Tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa) are effective treatments for many patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. However, patients who also have a certain version of the BIM gene are resistant to TKIs. Vorinostat (Zolinza), a member of a family of drugs called histone deacetylase (HDAC) inhibitors, restored the antitumor activity of Iressa in EGFR-mutant NSCLC cells and in animal models of EGFR-mutant NSCLC that carried the resistant BIM version. Combining Zolinza with TKIs may therefore help circumvent TKI resistance in patients who have the resistant form of BIM.
Non-small cell lung cancer (NSCLC) patients with mutations in the EGFR gene are likely to benefit from treatment with tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa), while KRAS mutations predict poor TKI response. A study of patients who were not taking TKIs and had stages I/II/III NSCLC that had been surgically removed found no difference in recurrence or survival between patients with or without EGFR or KRAS mutations. This finding suggests that, while EGFR and KRAS mutations are useful for identifying patients who may benefit from targeted treatments like TKIs, they do not predict overall clinical outcomes by themselves.
Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.
Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf
The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.
A retrospective study in Japan examined 55 patients aged 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well tolerated and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.
A study of individuals with and without lung cancer in North India found that those carrying a particular version (or “polymorphism”) of a gene for the protein p53 were more likely to have lung cancer, independent of their age or smoking rate. P53 belongs to a class of proteins called “tumor suppressor proteins,” and is involved in DNA repair, regulating cell growth, and inducing cell death in damaged or abnormal cells. The findings suggest that this version of the p53 gene, called Arg72Pro, may contribute to higher susceptibility for lung cancer, at least in the North Indian population.
Research paper: http://online.liebertpub.com/doi/full/10.1089/dna.2012.1792
A recent study examined first-line treatment with the chemotherapy agent carboplatin (Paraplatin), combined with either albumin-bound paclitaxel (Abraxane) or standard solvent-based paclitaxel (Taxol), in both elderly and younger patients with advanced non-small cell lung cancer (NSCLC). Patients treated with Abraxane/Paraplatin exhibited higher treatment response rates and fewer toxic side effects in both age groups; elderly patients (age 70+ years) experienced longer periods without cancer progression and longer overall survival with Abraxane/Paraplatin compared to Taxol/Paraplatin treatment. Abraxane plus Paraplatin may constitute a safe, effective first-line treatment for elderly patients with advanced NSCLC, a group that has been traditionally undertreated.
Research paper: http://annonc.oxfordjournals.org/content/24/2/314.long
Variations in genes for a family of proteins called matrix metalloproteases (MMPs) have been suggested to play a role in lung cancer risk. A meta-analysis of several studies on MMP genes found that a particular version (or “polymorphism”) of the MMP1 gene, called MMP1-1607 1G/2G, is associated with higher susceptibility for lung cancer in Asian patients. In contrast, the MMP2-1306 C/T version of the MMP2 gene decreases lung cancer risk in Asian patients and the MMP9-1562 C/T version of the MMP9 gene decreases lung cancer risk in white patients.
National Jewish Health is performing a clinical trial to examine the benefits of lung cancer screening that combines a computed tomography (CT) chest scan with a blood test. The blood test detects anticancer antibodies created by the immune system. The trial seeks to find out whether adding the blood test, called EarlyCDT-Lung, will further improve the ability of CT chest scans to prevent lung cancer deaths in high-risk populations and avoid invasive follow-up testing in the case of CT scan “false alarms.” Participants can enroll if they are between ages 50 to 75 years, have a smoking history of at least 20 pack-years (meaning 1 pack a day for 20 years, or 2 packs a day for 10 years, etc.), are current smokers or quit fewer than 10 years ago, and have no serious illness or history of cancer other than skin cancer. Call 303-398-1911 to find out more.