Comparison of paclitaxel-cetuximab chemotherapy versus metronomic chemotherapy consisting of methotrexate and celecoxib as palliative chemotherapy in head and neck cancers.

BACKGROUND: The present match pair analysis was planned to compare the efficacy of cetuximab-paclitaxel-based chemotherapy versus metronomic therapy. MATERIALS AND METHODS: Sixty patients with metastatic/recurrent head and neck squamous cell cancer treated with weekly paclitaxel (80 mg/m2) and cetuximab were matched with sixty patients treated with oral metronomic chemotherapy consisting of methotrexate and celecoxib. The progression-free survival (PFS) and overall survival (OS) between the cohorts were compared using log-rank test. Cox proportional regression model was used to identify independent factors affecting PFS and OS. RESULTS: The median OS was 191 days (95% confidence interval [CI]: 122.2-259.8 days) in metronomic cohort and 256 days (95% CI 177.0-334.9 days) in cetuximab cohort (hazard ratio: 0.58, 95% CI: 0.35-0.95, P = 0.031). On Cox proportional hazard model, Eastern Cooperative Oncology Group Performance Status (0-1 vs. 2) and therapy (cetuximab versus metronomic) had a statistically significant impact on OS. CONCLUSION: Cetuximab-based chemotherapy leads to a significant improvement in OS in the match pair analysis in comparison to metronomic chemotherapy.

Retrospective analysis of palliative metronomic chemotherapy in head and neck cancer.

BACKGROUND: Metronomic chemotherapy has shown promising results in selected patients of head and neck cancer in a small randomized study. This retrospective analysis was done to see whether the efficacy of metronomic chemotherapy in an unselected cohort of head and neck cancer patients is similar to that reported in the randomized study and the influence of the site and subsite of head and neck cancer on survival. MATERIALS AND METHODS: This was a retrospective analysis of head and neck cancer patients who received palliative metronomic chemotherapy between January 2013 and February 2015. The data of these patients were collected from our palliative chemotherapy database maintained in medical oncology outpatient department. The overall survival (OS) was calculated in days from the date of start of chemotherapy to the date of death. Patients who had not expired at last follow-up were censored during estimation of OS by Kaplan-Meier method. Factors affecting OS were identified by COX regression analysis. RESULTS: Over the stipulated time period, 340 patients received palliative metronomic chemotherapy. The median age of these patients was 48 years (22-90 years). The sites of tumor origin were oral cavity in 281 patients (82.6%), oropharynx in 33 patients (9.7%), larynx in seven patients (2.1%), hypopharynx in 12 patients (3.5%), and maxilla in seven patients (2.1%). Previous treatment was received by 286 patients (84.1%). The median time to failure was 3.5 months (interquartile range 2.0-6.0 months). The overall median survival was 155 days (95% confidence interval 140.2-169.8 days). Failure within 6 months of previous treatment was the most important factor influencing OS. There was a trend toward lower OS in patients with oral cancers (139 days vs. 210 days). Among the various oral cancer subsites, oral tongue primary had a lower OS. CONCLUSION: Oral metronomic chemotherapy has promising results when used in a selected cohort of patients but has dismal results in patients who failed within 6 months of previous treatment.

Predictivity of human papillomavirus positivity in advanced oral cancer.

BACKGROUND AND OBJECTIVE: Human papillomavirus (HPV) is a known prognostic factor world over in patients of carcinoma oropharynx. The role of HPV in oral cancers has not been investigated adequately. We tried to identify standard clinicopathological features in oral cancer, which would predict HPV-positivity. METHODS: This was a retrospective analysis of 124 cases of T4 oral cancer patients at our center. HPV-positive was defined in accordance with positive p16 immunohistochemistry done on pretreatment local tumor site biopsy. Age, sex, habits (smoking history and oral tobacco), Eastern Cooperative Oncology Group performance status (ECOG PS), T stage, N stage, grade, and site were selected, for testing of prediction for HPV-positivity. The analysis was performed by R studio version 3.1.1. Two-sample test for equality of proportions with continuity correction was used to identify factors predicting for HPV-positivity. P = 0.05 was considered as significant. RESULTS: Of 124 patients, 16 patients (12.9%) were HPV-positive. The median age of the whole cohort was 43 years (interquartile range 37-52 years) with 15 females (12.1%). All had squamous cell carcinoma (100%). The grade of the tumor was well differentiated in 9 patients (7.2%), moderately differentiated in 98 patients (79.1%), and poorly differentiated in 17 patients (13.7%). The ECOG PS 0 in 19 patients (15.3%), 1 in 104 patients (83.9%), and 2 in 1 patient (0.8%). The subsite of the tumor was buccal mucosa in 74 patients (59.7%), anterior two-third of tongue in 33 patients (26.6%), and others in 17 patients (13.7%). None of the tested factors except the use of oral tobacco were statistically significantly associated with HPV-positivity. History of tobacco usage had a statistical trend toward ability to predict HPV-positivity. The proportion of patients with HPV-positive oral cancer in patients without history usage of oral tobacco was 31.3% while it was 10.2% in patients with previous history of tobacco use (P = 0.03). CONCLUSION: Standard clinicopathological variables could not predict for HPV-positivity. Negative history of tobacco (smokeless) usage showed statistical trends toward ability to predict HPV-positivity in oral cancer patients.

