Oral Metronomic Chemotherapy Research Articles

Novel Effective Therapeutic Regimen for Recurrent/Metastatic Head and Neck Squamous Cell Cancer: Concurrent Triple Oral Metronomic Chemotherapy and Immunotherapy.

Novel Effective Therapeutic Regimen for Recurrent/Metastatic Head and Neck Squamous Cell Cancer: Concurrent Triple Oral Metronomic Chemotherapy and Immunotherapy.

Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: a retrospective analysis from two institutions in India

Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 & PFS-2), overall survival (OS), and safety were evaluated. Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.

Long term results of phase 3 randomized study evaluating the addition of low dose nivolumab to palliative chemotherapy in head and neck cancer.

LBA6054 Background: The addition of low-dose nivolumab to metronomic chemotherapy (MC) improved 1-year overall survival in relapsed and refractory head and neck squamous cell carcinoma (HNSCC). However, sustained benefit over the long term is an important aspect of immunotherapy and it has never been studied in a prospective randomized study for low-dose nivolumab. Methods: This was an open-label randomized phase 3 superiority study. Adult patients (age= or >18 years), ECOG PS (0-1), relapsed -recurrent or newly diagnosed advanced HNSCC, and normal organ functions were eligible. Patients were randomly assigned 1:1 to oral metronomic chemotherapy consisting of methotrexate 9 mg/m2 weekly, celecoxib 200 mg twice daily, and erlotinib 150 mg daily, with (TMC-I) or without (TMC) with intravenous nivolumab 20 mg flat dose once-every-3-weeks. Systemic therapy was continued till the development of intolerable side effects or progression of disease. The primary endpoint was overall survival (OS). Landmark analysis was performed to compare OS between 2 arms. Results: The median follow-up was 32.5 months (95% CI 29.6-32.7). The 1 year, 2 year and 2.5 year OS were 20% (95%CI 11.9-29.7) versus 35.5% (95%CI 25-46.2) {Hazard ratio (HR)= 0.6534, 95%CI 0.4473 -0.956: P=0.028}, 5.3% (95%CI 1.7-12.3) versus 18.4 %(95%CI 10.7-27.8) {HR= 0.6318, 95%CI 0.4476 -0.8919: P=0.009} and 5.3% (95%CI 1.7-12.3) versus 17.1 % (95%CI 9.66.-26.3) {HR= 0.6379, 95%CI 0.4524 -0.8993: P=0.01} in the TMC and the TMC-I arms respectively. The benefit of the addition of nivolumab was independent of other factors like age, gender, ECOG PS, Site of malignancy, time to failure, PDL1 score, and previous exposure to platinum (Table). Conclusions: The addition of low-dose nivolumab to triple metronomic chemotherapy leads to a tripling of OS thus suggesting that even low-dose nivolumab has sustainable benefits. The benefit observed is irrespective of known prognostic factors in HNSCC. Clinical trial information: CTRI/2020/11/028953 . [Table: see text]

Efficacy and Safety of Oral Metronomic Chemotherapy in Recurrent Refractory Advanced Gynaecological Cancer: An Experience From the Regional Cancer Centre of Eastern India.

The outcome of recurrent/metastatic gynaecological malignancy has drastically improved with the introduction of poly(ADP-ribose) polymerase inhibitors and immunotherapy, but the use of these drugs in routine practice is complicated due to access barriers and their high cost in developing countries. The purpose of this study is to present the clinical response, outcome and safety of oral metronomic chemotherapy (OMCT) in resource-limited, financially constrained populations. This is a retrospective study on patients with advanced gynaecological cancer treated at Chittaranjan National Cancer Institute, Kolkata, India, from 2021 to 2023. The patients were treated with one of these two regimens: a split-dose course of cyclophosphamide (50 mg orally once daily for 21 days) and capecitabine (500 mg twice daily continuous) or a fixed-dose combination (capecitabine 1800 mg and cyclophosphamide 80 mg orally for 14 days in every 21 days) until disease progression or unacceptable toxicities occurred. All data was captured from the hospital's medical records until June 2023. Toxicity data was reported per the Common Terminology Criteria for Adverse Events (CTCAE) v5.1, and progression-free survival (PFS) was estimated using Kaplan-Meier methods. Among 34 screened patients, 10 were excluded due to noncompliance. This study analysed 24 patients with a median age at diagnosis of 56 years (IQ range 44-75). Sixteen (67%) patients were at stage IV disease with an Eastern Cooperative Oncology Group (ECOG) performance status of 3. Ovarian and cervical cancers were 80% and 20%, respectively; among them, 16 (67%) patients were platinum-refractory. Forty-two per cent of patients received three lines of chemotherapy before OMCT. A split course versus fixed dose was given to 67% versus 33% of the population; the best responses per the Response Evaluation Criteria in Solid Tumours v1.1 were complete response in 12%, partial response in 67% and stable disease in 21%. The most common toxicities were grade I anaemia (54%), grade I chemotherapy-induced nausea and vomiting (46%), grade I fatigue (42%) and grade I neutropenia (21%). Twenty-five per cent of patients were offered next-line systemic therapy after progression. The entire cohort had a median PFS of nine months (95%, CI: 5.2-12.7). Cox regression analysis identified a median PFS of 12 months (95%, CI: 6.2-17.7) among platinum-refractory groups. OMCT was a well-tolerated, affordable regimen with durable clinical response and survival outcome (median PFS of nine months) in recurrent, refractory advanced gynaecological cancer and can be offered to patients at resource-limited centres.

