Genetic alterations in pancreatic cancer

The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

Incidence and management of ZIv-aflibercept related toxicities in colorectal cancer

Ziv-afilbercept(Zaltrap, Ziv) is a humanized fusion protein constructed by joining the vascular endothelial growth factor(VEGF) binding portions of human VEGF receptors 1 and 2 to the Fc portion of human immunoglobulin IgG 1. Recently, a randomized, open-label, phase Ⅲ study compared 5-fluorouracil, leucovorin, irinotecan(FOLFIRI)/Ziv with FOLFIRI/placebo in patients who had been previously treated with oxaliplatin based chemotherapy for metastatic colon cancer(mC RC). Patients who had received prior bevacizumab therapy were also eligible. This study showed that the addition of Ziv improved overall survival with median survival time of 13.5 mo vs 12.06 mo in ziv vs placebo arm. Ziv also improved progression free survival from 4.67 mo to 6.9 mo with a response rate of 19.8% in the Ziv/FOLFIRI group vs 11.1% in FOLFIRI alone group. This led to the approval of Ziv in combination with FOLFIRI in metastatic colon cancer patients treated with prior oxaliplatin regimens. The mostcommon side effects were diarrhea, stomatitis, fatigue, hypertension, weight loss, loss of appetite, abdominal pain, and headache. As the use of Ziv has become more widespread in oncology practices, familiarity with the toxicity profile of the drug and the use of practice guidelines for their treatment has become increasing important. This review will address the toxicities noted in trials using Ziv for the treatment of mC RC, and will provide recommendations for toxicity management.

Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction

Hypersensitivity reactions (HSR) to oxaliplatin in patients with colorectal cancer include facial ushing, erythema, pruritis, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions, she developed fever to a maximum of 38.3℃ with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea, vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8℃, BP dropped to 95/43 mm Hg, pulse of 116/min and O2 saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.

Developments in the Management of Advanced Non Small Cell Lung Cancer

Background: Overall survival (OS) and quality of life in patients with advanced non small cell lung cancer (NSCLC) remains to the day highly unsatisfactory. Better understanding of the mechanisms of oncogenesis resulted in the development of new drugs, which target a specific stage in tumor development. Additionally, optimal timing of chemotherapy administration has been readdressed with the introduction of maintenance treatment in clinical practice. The aim of this review is to briefly summarize the developments in first line treatment of NSCLC with small molecule tyrosine kinase inhibitors, the role of crizotinib and the current options in maintenance treatment. Methodology A search was performed in the PubMed database and in Clinical Trials.gov using the keywords erlotinib, gefitinib, crizotinib and maintenance treatment. Findings were reported in form of a narrative review. Conclusions: First line treatment with small molecule TKIs for NSCLC is both effective and feasible. EGFR mutation status remains the main prognostic factor of response. Pemetrexed and Erlotinib, currently approved for Maintenance Treatment in NSCLC, seem to benefit patients with advanced disease. Identification of suitable candidates for Maintenance Treatment, optimal timing and agent selection are issues that still remain largely unanswered. Early study results promise that addition of crizotinib to the treatment regimen of ALK positive NSLCL is likely to be beneficiary for a substantial number of patients.