Efficacy of second-line erlotinib in patients postprogression of first-line chemotherapy in head and neck cancers.

BACKGROUND: Oral tyrosine kinase inhibitor (gefitinib and erlotinib) have been used in the palliative treatment of head and neck cancers with limited success. In this report, we aim to quantify the symptomatic benefit, progression-free survival (PFS) and overall survival (OS) when erlotinib is given as second-line treatment in Head and neck cancers. METHODS: This was a post-hoc retrospective analysis of a randomized study comparing metronomic chemotherapy with cisplatin. A patient who progressed on chemotherapy and had a PS0-2 were offered second-line chemotherapy. Patients who had received erlotinib (150 mg PO OD) as second line treatment were selected for this analysis. Erlotinib was discontinued in case of either progression of disease or if the patient had intolerable side effects. Patient were monitored 1-week after the start of erlotinib and subsequently at monthly intervals. The toxicity was recorded in accordance with CTCAE version 4.02 (NCI,USA) and the response were graded in accordance with RECIST version 1.1. All of these patients were followed-up till death. RESULTS: Twenty-three patients were identified. The median age of these patients at the start of the second line was 47 years (interquartile range 40.5-51.75 years). The primary site of distribution was oral cavity primary in 17 patients (77.3%) and nonoral cavity primary in 05 (22.7%) patients. The immediate last chemotherapy regimen received was cisplatin in 9 patients (40.9%) and metronomic chemotherapy in 13 patients (59.1%). Symptomatic benefits post second-line erlotinib was seen in 18 patients (81.8%). The most common adverse events (any grade) seen were anemia in 20 patients (90.9%), rash in 10 patients (45.5%) and diarrhea in 7 patients (31.8%).The best radiological response documented were a partial response in 04 patients (19.2%). The median estimated PFS and OS were 110 days (95% confidence interval [CI]: 61-175 days) and 156 days (95% CI: 126-185 days) respectively. CONCLUSION: Erlotinib single agent has promising activity in the second line and needs to be explored in future studies.

Referral pattern for neoadjuvant chemotherapy in the head and neck cancers in a tertiary care center.

BACKGROUND: Use of any treatment modality in cancer depends not only on the effectiveness of the modality, but also on other factors such as local expertise, tolerance of the modality, cost and prevalence of the disease. Oropharyngeal and laryngeal cancer are the major subsites in which majority of neoadjuvant chemotherapy (NACT) literature in the head and neck cancers is available. However, oral cancers form a major subsite in India. MATERIALS AND METHODS: This is an analysis of a prospectively maintained data on NACT in the head and neck cancers from 2008 to 2012. All these patients were referred for NACT for various indications from a multidisciplinary clinic. Descriptive analysis of indications for NACT in this data base is presented. RESULTS: A total of 862 patients received NACT within the stipulated time period. The sites where oral cavity 721 patients (83.6%), maxilla 41 patients (4.8%), larynx 33 patients (3.8%), laryngopharynx 8 patients (0.9%) and hypopharynx 59 patients (8.2%). Out of oral cancers, the major indication for NACT was to make the cancer resectable in all (100%) patients. The indication in carcinoma of maxilla was to make the disease resectable in 29 patients (70.7% of maxillary cancers) and in 12 patients (29.3% of maxillary cancers) it was given as an attempt to preserve the eyeball. The indication for NACT in laryngeal cancers was organ preservation in 14 patients (42.4% of larnyngeal cancer) and to achieve resectability in 19 patients (57.6% of larnyngeal cancer). The group with laryngopharynx is a cohort of eight patients in whom NACT was given to prevent tracheostomy, these patients had presented with early stridor (common terminology criteria for adverse events Version 4.02). The reason for NACT in hypopharyngeal cancers was for organ preservation in 24 patients (40.7% of hypopharyngeal cancer) and for achievement of resectability in 35 patients (59.3% of hypopharyngeal cancer). CONCLUSION: The major indication for NACT is to make disease resectable at our center while cases for organ preservation are few.

Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers.

BACKGROUND: The median survival of technically unresectable oral-cavity cancers (T4a and T4b) with non surgical therapy is 2-12 months. We hypothesized that neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in successful resection and ultimately improved outcomes. We present a retrospective analysis of consecutive patients who received NACT at our centre between January 2008 and August 2012. PATIENTS AND METHODS: All patients with technically unresectable oral cancers were assessed in a multidisciplinary clinic and received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT, RT or palliation. SPSS version 16 was used for analysis of locoregional control and overall survival (OS). Univariate and multivariate analysis was done for factors affecting the OS. RESULTS: 721 patients with stage IV oral-cavity cancer received NACT. 310 patients (43%) had sufficient reduction in tumour size and underwent surgical resection. Of the remaining patients, 167 received chemoradiation, 3 radical radiation and 241 palliative treatment alone The locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in patients undergoing surgery and 15% in patients undergoing non surgical treatment (p=0.0001). The median estimated OS in patients undergoing surgery was 19.6 months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76) in patients treated with non surgical treatment (p=0.0001). CONCLUSION: In our analysis, NACT led to successful resection and improved overall survival in a significant proportion of technically unresectable oral-cancer patients.