Impact of cetuximab plus cisplatin alone and cetuximab plus cisplatin and paclitaxel regimen on humanistic outcome in head and neck cancer.

BACKGROUND: The prevalence of head and neck cancer (HNC) is increasing rapidly, and the prognosis is poor in the advance stage. For the patient suffering from advance stage HNC, the improvement in quality of life and decrease mortality remain as the mainstay of treatment. The aim was to assess the change in quality-adjusted life-years (QALYs) in recurrent or metastatic HNC patients receiving cetuximab plus cisplatin and cetuximab plus cisplatin-paclitaxel. METHODS: It was a single-centric prospective-observational study. Patients were divided into two cohorts based on the chemotherapy regimens they were prescribed. Patients in cohort 1 were prescribed with cetuximab and cisplatin and in cohort 2 were prescribed with cetuximab, cisplatin, and paclitaxel. The QALYs were the primary outcome of the study, and it was calculated using EQ-5D-5L instrument. Patients were followed until the completion of the therapy, i.e., six chemotherapy cycles. The statistical analysis was carried out using SPSS for descriptive and inferential analysis. RESULTS: Amongst 175 patients screened, 100 patients were enrolled which further distributed in cohorts 1 and 2 equally. The mean QALYs were 0.016 and 0.017 at the time of diagnosis, i.e., before initiation of chemotherapy for patients in cohorts 1 and 2, respectively. At every chemotherapy cycle, the QALYs were calculated. After the completion of six chemotherapy cycles, the mean QALYs were 0.029 and 0.032 for patients in cohorts 1 and 2, respectively. CONCLUSION: The three-drug therapy consisting of cetuximab, cisplatin, and paclitaxel has shown significant improvement in patients' QALYs compared to two-drug regimens of cetuximab and cisplatin. Thus, if the therapy consisted of three-drug regimen is used instead of two-drug regimen, it will have a positive impact on humanistic outcome in recurrent or metastatic HNC patients.

A review of efficacy and safety of cetuximab and bevacizumab-based monoclonal antibodies in head and neck cancer.

A combination of monoclonal antibodies prescribed along with the conventional standard of care has a potential to provide significant improvement in patients suffering from head and neck cancer. This combination has also shown a significant decrease in toxicities and improved overall quality of life. Cetuximab acts by inhibiting the human epidermal growth factors as its overexpression in head and neck tumours that are responsible for treatment failure, resistance, and metastasis. Whereas, bevacizumab acts by inhibiting the vascular endothelial growth factor since its overexpression leads to induction of tumour angiogenesis. Current research has not shown any remarkable beneficial effect in disease outcomes. Thus, the addition of these monoclonal antibodies to the standard regimen for head and neck cancer can be considered a prospect that might be beneficial. Cetuximab has already been included as an option under special recommendations in recurrent/metastatic head and neck cancer by NCCN in a platinum-based regimen as well as in combination with radiation therapy. This review outlines the applicability of cetuximab and bevacizumab in the treatment of head and neck cancer as well as the clinical trials performed that give an idea about the efficacy and safety of these monoclonal antibodies. Based upon the literature reviewed, it can be deduced that immunotherapy is to be adopted and different targets are to be explored in it in order to combat head and neck cancer. Currently, immunotherapeutic drugs of two major targets have been discussed. These agents are even effective in combination with other therapeutic modalities that are not being able to achieve desirable outcomes due to issues such as resistance and toxicities. Thus, newer targets as well as newer agents acting on established targets are to be explored in order to improve disease outcomes.

In-silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV-2.

Due to alarming outbreak of pandemic COVID-19 in recent times, there is a strong need to discover and identify new antiviral agents acting against SARS CoV-2. Among natural products, lignan derivatives have been found effective against several viral strains including SARS CoV-2. Total of twenty-seven reported antiviral lignan derivatives of plant origin have been selected for computational studies to identify the potent inhibitors of SARS CoV-2. Molecular docking study has been carried out in order to predict and describe molecular interaction between active site of enzyme and lignan derivatives. Out of identified hits, clemastatin B and erythro-strebluslignanol G demonstrated stronger binding and high affinity with all selected proteins. Molecular dynamics simulation studies of clemastin B and savinin against promising targets of SARS CoV-2 have revealed their inhibitory potential against SARS CoV-2. In fine, in-silico computational studies have provided initial breakthrough in design and discovery of potential SARS CoV-2 inhibitors.

