cetuximab

An effective and well-tolerated strategy in recurrent and/or metastatic head and neck cancer: successive lines of active chemotherapeutic agents

Source: 7thspace.com Author: staff The combination platinum, 5-fluorouracil (5-FU) and cetuximab is the standard first-line regimen of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Due to the toxicity of this treatment, alternative therapies are often offered to patients. The aim of this study was to evaluate the overall survival obtained with a first line chemotherapy adapted to patients functional status and the administration of all active drugs within successive lines of chemotherapy. Methods: This series included a total of 194 patients with recurrent and/or metastatic HNSCC treated from 2006 to 2011 in a single institution where the administration of successive lines of chemotherapies has been the standard clinical approach. Treatment was administered according to clinical practice guidelines. Results: Most patients received at least two treatment lines. Only 11 patients (6%) were treated with a combination of cisplatin, 5-FU and cetuximab in front line, but most patients received at least one platinum-based regimen (n = 154 patients, 78%); 162 (82%) received taxanes, 36 (18%) received 5-FU, 27 (14%) received capecitabine, 67 (34%) received methotrexate and 134 (68%) received cetuximab. The median overall survival was 9.8 months (95% CI: 8.1-11.4 months) and reached 13.1 months among the subgroup of 131 patients eligible for inclusion in a clinical trial. Conclusion: The survival outcomes of patients treated in the first-line setting with chemotherapy regimens adapted to their functional status, followed by several subsequent regimens were comparable with published outcomes of patients treated by platinum, 5-FU and cetuximab. Credits/Source: BMC Cancer 2014, [...]

Oral Cancer Foundation News Team - A2014-07-12T08:48:52-07:00July, 2014|Oral Cancer News|

Lower radiation dose may be given to HPV-positive head and neck cancer patients

Source: Vanderbilt UniversityPublished: June 19, 2014By: Dagny Stuart A new study suggests that lowering the dose of radiation therapy for some head and neck cancer patients may improve outcomes and cause fewer long-term side effects. The research was presented by lead author Anthony Cmelak, M.D., professor of Radiation Oncology at Vanderbilt-Ingram Cancer Center, during the 50th annual meeting of the American Society of Clinical Oncology (ASCO), held May 30 to June 3 in Chicago. The study focused on patients with newly diagnosed oropharyngeal cancers related to the human papilloma virus (HPV). More than two-thirds of new head and neck cancer patients have HPV-positive tumors and the number of these patients is on the rise. Cmelak’s prior study found that patients with HPV-positive oropharyngeal cancer have significantly longer survival rates than patients whose tumors are HPV negative. For the new study, 80 HPV-positive patients with stage III, or IVa,b squamous cell cancer of the oropharynx received induction chemotherapy, including paclitaxel, cisplatin and cetuximab. After chemotherapy, 62 of the patients showed no sign of cancer and were assigned to receive a 25 percent lower dose of intensity-modulated radiation therapy (IMRT) — an advanced technology that targets the radiation beam more accurately to treat the tumor without harming surrounding tissue. The rest of the patients received a standard IMRT dose. The drug cetuximab was also given to both groups of patients along with the IMRT treatment. Two years after treatment, the survival for the low-dose IMRT patients was 93 percent. Those who did [...]

Charlotte Parker2014-06-20T12:41:01-07:00June, 2014|Oral Cancer News|

Low-dose IMRT may be safe for patients with HPV-positive head and neck cancer

Source: www.oncologypractice.com Author: Laura Nikolaides Lower-dose radiation therapy may be safe for some patients with human papillomavirus (HPV)-positive oropharyngeal cancer, decreasing the risk of often long-term side effects, such as trouble swallowing, dry mouth, loss of taste, neck stiffness, and thyroid problems, investigators reported at the annual meeting of the American Society of Clinical Oncology. Two-year overall survival and progression-free survival were 93% and 80%, respectively, among 62 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma who received lower-dose intensity-modulated radiation therapy (IMRT) after clinical complete response to induction chemotherapy, reported Dr. Anthony Cmelak, professor of radiation oncology at Vanderbilt University, Nashville, Tenn., and medical director of the Vanderbilt-Ingram Cancer Center at Franklin. Overall, the phase II study enrolled 90 patients, median age 57 years, who all received induction chemotherapy with paclitaxel, cisplatin, and cetuximab. The response to induction chemotherapy determined IMRT dose. The 62 patients who had a complete clinical response received a reduced dose (54 Gy) of IMRT, and the rest of the patients received standard dose IMRT (70 Gy). All patients received standard cetuximab along with radiation. Two-year overall survival and progression-free survival for the higher-risk patients who received the standard dose of IMRT were 87% and 65% respectively. Among those patients receiving low-dose IMRT, survival was slightly higher for those with less than 10 pack-years of smoking and earlier-stage disease; in those patients 2-year progression-free and overall survival were 92% and 97%, respectively. However, Dr. Cmelak does not yet recommend modifying regimens for patients with [...]

