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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Erlotinib appears to be generally well tolerated by patients, with rash and diarrhea proving to be the main side effects which occur in 75% of patients. Other common side effects include GI disturbances, depression, neuropathy, headache, and fatigue. Rarer side effects include hepatic failure, and very rarely inflammation or puncture of the cornea, GI perforation, and bleeding, all of which could be associated with a general down-regulation of EGFR. Stephens-Johnson syndrome, and toxic epidermal necrosis may also occur. The manufacturer advises to avoid in breastfeeding, and contraception should be used during and for at least two weeks after treatment.
Hepatocellular Carcinoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Daniel H. Palmer, Philip J. Johnson
A number of studies have explored sorafenib in combination with other agents based on rational pre-clinical data. Pre-clinical models suggest that EGFR signaling is a pre-requisite for angiogenesis in HCC via up-regulation of VEGF.86 A phase II trial has investigated the combination of bevacizumab with erlotinib, with an objective response rate of 25 per cent (including one complete response), median progression-free survival of 9 months, and median survival 15.6 months.87 However, a randomized phase III trial of erlotinib in combination with sorafenib reported no significant survival benefit and greater toxicity compared with sorafenib alone.88 There is also pre-clinical evidence of synergy between doxorubicin and raf inhibition. In a vascular endothelial model, resistance to doxorubicin is, at least in part, mediated via FGF-mediated raf-dependent survival signals, and can be overcome by inhibition of raf, providing rationale for combining doxorubicin with sorafenib or inhibitors of FGFR such as brivanib.89 A randomized phase II study has investigated the combination of sorafenib and doxorubicin compared to doxorubicin alone.90 The overall survival in the combination arm was more than double the control arm (13.7 months compared to 6.5 months, HR 0.45). However, these data were not reproduced in the phase III trial, which reported no survival benefit and, again, additional toxicity, for the addition of doxorubicin to sorafenib.91
Trial Designs for Rare Diseases and Small Samples in Oncology
Published in Susan Halabi, Stefan Michiels, Textbook of Clinical Trials in Oncology, 2019
Robert A. Beckman, Cong Chen, Martin Posch, Sarah Zohar
Seven clinical trials evaluating the erlotinib dose in adults have been gathered (Table 15.1) for the computation of the overall dose-toxicity relationship. The method proposed by Zohar et al., described above, can be computed with the R package “dfped” [12] as follows:
EGFR-mutant NSCLC: monitoring the molecular evolution of tumors in 2022
Published in Expert Review of Anticancer Therapy, 2022
Nicolas Girard, Clémence Basse
Second, it is important to clinically differentiate patients with rapid multi-site progression that warrants switch of the systemic treatment, and those with slow or oligo-site progression that could benefit from exclusive locoregional ablative treatment (surgery, radiotherapy, radiofrequency) with the continuation of TKI beyond progression defined by RECIST [3]. Similarly, it is essential to perform dedicated brain imaging to monitor exclusive central nervous system progression that may remain sensitive to TKI and are accessible to stereotactic brain radiotherapy, particularly if cerebral magnetic resonance imaging confirms the unique or oligo-metastatic and meningitis-free nature of the progression. In this setting, continuation of the TKI beyond progression is standard. The prospective ASPIRATION study [19] described this clinical situation in a cohort of 207 EGFR-mutant NSCLCs treated with erlotinib; 36 (17%) had to discontinue treatment before progression, 78 (38%) changed treatment at progression, and 93 (45%) continued erlotinib beyond RECIST progression. Overall survival for the cohort was 30.1 months. For patients who continued erlotinib beyond progression, it was 33.6 months. In the most recent clinical trials conducted with EGFR TKIs, treatment beyond progression was delivered in more than 70% of patients, for median duration ranging from 2 to 4 months [20].
Development of asolectin-based liposomal formulation for controlled and targeted delivery of erlotinib as a model drug for EGFR monotherapy
Published in Journal of Liposome Research, 2022
Snehal Pardeshi, Amrendra Tiwari, Uday Titame, Pankaj K Singh, Pavan Kumar Yadav, Manish K. Chourasia
Erlotinib, an EGFR tyrosine kinase inhibitor, belonging to BCS class II drug, has been approved by USFDA and marketed for the management of pancreatic cancer and metastatic non-small cell lung cancer (NSCLC). The tablet formulation of erlotinib is commercially available with a dose of 25 mg per tablet (Segaert and Cutsem 2005). It has been reported by Ranson et al. (2010) that oral formulation of erlotinib cannot be preferred with patients having serious gastrointestinal problems, vomiting, and abdominal pain. Consequently, in the recent time, there has been an upsurge of interest in the development of newer carrier systems for the delivery of this chemotherapeutic agent. Amongst various carrier systems, liposomes have demonstrated superiority especially in terms of industrial development and scalability. Liposomes are self-assembling concentric spherical vesicles with size broadly varies from 20 nm to 10 μm (Starling et al.2006, Hua and Wu 2013). Liposomes possess the capability to function as drug carriers for both hydrophilic and lipophilic moiety that lead to a controlled release effect (Pathak et al.2012, Daraee et al.2016).
Multifunctional magnetic nanoparticles for MRI-guided co-delivery of erlotinib and L-asparaginase to ovarian cancer
Published in Journal of Microencapsulation, 2022
Seraj Mohaghegh, Ali Tarighatnia, Yadollah Omidi, Jaleh Barar, Ayuob Aghanejad, Khosro Adibkia
Erlotinib (ERL), a tyrosine kinase inhibitor, is used for the treatment of inoperable or metastatic pancreatic cancer and metastatic non-small cell lung cancer (Asgari et al.2011). Nowadays, the potential of ERL has been investigated in treating various tumours such as glioblastoma, ovarian cancer and head and neck cancers (Raizer et al.2016, Anisuzzaman et al.2017). On the other hand, L-asparaginase (L-ASPN) has been approved for the treatment of acute lymphoblastic leukaemia (ALL) to deprive tumour cells with the asparagine amino acid formation. The results of some studies suggested that the proliferation of ovarian cancer cells having low to moderate levels of asparagine synthetase (ASNS) may be affected by the diminution of extracellular asparagine. This may propose L-ASPN as a potential drug in the treatment of OC when used in combination with ERL-loaded NSs (Abdolahinia et al.2019, Ajoolabady et al.2020).