Simultaneous Estimation of Six Nitrosamine Impurities in Valsartan Using Liquid Chromatographic Method.

BACKGROUND: Nitrosamine impurities are potent carcinogens in animals and probable carcinogens in humans. There is a need for effective analytical methods to detect and identify various nitrosamine impurities, and to develop rapid solutions to ensure the safety and quality of the drugs. OBJECTIVE: A liquid chromatographic method was developed for estimation of six nitrosamine impurities in valsartan. METHODS: The developed method employed: a C18 (250 × 4.6 mm, 5 µm) column as a stationary phase; a combination of acetonitrile, water (pH 3.2 adjusted with formic acid), and methanol with gradient elution as mobile phase; and 228 nm as the detection wavelength. The developed method was validated as per International Conference on Harmonization Q2(R1) guidelines. The method was successfully applied to estimate six nitrosamine impurities in valsartan API (active pharmaceutical ingradient) and formulation (tablets). RESULTS: The method was able to separate each impurity and valsartan with resolved and sharp peaks. Results indicated that the developed method is linear in selected ranges (coefficient of regressions >0.9996), precise (RSD <2%), accurate (recovery in a range of 99.02-100.16%), sensitive (low detection and quantitation limits), and specific for estimation of each impurity in valsartan. Assay results were in agreement with the spiked amount of each impurity. CONCLUSION: The developed method can be applied for simultaneous estimation of six nitrosamine impurities in valsartan raw material, tablets, and fixed dose combination at very low levels. HIGHLIGHTS: Development, validation, and application of a HPLC method for the estimation of six nitrosamine impurities in valsartan API and formulation samples.

A decennary update on applications of metal nanoparticles (MNPs) in the synthesis of nitrogen- and oxygen-containing heterocyclic scaffolds.

Heterocycles have been found to be of much importance as several nitrogen- and oxygen-containing heterocycle compounds exist amongst the various USFDA-approved drugs. Because of the advancement of nanotechnology, nanocatalysis has found abundant applications in the synthesis of heterocyclic compounds. Numerous nanoparticles (NPs) have been utilized for several organic transformations, which led us to make dedicated efforts for the complete coverage of applications of metal nanoparticles (MNPs) in the synthesis of heterocyclic scaffolds reported from 2010 to 2019. Our emphasize during the coverage of catalyzed reactions of the various MNPs such as Ag, Au, Co, Cu, Fe, Ni, Pd, Pt, Rh, Ru, Si, Ti, and Zn has not only been on nanoparticles catalyzed synthetic transformations for the synthesis of heterocyclic scaffolds, but also provide an inherent framework for the reader to select a suitable catalytic system of interest for the synthesis of desired heterocyclic scaffold.

A Review on DNA Repair Inhibition by PARP Inhibitors in Cancer Therapy.

The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells. Current clinical data shows the role of PARP inhibitors is not restricted to BRCA mutations but also effective in HR dysfunctions related tumors. Therefore, investigation in this area could be very helpful for future therapy of cancer. This review gives detail information on the role of PARP in DNA damage repair, the role of PARP inhibitors and chemistry of currently available PARP inhibitors.

Synthesis of some novel pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives as potential antimicrobial agent.

OBJECTIVES: The aim of the present work was to synthesize a novel series of pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives and evaluate their in vitro antimicrobial activity. METHODS: Cyclization of an ortho-amino ester of 1-(2,4-dinitrophenyl)pyrazole with various aliphatic/aromatic nitriles under different reaction conditions such as conventional and microwave assisted synthesis, provided pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives. All the synthesized compounds were evaluated in vitro for their antimicrobial activity against selected bacteria and fungi by agar well diffusion method. RESULTS: All newly synthesized compounds were characterized using spectral and elemental analysis. Compounds 2e, 2f, and 2g showed significant antimicrobial activity as compared to standard drugs used. CONCLUSION: The newly synthesized compounds could be useful templates for the design and optimization of more active analogs as a possible antimicrobial agent.