@lmcp.ac.in
Assistant Professor, Department of Pharmacology
L.M. College Of Pharmacy
Pharmacoepidemiology, Pharmacoeconomics, Pharmacovigilance, Oncology Pharmacy Practice, Drug utilization.
Scopus Publications
Avinash Khadela, Kaivalya Megha, Vraj B Shah, Shruti Soni, Aayushi C Shah, Hetvi Mistry, Shelly Bhatt, and Manthan Merja
SAGE Publications
Antibody-drug conjugates (ADCs), combining the cytotoxicity of the drug payload with the specificity of monoclonal antibodies, are one of the rapidly evolving classes of anti-cancer agents. These agents have been successfully incorporated into the treatment paradigm of many malignancies, including non-small cell lung cancer (NSCLC). The NSCLC is the most prevalent subtype of lung cancer, having a considerable burden on the cancer-related mortality and morbidity rates globally. Several ADC molecules are currently approved by the Food and Drug Administration (FDA) to be used in patients with NSCLC. However, the successful management of NSCLC patients using these agents was met with several challenges, including the development of resistance and toxicities. These shortcomings resulted in the exploration of novel therapeutic targets that can be targeted by the ADCs. This review aims to explore the recently identified ADC targets along with their oncologic mechanisms. The ADC molecules targeting these biomarkers are further discussed along with the evidence from clinical trials.
Avinash Khadela, Bhavarth Dave, Yatvi Premal, Nishi Patel, and Devang Sadhwani
SAGE Publications
Background: Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Case: Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. Conclusion: In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
Rashi Shukla, Krupa Vyas, Avinash Khadela, Lalitkumar K. Vora, and Dharmendra Kumar Khatri
Elsevier
Manish P. Patel, Vaishnavi M. Oza, Hemangi B. Tanna, Avinash D. Khadela, Praful D. Bharadia, and Jayvadan K. Patel
Wiley
Prashantkumar Patel, Hemraj Singh Rajput, Khushboo Chavda, Smit Mistry, Sandesh Bhagat, Rajesh Hadia, Moinuddin Saiyed, and Avinash Khadela
SAGE Publications
Background and objectives Arthralgia, myalgia, and neuropathic pain are the most common side effects observed due to paclitaxel chemotherapy. The aim of this study was to investigate the prophylactic role, maintenance, remission, and re-occurrence of arthralgia, myalgia, and neuropathic pain post-gabapentin therapy. Methodology This study was conducted in the Department of Oncology, Dhiraj Hospital, Vadodara with a sample of 51 patients. Newly detected cancer patients who observed arthralgia, myalgia, and neuropathic pain due to paclitaxel were taken and a baseline pain assessment was done using the Common Terminology Criteria for Adverse Events (CTCAE) and painDETECT questionnaire. Gabapentin was given in the first cycle after symptoms appeared and prophylactic treatment was given in the subsequent three cycles and evaluation of pain was done post-gabapentin therapy to assess the symptomatic as well as prophylactic effect. Results At baseline, neuropathic pain score was 22.7 ± 3.6 which reduced to 0.01 ± 0.14 on subsequent follow-ups. Grade 2 arthralgia, myalgia, and neuropathic pain were more observed at baseline which reduces to Grade 0 in the third cycle. The difference in baseline and post-gabapentin therapy was statistically analyzed by conducting t-test which showed p-value <0.00001 and t-value was less than −2 which indicated a statistically significant result. Conclusion This study shows that gabapentin reduces neuropathic pain. Prophylactic usage of gabapentin was highly effective at bringing about quick pain relief when compared to symptomatic treatment. In further follow-ups, it was noted that gabapentin maintained the impact throughout the cycles.
Deval K. Rana, Tithi S. Shah, Mansi H. Rohit, Nayankumar H. Patel, Avinash D. Khadela, Yaksh P. Oza, and Jigna K. Padhiyar
Wiley
AbstractBackgroundThe present epidemic of dermatophytosis in India is marked by an increase in chronic, recurrent and disseminated cases. A combination of oral itraconazole and topical luliconazole is being increasingly utilised by dermatologists in India. The superiority of this combination is not supported by robust clinical trial data.ObjectiveWe conducted this randomised, open‐label, two arms, parallel assignment intervention trial between November 2022 and May 2023 to determine the superiority of topical 1% Luliconazole over bland emollient as adjuvant to systemic Itraconazole therapy in the management of dermatophytosis.MethodIn this study, 135 patients of either sex were randomised to two study cohorts. Major exclusions being concomitant medical illness, use of concomitant medication and substance abuse. Participants were randomly assigned to receive topical bland emollient, (Cohort I, n = 67) or topical luliconazole, (Cohort II, n = 68). Both cohorts received oral itraconazole 200 mg/day (100 mg BID) and levocetirizine 5 mg twice a day as a systemic regime. Clinical and mycological cure at the end of 6 weeks and clinical relapse among cure patients during 10‐week follow‐up were observed.ResultsThe cure rates for Cohorts I and II at 6 weeks were 50 (74.62%) and 56 (82.35%), (p = .46), respectively. During the 4‐week follow‐up period, clinical relapses were observed in 16 (32%) of the 50 patients in Cohort I and 12 (21.43%) of the 56 patients in Cohort II (p = .18). Luliconazole cohort shows a significantly higher medical cost (p < .05).ConclusionOur study shows a similar cure rate and relapse rate for patients receiving topical Luliconazole versus topical bland emollient as an adjuvant to the systemic itraconazole regime.
