Safety and efficacy of neoadjuvant chemotherapy with paclitaxel, carboplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma.

BACKGROUND: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen. METHODS: We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75 years and those with an estimated glomerular filtration rate (eGFR) < 60 mL/min were classified as ineligible for cisplatin. RESULTS: The median age was 70 (27-81) years. The median eGFR at treatment initiation was 63.2 (41.1-89.7) mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed. CONCLUSION: NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy.

Feasibility of concomitant cisplatin with hypofractionated radiotherapy for locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumor sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). METHODS: This single-arm trial was designed to evaluate the safety and feasibility of HYP-RT with concomitant CDDP in LAHNC. Stage III and IV patients withnonmetastatic disease were enrolled. Patients were submitted to intensity modulatedradiation therapy, which comprised 55 Gy/20 fractions to the gross tumor and44-48 Gy/20 fractions to the areas of subclinical disease. Concomitant CDDPconsisted of 4 weekly cycles of 35 mg/m2. The primary endpoints were the treatment completion rate and acute toxicity. RESULTS: Twenty patients were enrolled from January 2015 to September 2016, and 12 (60%) were classified as unresectable. All patients completed the total dose of radiotherapy, and 19 patients (95%) received at least 3 of 4 cycles of chemotherapy. The median overall treatment time was 29 days (27-34). Grade 4 toxicity was reported twice (1 fatigue and 1 lymphopenia). The rates of grade 3 dermatitis and mucositis were 30% and 40%, respectively, with spontaneous resolution. Nasogastric tubes were offered to 15 patients (75%) during treatment; 4 patients (20%) needed feeding tubes after 2 months, and only 1 patient needed a feeding tube after 12 months. CONCLUSION: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted. TRIAL REGISTRATION: ClinicalTrials, NCT03194061 . Registered 21 Jun 2017 - Retrospectively registered.

A comparative study of concomitant boost radiation versus concomitant boost with concurrent chemoradiation versus standard fractionation chemoradiation in locally advanced head-and-neck cancer.

CONTEXT: As the number of head-and-neck cancer (HNC) patients are high in our subcontinent, the study was designed to reduce the treatment time and increase efficacy. AIMS: Comparative evaluation of the efficacy, toxicity, local control, and survival of concomitant boost radiotherapy (CBRT), CBRT with concurrent chemoradiation (CBRT + CCT) and conventionally fractionated radiotherapy with concomitant chemotherapy (CFRT + CCT) in locally advanced HNC (LAHNC). MATERIALS AND METHODS: Patients with LAHNC were randomly assigned to 3-groups of 30-patients each. Group I (CBRT) received, 45 Gy/25#/5-weeks and 18 Gy/10# concomitant boost in the last 2-week of treatment, receiving a total dose of 63 Gy. Group II (CBRT + CCT) received CBRT with concomitant cisplatin 75 mg/m 2 on day 1, 17, and 34. Group III (CFRT + CCT) received 64 Gy/32#/6.2 weeks, concurrent with injection cisplatin 75 mg/m 2 on day 1, 22, and 42. STATISTICAL ANALYSIS USED: Stata 9.0 SPSS and Chi-square test were used for analysis and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method. RESULTS: The median follow-up period was 8.2 months. At last follow-up, locoregional control was 36%, 57%, and 40% and DFS was seen in 33%, 53%, and 40% of patients in Group I, II, and III, respectively. Grade-3 cutaneous reactions were significantly higher in Group-II as compared to that of Group-III (P = 0.033) and Group-I (P = 0.715). CONCLUSION: All three groups have similar response rates and DFS with manageable toxicity.

Efficacy and safety of concurrent chemoradiotherapy with or without Nimotuzumab in unresectable locally advanced squamous cell carcinoma of head and neck: Prospective comparative study - ESCORT-N study.

BACKGROUND: Nimotuzumab is an anti-epidermal growth factor receptor monoclonal antibody which can be added to chemoradiotherapy (CRT) to improve efficacy for management of locally advanced squamous cell carcinoma of the head and neck (LASCCHN). We prospectively evaluated the efficacy and safety of nimotuzumab with CRT for LASCCHN and compared with CRT alone. MATERIALS AND METHODS: In this prospective study, 29 LASCCHN (Stage III-IVb) patients received Nimotuzumab plus CRT or CRT alone. Treatment included six cycles of cisplatin (40-50 mg/week) or carboplatin (area under the curve-based), nimotuzumab (200 mg/week), and radiotherapy (60-70 Gy). Tumor response was evaluated as per response evaluation criteria in solid tumors criteria. MoS was estimated using the Kaplan-Meier method. Toxicity and adverse events (AE's) were assessed as per CTCAE v 4.0. RESULTS: At 24 weeks after completion of treatment, the tumor response rate (complete response, partial response, stable disease) was 53.3% and 35.7% favoring nimotuzumab arm while progression of disease was 40% and 35.7% in Nimotuzumab plus CRT and CRT groups, respectively. However, the objective response rate was 57% and 30% in favor of nimotuzumab arm. At median follow-up of 45.5 months, MoS was 33 months in Nimotuzumab plus CRT and 27 months in CRT group. The 5-year survival rate was 33.3% in Nimotuzumab plus CRT versus 7.1% in CRT group. Nimotuzumab was observed to be safe with no additional AE's such as hypersensitivity, hypomagnesemia, and allergic reaction was reported. CONCLUSION: Addition of Nimotuzumab to standard CRT showed improved survival rate in unresectable, LASCCHN patients without producing additional toxicity.