China
Africa
Explore chapters and articles related to this topic
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
There is emerging evidence that afatinib is efficacious in other tumor types, and it is currently undergoing clinical studies in HER2/Neu+ uterine, esophageal, and gastric cancers as well as triple-negative breast cancer. Furthermore, research into the delivery of afatinib into brain metastases is underway. As most therapeutic agents fail to cross the blood–brain barrier, this study is investigating the use of low-dose radiotherapy to disrupt the blood–brain barrier to facilitate the delivery of afatinib into brain tumors.
Biologically Targeted Agents in Head and Neck Cancers
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Kevin J. Harrington, Magnus T. Dillon
Afatinib has been assessed in the phase III LUX head and neck-1 study in patients receiving second-line therapy for relapsed/metastatic SCCHN.55 A total of 583 patients were treated with afatinib (322 patients) or methotrexate (161 patients). Afatinib significantly increased median progression-free survival (2.6 vs. 1.7 months, p = 0.03) but did not improve median overall survival (6.8 vs 6.0 months) relative to methotrexate. The overall response rates of the two study arms were low—10.2% and 5.6%, respectively. In an integrated analysis of quality of life, afatinib showed a delay in deterioration of global health status, pain and swallowing problems (all p ≤ 0.03). The profile of toxicities was markedly different between the two treatments, with afatinib causing more rash and diarrhoea and methotrexate causing more stomatitis and leukopenia. A randomized phase II comparison of afatinib and cetuximab has also demonstrated that afatinib has similar antitumour activity to cetuximab, as assessed by tumour shrinkage on treatment.56 It remains to be seen if, on the basis of these data, afatinib finds a place in the treatment process for patients with relapsed/metastatic SCCHN.
A
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Exposure to afatinib was found to be increased in patients with moderate or severe renal impairment. Adjustments to the starting dose are not necessary in patients with mild (eGFR=60–89 mL/min/1.73m²), moderate (eGFR=30–59 mL/min/1.73 m2) or severe (eGFR=15–29 mL/min/1.73 m2) renal impairment. Monitor patients with severe renal impairment (eGFR=15–29 mL/min/1.73 m2) and adjust dose if not tolerated. Treatment in patients with eGFR<15 mL/min/1.73 m2 or on dialysis is not recommended by manufacturer due to lack of studies.
Targeting the EGFR signaling pathway in cancer therapy: What’s new in 2023?
Published in Expert Opinion on Therapeutic Targets, 2023
Sushanta Halder, Soumi Basu, Shobhit P. Lall, Apar K. Ganti, Surinder K. Batra, Parthasarathy Seshacharyulu
Afatinib (BIBW 2992/Gilotrif): Afatinib is an orally active anilino-quinazoline derivative EGFR-TKI which binds and inhibits selectively and irreversibly to EGFR, HER2, and HER4. It was approved by the US FDA and European Medical Agency (EMA) in 2013 to treat advanced metastatic EGFR mutation harboring NSCLC [73]. This is also under investigation as monotherapy to treat HER2-positive breast cancer patients who have progressed to trastuzumab [74]. Our group has extensively investigated the effect of afatinib on multiple cancers. Recently, we found a synergistic effect of afatinib with gemcitabine in reducing pancreatic cancer (PC) progression and metastasis by impeding cancer stem cell (CSC) growth using preclinical organoid and mouse models [17]. Afatinib has a synergistic effect with temozolomide in inhibiting the growth, proliferation, and tumorigenesis ability of glioblastoma cells modulated to express EGFR (wild type), mutant EGFRvIII, and EGFR dead kinase [75]. Furthermore, our group demonstrated afatinib’s anti-proliferation, migration, and anti-survival action in pancreatic cancer cells [16]. We have also reported that afatinib shows an anti-tumorigenic effect and radio-sensitizes head and neck squamous cell carcinoma (HNSCC) cells by eradicating the CSC population [18].
Heterogeneous clinical and pathological landscapes of HER2 positive colorectal cancer
Published in Expert Review of Anticancer Therapy, 2021
Zhiqin Chen, Jinde Chen, Yong Gao, Ming Quan
Clinical trial shows that lung cancer patients with HER2 mutations have benefited from Afatinib (an irreversible EGFR/HER2 inhibitor) [39]. Afatinib can also inhibit tumor cell growth and promote apoptosis in HER2 overexpressing CRC cells in vitro and vivo [40]. It is noteworthy that BRAFwt -microsatellite instability (MSI) CRC has a higher frequency of HER2 mutations, notably with regard to the common L755S and V842I substitutions. The authors demonstrated that HER2-mutated MSI CRC cells were susceptible to afatinib and neratinib [41]. In addition, complementary medicine has also provided a novel mechanism including the ability of simvastatin to significantly abrogate HER2-induced tumors angiogenesis by impeding VEGF secretion [42]. The findings suggested that simvastatin can remodel the abnormal tumor vasculature to improve current treatment.
AGAPP: efficacy of first-line cisplatin, 5-fluorouracil with afatinib in inoperable gastric and gastroesophageal junction carcinomas. A Hellenic Cooperative Oncology Group study
Published in Acta Oncologica, 2021
George Zarkavelis, Epaminontas Samantas, Georgia-Angeliki Koliou, Kyriaki Papadopoulou, Davide Mauri, Gerasimos Aravantinos, Anna Batistatou, Elissavet Pazarli, Dimitrios Tryfonopoulos, Anna Tsipoura, Mattheos Bobos, Amanda Psyrri, Thomas Makatsoris, Constantina Petraki, Dimitrios Pectasides, George Fountzilas, George Pentheroudakis
The modified regimen of cisplatin, 5FU and afatinib (mCisFU-A) was administered every 21 days. Cisplatin was administered at 75 mg/m2 diluted in 1 liter of normal saline solution (0.9% N/S) over 60–120 min on day 1, with rigorous saline-based intravenous hydration. 5-Fluorouracil (5FU) was infused intravenously over 24 h at a daily dose of 750 mg/m2 for a total of 96 h (days 1–4) every 21 days. Afatinib was administered orally at a daily dosage of 40 mg between 08:00 and 09:00 a.m., at least 1 h before breakfast. Afatinib administration started on day 3 of each therapy cycle, having been preceded by cisplatin infusion on day 1 and 5FU infusion on days 1 and 2. The once-daily oral administration of afatinib continued throughout the week with intervals during weekends (‘Weekday-on – Weekend-off’). Therefore, in each 21-day therapy cycle the administration of afatinib took place once daily on days 3–5 of week 1, days 1–5 of week 2, and days 1–5 of week 3. The total daily dosage of 40 mg was administered independently of the patient’s body surface area. If vomiting occurred after administration, the patient was not given a replacement dose.