Selected current data on metronomic therapy (and its promise) from India

BACKGROUND: Addition of erlotinib to metronomic chemotherapy (MCT) may lead to further improvement in progression free survival (PFS) and overall survival in head and neck cancers. The aim of this study was to study the PFS with MCT + erlotinib combination in our setting. METHODS : Single arm prospective observational study conducted at Malabar Cancer Center. Patients warranting palliative chemotherapy for head and neck cancers, having adequate organ function, not affording cetuximab and not willing for intravenous chemotherapy were included in this study. Oral methotrexate (15 mg/m 2 /week), oral celecoxib (200 mg twice daily) and erlotinib (150 mg once daily) were administered till the progression of the disease or till intolerable side effects. Patients underwent toxicity (CTCAE version 4.02) and response (RECIST version 1.1) assessment every 30 days. Statistical analysis was performed using SPSS version 16((IBM New York). Descriptive statistics and Kaplan– Meier analysis have been performed. RESULTS : A total of 15 patients received MCT. The median age of these patients was 65 years (range 48–80). The Eastern Cooperative Oncology Group performance status was 0–1 in 7 patients (46.7%), while it was 2 in 8 patients (53.3%). The primary sites of tumor were predominantly oral cavity, 11 (73.4%). Prior to MCT, treatment with palliative radiation therapy was given in 11 patients and curative treatment in 2 patients. The best response post MCT was complete remission in 2 patients, partial remission in 7 patients, stable disease in 4 patients, and progressive disease in 2 patients. The median estimated PFS was 148 days (95% confidence interval 95.47–200.52 days). For a median follow up of 181 days there were only three deaths. Grade 3–4 toxicity was seen in 6 patients (40%). Dose reduction was required in 4 patients (26.7%). CONCLUSION : The addition of erlotinib to a MCT schedule of methotrexate and celecoxib resulted in a promising PFS and should be tested in future studies tobacco is paucity of of oral cancer among rural population. evaluate outcomes of operable oral cavity carcinoma. evaluate disease free survival (DFS) and factors affecting outcome in operable oral cavity cancer. MATERIAL METHODS : Data of patients diagnosed with oral cavity cancer registered between to 2014 were retrieved from hospital based cancer database. Only those patients who presented with operable Oral cavity cancer and subsequent underwent upfront definitive surgery were included for analysis. Demographic profile, stage, tobacco consumption, adjuvant therapy and pattern of failure were collected. Kaplan Meir survival analysis was used to determine disease free survival and overall survival. Log rank test was used to evaluate factors affecting outcome. RESULTS : Median follow up is 24 months. Out of 335 patients, 225 (67%) had advanced operable cancer with 42/225 (18%) and 183/225 (82%) as stage III and IV respectively. followed by tongue (63/335, 19%). 92% patients were addicted to smokeless tobacco, while 27% were smokers and 27% were chronic alcoholics. Out of 225 patients who required adjuvant radiotherapy, 196(87%) completed planned dose. Local relapse was most common (82/127, 65%) followed by metastasis (19%), regional (11%) and loco regional failure (5%). Median DFS is 13 months with 2 yr relative DFS 32%. Median Overall Survival is 30 months, with 2 yr OS of 54%. Metronomic adjuvant oral chemotherapy was given in 130/225(58%); Stage III and IVA patients with median of 12 months (3-18 months).Use of metronomic chemotherapy improved DFS( 8 vs 14 months, p=0.22) and overall survival. (14 vs 26 months, p= 0.04 ) CONCLUSION : Oral cavity cancer is a major health care problem in rural India due to various smokeless tobacco preparations. Presentation at advanced stage leads to suboptimal outcomes. Benefit of metronomic maintenance chemotherapy in locally advanced oral cavity needs to be further evaluated prospectively. BACKGROUND : Cetuximab based palliative chemotherapy is the standard of care in metastatic head and neck cancers. However, only few patients can afford cetuximab in developing countries. A recent study showed the superiority of oral metronomic chemotherapywith daily celecoxib and weekly methotrexatein palliative setting over maximum tolerable dose chemotherapy which did not include cetuximab.The present match pair analysis was planned to compare the efficacy of cetuximab based chemotherapy versus metronomic therapy. METHOD : 60 patients with metastatic/recurrent head and neck squamous cell cancer treated with weekly Paclitaxel (80 mg/m2) and cetuximab were matched with 60 patients treated with oral metronomic chemotherapy. The matching was done on 1:1 basis for site of primary and event free period from prior treatment.The primary endpoint of the analysis was overall survival (OS). OS was estimated by Kaplan–Meier method. The cohorts were compared using the log-rank test.A