Indian clinical practice consensus guidelines for the management of very advanced head-and-neck squamous cell carcinoma: Update 2022

The management of recurrent or metastatic head-and-neck cancers is evolving. Promising novel immunotherapies and targeted therapies have led to a paradigm shift in the management of very advanced disease. Single-agent systemic therapy including cisplatin/carboplatin/paclitaxel/docetaxel/5-florouracil/methotrexate/cetuximab/gemcitabine/capecitabine or combination chemotherapy may be considered. Immunotherapy alone or in combination with chemotherapy has improved survival and should be considered. Oral metronomic chemotherapy with or without immunotherapy also improves oncologic outcomes. The challenges associated with the disease may be resolved by using an integrated approach of combining locoregional and systemic therapies. Salvage treatments like re-radiation or surgery are useful for the management of locoregional recurrences.

A retrospective analysis of outcome with triplet oral metronomic chemotherapy in head and neck cancers in a resource comprising setting during COVID 19 pandemic, a single institute experience

A retrospective analysis of outcome with triplet oral metronomic chemotherapy in head and neck cancers in a resource comprising setting during COVID 19 pandemic, a single institute experience

Enigma of Esophageal - Respiratory Fistula in Advanced Esophageal Cancer

Background: The incidence of malignant esophageal-respiratory fistulas in esophageal cancer patients is not so frequent. The fistula development in esophageal cancer may be due to advanced disease or a radiotherapy-related complication. Rarely, a pulmonary abscess may develop, which is the most dreadful complication resulting in dismal outcomes. Here, we reported 2-cases of esophageal-respiratory fistula; one with esophageal bronchial fistula and the other with esophageal pleural fistula.
 Case reports: A 46-year-aged man presented with complaints of difficulty in swallowing for 4 months. CECT chest showed an esophageal growth of 8.5 cm in the lower esophagus. The patient received palliative radiotherapy followed by palliative chemotherapy and showed some improvement in dysphagia. Nine months after the start of treatment, the patient’s dysphagia began to worsen, and he was put on oral metronomic chemotherapy. After 1-year of metronomic chemotherapy, the patient developed cough and chest pain and was diagnosed with an esophageal-pleural fistula with chest wall collection and pleural effusion. The patient was managed conservatively and later lost to follow-up. Another 65-year-old patient presented with dysphagia for 3-months. CECT chest showed an esophageal growth of 5.5 cm in the middle esophagus. The patient received palliative radiotherapy, after which the dysphagia improved. In 3rd month of follow up patient’s dysphagia worsened; barium swallow showed esophageal-bronchial fistula. The patient was managed symptomatically and later lost to follow-up.
 Conclusions: Fistula formation and subsequent abscess results in a poor prognosis. With advancing disease and compromised general condition of the patient, palliation of symptoms is a significant challenge. Treatment becomes difficult due to the rare occurrence of fistulas and the non-standardization of the treatment protocol. Invasive treatment includes esophageal-pulmonary resection, endoscopic placement of self-expandable covered stents, drainage of empyema and obliteration of empyema cavity, esophageal diversion, and non-invasive treatment includes best supportive care. However, even with appropriate treatment, the outcome is dismal.

