epidermal growth factor receptor

Dr Jennifer Choe discusses head and neck dancer relapse, new treatment trials, promising responses

Source: www.ajmc.com Author: Brooke McCormick Jennifer Choe, MD, PhD, shared her thoughts on why head and neck cancer patients relapse after radiation therapy, new head and neck cancer treatment trials, and promising responses from these trials. Choe is a head and neck oncologist at Vanderbilt University Medical Center and was a presenter at The American Journal of Managed Care®’s Institute for Value-Based Medicine® held in Nashville, Tennessee on August 17, 2023. Transcript Can you explain some of the thought behind why there is disease relapse in head and neck cancers after radiation treatment? There's a lot of theoretical basis as to why we think this is the case. A lot is driven by just aggressive biology; it's really not known. Head and neck cancers are considered immune responsive, technically speaking, but the response rates still are pretty low, in general, and whether or not the immune system and head and neck cancer patients are depressed compared to other cancers. I, in theory, think that a part of it is actually the radiation creating an environment where there could be a reduction in the body's ability to regulate the immune system. There's an immune suppressed state for these patients that could be due to radiation of the lymph nodes that's decreasing the ability for the immune system to respond, but also the local radiation induced immune suppression effects that may be producing a more conducive environment for the cancer to return. What are some of the trials evaluating new treatment regimens [...]

Oral Cancer Foundation News Team - A2023-09-02T07:41:01-07:00September, 2023|Oral Cancer News|

Docetaxel regimen tops cisplatin in head and neck cancer

Source: www.cancernetwork.com Author: Anna Azvolinsky, PhD A phase II study has demonstrated that combining docetaxel-based chemoradiotherapy and the antibody cetuximab postoperatively in patients with high-risk squamous cell carcinoma of the head and neck led to improved disease-free and overall survival, with no unexpected toxicities. The results of the study were published in the Journal of Clinical Oncology. Two-hundred and thirty-eight stage III and IV patients were randomized to receive radiation therapy (60 Gy) plus cetuximab and either cisplatin (30 mg/m2) or docetaxel (15 mg/m2) once per week as part of the Radiation Therapy Oncology Group (RTOG) 0234 clinical trial. The 2-year overall survival (OS) was 69% in the cisplatin treatment arm and 79% in the docetaxel treatment arm. The 2-year disease-free survival (DFS) was 57% and 66% in the cisplatin and docetaxel arms, respectively. Previously, two large phase III trials, the RTOG 9501 and the European Organisation for Research and Treatment of Cancer (EORTC) 22931 trials, both showed a small but significant survival benefit for postoperative head and neck cancer patients who received adjuvant radiation and chemotherapy concurrently, resulting in the incorporation of cisplatin in an adjuvant regimen for high-risk patients. The drawback was that adding cisplatin to radiation therapy increased toxicity. Many of these patients are not candidates for the combination therapy due to poor performance status, older age, and renal insufficiency. The purpose of the current trial was to test whether combining a molecular therapy such as cetuximab with chemotherapy would improve survival with a better toxicity profile, [...]

Oral Cancer Foundation News Team - A2014-07-19T07:13:12-07:00July, 2014|Oral Cancer News|

Experimental EGFR inhibitor added nothing but rash

Source: www.oncologypractice.com Author: Neil Osterweil, Oncology Report Digital Network The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up. The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark. Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium. The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison. "Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge," Dr. Harari said. "We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition," he said. Dr. Overgaard and [...]

Oral Cancer Foundation News Team - A2014-03-19T07:20:46-07:00March, 2014|Oral Cancer News|

Are combination therapies effective for advanced SCCHN?

Source: Author: DrBicuspid Staff In a recent study, researchers from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center examined whether the addition of multiple drugs to radiation therapy is superior to the current standard of care therapy with one drug and radiation for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Their data, published in the Journal of Clinical Oncology, suggests that it does not (March 4, 2013). Standard therapy for SCCHN is a combination of the drug cisplatin and radiotherapy. This clinical trial compared this combination to the combination with the addition of a small-molecule inhibitor of the epidermal growth factor receptor (EGFR) erlotinib. For the study, 204 patients with locally advanced SCCHN were recruited between December 2006 and October 2011. Participants were assigned to receive either cisplatin and radiotherapy or the same chemoradiotherapy with erlotinab. EGFR is a therapeutic target for this type of cancer, and at least one other EGFR is approved for multiple uses in treating head and neck cancer, including in combination with radiation. To date, no data have been published on the use of EGFR inhibitors in combination with chemotherapy and radiation. The goal of the current study was to determine if adding EGRF inhibition improved efficacy when combined with standard of care radiation. Unfortunately, the researchers found that the addition of EGRF did not improve clinical response rate or progression-free survival. "There has been great enthusiasm and some confusion about the combinations of chemotherapy and biologic therapy such [...]

