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Drug Delivery
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Gudrun Fleischhack, Martin Garnett, Kévin Beccaria
Metronomic therapy, defined as repetitive low-dose administration of cytotoxic agents with no prolonged drug-free interval, has emerged as a new treatment option in solid malignancies, including CNS tumors. This kind of therapy inhibits tumor progression indirectly by inhibition of vascular formation. In contrast to conventional chemotherapy, this low-dose metronomic scheduling reduces the release of endothelial progenitor cells into the circulation and halts tumor growth by activating antitumor immunity.119,120 It has been shown that such a schedule can be more effective than conventional cyclic chemotherapy and could overcome drug resistance.121 In the current metronomic trials different drug combinations are used consisting of low-dose chemotherapeutic drugs and different agents acting as direct target therapy without inducing excessive toxicity. These combination therapies represent a form of multitarget therapy which has the ability to damage the genetically stable, host endothelial cell, with subsequent induction of tumor dormancy or cytostasis.122 Several trials have reported relevant activity of a four- to six-drug metronomic therapy also in recurrent or poor-prognosis pediatric CNS tumors.95,96,123,124 Most promising results with prolonged or persistent disease-free status in patients with recurrent embryonal brain tumors were documented by Peyrl et al.95 using a combination of bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide, and cyclophosphamide and additional intraventricular therapy (etoposide and liposomal cytarabine).
Advances in pharmacotherapy for head and neck cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Shikhar kumar, Vanita Noronha, Vijay Patil, Amit Joshi, Nandini Menon, Kumar Prabhash
Oral metronomic therapy is a useful therapeutic option, particularly for low-middle-income countries where the majority of patients cannot afford EGFR-directed antibody therapy/immune checkpoint inhibitor therapy. The phase III trial by Patil et al. has demonstrated non-inferiority of this oral combination therapy compared to single-agent cisplatin. It can be argued that single-agent cisplatin was a substandard control arm, especially when nearly half the enrolled patients in the study had platinum refractory disease, however, no study has proven that combination chemotherapy improves overall survival compared with single-agent cisplatin. The excellent tolerability and low cost of oral metronomic therapy makes it an appealing choice for first line use in patients with R/M HNSCC, especially in the resource-constrained setting, when immunotherapy and cetuximab are not affordable or available options.
Intraperitoneal chemotherapy for ovarian cancer using sustained-release implantable devices
Published in Expert Opinion on Drug Delivery, 2018
Smrithi Padmakumar, Neha Parayath, Fraser Leslie, Shantikumar V. Nair, Deepthy Menon, Mansoor M. Amiji
The cytotoxic neoplastic drugs are often administered in singe doses or as intermittent short courses at the highest possible dose called maximum-tolerated dose (MTD) in order to provide complete eradication of cancer cells. MTD therapy thus requires the imposition of drug-free rest periods (generally 2–3 weeks in duration) interspersed with short bursts of toxic MTD therapy, to heal the damage caused to normal tissues and allow their recovery. Such a practice could also invoke re-growth of tumor cells, as well as growth of therapy-resistant clones of cells, thereby leading to growth of more metastatic tumors with no therapeutic response. Metronomic chemotherapy refers to administering low doses of single or combination chemotherapeutic drugs on a frequent or continuous and accelerated schedule, without extended interruptions or drug-free break, yet achieving enhanced anti-tumor efficacy with very low toxicity [71]. The integration of metronomic scheduling of cytotoxic chemotherapy could be a meaningful alternative to improve the anti-tumor efficacy as well as to minimize the ill-effects of MTD dosing regimen [72,73]. The need to treat patients for longer periods supports the use of metronomic scheduling for chemotherapy with enhanced anti-tumor activity and less systemic toxicity [74]. Thus the success rate of metronomic therapy is based on the crucial aspects of continuous administration which exposes tumor cells to drug concentrations for longer times, cancer immunology activation as well as anti-angiogenic effects [73,75].
Simultaneous estimation of paclitaxel and erlotinib in plasma by liquid chromatography/(+) electrospray tandem mass spectrometry: application in formulation development and pharmacokinetics
Published in Drug Development and Industrial Pharmacy, 2022
Tahir Khuroo, Umme Atifa, Arshad Khuroo, Mohd Aamir Mirza, Asgar Ali, Zeenat Iqbal
Erlotinib (ERL) specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. Epidermal growth factor receptor (EGFR/HER1) is a member of the ErbB superfamily of type I receptor tyrosine kinases, which also include HER2, HER3, and HER4 [4]. There is also a rationale to support the simultaneous blockade of VEGF (Vascular endothelial growth factor) and the epidermal growth factor receptor (EGFR) pathways. The EGFR also appears to regulate VEGF and several studies have demonstrated that blockade of the EGFR resulted in an antiangiogenic effect. Furthermore, data have suggested that increased production of VEGF represents one mechanism by which tumor cells escape anti-EGFR monoclonal antibody therapy. One study has tested the strategy of combining Erlotinib (EGFR tyrosine kinase inhibitor) with bevacizumab in solid tumors of breast cancer and its metastasis [3]. Since both the drugs produce side effects different from each other at higher doses but when used in combination, the dose can be reduced and hence the side effects like bone marrow depression especially neutropenia from PAC and interstitial lung disease, renal failure, hepatotoxicity with or without hepatic impairment, gastrointestinal perforation, myocardial infarction/ischemia by ERL can be prevented to a large extent. Mitigation of severe side effects is the primary premise of metronomic therapy. Treatment with metronomic chemotherapy in combination with Bevacizumab and Erlotinib was found effective in HER2-, estrogen receptor (ER)- and progesterone receptor (PR)- poor advanced breast tumors [5,6].