Metronomic Chemotherapy in Oral Cancer: A Review.

Treatment of locally advanced oral cancer requires multidisciplinary care, including surgery, radiotherapy, and chemotherapy, which varies based on the stage of the disease, site of involvement, and surgical access. Oral cancer usually presents with an increased recurrence rate and potential for distant metastatic spread. It confers a poor prognosis with a 50% mortality rate after five years. Oral metronomic chemotherapy aims to achieve higher patient compliance due to its ease of administration, lower dosage, and lesser side effects than conventional IV regimens of platinum-based drugs. In this review, we have summarized the relevant literature to benefit the readers regarding the potential application of metronomic therapy in the management of oral cancer.

313P Efficacy and safety of oral metronomic chemotherapy in recurrent refractory advanced gynaecological cancer: Experience from regional cancer center of eastern India

313P Efficacy and safety of oral metronomic chemotherapy in recurrent refractory advanced gynaecological cancer: Experience from regional cancer center of eastern India

936P Triple oral metronomic chemotherapy (OMCT) versus physician choice chemotherapy after failure of platinum-based therapy in advanced head and neck squamous cell cancer (HNSCC): A phase III randomized open-label study

936P Triple oral metronomic chemotherapy (OMCT) versus physician choice chemotherapy after failure of platinum-based therapy in advanced head and neck squamous cell cancer (HNSCC): A phase III randomized open-label study

Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: a retrospective analysis from two institutions in India

Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 & PFS-2), overall survival (OS), and safety were evaluated. Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.

Metronomic adjuvant chemotherapy evaluation in locallyadvanced head and neck cancers post radical chemoradiation - a randomised trial.

Locally advanced head and neck cancers treated with radical chemoradiation have unsatisfactory outcomes. Oral metronomic chemotherapy improves outcomes in comparison to maximum tolerated dose chemotherapy in the palliative setting. Limited evidence suggests that it may do so in an adjuvant setting. Hence this randomized study was conducted. Patients of head and neck (HN) cancer with primary in oropharynx, larynx or hypopharynx, with PS 0-2 post radical chemoradiation with documented complete response were randomized 1:1 to either observation or oral metronomic adjuvant chemotherapy (MAC) for 18 months. MAC consisted of weekly oral methotrexate (15mg/m2) and celecoxib (200mg PO BD). The primary endpoint was OS and the overall sample size was 1038. The study had 3 planned interim analyses for efficacy and futility. Trial registration- Clinical Trials Registry- India (CTRI): CTRI/2016/09/007315 [Registered on: 28/09/2016] Trial Registered Prospectively. 137 patients were recruited and an interim analysis was done. The 3 year PFS was 68.7% (95% CI 55.1-79.0) versus 60.8% (95% CI 47.9-71.4) in the observation and metronomic arm respectively (P value=0.230). The hazard ratio was 1.42 (95% CI 0.80-2.51; P value=0.231). The 3 year OS was 79.4% (95% CI 66.3-87.9) versus 62.4% (95% CI 49.5-72.8) in the observation and metronomic arm respectively (P value=0.047). The hazard ratio was 1.83 (95% CI 1.0-3.36; P value=0.051). In this phase 3 randomized study, oral metronomic combinations of weekly methotrexate and daily celecoxib failed to improve the PFS or OS. Hence observation post-complete response post radical chemoradiation remains the standard of care. ICON funded this study.

Long term outcomes of phase I/II study of palliative triple metronomic chemotherapy in platinum-refractory/early failure oral cancer.