Oral Cancer Foundation News Team - A2013-03-12T07:00:53-07:00March, 2013|Oral Cancer News|

New drug combination could prevent head and neck cancer in high-risk patients

Source: www.sciencedaily.com Author: staff A new drug combination shows promise in reducing the risk for patients with advanced oral precancerous lesions to develop squamous cell carcinoma of the head and neck. The results of the study, which included preclinical and clinical analyses, were published in Clinical Cancer Research, a journal of the American Association for Cancer Research. "Squamous cell carcinoma of the head and neck (SCCHN) is the most common type of head and neck cancer," said Dong Moon Shin, M.D., professor of hematology, medical oncology and otolaryngology at Emory University School of Medicine, and director of the Cancer Chemoprevention Program at Winship Cancer Institute at Emory University in Atlanta, Ga. "The survival rate for patients with SCCHN is very poor. An effective prevention approach is desperately needed, especially since we can identify patients who are at extremely high risk: those with advanced oral precancerous lesions." Based on prior research suggesting a role for epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in promoting SCCHN, Shin and colleagues believed combining an EGFR inhibitor and a COX-2 inhibitor could provide an effective chemopreventive approach. They found that the combination of the EGFR inhibitor erlotinib and the COX-2 inhibitor celecoxib was more effective for inhibiting the growth of human SCCHN cell lines compared with either drug alone. In addition, treating mice with the drug combination prior to transplanting them with human SCCHN cells more effectively suppressed cancer cell growth than did pretreating the mice with either drug alone. Based on these preclinical [...]

Oral Cancer Foundation News Team - A2013-02-20T07:38:26-07:00February, 2013|Oral Cancer News|

Scientists find new way to boost cancer drugs

Source: www.drbicuspid.com Author: DrBicuspid Staff Shutting down a specific pathway in cancer cells appears to improve the ability of common drugs to wipe those cells out, according to new research from scientists at Fox Chase Cancer Center (Cancer Discovery, January 2013, Vol. 3:1, pp. 96-111). The new approach appears to enhance the tumor-killing ability of a commonly prescribed class of drugs that includes cetuximab (Erbitux), used to treat head and neck cancers. These drugs work by blocking the activity of the epidermal growth factor receptor (EGFR), which sits on the cell surface and senses cues from the environment, telling cancer cells to grow and divide, according to co-author Igor Astsaturov, MD, PhD, an attending physician in the department of medical oncology at Fox Chase. In 2010, Dr. Astsaturov and his colleagues identified a pathway in the cell that, when blocked, completely suppressed EGFR activity. Interestingly, the pathway consists of a series of enzymes that, when working in concert, synthesize new molecules of cholesterol. Working with cancer cells in the lab, the researchers inactivated a key gene in the cholesterol synthesis pathway, and found the cells became more vulnerable to treatment with cetuximab. The same was true in mice that lacked this particular pathway, according to Dr. Astsaturov. "Most tumors are only moderately sensitive to inhibitors of EGFR, but when these tumors lack an essential gene in the cholesterol pathway, they become exquisitely sensitive to the anti-EGFR drugs," he said. "The cancers literally melt away in mice." The researchers then removed [...]

Oral Cancer Foundation News Team - A2013-01-21T07:05:01-07:00January, 2013|Oral Cancer News|

The Impact of Timing of EGFR and IGF-1R Inhibition for Sensitizing Head and Neck Cancer to Radiation

Source: AntiCancer Research Abstract Background: Targeting the epidermal growth factor receptor (EGFR) improved radiotherapy outcome by 10-15% in head and neck tumors (HNSCC). We tested the therapeutic benefits of co-targeting EGFR and insulin-like growth factor-1 receptor (IGF-1R) to further enhance tumor response to radiation. Materials and Methods: Mice bearing FaDu tumor xenografts were treated with ganitumab (previously known as AMG479, an anti-IGF-1R antibody), panitumumab (an anti-EGFR antibody), or both in combination with fractionated doses of radiation. Tumor growth delay and tumor cure/recurrence served as end-points. Results: The best tumor growth delay was achieved when ganitumab and panitumumab were given concurrently with radiation. Tumor cure/recurrence studies showed that combining ganitumab, panitumumab and radiation resulted in significantly higher radiocurability rates than use of either of the agents given with radiation. Conclusion: These findings provide the rationale for clinical testing of the combination of ganitumab and panitumumab for the treatment of HNSCC. This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Charlotte Parker2012-07-26T09:29:45-07:00July, 2012|Oral Cancer News|

