Iosune Baraibar

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS oncogene in NSCLC remains unclear and its predictive and prognostic impact remains controversial. The study of the underlying biology of KRAS in NSCLC patients could help to determine potential candidates to evaluate novel targeted agents and combinations that may allow a tailored treatment for these patients. The aim of this review is to update the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated NSCLC patients.

Combination of pegylated liposomal doxorubicin plus gemcitabine in heavily pretreated metastatic breast cancer patients: Long-term results from a single institution experience

The combination of Pegylated Liposomal Doxorubicin (PLD) plus Gemcitabine (GEM) has been previously investigated in the treatment of metastatic breast cancer (MBC). PLD is a doxorubicin formulation with prolonged circulation time and better tissue distribution. GEM is a nucleoside analog with nonoverlapping toxicity compared to PLD. The aim of our study was to assess efficacy, toxicity, and long‐term outcome of this combination. Patients with heavily treated MBC were retrospectively analyzed. Chemotherapy consisted of PLD 25 mg/m2 and GEM 800 mg/m2 day 1, on a three‐week schedule. Cardiac function was evaluated baseline and during treatment. Radiological response was graded according to RECIST criteria v1.1. Toxicity was scored according to CTCAE v4.0. Progression‐free survival (PFS) and overall survival (OS) were evaluated. From 2001 to 2014, 122 pts were included. Median age was 55 (range: 28‐84). Median previous treatment schedules in the metastatic scenario were 3 (range: 1‐15). Most patients received prior anthracyclines (85%). Median number of metastatic sites was 2 (range: 1‐7). Median number of cycles delivered was 5 (range: 1‐36). Overall response rate was 31% (5% complete responses; 26% partial responses). Stable and progressive diseases were observed in 32% and 26% of patients. Grade ≥3 neutropenia was observed in 29 patients (24%). Grade ≥3 hand‐foot syndrome was detected in 17 patients (14%), mostly since cycle 3 (88%). Median cumulative PLD dose was 125 mg/m2. At a median follow‐up of 101 months, median PFS and OS were 7 and 22 months, respectively. PLD‐GEM combination achieves remarkable long‐term outcomes with an acceptable toxicity profile in patients with MBC.

Pazopanib-induced asymptomatic radiological acute pancreatitis: A case report

The universal clinical use of multi-targeted tyrosine kinase inhibitors (TKIs) in patients diagnosed with advanced renal cell carcinoma (RCC) has significantly prolonged their estimated survival times and their quality of life. However, several adverse side-effects associated predominantly with the inhibition of the vascular endothelial growth factor receptor by these drugs may prove to be potentially life-threatening. One adverse event that is only rarely observed with the use of TKIs in this clinical setting is acute pancreatitis. In the present study, to the best of our knowledge, the first case of asymptomatic radiological acute pancreatitis associated with the use of pazopanib in monotherapy in a patient with RCC is presented. In addition, a comprehensive review of the literature on this topic is provided, and certain potential measures that may aid in early diagnosis and treatment are discussed.