Triple metronomic chemotherapy is one of the options of treatment in platinum-refractory/early failure oral cancer. However, long term outcomes with this regimen are unknown. Adult patients with platinum-refractory/early-failure oral cancer were enrolled in the study. Patients were administered triple metronomic chemotherapy ie erlotinib 150mg once daily celecoxib 200mg twice daily and methotrexate weekly (phase 1 in variable dose 15-6 mg/m2 & 9 mg/m2 in phase 2), all taken orally till progression of disease or development of intolerable adverse events. The primary objective was to estimate the long-term overall survival and factors impacting it. The Kaplan Meier method was used for time-to-event analysis. Cox proportional hazard model was used to identify factors impacting overall survival (OS) and progression-free survival (PFS). The factors included in the model were age, sex, Eastern Cooperative Oncology Group - performance status (ECOG PS), tobacco exposure and a subsite of primary and circulating endothelial cell levels at baseline. A p-value of 0.05 was considered significant. Clinical trials information: CTRI/2016/04/006834. A total of 91 patients were recruited (15 in phase 1 & 76 in phase 2), the median follow-up was 41 months and 84events of death had occurred. The median OS was 6.7 months (95% CI 5.4-7.4). The 1-year, 2-years and 3-year OS' were 14.1% (95% CI 7.8-22.2), 5.9% (95% CI 2.2-12.2) and 5.9% (95% CI 2.2-12.2) respectively. The only factor favorably impacting OS was the detection of circulating endothelial cells at baseline (HR=0.46; 95% CI 0.28-0.75, P=0.0020). The median PFS was 4.3 months (95% CI 4.1-5.1) and the 1-year PFS was 13.0% (95% CI 6.8-21.2). The factors with statistically significant impact on PFS were detection of circulating endothelial cells at baseline (HR=0.48; 95% CI 0.30-0.78, P=0.0020) and no tobacco exposure at baseline (HR=0.51; 95% CI 0.27-0.94, P=0.030). The long-term outcomes with triple oral metronomic chemotherapy ie erlotinib, methotrexate and celecoxib are unsatisfactory. Detection of circulating endothelial cells at baseline is a biomarker predicting efficacy of this therapy. The study was funded by an intramural grant from Tata Memorial Center Research Administration Council (TRAC) and Terry Fox foundation.

High-Risk Peritoneal Mesothelioma: Does Metronomic Chemotherapy Have a Role?

To evaluate the feasibility, tolerance, and efficacy of OMCT (oral metronomic chemotherapy) after CRS + HIPEC for peritoneal mesothelioma in patients with poor prognostic factors: PCI > 20, incomplete CRS, poor performance status, or progression on systemic chemotherapy. A retrospective analysis of patients undergoing CRS + HIPEC for peritoneal mesothelioma and receiving OMCT for poor risk factors. Sixteen patients underwent CRS + HIPEC between 2013 and 2017. The median PCI was 31.5. Complete cytoreduction (CC-0/1) was obtained in 8 patients (50%). All 16 received HIPEC except one patient with baseline renal dysfunction.Thirteen patients had PCI > 20 where only 5 had CC-0/1. Of 8 suboptimal cytoreduction (CC-2/3), 7 received OMCT (6 for progression on chemotherapy and one for mixed histology). Three patients had PCI < 20 and all had CC-0/1 clearance. Only one received OMCT for progression on adjuvant chemotherapy. Patients receiving OMCT for progression on adjuvant chemotherapy (ACT) were in poor PS.The median follow-up was 13.4months. Five are alive with the disease (three are on OMCT). Six are alive without disease (2 are on OMCT). The mean OS was 24.3months and the mean DFS was 18months. Outcomes were similar between CC-0/1 and CC-2/3 groups, OMCT vs no OMCT groups.All patients receiving OMCT for progression on neoadjuvant chemotherapy had better survival (alive at 12, 20, 32, 36months) compared to those receiving OMCT for progression on the ACT (p = 0.012). OMCT is a good alternative in high-volume peritoneal mesothelioma with incomplete cytoreduction and progression on chemotherapy. OMCT may improve outcomes in these scenarios when started early.

Impact of Oral Metronomic Chemotherapy in Locally Advanced Carcinoma of the Laryngopharynx: A Case Report

Oral cancer continues to be a significant health concern in Southeast Asia. The primary treatment involves surgical resection with or without reconstruction, along with adjuvant therapy. However, the survival rates for patients with stage I-II oral cancer range from 70% to 80%, whereas in more advanced stage III-IV cancers, these rates drop significantly to 40%-50%. Unresectable oral cancers are primarily managed with palliative intent, utilising systemic therapy and/or radiotherapy. Unfortunately, a substantial portion of these cases (around 60%-80%) are diagnosed at an advanced stage due to delayed diagnosis, limited access to definitive treatment, and financial constraints. These challenges underscore the critical need for therapies that can effectively halt cancer progression, promote regression, and maintain the disease in an operable state while awaiting definitive treatment, typically involving surgery. In this context, Oral Metronomic Chemotherapy (OMCT) emerges as a promising alternative. OMCT offers costeffectiveness and involves the regular administration of chemotherapeutic drugs at low doses without interruption. The concept of “metronomic” chemotherapy draws inspiration from a metronome, which produces regular ticks representing a constant pulse. Herein, the authors presented case report of a 55-year-old male patient to compile evidence-based data on the use of OMCT in treating locally advanced carcinoma of the laryngopharynx. It explores the mechanism of action, utility, and potential future directions of OMCT. By analysing a real-world case, it seeks to highlight the effectiveness and advantages of OMCT as a treatment option for oral squamous cell carcinoma.

