inoperable LASCCHN patients. Methodology: This is a single-centre, single arm, retrospective study evaluating 35 patients with histologically confirmed inoperable LASCCHN (stages III-IV). The patients were administered IV cisplatin 50 mg/m2 and IV nimotuzumab 200 mg for 6 - 7 weeks, along with radiotherapy of 6600 - 7000 cGy over 35 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 12 weeks after the last cycle of chemotherapy. They were also followed up for overall survival and relapse free survival. Results: The median duration of follow-up was 20 months. The most common site of cancer was oropharynx (68.6%). One patient was lost to follow up. Objective Response Rate (ORR) was observed in 97% of the patients with 17 patients (48.6%) achieving complete response (CR) and 17 patients (48.6%) achieving partial response (PR). The median overall survival was 22.7 months (95% CI: 21.30, 34.27). The median relapse free survival was 16.7 months (95% CI: 9.80, 24.50). Nimotuzumab was safe and well tolerated with few mild, self-limiting adverse events. Conclusion: Nimotuzumab with chemoradiation is a safe and efficacious option in patients with LASCCHN. Larger studies are needed to verify the same.

A phase I study of cabazitaxel in combination with platinum and 5-fluorouracil (PF) in locally advanced squamous cell carcinoma of head and neck (LA-SCCHN)

BackgroundThere is a clinical need to improve outcomes for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), especially in Human Papilloma Virus (HPV) negative and HPV positive subtypes with a significant history of tobacco use. In animal models bearing SCCHN, Cabazitaxel showed an excellent response rate compared to docetaxel and might prove useful in treatment of patients. The primary objective of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of cabazitaxel when combined with cisplatin and 5-fluorouracil (PF) in induction chemotherapy (IC) for patients with SCCHN. Cabazitaxel-PF IC administered in 3 cycles (each 21 days) followed by concurrent chemoradiation (CRT) or surgery has been evaluated to assess overall response rate (ORR) and progression-free survival (PFS) in this population. MethodsThis phase I study employed a standard 3+3 design. DLT was defined as grade 4 or 5 toxicity or grade 3 toxicity lasting >7days. Out of 40 consented patients with stage IV, curable, previously untreated, LA-SCHHN and poor prognosis, 35 (32M, 3F) were enrolled and evaluated for toxicity: 19 oropharynx, 10 larynx, 2 oral cancer, 1 nasopharynx and 3 hypopharynx. Five dose levels of cabazitaxel (10, 12.5, 15, 17.5 and 20mg/m2) were tested in combination with cisplatin 100mg/m2 and 5-fluorouracil (5-FU) 800mg/m2/d×4days. Dose escalation for cabazitaxel was terminated upon the occurrences of 2 DLTs and the establishment of MTD. Cabazitaxel was then further escalated with cisplatin 75mg/m2 and 5-FU 800mg/m2/d×4days in the subsequent 3 dose levels (17.5, 20 and 22.5mg/m2). In the expansion cohort, 9 patients were enrolled at the 22.5mg/m2 dose level. Following 3 cycles of IC, patients were evaluated for clinical, radiographic, and pathologic response to cabazitaxel-PF before beginning CRT or surgery. ResultsThere were two DLTs (grade 4 hyperuricemia; neutropenic fever, sepsis, and grade 4 thrombocytopenia) among 2 patients in cohort 5 at the dose of 20mg/m2 of cabazitaxel. There were no DLTs reported with cohorts using a lower dose of cisplatin, even in the expansion cohort. The study was stopped at the dose of 22.5mg/m2 in accordance with the initial study design. With 33 evaluable patients for response, the Overall Response Rate (ORR) rate was 57.6%: 9.1% Complete Responses (CR) and 48.5% Partial Responses (PR) were noted. ConclusionsThe recommended phase II dose for cabazitaxel in combination with cisplatin 75mg/m2 and 5-FU 800mg/m2/d×4days is 22.5mg/m2 and for cisplatin 100mg/m2 and 5-FU 800mg/m2/d×4days is 17.5mg/m2. With a median follow-up of 39months, PFS for the entire non-metastatic population at 3years was approximately 58%.

A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of head and neck (LASCCHN).

6082Background: Many randomized controlled trials (RCTs) have evaluated definitive radiotherapy (RT) with different sequencing (induction (I+RT), concurrent (CRT), adjuvant, induction + concurrent ...

