The oncologist
-
Cancer-related neuropathic pain syndromes are common and serious complications of a patient's primary malignancy or its treatment, whether by surgery, radiation, or chemotherapy. They may compromise the patient's quality of life as well as their ability to receive effective treatment. In many patients, there may be more than one coexistent neuropathic pain syndrome, posing a diagnostic dilemma that, if unresolved, may result in the institution of therapies that are of limited scope or not targeted at the primary underlying pathophysiology. ⋯ Clinical assessment of cancer-related neuropathic pain poses some important challenges diagnostically as well as in defining a clear and reliable endpoint assessment in controlled clinical trials. Many different approaches have been applied to the development of assessment or diagnostic tools. Careful review of these methods has been helpful in developing a clearer vision for the future design and refinement of more reliable tools, and more importantly, validation of the clinical utility as well as the reliability of such tools when employed as endpoints in clinical trials focused on prevention, mitigation, or treatment of cancer neuropathic pain.
-
The identification of certain molecular mechanisms underlying lung carcinogenesis and progression has led to the development of targeted agents against different families of growth factors and receptors. The epidermal growth factor receptor (EGFR) is one such target for therapeutic exploitation. ⋯ Several novel agents with the potential to overcome such resistance are currently in clinical development, including irreversible EGFR TKIs, monoclonal antibodies, and TKIs directed against multiple signaling pathways. Here we discuss the clinical application of the currently available EGFR-targeted agents in NSCLC, the underlying mechanisms of resistance, and the novel agents in clinical development that may overcome resistance.
-
Delirium remains the most common and distressing neuropsychiatric complication in patients with advanced cancer. Delirium causes significant distress to patients and their families, and continues to be underdiagnosed and undertreated. ⋯ The early symptoms and signs of delirium and the use of delirium-specific assessment tools for routine delirium screening and monitoring in clinical practice are summarized. Finally, management options are reviewed, including pharmacological symptomatic management and also the provision of counseling support to both patients and their families to minimize distress.
-
Vandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses < or =300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. ⋯ Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a preplanned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib.