Authors: Roshan James, Siddharth Vishwakarma, Indira V. Chivukula, Chetana Basavaraj, Ramakrishnan Melarkode, Enrique Montero, Pradip Nair

Date: 2012/08/01

Link: https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.21

Abstract:

Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, has been used extensively in many solid tumors and confers significant survival advantage. The antibody has limited skin toxicity and is generally well tolerated. Similar to other anti-EGFR therapies, patients may relapse a few months after treatment. In this study we show for the first time, the use of Nimotuzumab along with Sirolimus has synergistic effect on tumor inhibition as compared with the drugs used individually, in Nimotuzumab responsive and nonresponsive cell lines. In vitro studies prove that while Sirolimus (25 nmol/L) affects the signal downstream to mammalian target of rapamycin (mTOR), Nimotuzumab (83 nmol/L) downregulates pTYR, pMAPK and pSTAT3 by 40%, 20% and 30%, respectively. The combination, targeting these two different signaling hubs, may be associated with the synergistic inhibition observed. In vivo, the use of half human therapeutic equivalent doses for both the drugs substantially reduces tumors established in nude as well as severe combined immunodeficiency (SCID) mice by EGFR overexpressing A-431 cells. The drug combination reduces cell proliferation and the expression of signal transduction molecules. Treated tumors are better differentiated as compared with those established in the control mice. Tumor microarray demonstrates that Nimotuzumab and the combination groups segregate independently to the Sirolimus and the control treatment. The combination uniquely downregulated 55% of the altered tumor genes, extending beyond the typical pathways associated with Nimotuzumab and Sirolimus downstream pathways inhibition. These results would suggest that this nontoxic drug combination improves therapeutic benefit even in patients with low-EGFR expression and severely immunocompromised because of their current medication.

Authors: Suresh VS Attili, Dilip Pawar, Chinnababu Sunkavalli

Year: 2017

Link: https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e21635

Abstract:

• Background: Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. However when used without radiation, its always used in adjunct to chemotherapy. With encouraging results of other EGFR monoclonal antibodies as single agent therapies, we explored the possibility of using Nimotuzumab as single agent by which we could avoid chemo related side effects. In view of the limited options availability for subjects with PS 3 and more we thought of choosing this population for analysis of Nimotuzumab as single agent palliative therapy in PS 3 and above EGFR expressing tumors for safety and efficacy
• Methods: Details of the 38 subjects with pre-treated advanced refractory or progressive solid tumors having PS of more than 2 were evaluated. Nimotuzumab was administered weekly at 200 mg/m2 as single agent for 4 weeks (induction phase) and patients were stratified into those with improved PS and those without. The subjects without PS improvement were continued on the single agent and those with improvement were offered additional chemotherapy . Nimotuzumab could be continued beyond disease progression.

Authors: D. Pawar, S. Chaudhari, B. PMS Study Group

Year: 2017

Link: https://simul-europe.com/2017/mascc/Files/(dilippawar@hotmail.com)eP554%20POST%20MARKETING%20SURVEILLANCE%20OF%20NIMOTUZUMAB%20A.ppt.pdf

Abstract:

• Introduction: Nimotuzumab is approved for head and neck cancer in India and has few incidences of toxicityl. Anti EGFR are known to produce severe toxicities including grade III / IV rashes.
• Objectives: Present study is aimed to evaluate safety and tolerability of nimotuzumab in the real life clinical conditions.
• Methodology: Patients with head and neck cancer or any other tumour who were suitable for nimotuzumab therapy were included. All patients received 200mg nimotuzumab IV infusion weekly for six weeks along with SOC. All Patients who received the treatment were considered for the analysis.

Authors: Dilip Pawar, Suresh VS Attili, Chinnababu Sunkavalli

Year: 2017

Link: https://simul-europe.com/2017/mascc/Files/(dilippawar@hotmail.com)eP554%20POST%20MARKETING%20SURVEILLANCE%20OF%20NIMOTUZUMAB%20A.ppt.pdf

Abstract:

• Background: Head and neck Squamous Cell Cancer (HNSCC) have poor prognosis in recurrent and metastatic setting with limited treatment options. The treatment decision are predominantly driven by quality of life (QOL) issues, pharmaco-economics besides the survival and response rates. Present TWISTT analysis was based on the earlier “open labeled multicentric study of Nimotuzumab in head and neck cancers with chemotherapy and/or radiotherapy”, to evaluate the QOL outcomes
• Methods: The active part study was conducted between Nov 2007 and Jan 2009 followed by long term follow up. Patients received Nimotuzumab w at 200 mg/m2 / week along with RT or chemotherapy

Authors: B.S. Ajaikumar, K. Swamy, N. Radheshyam, S. Patil, H.P. Shashidhara, M.S.A. Vishweshwara, N.K. Rao, Y. Madhavi, N. Ravi, R. Bilimagga, R. Rao, D. Pawar

Year: 2017/09/09

Link: https://oncologypro.esmo.org/meeting-resources/esmo-2017-congress/An-Investigator-Initiated-Open-Label-Randomized-Controlled-Multicentric-Study-to-assess-the-Safety-and-Efficacy-of-Nimotuzumab-BIOMAb-EGFR-concurrent-with-Cisplatin-and-Radiotherapy-RT-in-histologically-documented-Squamous-Cell-Carci

Abstract:

• Background: EGFR inhibitors have proven to improve the efficacy of anticancer treatments in lung, colon, pancreas, or HNC. Results from studies show EGFR expression in cervical Ca to improve survival outcomes in the same. This study was designed to assess safety and efficacy of Nimotuzumab with concurrent cisplatin and RT in patients with Ca Cervix.
• Methods: In this open-label randomized controlled multicentric study 100 patients with histologically confirmed Ca Cervix were recruited over a 4 year period with an equal allocation of 1:1 for intervention (Standard arm- concurrent CTRT (Cisplatin 40mg/m2 weekly IV +RT) plus 200mg weekly BIOMAB IV (n = 50) on same day of cisplatin infusion) vs. standard arm only (n = 50). At 2 years data were available for 39 patients in the intervention arm and 35 patients in standard arm. The size of the lesion was documented using CT/PETCT at baseline. The response was analyzed using RECIST criteria at the following treatment every 3 months for subsequent 2 years. Toxicity was assessed using CTCAE v4 toxicity criteria.