P2-9-9 - Concurrent CBDCA plus radiotherapy for locally advanced head and neck cancer patients inappropriate for use of CDDP

Background: Cisplatin (CDDP)-based chemoradiotherapy has been recognized as the standard treatment for patients with locally advanced squamous cell carcinoma of head and neck (LASCCHN). However, CDDP is inappropriate for the patients with advanced age, renal, cardiac, or neurogenic dysfunction. We evaluated the safety and efficacy of concurrent carboplatin (CBDCA) plus radiotherapy (RT) for patients who were inappropriate for use of CDDP. Methods: We retrospectively analyzed 25 consecutive LASCCHN patients who received concurrent CBDCA plus RT at Shizuoka Cancer Center between August 2006 and March 2014. All patients were planned to receive concurrent CBDCA with conventionally fractionated RT (2 Gy per fraction, 5 fractions per week).CBDCA was administered tri-weekly (AUC:4-6, days on 1, 22, and 43) or weekly (AUC:2, days on 1, 8, 15, 22, 29, 36, and 43). Results: The characteristics of the 25 patients were as follows: median age, 75 years (range,54-82); male/female, 24/1; PS, 0-1/2, 23/2; Primary tumor site, oropharynx/hypopharynx/larynx/oral cavity, 10/12/1/2; cStage (UICC 7th edition), III/IVa/IVb, 3/19/3; induction chemotherapy, +/-, 2/23; median creatinine clearance, 62 ml/min (range, 37-117).Main reasons for choosing CBDCA were age (40%), renal impairment (36%), cardiac dysfunction (20%), hearing impairment (8%), performance status 2 (8%), and severe emphysema(4%).All patients received planned irradiation dose of 70Gy. Relative dose intensity of CBDCA was 83%. CR rate was 76 %. The median follow-up period was 30.9 months.Median progression free survival (PFS) was 42.7 months and median overall survival (OS) was not reached yet. 2-year PFS and OS rate were 68% and 74%. Main grade 3/4 adverse events were oral mucositis (56%), anemia (36%), thrombocytopenia (34%), neutropenia (28%), and infection (24%). Conclusion: Concurrent CBDCA plus RT is tolerable and may be an option for the treatment of LASCCHN patients who are inappropriate for use of CDDP.

Induction chemotherapy with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of head and neck: a meta-analysis

Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). Whether induction chemotherapy (IC) with CCRT will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens for LA-SCCHN. Literature searches were carried out in PubMed, Embase, Cochrane Library and Chinese Biology Medicine from inception to November 2014. Five prospective randomized controlled trials (RCTs) with 922 patients were included in meta-analysis. Results were expressed as hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). Compared with CCRT, IC with CCRT showed no statistically significant differences in overall survival (OS), progression-free survival (PFS), overall response rate (ORR) or locoregional recurrence rate (LRR), but could increase risks of grade 3–4 febrile neutropenia (P = 0.0009) and leukopenia (P = 0.04). In contrast, distant metastasis rate (DMR) decreased (P = 0.006) and complete response rate (CR) improved (P = 0.010) for IC with CCRT. In conclusion, the current studies do not support the use of IC with CCRT over CCRT, and the further positioning of IC with CCRT as standard treatment for LA-SCCHN will come from more RCTs directly comparing IC followed by CCRT with CCRT.

Nimotuzumab with Concurrent Chemo-Radiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN)

Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the prognosis remains dismal. This underscores the need for newer treatment options in these cases. Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was safer when combined with chemo- or radio-therapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with advanced inoperable squamous cell carcinomas of head and neck (LASCCHN). Methods: This was an open-label, single arm study evaluating 57 patients with histologically confirmed inoperable LASCCHN (stages III and IV) and eastern co-operative oncology group (ECOG) performance status 2 and IV nimotuzumab 200 mg weekly for 6 weeks, along with radiotherapy of 6600 cGy over 33 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 24 weeks after the last cycle of chemotherapy. Results: Mean age of patient was 50 years old (29 - 79 years old). The most common site of cancer was oral cavity (56.1%). Forty six patients (80.7%) completed 6 cycles of therapy. Objective response rate (ORR) was 80.7%, with 34 patients (59.6%) achieving complete response (CR), and 12 (21%) achieving partial response (PR). Stable disease (SD) was noted in 8 (14%) patients and progressive disease in 3 (5.2%) patients. Conclusion: Addition of nimotuzumab is a safe and efficacious option in patients with inoperable LASCCHN. Our observations confirm the available Phase II data. The long term survival benefits based on this encouraging response rate need to be further evaluated in this subset of cancer patients.

Assessment of early tumor response to induction chemotherapy (IC) in locally advanced squamous-cell carcinoma of head and neck (LASCCHN) with 18FDG PET-CT: A prospective trial.

