Track topics on Twitter Track topics that are important to you
There is no optimal treatment for patients with recurrent head and neck cancer after previous radiation. Chemotherapy alone is not curative and patients survive an average of only 6 to 10 months. Surgery is not always possible and often cannot remove every cancerous cell. On the other hand, reirradiation with chemotherapy cures approximately 25 to 30% of patients but has significant toxicity with as many as 15 to 20% suffering from life-threatening or fatal complications. Therefore, less toxic and more effective reirradiation regimens are urgently needed. There are extensive data from animal studies and preliminary human studies showing that blocking epidermal growth factor receptor (EGFR) and COX-2 enhances radiation effect and is more effective than either treatment alone. Erlotinib is a FDA approved oral inhibitor of EGFR and celecoxib is a FDA approved COX-2 inhibitor. Both have been well studied in humans and appear to have less severe toxicity than conventional chemotherapeutic agents.
Despite advances in the treatment of head and neck cancer, locoregional recurrences are the predominant site of treatment failure and are frequently the cause of death. Second primary tumors in the head and neck occur in up to 30% of patients at 10 years of follow-up after eradication of the original tumor due to field cancerization. The standard approach to patients with recurrent but non-metastatic disease has been surgical salvage alone. Unfortunately, this strategy is feasible in only a select group of patients and 5 year survival rates have ranged from 15-40%.
Most patients with previously irradiated unresectable recurrent or metastatic head and neck cancer are treated with chemotherapy alone. This approach has offered limited palliation with response rates of 10-40%, median survival of 5 to 10 months. While this may be an acceptable option for patients with clearly incurable widespread metastatic disease, it may not be the best approach for those patients with potentially curable locoregional disease.
While geographic misses and second primary tumors occur, the majority of patients have radioresistant tumors. Therefore, reirradiation alone is unlikely to be effective. High dose reirradiation with concomitant chemotherapy represents a more aggressive approach resulted in encouraging 3-year survival rates of 15 to 35%. This approach represents a potentially curative option for patients with unresectable or partially resected disease arising in a previously irradiated volume. However, the high rates of acute and late toxicity with this approach have limited widespread application of this approach.
Extensive preclinical and clinical data suggest that both epidermal growth factor receptor (EGFR) antagonists and cycloxygenase-2 (COX-2) inhibitors enhance the effectiveness of ionizing radiation. In locally advanced head and neck cancer, a recent phase III trial concurrent anti-EGFR monoclonal antibody and radiation demonstrated improved local control, disease free survival and overall survival compared to radiation alone without the increased mucosal toxicity associated with concurrent chemotherapy. COX-2 inhibition and anti-EGFR therapy demonstrates activity against recurrent/metastatic head and neck cancer in a recent phase I study. Head and neck cancer represents an ideal site to study biologic markers of tumor response because of the accessibility of tumors for biopsy. Therefore, we propose the combination of Erlotinib and Celecoxib with radiation in a cohort of previously irradiation patients with head and neck cancer.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Cancer of the Pharynx
erlotinib + celecoxib
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Published on BioPortfolio: 2014-07-23T21:13:28-0400
RATIONALE: Celecoxib and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Celecoxib may also stop the growth of liver cancer by blockin...
RATIONALE: Erlotinib and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Celecoxib may also stop the growth of lung cancer by blocking ...
This phase II trial is studying how well giving erlotinib together with celecoxib works in treating patients with recurrent stage IIIB or stage IV non-small cell lung cancer. Erlotinib and...
RATIONALE: Celecoxib and erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase I trial is studying the side effects and best...
This is phase II randomized clinical trial to study the effect of COX-2 inhibitor Celecoxib and EGFR tyrosine kinase inhibitor Erlotinib alone or in combination on molecular markers of apo...
Erlotinib is used for treating non-small cell lung cancer (NSCLC). Intestinal absorption of erlotinib is impaired under gastric pH elevation, therefore, co-administration of gastric acid suppressants ...
The present study investigated the preventive effect of the cyclooxygenase (COX)-2 inhibitor, celecoxib, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer in a rat model.
The phase II JO28638 study evaluated first-line onartuzumab plus erlotinib in patients with MET-positive advanced, metastatic, or post-operative recurrent non-small-cell lung cancer (NSCLC) with epide...
Erlotinib is used to treat non-small-cell lung cancer (NSCLC). Erlotinib was subsidized on the Pharmaceutical Benefits Schedule in Australia for the treatment of advanced stage (IIIB or IV) NSCLC (Aug...
Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations are often successfully treated with EGFR tyrosine kinase inhibitor (TKI) such as erlotinib; however, treatment resistance ine...
A quinazoline derivative and ANTINEOPLASTIC AGENT that functions as a PROTEIN KINASE INHIBITOR for EGFR associated tyrosine kinase. It is used in the treatment of NON-SMALL CELL LUNG CANCER.
Tumors or cancer of the PHARYNX.
A general concept for tumors or cancer of any part of the EAR; the NOSE; the THROAT; and the PHARYNX. It is used when there is no specific heading.
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
An accumulation of purulent material in the space between the PHARYNX and the CERVICAL VERTEBRAE. This usually results from SUPPURATION of retropharyngeal LYMPH NODES in patients with UPPER RESPIRATORY TRACT INFECTIONS, perforation of the pharynx, or head and neck injuries.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...