Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

Formulation and characterization of starch-based novel biodegradable edible films for food packaging.

Petroleum-based plastics were widely used as packaging materials. However, plastic materials were not reusable and biodegradable, causing a severe negative impact on the environment. Edible films can be a suitable alternative to plastic films, particularly in food packaging. This research work prepared edible films containing blends of cornstarch, arrowroot powder, refined wheat flour, vinegar, and glycerol. Arrowroot powder added strength and nutritional value to the films. Glycerol, as a plasticiser, improved the flexibility of films. The combination of vinegar and glycerol increased the film's strength. The characteristic properties of prepared films, like thickness, bursting strength, moisture content, transparency, water-solubility, water vapour permeability, tensile strength, elongation, and Young's modulus, were analysed. The thermal stability of the films was evaluated by thermogravimetric analysis. The films were characterised by FTIR spectroscopy, and their surface morphology was analysed by scanning electron microscopy. The prepared films exhibited excellent properties suitable for food packaging. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05803-2.

Validation of the Onco-MPI in predicting short-term mortality in older Indian patients with cancer.

INTRODUCTION: The number of older patients with cancer is increasing exponentially worldwide, and a similar trend has also been noted in India. The Multidimensional Prognostic Index (MPI) strongly correlates the presence of individual comorbidities with mortality, and the Onco-MPI prognosticates patients accurately for overall mortality. However, limited studies have evaluated this index in patient populations beyond Italy. We evaluated the performance of the Onco-MPI index in predicting mortality in older Indian patients with cancer. MATERIALS AND METHODS: This observational study was conducted between October 2019 and November 2021 in the Geriatric Oncology Clinic at Tata Memorial Hospital in Mumbai, India. The data of patients aged ≥60 years with solid tumors who underwent a comprehensive geriatric assessment was analysed. The study's primary aim was to calculate the Onco-MPI for patients in the study and correlate it with one-year mortality. RESULTS: A total of 576 patients aged ≥60 years were included in the study. The median age (range) of the population was 68 (60-90) years, and 429 (74.5%) were male. After a median follow-up of 19.2 months, 366 (63.7%) patients had died. The proportion of patients classified as low risk (0-0.46), moderate risk (0.47-0.63) and high risk (0.64-1.0) were 38% (219 patients), 37% (211 patients) and 25% (145 patients), respectively. There was a significant difference in one-year mortality rates between the low-risk patients compared to medium and high-risk patients (40.6% vs 53.1% vs 71.7%; p < 0.001). DISCUSSION: The current study validates the Onco-MPI as a predictive tool for estimating short-term mortality in older Indian patients with cancer. Further prospective studies need to build on this index to obtain a score with greater discrimination in the Indian population.

PENS approach for breaking bad news in the oncology outpatient setting: a real-world report.

PURPOSE: Breaking bad news (BBN) is a vital part of oncology practice. We conducted this study to assess an abbreviated PENS protocol [Patient preference, Explanation, Next appointment, and Support] for BBN in oncology outpatient (OP) settings. METHODS: This observational study was conducted in a university teaching hospital, including cancer patients who were unaware of their condition and willing to discuss their disease status. The duration of BBN was the primary outcome. After the BBN session, patients filled a validated questionnaire; response scores of ≤ 13 were classified as content with BBN. RESULTS: Fifty patients (mean age 53.7 years, range 28-76) were included in the study. The average duration of BBN was 6.1 (range 2-11) min. Assessed by the response score sum, 43 (86%) patients were satisfied with BBN. Only three (6%) of the discontented patients felt that the BBN duration was too short. Most (94%) of patients reported that they understood the information imparted during the BBN session. After the session, 36 (72%) patients admitted to either feeling the same or reassured compared to before the session. The oncologists also were comfortable with PENS. CONCLUSIONS: The PENS approach is a practical method for BBN, especially when the oncologists have higher OP workloads. More extensive trials are required to validate the protocol in other settings. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2021/07/034707).

Feasibility of Delivering High-Dose Methotrexate in Adolescent and Adult All Patients: A Retrospective Study.

Introduction HD-MTX is a key drug in the treatment protocols for ALL. The regimen needs to be administered with appropriate supportive measures and serum methotrexate level monitoring. A limited testing strategy is relevant in resource constraint settings since it allows a shorter duration of hospitalization. We report our experience with this strategy and its impact on the patient safety outcomes. Methods This is a retrospective study of all patients ≥ 15 years of age with newly diagnosed ALL or Lymphoblastic lymphoma (LBL) who were administered HDMTX (part of BFM-90 ALL protocol) at our institute between March 2013 to November 2013.The medical records were reviewed for clinical characteristics, disease-related details, HDMTX dose and cycles administered, leucovorin rescue and toxicities. Results A total of 423 cycles of HD-MTX were administered to 106 patients during the study period. The median duration for completion of all 4 cycles of HDMTX was 53 (IQR 49-60) days. The grade 3 or higher toxicities were anemia in 9.6%, neutropenia 19.4%, febrile neutropenia 5.7%, thrombocytopenia 4.4% and mucositis in 0.7%. There was statistically significant correlation between the levels at 42 h (≤ 1 mmol/L vs > 1 mmol/L) and toxicity- anemia, FN and mucositis observed more in the late clearance group. With limited sampling strategy whereby if the 42- hour level MTX level are < 1 mmol/L, 57% of patients could be discharged early. Conclusion HD-MTX can be safely administered to adolescent and adult ALL patients. A limited methotrexate level monitoring is a safe strategy that can optimize the resources better.

Clinical Profile and Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer With Brain Metastases: Real-World Experience.

PURPOSE: There are sparse data in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases from real-world settings, especially where access to newer targeted therapies is limited. METHODS: This was a single institution, retrospective cohort study of patients with HER2-positive breast cancer diagnosed between January 2013 and December 2017 to have brain metastases and treated with any HER2-targeted therapy. The main objectives were to estimate progression-free survival (PFS) and overall survival (OS) from the time of brain metastases. RESULTS: A total of 102 patients with a median age of 52 (interquartile range, 45-57) years were included, of whom 63 (61.8%) had received one line and 14 (13.7%) had received two lines of HER2-targeted therapies before brain metastasis, 98 (96.1%) were symptomatic at presentation, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions, and 43 (49.4%) had ≥ 5 lesions. Local treatment included surgical resection in nine (8.9%) and radiotherapy in all (100%) patients. The first HER2-targeted therapy after brain metastasis was lapatinib in 71 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in three (2.9%), trastuzumab emtansine in four (3.9%), and intrathecal trastuzumab in five (4.9%) patients. At a median follow-up of 13.9 months, the median PFS and OS were 8 (95% CI, 6.2 to 9.8) months and 14 (95% CI, 10.8 to 17.2) months, respectively, with a 2-year OS of 25% (95% CI, 16.7 to 34.4). The median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95% CI, 7.3 to 10.7) months. CONCLUSION: There was a substantial clinical benefit of local and systemic therapy in patients with brain metastases and HER2-positive disease in a real-world setting with limited access to newer HER2-targeted drugs.

Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma: an open-label, parallel-group, non-inferiority, randomised, phase 3 trial.

BACKGROUND: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. METHODS: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m2 methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m2 intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. FINDINGS: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6-12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615-0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7-12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616-0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01). INTERPRETATION: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible. FUNDING: Tata Memorial Center Research Administration Council. TRANSLATIONS: For the Hindi, Marathi, Gujarati, Kannada, Malayalam, Telugu, Oriya, Bengali, and Punjabi translations of the abstract see Supplementary Materials section.