multivariable Cox proportional regression model was used to identify independent factors affecting PFS and OS. RESULT : The median OS was 191 days (95% CI 122.2-259.8 days) in metronomic cohort and 256 days (95%CI 177.0-334.9 days) in cetuximab cohort. On cox proportional hazard model, ECOG PS (0-1 versus 2) & therapy (cetuximab versus metronomic) had a statistically significant impact on OS. The hazard ratio was 0.58 in favour of cetuximab cohort (95% CI 0.35-0.95, p=0.031). CONCLUSION : Cetuximab based chemotherapy leads to significant improvement in OS as compared to metronomic chemotherapy in palliative chemotherapy of head and neck cancers. , time The for (CTCAE) 4.03. EORTC Quality of life(QOL) questionnaires – QLQ –C30 and QLQ – H&N35 were used to estimate the QOL scores. RESULTS: 30 patients(20 males,10 females) were analysed. The median age was 58 years. At the end of four months, 60% had stable disease (SD), 10% had partial response(PR), and 30% had progressive disease(PD). The clinical benefit rate (PR+SD) was 70%. The estimated median time to progression was eight weeks. The pain control was achieved in about 80% of patients. Only 1 patient had Grade III mucosal toxicity, 11 patients had Grade I/II mucosal toxicity and 18 patients had no mucosal toxicity. Mean QOL scores were improved with this metronomic chemotherapy. for patients with was effective, tolerated, good pain control and improves Quality of life with least toxicity profile. BACKGROUND : To assess baseline nutritional status of advanced head and neck cancer patients and its implications to response after oral metronomic chemotherapy (OMCT). MATERIALS AND METHODS: A retrospective audit of 75 patients of advanced head and neck cancers who were treated with oral metronomic chemotherapy was conducted based on the electronic medical records. Patients who received at least 2 months of OMCT were included. RESULTS : The male to female ratio was 9: 1. Median age was 48 yrs (30-71yrs). 65% of patients had oral cavity cancers. 40% had albumin <4g/dl. The mean baseline albumin was 4.02+/-0.6. 25% patients had Hb <11g/dl. The mean Hb was 12.4+/-1.27. 50% had BMI < 18.5 of which 21% had BMI <16. Mean baseline BMI was 18.8+/-3.7. Post 2 months of OMCT, symptomatic benefit was reported by 75% of patients and 25% had either no relief or had increase in symptoms. 30% of patients with albumin <4g/dl had no symptomatic benefit with OMCT when compared to 20% of patients with albumin >4 g/dl.55% of patients with Hb < 11g/dl had no benefit with OMCT versus 20% of patients with Hb >11g/dl. Mean BMI of patients with albumin < 4g/dl was 16.6 which was significantly lower than patients with albumin >4g/dl (20.2, p=0.001). CONCLUSION : Half of patients with advanced head and neck cancer have co-existing malnutrition with one fifth severely malnourished. 40% of patients have low albumin levels. One fourth of patients have moderate anemia. Poor symptomatic response in patients with low baseline albumin and hemoglobin needs to be studied further to define them as prognostic factors. Early nutritional intervention even prior to start of OMCT or palliative chemotherapy is mandatory. prognosis. Standard cetuximab-based palliative chemotherapy expensive benefit and significant toxicity. using results. study 3-drug oral combination in a metronomic schedule in cetuximab chemotherapy. OBJECTIVES : To determine progression free survival (PFS) and overall survival (OS) in treated with 3-drug metronomic (MCT). PFS overall survival. Other endpoints were clinical response, tolerance and toxicity profile. RESULTS : 13 patients with median age of 52 years (range 33-75), 11 males and 2 females, received MCT. The primary site was tongue (5 patients), buccal mucosa (6), soft palate (1) and hypopharynx (1). The median time to relapse was 5 months (1-24 months). None of the patients received palliative chemotherapy. The reasons included nonaffordability, age and unwillingness for chemotherapy. The performance status was 1 in 8 patients and 2 in 5 patients. With a median follow up of 6 months, the estimated median PFS was 7.8 months and the median OS has not been reached. Twelve patients had clinical response after 2 months. Grade 3 rash was seen in 3 patients. Overall, dose reduction for erlotinib was done in 7 patients due to rash, mucositis or weakness. None of the patients needed hospitalization and were treated on outpatient basis. CONCLUSIONS : In patients with recurrent and metastatic HNSCC, 3 drug MCT as the initial therapy favourable clinical response and PFS with toxicity profile. To the safety and efficacy of weekly chemotherapy (ECOG of uncontrolled co morbidities, BMI below 18.5 kg/m2 and more than 60 Package for the Social Sciences (SPSS version for analysis. The rates, with vs. completion rate (Cp) of radical intent treatment post neoadjuvantchemotherapy (NACT), progression-free survival (PFS) and overall survival (OS) are reported. RESULTS: Fifteen patients were considered for suchtherapy. Fourteen out of fif