6017 Background: Response to IC with triplet regimens adding taxanes to cisplatin and 5-fluorouracil (TPF), followed by chemoradiotherapy (CRT) for LASCCHN, is usually evaluated after 2 cycles of IC, based on bidimensional WHO or modified WHO criteria. Concerns regarding toxicity profile of TPF suggest a potential benefit of an early response evaluation approach that could select patients who would be spared from a toxic regimen and promptly started on an alternative treatment. The aim of this study is to assess the ability of evaluating early response after the first IC cycle based on a 40% decrease in standard-uptake value (SUV) measured by 18 FDG PET-CT on the 14th day. Methods: Patients with LASCCHN who underwent IC with TPF were prospectively evaluated. Staging procedure included locoregional and chest imaging, endoscopic examination and FDG PET-CT. At day 14 of first cycle, a second FDG PET-CT was performed and treating physicians were blinded for these findings. All cases were conducted according to the usual post-cycle 2 WHO or modified WHO criteria evaluation. Written informed consent was obtained from all recruited patients. Results: Between February 2010 and October 2012, 40 stage III/IV LASCCHN patients (34 oropharyngeal, 3 hypopharyngeal and 3 laryngeal) were recruited. With a median follow up of 11.4 months the actuarial 2 years overall (OS) and disease free survival (DFS) of all patients were 81.4% and 69.2%, respectively. Responders (any decrease of SUV) at day 14 PET CT had a better OS (90 vs. 27% - p&lt;0,001) and DFS (76 vs. 0% - p&lt;0,001) as compared to non-responders. Decrease of at least 40% in the SUV of primary tumor predicted a better DFS (100 vs. 51% - p=0,007). Conclusions: These results suggest a potential role of early response evaluation with 18 FDG PET-CT in patients with LASCCHN undergoing IC. A SUV decrease of at least 40% predicts better DFS. An increase in the SUV predicts a poor prognosis.

Paclitaxel and Carboplatin Concurrent with Three-Dimensional Conformal Radiotherapy (3D-CRT ) for Treatment of Locally Advanced Squamous Cell Carcinoma of Head and Neck (LA-SCCHN)

Paclitaxel and Carboplatin Concurrent with Three-Dimensional Conformal Radiotherapy (3D-CRT ) for Treatment of Locally Advanced Squamous Cell Carcinoma of Head and Neck (LA-SCCHN)

Retrospective analysis of head and neck cancer patients successfully treated with chemoradiation plus nimotuzumab.

e16013 Background: Nimotuzumab with chemoradiation is found to be efficacious and safe in treatment of locally advanced squamous cell carcinoma of head and neck (LASCCHN). We did retrospective anal...

Concurrent chemoradiation in locally advanced head and neck cancers: A comparison of weekly paclitaxel with cisplatin-based regimen

17032 Background: Concurrent cisplatin-based chemoradiation is the standard of care for patients with unresectable locally advanced squamous cell carcinoma of head and neck (LA-SCCHN) with 5-year locoregional control rates between 35–70%. Taxane-based chemotherapies might improve locoregional control as has been shown in phase I and II trials. This retrospective analysis compares the outcome and toxicity of weekly paclitaxel with weekly cisplatin-based concurrent chemoradiation in LA-SCCHN. Methods: 107 patients of unresectable stage III, IVA and IVB cancers of oropharynx, hypopharynx and larynx were retrospectively analyzed for outcome and toxicity. A retrospective chart review was used to create a data base of clinical and pathologic characteristics of these patients using Microsoft Excel. 58 patients received concurrent weekly paclitaxel (30 mg/m2) and 49 patients were administered weekly cisplatin (40 mg/m2) during radiation therapy with conventional fractionation and curative intention. Results: The median duration of follow up was 12 months in each group (range 3–53 months). In the paclitaxel arm, 43 (74.13%) patients remained alive and disease-free whereas in the cisplatin arm, 33 (67.34%) patients were alive disease-free. This difference was not statistically significant (p=0.34). In the paclitaxel group, among the patients completing radiation in 47 or less days, 26 (81.25%) were alive and disease free in comparison with 17 (65.38%) in those completing radiation in longer than 47 days (odds ratio = 2.29, p=0.16). In the cisplatin arm, alive disease-free status was seen in 18 (67.34%) patients completing radiation in 47 days or less and 15 (65.21%) in those taking longer than 47 days to complete radiation therapy (odds ratio=1.2, p=0.76). The projected mean locoregional relapse free survival in Paclitaxel arm was 33.42 months, and 32.18 months in the cisplatin arm (p=0.73). The 2-year locoregional relapse free survival was 60% in the Paclitaxel arm and 52% in the Cisplatin arm. Conclusion: At 12 months median follow up, weekly paclitaxel-based concurrent chemoradiation regimen provides no additional efficacy and tolerability benefits over and above those provided by weekly cisplatin. No significant financial relationships to disclose.