Deficient state-supported cancer care: A source of deep concern

Deficient state-supported cancer care: A source of deep concern

Oral metronomic chemotherapy as a feasible preoperative therapy in advanced resectable oral cavity squamous cell carcinomas- a preliminary experience.

IntroductionSurgery is an important component of multimodality treatment in advanced oral cavity cancers. But in low-middle-income countries like India, with limited centres offering complex head and neck surgeries, prolonged waiting times for surgery is a major problem. An increase in waiting times for treatment has been shown to be a negative prognosticator in head and neck cancer and many patients can develop interim progression making them ineligible for radical treatment. We share our preliminary experience of using oral metronomic chemotherapy as a preoperative treatment in patients expecting delay in surgery.MethodsThis was a retrospective analysis of case records of patients with resectable Stage III and Stage IV (IVA & IVB) oral cavity cancers who had received preoperative oral metronomic chemotherapy (POMT). The POMT schedule consisted of oral Methotrexate 15 mg/m2 weekly, Celecoxib 200 mg twice daily and Erlotinib 100 mg daily. Clinico-radiological assessments were done prior to surgery using standard response assessment criteria.ResultsA total of 68 patients received POMT with a median age of 55 years (range: 34–73 years). Forty-eight (70%) were males, 29 (42%) had carcinoma tongue and majority (N = 52, 76%) had Stage IVA cancer. Mean duration of POMT administration was 30.45 days (standard deviation: 8.22). Thirty-seven (54%) patients had partial responses and another 23 (34%) had stable disease. Two (3%) had disease progression on POMT. Fifty-eight (85%) underwent surgery after POMT. Margin positive resection was seen in two patients. Half of the patients who received POMT did not experience any toxicity. Grade 3/4 toxicities were seen in four (6%) patients.ConclusionsPOMT is a feasible strategy worth considering in cases where there are prolonged waiting times to surgery.

Metronomic systemic PCm (paclitaxel, carboplatin + metronomic) neoadjuvant chemotherapy in head and neck cancer.

e18073 Background: Neoadjuvant chemotherapy (NACT) in head and neck cancers (HNC) with taxane, platinum, 5-FU (TPF) regimen is both toxic as well as difficult to use in resource-constrained settings. We used a novel combination of weekly chemotherapy and oral metronomic chemotherapy (OMCT) and assessed the efficacy and safety of this combination as NACT in locally advanced HNC patients. Methods: This is a retrospective analysis of prospectively maintained data. 56 patients with technically unresectable HNC received NACT with paclitaxel (80mg/m2) plus carboplatin (AUC2) - weekly schedule and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily, and erlotinib 150mg once daily) - PCm regimen. Patients were assessed clinically and radiologically after a minimum of six cycles for resectability. The radiological response was evaluated as per RECIST 1.1. We report the response rate, resectability, survival, and tolerance of this NACT regimen. Results: The median age of the patients was 41 years. Fifty-two patients (92.9%) were male. Buccal mucosa (60.7%) and oral tongue (17.9%) were the commonest sites of primary seen followed by alveolus (10.7%), the floor of mouth (5.4%), and larynx (5.4%). AJCC 2017 stage IVA and IVB disease were present in 64.3% and 35.7% of patients respectively. Edema up to zygoma (44.6%), high ITF involvement (19.7%), technically unresectable nodal disease (16.1%) and disease reaching up to vallecula (12.5%), or hyoid bone (5.4%), and nodal encasement (180-270 degree) of the internal carotid artery (1.8%) were the reasons for technical unresectability. The median number of NACT administered was six. The tumor showed partial response in 54 (96.4%) patients, 2 (3.6%) patients had stable disease and none of the patients had tumor progression. Surgery was planned in 47 (83.9%) patients after NACT, however due to logistic issues only 35 (62.5%) patients could undergo surgery. Pathological complete response was seen in 27 (48.21%) patients. After a median follow-up of 7.36 months, median PFS was not reached in the whole cohort and surgery group of patients, whereas it was 5.23 (95% CI, 4.08 -6.38) months in the non-surgery group. Median OS was not reached in our cohort. Common grade 3/4 toxicities (CTCAE 5.0) observed were oral mucositis in 6 (10.7%) patients, diarrhea in 4 (7.1%), and febrile neutropenia in 1 (1.7%) patients. Conclusions: Weekly scheduled PCm is an efficacious and well-tolerated regimen and can easily be administered in resource-constrained settings.