Oral Cancer Foundation News Team - A2014-06-03T05:55:31-07:00June, 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|

PTEN loss, PIK3CA mutation predicted resistance to cetuximab in HNSCC

June 2, 2013Source: Helio.com CHICAGO — PTEN loss or PIK3CA mutation predicted resistance to treatment with cisplatin plus cetuximab in a cohort of patients with head and neck squamous cell carcinoma, according to phase 3 study results presented at the ASCO Annual Meeting. “Cetuximab is the only targeted therapy in use in head and neck cancer, and although it prolongs survival, the effects are modest. For patients who receive [cetuximab] in the setting of metastatic or recurrent disease, median survival remains less than 1 year,” Barbara Burtness, MD, a medical oncologist at Fox Chase Cancer Center who specializes in head and neck cancers and a HemOnc Today Editorial Board member, said in an interview. “In colon cancer, patients are tested for KRAS mutations to detect patients with upfront resistance to cetuximab, but KRAS mutation is rare in head and neck cancer, and we haven’t had a biomarker to separate the sensitive from resistant patients.” Burtness and colleagues compared cisplatin plus placebo vs. cisplatin plus cetuximab (Erbitux, Eli Lilly) in 117 patients. The researchers also assessed PIK3CA mutations and loss of PTEN expression in the cohort. Results indicated that 34% of tumors studied had a loss of PTEN expression and 4% had PIK3CA mutations in the three hotspots studied. Researchers did not observe any statistically significant differences in OS, PFS or overall response rates. However, among patients with PIK3CA and PTEN expression, median PFS was 4.2 months for those assigned to cetuximab vs. 2.9 months for those assigned to placebo (adjusted [...]

Charlotte Parker2013-06-03T10:20:56-07:00June, 2013|Oral Cancer News|

Erbitux add-on falls short in esophageal cancer

Source: www.medpagetoday.com Author: Charles Bankhead, Staff Writer, MedPage Today The addition of a targeted agent to definitive chemoradiation failed to improve survival in an unselected population with esophageal cancer, a randomized trial showed. In fact, patients who received cetuximab (Erbitux) with chemoradiation had significantly worse overall survival (OS) reflected in a 50% increase in the hazard versus chemoradiation alone, reported Thomas Crosby, MD, of Velindre Hospital in Cardiff, Wales, and colleagues. Investigators could not find any subgroup of patients who benefited from cetuximab, they said in a presentation at the Gastrointestinal Cancers Symposium. "The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Crosby said. "The use of high-quality definitive chemoradiotherapy in the treatment of localized, poor-prognosis esophageal cancer was associated with excellent survival compared with previous radiotherapy and surgical series," he added. Randomized trials have shown that definitive (or primary) chemoradiation improves survival in localized esophageal cancer compared with a single treatment modality. In England, definitive chemoradiation has been used primarily for patients with localized disease that is unsuitable for surgery, Crosby said. Add-on therapy with cetuximab has improved outcomes in other cancers, notably head and neck cancer and colorectal cancer. The findings provided a rationale for evaluating the addition of cetuximab to primary radiation therapy for localized esophageal cancer. Crosby presented results of a randomized trial wherein patients with localized (stage I-III) esophageal cancer (less than 10 cm). Patients were excluded if they had celiac lymph-node involvement. The [...]

Oral Cancer Foundation News Team - A2013-01-28T14:40:16-07:00January, 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|

Facing the facts: HPV-associated head and neck cancers get a second look

Source: www.curetoday.com Author: Charlotte Huff Kevin Pruyne knew he didn’t fit the stereotype of a hard drinker or heavy smoker who one day develops an oral cancer. The 52-year-old mechanic had been working a three-week stint in a remote section of northern Alaska, repairing trucks on an oil field, when he noticed a hard lump beneath his jaw while shaving. For nearly three months, as Pruyne was prescribed antibiotics for a possible infection and then later shuttled between physician specialists, he kept hearing the same thing: the lump could not be cancer. Pruyne only occasionally consumed alcohol and had never smoked. His wife, Kathy, began researching her husband’s symptoms, which included repetitive throat clearing, a nagging sensation that something was lodged in his throat and ringing in his ears. And the lump, which looked like the top half of an egg, felt solid to the touch. This wasn’t some inflamed lymph node from a lingering head cold, Kathy Pruyne says. “He had every symptom [of cancer], but nobody would listen to me.” Pruyne received a diagnosis of stage 4 oral cancer, which started with a tumor at the base of his tongue. He had already begun chemotherapy when he learned that researchers had discovered an association between the human papillomavirus (HPV) and increasing rates of oropharyngeal cancers. He asked that his tissue be tested; the results came back positive. Pruyne says he wanted to know whether his cancer was caused by HPV because “the prognosis is considerably better with HPV-positive cancer.” [...]

Oral Cancer Foundation News Team - A2012-07-03T17:34:09-07:00July, 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|