A melanoma patient treated with vemurafenib also developed leukemia temporarily, according to a case report in The New England Journal of Medicine. This drug was already known to cause squamous cell skin cancers in some people with melanomas that have BRAF mutations. Vemurafenib activates proteins called extracellular signal-regulated kinases (ERK), which are involved in cell division and can lead to cancer in cells that have RAS mutations. The leukemia in the vemurafenib-treated patient had a RAS mutation and disappeared after treatment ended. The patient’s melanoma tumors, which did not have a RAS mutation, shrank during treatment.
A new blood test could show whether melanomas are likely to return in patients who are clinically free of the disease, according to a study in the Journal of Clinical Oncology. Cancer cells that break off tumors can enter blood vessels; this test identifies three tumor cell biomarkers in blood. The researchers periodically tested blood samples of 322 patients and found those with up to one cancer biomarker were more likely to be melanoma-free compared to those with two or more cancer biomarkers (73% vs 59%). This test could show which patients would benefit from aggressive treatments.
Treatments that target a protein called MEK could work better when combined with drugs that inhibit a protein called SMURF2, according to research in the British Journal of the National Cancer Institute. MEK is involved in cell division and can be activated by BRAF and NRAS mutations. However, melanomas often resist MEK inhibitors. The researchers found that MEK inhibitors made melanoma cells grown in the laboratory produce too much of a protein called SMURF2. This in turn led to overproduction of another protein called MITF, which protects melanomas against MEK inhibitors. When treated with both a MEK inhibitor called selumetinib and a SMURF2 inhibitor, tumor growth was suppressed by 98% in mice.
The impressive, but still short-term, benefits of vemurafenib for melanoma patients may not justify the hefty cost to a Massachusetts Medicaid program, according to an analysis presented at an American Society of Health-System Pharmacists meeting. Vemurafenib targets the most common mutation of BRAF, which is one of the genes that is most often abnormal in melanomas. The analysis noted that vemurafenib boosted 6-month survival rates over those of the conventional chemotherapy drug dacarbazine (84% and 64%, respectively). However, vemurafenib is also more expensive than dacarbazine, with relative per patient costs estimated at $9,995 and $1,811 per month, respectively.
Annals of Cancer Research and Therapy | Sep 28, 2012
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
Cancer Chemotherapy and Pharmacology | Jan 12, 2013
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.
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