Phase III randomized control study evaluating adjuvant metronomic chemotherapy in locally advanced head and neck cancers post-radical chemoradiation (MACE-CTRT).

6073 Background: Locally advanced head and neck cancer treated with radical chemoradiation have unsatisfactory outcomes. Oral metronomic chemotherapy improves outcomes in comparison to maximum tolerated dose chemotherapy in the palliative setting. There is also limited evidence that it may do so in an adjuvant setting. Hence this randomised study was conducted. Methods: Patients of HN cancer with primary in oropharynx, larynx or hypopharynx, with PS 0-2 post radical chemoradiation with documented complete response were 1:1 randomised to either observation or oral metronomic adjuvant chemotherapy (MAC) for 18 months. MAC consisted of weekly oral methotrexate (15 mg/m2) and celecoxib (200 mg PO BD). The primary endpoint was OS and the overall sample size was 1038. The study had 3 planned interim analyses for efficacy and futility. Results: 137 patients were recruited and an interim analysis was done. The 3 year PFS in the observation arm was 67.1% (95% CI 53.8-77.3) and the same in the MAC arm was 62.5%(95%CI 49.4-73.1). The corresponding hazard ratio was 1.402 (95% CI 0.7393-2.66, P-value = 0.3). The 3 year OS in the observation arm was 77.3% (95% CI 64.4-86) and the same in the MAC arm was 64.1% (95%CI 51-74.5). The corresponding hazard ratio was 1.588 (95% CI 0.8734-2.886, P-value = 0.1). Any grade mucositis was seen in 30 patients (45.5%) in the MAC arm and 20 patients (28.2%) in the observation arm (P-value = 0.05). The rate of grade 3 or above mucositis was 7.6%(n = 5) in the MAC arm and 1.4%(n = 1) in the observation arm (P-value = 0.106). Conclusions: Both arms had similar OS. Hence observation post complete response post radical chemoradiation remains the standard of care. Clinical trial information: CTRI/2016/09/007315.

A retrospective analysis of patients administered neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin with oral metronomic chemotherapy (OMCT) in locally advanced borderline resectable/technically unresectable head and neck cancers.

6030 Background: Neoadjuvant chemotherapy with TPF though the standard is seldom used in India due to its adverse events rate. Two drug regimen of Paclitaxel and Carboplatin (PC) though favoured has inferior outcomes. Hence, we did an analysis to estimate the efficacy and adverse event rate of addition of 3 drug metronomic schedule to PC. Methods: Patients of locally advanced head and neck cancer referred from multidisciplinary board for neoadjuvant chemotherapy and unsuitable for TPF were selected for this analysis. These patients had received 2 drug regimen of intravenous PC with 3 drug regimen of weekly methotrexate 9 mg per m2, Celecoxib 200 mg twice daily, erlotinib 150 mg once daily all administered orally. All patients underwent a response assessment at 5-7 weeks post start of therapy and we're discussed in MDT for further treatment. Adverse events were recorded in accordance with CTCAE version 4.03 and response in accordance with RECIST version 1.1. PFS and OS were estimated with Kaplan Meier method. Results: 72 patients were identified with the median age being 45 (27-80) and M:F ratio (67:5). The indication for NACT were borderline resectability in all patients.. The response rate was 61.1% and grade 3 and above adverse event rate was 33.5%. A total number of 34 among 40 borderline resectable patients underwent surgery. The overall estimated PFS and OS were 18.5 (95%CI = 14.4-22.7) months and 18.05 (95%CI = 14.2-21.8) months respectively. The three most adverse events observed were grade 3 thrombocytopenia in 2 patients (2.8%), grade 3 aspartate aminotransferase (AST) derangement in 4 patients (5.6%) and grade 3 alanine aminotransferase (ALT) in 4 patients (5.6%). Conclusions: The 5 drug combination regimen is safe, tolerable and seems to have similar efficacy as a three drug TPF regimen.