Head and neck cancer presentation highlights

Source: www.dailyrx.com Author: Travis Giddings The field of head and neck cancer from ASCO 2012 A recent presentation at the American Society of Clinical Oncology expanded on several molecular breakthroughs concerning head and neck cancers, and a team of doctors gave an overview of recent conclusions from their respective fields. The newly identified molecular pathway for cancers of the head and neck that involves the epidermal growth factor receptor (EGFR) led to developments of highly effective drugs specific for the cancerous cells, EGFR inhibitors. Soon afterwards, scientists discovered the increasingly important role that the human papillomavirus (HPV) played in the development of cancers in the head and neck. Following the explosion of research in the field of molecular pathways involved in head and neck cancers, doctors quickly found that the cancer was a lot more complicated than previous believed. Additional research continues as scientists try to make sense of the data. Approaching the treatment of head and neck cancer from their perspectives from surgery, radiology, and oncology, doctors on the panel discussed the difficulties the field currently faced. The director of Johns Hopkins' Head and Neck Cancer Research department, oncologist David Sidransky, MD, opened the meeting. “The genetic and epigenetic alterations in human tumors are becoming increasingly important for devising and implementing personalized oncology approaches,” said Dr. Sidransky. “Unlike in some other cancers, in head and neck cancer the common mutations that have been identified have not been very helpful for treatment.” The chair of the conference was held by [...]

Oral Cancer Foundation News Team - A2012-06-08T07:56:18-07:00June, 2012|Oral Cancer News|

Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer

Source: Journal of Clinical Oncology To the Editor: In their article, Chaturvedi et al1 document the rise in human papillomavirus (HPV) –associated cancers as a proportion of squamous cell carcinomas of the oropharynx over the last 25 years. The contemporary figures are mirrored by two recent British studies2,3 demonstrating that the majority of oropharyngeal cancers are now HPV related. In the accompanying editorial,4 Mroz et al rightly highlight the importance of evaluating HPV vaccination for both men and women in the light of these data and lament the lack of significant improvement in the outcomes for non–HPV-associated head and neck cancers. However, they also suggest that the benefit of targeting epidermal growth factor receptor (EGFR) through concurrent cetuximab may be confined to HPV-associated tumors. Although EGFR expression per se does not correlate closely with response to cetuximab, there is increasing evidence of an inverse correlation between p16INK4A expression (as a marker of HPV association) and EGFR expression shown by immunohistochemistry.5,6 Though suppressed by viral oncogenes, HPV-associated tumors retain wild-type P53,7 and patients with this tumor type have demonstrated excellent survival with existing protocols such as concurrent chemoradiotherapy or surgery with postoperative radiotherapy. Conversely, non-HPV tumors, harboring a range of mutations,8 may respond less well to DNA-damaging agents, but patients with these tumors might benefit from the addition of concurrent EGFR blockade to radiotherapy. Data from the recent SPECTRUM (Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer) study of adding another EGFR-targeting monoclonal antibody, panitumumab,9 [...]

Charlotte Parker2012-03-09T10:34:29-07:00March, 2012|Oral Cancer News|

Erlotinib dose doubled for smokers with head/neck cancer

Source: www.oncologyreport.com Author: Miriam E. Tucker Giving smokers a higher, short-course dose of erlotinib before definitive surgery for squamous cell carcinoma of the head and neck resulted in favorable responses for the first patients evaluated in a small pilot study. Investigators gave 300 mg of erlotinib (Tarceva) to smokers daily and 150 mg daily to nonsmokers who had a waiting period of more than 14 days before scheduled surgery for head and neck cancer. Seven of the 10 patients evaluated so far had partial responses and 3 had stable disease, according to a poster presented at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology. The study was based on recent data in non–small cell lung cancer (NSCLC) patients showing that smokers metabolize erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, twice as quickly as do nonsmokers (J. Clin. Oncol. 2009;27:1220-6), said lead author Dr. Mercedes Porosnicu of Wake Forest Baptist Medical Center in Winston Salem, N.C. That study established the maximum tolerated dose of erlotinib at 300 mg daily in NSCLC patients who smoke. Dr. Poroniscu’s presentation included the case study of a smoker with a very large oral cavity tumor protruding through his lips. He was described as being in significant pain and unable to eat or chew. The first CT scan showed a tumor of at least 8 cm and there was "significant metabolic activity" on PET scan. "At 6 days of erlotinib treatment, his tumor was obviously smaller and he could [...]

Oral Cancer Foundation News Team - A2012-01-28T08:25:19-07:00January, 2012|Oral Cancer News|