Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial

The Lancet Oncology, Год журнала: 2015, Номер 16(8), С. 990 - 998

Опубликована: Июль 7, 2015

Язык: Английский

---

Towards personalized treatment for early stage HER2-positive breast cancer

Nature Reviews Clinical Oncology, Год журнала: 2019, Номер 17(4), С. 233 - 250

Опубликована: Дек. 13, 2019

Язык: Английский

---

Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 7, 2023

Since their invention in the early 2000s, tyrosine kinase inhibitors (TKIs) have gained prominence as most effective pathway-directed anti-cancer agents. TKIs shown significant utility treatment of multiple hematological malignancies and solid tumors, including chronic myelogenous leukemia, non-small cell lung cancers, gastrointestinal stromal HER2-positive breast cancers. Given widespread applications, an increasing frequency TKI-induced adverse effects has been reported. Although are known to affect organs body lungs, liver, tract, kidneys, thyroid, blood, skin, cardiac involvement accounts for some serious complications. The frequently reported cardiovascular side range from hypertension, atrial fibrillation, reduced function, heart failure sudden death. potential mechanisms these unclear, leading critical knowledge gaps development therapy guidelines. There limited data infer best clinical approaches detection therapeutic modulation effects, universal consensus regarding various management guidelines is yet be reached. In this state-of-the-art review, we examine pre-clinical studies curate evidence on pathophysiology, mechanisms, reactions. We expect that review will provide researchers allied healthcare providers with up-to-date information natural history, risk stratification, emerging cancer patients.

Язык: Английский

---

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck

Annals of Oncology, Год журнала: 2014, Номер 25(9), С. 1813 - 1820

Опубликована: Июнь 16, 2014

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized the agent would have greater antitumor compared with cetuximab recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease progressed after platinum-containing therapy.Patients methodsAn open-label, randomized, phase II trial was conducted 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) (250 mg/m2/week) until progression intolerable adverse events (AEs) (stage I), optional crossover II). The primary end point tumor shrinkage before assessed by investigator (IR) independent central review (ICR).ResultsA total of 121 treated (61 afatinib, 60 cetuximab) 68 crossed over stage (32 36 respectively). In I, mean IR/ICR 10.4%/16.6% 5.4%/10.1% (P = 0.46/0.30). Objective response rate 16.1%/8.1% 6.5%/9.7% (IR/ICR). Comparable control rates observed (50%) (56.5%) IR; similar results seen ICR. Most common grade ≥3 drug-related AEs (DRAEs) rash/acne (18% versus 8.3%), diarrhea (14.8% 0%), stomatitis/mucositis (11.5% 0%) cetuximab, respectively. Patients DRAEs leading treatment discontinuation 23% 5% cetuximab. II, (IR/ICR) 38.9%/33.3% 18.8%/18.8% cetuximab.ConclusionAfatinib showed comparable R/M HNSCC this exploratory trial, although more on discontinued due AEs. Sequential EGFR/ErbB provided sustained clinical benefit crossover, suggesting a lack cross-resistance.

Язык: Английский

---

Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: Comparative pharmacokinetics and drug–drug interactions

Cancer Treatment Reviews, Год журнала: 2014, Номер 40(8), С. 917 - 926

Опубликована: Июль 2, 2014

Язык: Английский

---

Tyrosine Kinase Inhibitors: Their On-Target Toxicities as Potential Indicators of Efficacy

Drug Safety, Год журнала: 2013, Номер 36(6), С. 413 - 426

Опубликована: Апрель 26, 2013

Язык: Английский

---

Expert Consensus on the Management of Adverse Events from EGFR Tyrosine Kinase Inhibitors in the UK