Kashvi C. Shah, Nishi S. Patel, Paritosh Vasani, Avinash Khadela, Vivek P. Chavda, and Lalitkumar Vora
Springer Science and Business Media LLC
Abstract Background Dyskinesia is a movement disorder categorized by involuntary movement of muscle. Although dyskinesia can be brought on by taking medications, it can also be a symptom of a variety of diseases. Antiepileptic drug-induced involuntary movements have been well researched. Rare reports have been made for dyskinesia, a type of dystonia caused by phenytoin. The mechanism of its occurrence must be succinctly studied. Case presentation A 53-year-old Asian patient taking phenytoin (100 mg twice daily) experienced symptoms of perioral muscle involuntary movement, impaired speech, and generalized tremors and was admitted to the hospital. Brain magnetic resonance imaging showed significant development of encephalomalacia and porencephaly. The serum phenytoin levels were in the toxic range (33 g/ml). These were suggestive of phenytoin-induced dyskinesia. Levetiracetam and clonazepam were initiated, and the patient showed significant improvement in the symptoms. Conclusion This case presented a substantial reference value for the differential diagnosis and treatment prognosis of phenytoin-induced dyskinesia. The phenytoin-induced dyskinesia in this patient was successfully reversed with prompt identification and treatment. According to the case study’s findings, such people may benefit from periodic therapeutic drug monitoring.
Avinash Khadela, Bhavin Vyas, Mustakim Mansuri, Dipen Sureja, and Kunjan Bodiwala
Springer Science and Business Media LLC
Abstract 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.
Vivek Chavda, Kelsee K. Zajac, Jenna Lynn Gunn, Pankti Balar, Avinash Khadela, Dixa Vaghela, Shruti Soni, Charles R. Ashby, and Amit K. Tiwari
Wiley
BACKGROUND
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The incidence of HCC is affected by genetic and non-genetic factors. Genetically, mutations in the genes, tumor protein P53 (TP53), catenin beta 1 (CTNNB1), AT-rich interaction domain 1A (ARIC1A), cyclin dependent kinase inhibitor 2A (CDKN2A), mannose 6-phosphate (M6P), smooth muscle action against decapentaplegic (SMAD2), retinoblastoma gene (RB1), cyclin D, antigen presenting cells (APC), AXIN1, and E-cadherin, have been shown to contribute to the occurrence of HCC. Non-genetic factors, including alcohol consumption, exposure to aflatoxin, age, gender, presence of hepatitis B (HBV), hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD), increase the risk of HCC.
RECENT FINDINGS
The severity of the disease and its occurrence vary based on geographical location. Furthermore, men and minorities have been shown to be disproportionately affected by HCC, compared with women and non-minorities. Ethnicity has been reported to significantly affect tumorigenesis and clinical outcomes in patients diagnosed with HCC. Generally, differences in gene expression and/or the presence of comorbid medical diseases affect or influence the progression of HCC. Non-Caucasian HCC patients are significantly more likely to have poorer survival outcomes, compared to their Caucasian counterparts. Finally, there are a number of factors that contribute to the success rate of treatments for HCC.
CONCLUSION
Assessment and treatment of HCC must be consistent using evidence-based guidelines and standardized outcomes, as well as international clinical practice guidelines for global consensus. Standardizing the assessment approach and method will enable comparison and improvement of liver cancer research through collaboration between researchers, healthcare providers, and advocacy groups. In this review, we will focus on discussing epidemiological factors that result in deviations and changes in treatment approaches for HCC.
Vivek P. Chavda, Vrashabh V. Sugandhi, Chandrakantsing V. Pardeshi, Rahul Jaywant Patil, Mit Joshi, Bhoomika Patel, Avinash Khadela, Rajashri Bezbaruah, Bedanta Bhattacharjee, Pankti C. Balar,et al.
