Search

• Modest efficacy, toxicity, and poor effectiveness against brain metastasis are common limitations of multi-targeted novel molecular inhibitors. • A promising prospect was shown recently in selective RET inhibitors. • The development of multitarget agents and specific inhibitors has been evaluated in clinical trials. • More studies need to be conducted on the targeted therapies against RET arrangement cancer. Genomic profiling has revolutionized treatment options for patients with oncogene-driven cancers, such as epidermal growth factor receptor (EGFR) mutant carcinoma. Rearranged during transfection (RET) rearrangement, as one of the main activated oncogenes, has been well studied and found to be involved in the malignant behavior of carcinogenesis, resulting in acquired resistance to EGFR tyrosine kinase inhibitors and inducing an intrinsic resistance to immunotherapy. Thus, targeted therapies have been investigated against RET arrangement cancers, including several multi-kinase inhibitors and selective RET inhibitors. However, modest efficacy, a relatively high rate of toxicity, and poor effectiveness against brain metastasis are common limitations of multi-targeted novel molecular inhibitors. A promising prospect was shown recently in selective RET inhibitors in several ongoing clinical trials. In this review, we reviewed the concurrent dilemmas of targeted therapies against RET arrangement cancer from preclinical and clinical studies and proposed several clinical considerations for clinical practice prospectively. [ABSTRACT FROM AUTHOR]

Abstract: Purposes: This study was conducted to assess the efficacy and toxicity of gefitinib as first line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve patients with advanced (stage IIIB, IV and recurrent) NSCLC. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20 and 21. Sixty-one patients received 250mg of gefitinib daily until disease progression or unacceptable toxicity. Results: Out of 61 patients, 26 patients (42.6%) were EGFR mutations and 11 patients were wild type, 24 patients were status unknown. One patient achieved complete remission (CR). While 17 patients achieved partial remission (PR) and 23 experienced stable disease (SD). There were 20 patients developed progressive disease (PD). The tumor response rate and disease control rate was 29.5 and 67.2%, respectively, and symptom remission rate was 66.7% as well. Median remission time was 9 days. Median over survival time was 13.0 months. Median progression-free survival time was 5.0 months. The MST of patients with EGFR mutation was 17.0 months, while the MST of patients with EGFR status unknown or wild type was 11.0 months. The PFS of patients with EGFR mutation was 9.0 months and it in EGFR status unknown or wild type was 2.5 months .The most common toxicity included rash (54.1%) and diarrhea (31.1%). Dehydration and pruritus of skin was observed in 31.1 and 26.2% of the patients respectively. Hepatic toxicity occurred in 8.2% of patients and oral ulceration occurred in six patients (9.8%). Conclusion: Single agent treatment with gefitinib is effective in patients with advanced NSCLC, especially in patients with EGFR mutation, and well tolerated in Chinese patients. [Copyright &y& Elsevier]