Drugs, Год журнала: 2015, Номер 75(12), С. 1335 - 1348

Опубликована: Июль 17, 2015

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib are standard-of-care for first-line treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC). These drugs have a proven benefit in terms higher response rate, delaying progression improvement quality life over palliative platinum-based chemotherapy. The most common adverse events (AEs) gastrointestinal (GI) (diarrhoea stomatitis/mucositis) cutaneous (rash, dry skin paronychia). usually mild, but if they become moderate or severe, can negative impact on the patient's (QOL) lead to dose modifications drug discontinuation. Appropriate management AEs, including prophylactic measures, supportive medications, delays reductions, is essential. A consensus meeting UK-based multidisciplinary panel composed medical clinical oncologists with special interest cancer, dermatologists, gastroenterologists, nurse specialists oncology pharmacists was held develop guidelines prevention paronychia) GI (diarrhoea, stomatitis mucositis) AEs associated administration EGFR-TKIs. detail reductions Although focus support healthcare professionals UK practice, it anticipated that strategies proposed will also be applicable non-UK settings.

Язык: Английский

---

FDA- and EMA-Approved Tyrosine Kinase Inhibitors in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: Safety, Tolerability, Plasma Concentration Monitoring, and Management

Biomolecules, Год журнала: 2019, Номер 9(11), С. 668 - 668

Опубликована: Окт. 30, 2019

Non-small-cell lung cancer (NSCLC) is the most common form of primary cancer. The discovery several oncogenic driver mutations in patients with NSCLC has allowed development personalized treatments based on these specific molecular alterations, particular tyrosine kinase (TK) domain epidermal growth factor receptor (EGFR) gene. Gefitinib, erlotinib, afatinib, and osimertinib are TK inhibitors (TKIs) that specifically target EGFR currently approved by Food Drug Administration (FDA) European Medicines Agency (EMA) as first line treatment for sensitive EGFR-mutant patients. However, four drugs associated severe adverse events (AEs) can significantly impact patient health-related quality life monitoring. EGFR-TKIs commonly used together other types medication substantially interact. Here, we review approaches management TKI-AEs advanced to promote benefits minimize risk TKI discontinuation. We also consider potential TKI–drug interactions discuss usefulness plasma concentration monitoring TKIs chromatographic mass spectrometry guide clinical decision-making. Adjusting appropriate therapeutic strategies drug doses may improve performance therapy prognosis EGFR-mutated NSCLC.

Язык: Английский

---

Diarrhea associated with afatinib: an oral ErbB family blocker

Expert Review of Anticancer Therapy, Год журнала: 2013, Номер 13(6), С. 729 - 736

Опубликована: Март 18, 2013

Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGF receptor (EGFR; also known as HER1 or ErbB1) tyrosine kinase inhibitor therapy. GI AEs among the most common and impactful on a patient's quality of life. Severe diarrhea can result fluid electrolyte losses, leading to dehydration, imbalances renal insufficiency. Afatinib is an irreversible, oral, ErbB family blocker, inhibiting EGFR (ErbB1), HER2 (ErbB2) ErbB4 kinases. It inhibits transphosphorylation ErbB3. Similar reversible inhibitors EGFR, – particular, have been afatinib-treated patients. This article summarizes current data afatinib-associated provides strategies for its management. Patient education, early identification, timely management ongoing assessment will help prevent aggravation, afatinib dose reductions therapy discontinuation, encouraging patient compliance allowing obtain maximum therapeutic benefit from this agent.

Язык: Английский

---

Skin problems and EGFR-tyrosine kinase inhibitor

Japanese Journal of Clinical Oncology, Год журнала: 2016, Номер 46(4), С. 291 - 298

Опубликована: Янв. 29, 2016

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head neck cancers. receptor-tyrosine kinase inhibitor was first approved advanced lung cancer in 2002. plays an essential role cancer, especially patients harbouring epidermal activating mutation. Hence, skin toxicity most concerning issue treatment. Skin bothersome sometimes affects quality life compliance. Thus, it important physicians to understand background how manage inhibitor-associated toxicity. Here, author reviewed mechanism upfront preventive reactive treatments toxicities.

Язык: Английский

---