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1.  Immunotherapy for head and neck cancer: latest developments and clinical potential 
Head and neck squamous cell cancer (HNSCC) is a malignancy with a rapidly changing demographic profile, given the recent epidemic of human papilloma virus related cancers. Most patients present with locally advanced disease and receive combination therapeutic approaches with curative potential, albeit with significant toxicity. Up to a third of patients, however, will eventually develop recurrent or metastatic disease. The prognosis of such patients is dismal, as palliative treatment options remain limited. Immune-directed therapies offer a novel therapeutic strategy beyond cytotoxic chemotherapy and are currently being evaluated in a wide variety of malignancies. HNSCC is a particularly favorable disease for immunotherapy, as immune evasion and dysregulation have been shown to play a key role in the initiation and progression of HNSCC. This review focuses on the latest developments in immunotherapy in HNSCC, with a particular focus on checkpoint inhibitors, adoptive cellular therapies, and vaccines.
doi:10.1177/1758834016631529
PMCID: PMC4872249  PMID: 27239235
head and neck cancer; immunotherapy; PD-1 inhibitors; cancer vaccines; adoptive cellular therapies
2.  Evaluating the safety and efficacy of axitinib in the treatment of advanced renal cell carcinoma 
Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor-α, and c-kit. Phase I studies demonstrated 5 mg twice daily as the recommended starting dose with notable effects seen in renal cell carcinoma, an observation confirmed in Phase II trials. The trial of comparative effectivess of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS) was an international randomized Phase III study designed for registration purposes, compared axitinib to sunitinib. This trial randomized 723 patients with metastatic kidney cancer to axitinib or sunitinib in the second-line setting and demonstrated a median progression-free survival of 6.7 months for axitinib versus 4.7 months for sorafenib (P<0.0001). Clinical benefit was detected regardless of prior therapy, but no overall survival benefit has been observed. Axitinib is well tolerated without a significant effect on quality of life. The most common grade 3 toxicities are hypertension (16%), diarrhea (11%), and fatigue (11%), with other notable side effects being anorexia, nausea, hand–foot syndrome, and rash. Patients who developed diastolic blood pressure >90 mmHg were noted to have significantly longer median overall survival and overall response rates when compared to normotensive patients. Therefore, the manufacturer recommends escalating the twice-daily dose to 7 mg and 10 mg, as tolerated, if there is no significant increase in blood pressure on treatment. Currently, axitinib is approved for use in the second-line setting for patients with metastatic renal cell carcinoma. Research is ongoing in other disease settings.
doi:10.2147/CMAR.S74202
PMCID: PMC4334173  PMID: 25709499
axitinib; renal cell carcinoma; side effects; drug safety
3.  Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities 
Investigational New Drugs  2012;30(5):2066-2079.
Summary
Treatment of metastatic renal cell carcinoma (mRCC) has evolved rapidly over the last two decades as major pathways involved in pathogenesis have been elucidated. These include the vascular endothelial growth factor (VEGF) axis and mammalian target of rapamycin (mTOR). Therapies targeting the VEGF pathway include bevacizumab, sorafenib, sunitinib, pazopanib, and axitinib, whereas temsirolimus and everolimus inhibit the mTOR pathway. All of these novel therapies—VEGF and mTOR inhibitors—are associated with a variety of unique toxicities, some of which may necessitate expert medical management, treatment interruption, or dose reduction. Common adverse events with newer drugs include hypertension, skin reactions, gastrointestinal disturbances, thyroid dysfunction, and fatigue. Skilled management of these toxicities is vital to ensure optimal therapeutic dosing and maximize patient outcomes, including improved survival and quality of life. This review describes and compares the toxicity profiles of novel molecularly targeted agents used in the treatment of mRCC and presents guidance on how best to prevent and manage treatment-related toxicities. Particular attention is given to axitinib, the newest agent to enter the armamentarium. Axitinib is a second-generation receptor tyrosine kinase inhibitor with potent VEGF receptor inhibition that provides durable responses and superior progression-free survival in advanced RCC compared with sorafenib.
doi:10.1007/s10637-012-9796-8
PMCID: PMC3432793  PMID: 22327313
Axitinib; Renal cell carcinoma; Tyrosine kinase inhibitor; Toxicity; Adverse events
4.  The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer 
Recurrent and/or metastatic squamous cell carcinoma of the head and neck (HNSCC) continues to be a source of significant morbidity and mortality worldwide. Agents that target the epidermal growth factor receptor (EGFR) have demonstrated beneficial effects in this setting. Cetuximab, a monoclonal antibody against the EGFR, improves locoregional control and overall survival when used as a radiation sensitizer in patients with locoregionally advanced HNSCC undergoing definitive radiation therapy with curative intent. Cetuximab is also active as monotherapy in patients whose cancer has progressed on platinum-containing therapy. In the first-line setting for incurable HNSCC, cetuximab added to platinum-based chemotherapy significantly improves overall survival compared with standard chemotherapy alone. These positive results have had a significant impact on the standard of care for advanced HNSCC. In this review, we will discuss the mechanism of action, clinical data and common toxicities that pertain to the use of cetuximab in the treatment of advanced incurable HNSCC.
PMCID: PMC2921255  PMID: 20714355
cetuximab; squamous cell carcinoma of the head and neck; epidermal growth factor receptor

Results 1-4 (4)