Elsevier BV
Avinash Khadela, Shruti Soni, Kaivalya Megha, Shivam Bhagat, and Vivek Chavda
MDPI AG
The SARS-CoV-2 virus has caused a catastrophic impact on the world for the past 3 years. The virus has now returned with the emergence of the Omicron (B.1.1.529) variant. Within two months of its first emergence in South Africa, Omicron became the most dominating SARS-CoV-2 variant around the world, being the cause of the majority of new infections at present. Omicron has presented with the greatest transmission rate of all the previous variants despite the presence of mass vaccinations and acquired immunity. Several monoclonal antibodies and mRNA vaccines have failed to produce desired effects owing to a large number of mutations present in the Omicron variant. The introduction of the booster dose of the present mRNA vaccines has proven to be a great addition to the therapeutic armamentarium against the Omicron variant. Immunocompromised patients including the elderly, cancer patients, organ transplant recipients, and those with multiple comorbidities have been at a greater risk of developing severe diseases since the pre-Omicron era. The emergence of Omicron again raised a threat against this population. The protection from severe disease and mortality rates through the utilization of multiple immunizations and monoclonal antibodies has been controversial in this subgroup of patients. Thus, designing large-scale studies to evaluate the effectiveness of monoclonal antibodies and vaccines in these patients can provide evidence-based recommendations to improve survival in this population. This article attempts to discuss the different subvariants of Omicron, differences in the mutational aspects along with the particular focus on the consequences of the Omicron infection in the elderly population with diverse comorbidities.
Elena Lygina, Daria Morgacheva, Avinash Khadela, Humzah Postwala, Yesha Shah, and Yulia Dinikina
Spandidos Publications
Medulloblastoma (MB) is one of the most common pediatric malignant tumors arising from the central nervous system with an unknown etiology and variable prognosis. Relapsed or refractory MB in pediatric patients after intensive anticancer therapy (chemo-, radiotherapy) is associated with treatment resistance and poor survival prognosis. Metronomic chemotherapy in combination with mTOR inhibitors may have advantages due to an alternate mechanism of cytotoxicity and a favourable adverse effects profile. Furthermore, it is considered to be a prospective anticancer regimen regardless of the presence/absence of molecular targets. The present study reported a successful result of this treatment option with optimal tolerability in relapsed MB in a pediatric male patient and highlighted the advantages for a selected group of patients.
Avinash Khadela, Humzah Postwala, Deval Rana, Hetvi Dave, Ketan Ranch, and Sai H. S. Boddu
Springer Science and Business Media LLC
Vivek P. Chavda, Lakshmi Vineela Nalla, Pankti Balar, Rajashri Bezbaruah, Vasso Apostolopoulos, Rajeev K. Singla, Avinash Khadela, Lalitkumar Vora, and Vladimir N. Uversky
MDPI AG
As the world’s most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of treatment to eradicate invasive disease, the current chemotherapy regimen faces significant challenges associated with chemotherapy-induced side effects and the development of drug resistance. Therefore, serious concerns regarding current chemotherapeutics are pressuring researchers to develop alternative therapeutics with better efficacy and safety. Due to their extremely biocompatible nature and efficient destruction of cancer cells via numerous mechanisms, phytochemicals have emerged as one of the attractive alternative therapies for chemotherapeutics to treat breast cancer. Additionally, phytofabricated nanocarriers, whether used alone or in conjunction with other loaded phytotherapeutics or chemotherapeutics, showed promising results in treating breast cancer. In the current review, we emphasize the anticancer activity of phytochemical-instigated nanocarriers and phytochemical-loaded nanocarriers against breast cancer both in vitro and in vivo. Since diverse mechanisms are implicated in the anticancer activity of phytochemicals, a strong emphasis is placed on the anticancer pathways underlying their action. Furthermore, we discuss the selective targeted delivery of phytofabricated nanocarriers to cancer cells and consider research gaps, recent developments, and the druggability of phytoceuticals. Combining phytochemical and chemotherapeutic agents with nanotechnology might have far-reaching impacts in the future.
Manish P. Patel, Rutvi V. Patel, Mehul R. Chorawala, Avinash K. Khadela, Sandip P. Dholakia, and Jayvadan K. Patel
CRC Press
Avinash Khadela, Shruti Soni, and Kaivalya Megha
Medknow
Avinash Khadela, Sagar Popat, Jinal Ajabiya, Disha Valu, Shrinivas Savale, and Vivek P. Chavda
Wiley
Vivek P Chavda, Avinash Khadela, Yasha Shah, Humzah Postwala, Pankti Balar, and Lalit Vora
Ivyspring International Publisher
Cancer diagnosis and management have been a slow-evolving area in medical science. Conventional therapies have by far proved to have various limitations. Also, the concept of immunotherapy which was thought to revolutionize the management of cancer has presented its range of drawbacks. To overcome these limitations nanoparticulate-derived diagnostic and therapeutic strategies are emerging. These nanomaterials are to be explored as they serve as a prospect for cancer theranostics. Nanoparticles have a significant yet unclear role in screening as well as therapy of cancer. However, nanogels and Photodynamic therapy is one such approach to be developed in cancer theranostics. Photoactive cancer theranostics is a vivid area that might prove to help manage cancer. Also, the utilization of the quantum dots as a diagnostic tool and to selectively kill cancer cells, especially in CNS tumors. Additionally, the redox-sensitive micelles targeting the tumor microenvironment of the cancer are also an important theranostic tool. This review focuses on exploring various agents that are currently being studied or can further be studied as cancer theranostics.
Avinash Khadela, Vivek P. Chavda, Humzah Postwala, Ramya Ephraim, Vasso Apostolopoulos, and Yesha Shah
MDPI AG
Immune checkpoints are unique components of the body’s defense mechanism that safeguard the body from immune responses that are potent enough to harm healthy body cells. When proteins present on the surface of T cells recognize and bind to the proteins present on other tumor cells, immune checkpoints are triggered. These proteins are called immunological checkpoints. The T cells receive an on/off signal when the checkpoints interact with companion proteins. This might avert the host’s immune system from eliminating cancer cells. The standard care plan for the treatment of non-small cell lung cancer (NSCLC) has been revolutionized with the use of drugs targeting immune checkpoints, in particular programmed cell death protein 1. These drugs are now extended for their potential to manage SCLC. However, it is acknowledged that these drugs have specific immune related adverse effects. Herein, we discuss the use of immune checkpoint inhibitors in patients with NSCLC and SCLC, their outcomes, and future perspectives.
Avinash Khadela, Yesha Shah, Priya Mistry, Kunjan Bodiwala, and Avinash CB
SAGE Publications
The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted.
Avinash Khadela, Vivek P. Chavda, Shruti Soni, Kaivalya Megha, Aanshi J. Pandya, and Lalitkumar Vora
MDPI AG
Triple-negative tumors are progressively delineating their existence over the extended spectrum of breast cancers, marked by intricate molecular heterogeneity, a low overall survival rate, and an unexplored therapeutic approach. Although the basal subtype transcends the group and contributes approximately 80% to triple-negative breast cancer (TNBC) cases, the exceptionally appearing mesenchymal and luminal androgen receptor (LAR) subtypes portray an unfathomable clinical course. LAR with a distinct generic profile frequently metastasizes to regional lymph nodes and bones. This subtype is minimally affected by chemotherapy and shows the lowest pathologic complete response. The androgen receptor is the only sex steroid receptor that plays a cardinal role in the progression of breast cancers and is typically overexpressed in LAR. The partial AR antagonist bicalutamide and the next-generation AR inhibitor enzalutamide are being assessed in standard protocols for the mitigation of TNBC. There arises an inevitable need to probe into the strategies that could neutralize these androgen receptors and alleviate the trajectory of concerning cancer. This paper thus focuses on reviewing literature that provides insights into the anti-androgenic elements against LAR typical TNBC that could pave the way for clinical advancements in this dynamic sphere of oncology.
Avinash Khadela, Yesha Shah, Priya Mistry, Mustakim Mansuri, Dipen Sureja, and Kunjan Bodiwala
Springer Science and Business Media LLC
Avinash Khadela, Shruti Soni, Kaivalya Megha, Aayushi C. Shah, Aanshi J. Pandya, Nirjari Kothari, Ishika Shah, and C. B. Avinash
Springer Science and Business Media LLC
Avinash Khadela, Shruti Soni, Aayushi C. Shah, Aanshi J. Pandya, Kaivalya Megha, Nirjari Kothari, and Avinash CB
Springer Science and Business Media LLC
Vivek P. Chavda, Shailvi Soni, Lalitkumar K. Vora, Shruti Soni, Avinash Khadela, and Jinal Ajabiya
MDPI AG
An unheard mobilization of resources to find SARS-CoV-2 vaccines and therapies has been sparked by the COVID-19 pandemic. Two years ago, COVID-19’s launch propelled mRNA-based technologies into the public eye. Knowledge gained from mRNA technology used to combat COVID-19 is assisting in the creation of treatments and vaccines to treat existing illnesses and may avert pandemics in the future. Exploiting the capacity of mRNA to create therapeutic proteins to impede or treat a variety of illnesses, including cancer, is the main goal of the quickly developing, highly multidisciplinary field of biomedicine. In this review, we explore the potential of mRNA as a vaccine and therapeutic using current research findings.