Targeted therapy and promising novel agents for the treatment of advanced soft tissue sarcomas

Introduction: Soft tissue sarcomas (STS) are a rare and difficult to treat malignancy. Efforts to utilize targeted therapy have been ongoing for the last decade and have resulted in the approval of pazopanib for treatment of advanced disease. Although several other agents have been investigated, the inability to predict responses remains a limiting factor to the incorporation of these agents into treatment.

Areas covered: The authors summarize recent clinical findings from studies focused on targeted agents in STS. The authors also discuss the potential approaches and ongoing clinical trials with novel agents.

Expert opinion: A major challenge in the treatment of advanced STS remains a lack of predictive biomarkers to guide therapy and the heterogeneity of response among different histologies of sarcoma. Incorporation of predictive biomarker analysis into clinical trials is warranted. Additionally, mechanisms of treatment resistance and parallel pathways of tumor growth pose challenges in how we treat these tumors. An active area of research in STS is the use of novel combinations of agents, such as chemotherapy combined with multi-targeted agents. The potential of immune check point inhibitors is being explored in advanced STS and is hoped to further expand our treatment armamentarium.     

Treatment of multiple keratoacanthomas with erlotinib

An 82-year-old male presented with numerous pruritic erythematous nodules over his trunk and extremities. Histopathology was consistent with keratoacanthomas. Given the extent of his disease, medical therapy was recommended. Based on phosphorylated epidermal growth factor receptor expression in lesional keratinocytes, treatment with erlotinib 150 mg daily was initiated, with rapid improvement in the number and appearance of nodules. Immunohistochemistry following treatment revealed a decrease in lesional pEGFR expression, consistent with inhibition of this receptor activation. This is the first report of multiple keratoacanthomas responding to therapy with an EGFR tyrosine kinase inhibitor, and it supports an emerging role for the use of EGFR inhibitors in the management of cutaneous malignancies.     

Effectiveness of antigliadin antibodies as a screening test for celiac disease in children

OBJECTIVE: To test the effectiveness of serologic antigliadin antibody (AGA) testing in predicting celiac disease in children. DESIGN: Prospective clinical assessment. SETTING: Hôpital Sainte-Justine, montreal. PATIENTS: A total of 176 children with possible celiac disease who were referred for duodenal biopsy between January 1992 and June 1995. OUTCOME MEASURES: IgA and IgG AGA titres, as determined by enzyme-linked immunosorbent assay (ELISA); duodenal biopsy; clinical outcome on a gluten-free diet. RESULTS: Of the 176 children 30 were found to have celiac disease according to the criteria of the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN). The sensitivity and specificity of the IgA AGA titre, as well as its positive and negative predictive values, were 80%, 92%, 67% and 96% respectively; the corresponding values for the IgG AGA titre were 83%, 79%, 45% and 96%. The respective values for IgA and IgG AGA titres combined were 93%, 71%, 43% and 98%. Only 2 of the 30 patients with celiac disease had false-negative results for both IgA and IgG AGA titres. The IgA and IgG AGA titres decreased significantly (p < 0.005) in all 11 patients after being on a gluten-free diet for at least 10 months and reached normal values in 8. CONCLUSION: AGA screening for celiac disease permits better selection of patients for duodenal biopsy and adds specificity to the histologic diagnosis. Such screening cannot replace intestinal biopsy, which remains the gold standard for diagnosis.     

Stereotactic radiosurgery for brain metastases from primary head and neck carcinomas: a retrospective analysis

Journal of Neuro-Oncology - Patients with head and neck malignancies commonly develop metastatic disease, yet rarely do these carcinomas metastasize to the brain. Stereotactic radiosurgery (SRS) is...     

Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis : results from a Northwestern University Costs of Cancer Program pilot study with head and neck and nonsmall cell lung cancer patients who received care at a county hospital, a Veterans Administration hospital, or a comprehensive cancer care center

BACKGROUND.: Few studies have examined the costs of supportive care for radiochemotherapy-induced mucosits/pharyngitis among patients with head and neck cancer (HNC) or lung cancers despite the documented negative clinical impact of these complications. METHODS.: The authors identified a retrospective cohort of patients with HNC or nonsmall lung cancer (NSCLC) who had received radiochemotherapy at 1 of 3 Chicago hospitals (a Veterans Administration hospital, a county hospital, or a tertiary care hospital). Charts were reviewed for the presence/absence of severe mucositis/pharyngitis and the medical resources that were used. Resource estimates were converted into cost units obtained from standard sources (hospital bills, Medicare physician fee schedule, Red Book). Estimates of resources used and direct medical costs were compared for patients who did and patients who did not develop severe mucositis/pharyngitis. RESULTS.: Severe mucositis/pharyngitis occurred in 70.1% of 99 patients with HNC and in 37.5% of 40 patients with NSCLC during radiochemotherapy. The total median medical costs per patient were $39,313 for patients with mucositis/pharyngitis and $20,798 for patients without mucositis/pharyngitis (P = .007). Extended inpatient hospitalization accounted for $12,600 of the increased medical costs (median 14 days [$19,600] with severe mucositis/pharyngitis vs 5 days [$7000] without; P = .017). For patients who had HNC with mucositis/pharyngitis, incremental inpatient hospitalization costs were $14,000, and total medical costs were $17,244. For patients who had NSCLC with mucositis/pharyngitis, these costs were $11,200 and $25,000, respectively. CONCLUSIONS.: In the current study, the medical costs among the patients with HNC and NSCLC who received radiochemotherapy were greater for those who developed severe mucositis/pharyngitis than for those who did not. Cancer 2008. (c) 2008 American Cancer Society.     

Multidisciplinary Symposium on Head and Neck Cancer. 2 December 2005, Philadelphia, PA, USA

The Multidisciplinary Symposium on Head and Neck Cancer focused on the emerging data that underlie optimal treatment for head and neck cancers, with a particular focus on squamous cell carcinoma of the head and neck. In-depth discussions showcased the published Phase II and Phase III data on the treatment of locally advanced disease with both induction chemotherapy and concurrent chemoradiotherapy. Molecular targets of interest and relevance in this tumour type were identified, as were the agents which target these putative proteins or pathways of carcinogenesis. Preliminary results from trials incorporating molecularly-targeted agents have shown a promising role for these compounds in the management of both locally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck. The Symposium brought a clear message. The management of squamous cell carcinoma of the head and neck has evolved considerably, and with the advent of newer chemotherapeutic agents and molecularly targeted therapies, this field will continue to expand over time.