cetuximab

Use of carbon nanoparticles paves way to customized cancer therapy

Source: www.azonano.com Author: Cameron Chai A research study by Jeffrey Myers from the University of Texas MD Anderson Cancer Center and James Tour from the Rice University has reported that a combination of carbon nanoparticles and existing drugs has the capability to improve head-and-neck cancer treatment, particularly when coupled with radiation therapy. The novel technique encapsulates chemotherapeutic drugs using carbon nanoparticles, which sequester the drugs until their delivery into the targeted cancer cells, opening the door to develop customized therapies based on the requirements of individual patients. The researchers have developed a simple technique to mix Cetuximab, a targeting agent, and paclitaxel, a hydrophobic active chemotherapy agent marketed as Taxol, with hydrophilic carbon clusters that are functionalized with polyethylene glycol or PEG-HCC. According to the researchers, Cetuximab, paclitaxel and PEG-HCC ingredients combine easily and form a water-soluble compound that targets tumors more effectively than Taxol, while eliminating the toxic effects of Cremophor EL and paclitaxel on neighboring healthy cells. Cremophor EL is a carrier based on castor oil that makes the hydrophobic paclitaxel into a water-soluble compound and delivers it to patients intravenously. Tour commented that the novel technique utilizes a very small quantity of chemotherapy drug. Myers informed that tests involving the use of Cetuximab, paclitaxel and PEG-HCC ingredients and radiation therapy on mice demonstrated a substantial increase in destroying tumors. The researchers’ hypothesis is paclitaxel detects the tumor cells to the radiation effects and Cetuximab and PEG-HCC augment the delivery of paclitaxel into the cancer cells, Myers [...]

Oral Cancer Foundation News Team - A2012-02-19T10:42:23-07:00February, 2012|Oral Cancer News|

Fatal Infusion Reactions to Cetuximab: Role of Immunoglobulin E–Mediated Anaphylaxis

Source: Journal of Clinical Oncology To the Editor: In Journal of Clinical Oncology, Tronconi et al1 report a fatal hypersensitivity reaction to cetuximab in a 63-year-old patient with metastatic colon cancer and outlined a 0.1% incidence of death in the literature. We greatly acknowledge the authors' desire to communicate the risk of fatal anaphylactic reaction with cetuximab. Over the past 2 years in our center in Tours, France, four instances of grade 4 anaphylactic reactions occurred in patients treated for head and neck cancer (locally advanced or metastatic), with one immediately fatal; another patient died within 5 days (unpublished data). Seven lethal anaphylactic reactions were registered in a pharmacovigilance survey in France, based on spontaneous declarations (Grandvuillemin et al, manuscript in preparation). Anaphylaxis to cetuximab is a problem that merits serious clinical attention. In the authors' words, “the pathogenic mechanisms underlying the development of this phenomenon remain to be elucidated.”1 They raise the hypothesis of immunoglobulin E (IgE) –independent mechanisms, even in the context of a paradoxic atopic history. Moreover, Tronconi et al suggest that the field “search for reliable risk factors that can facilitate the safe selection of patients as candidates for cetuximab-based treatment.”1 These comments are quite surprising, because they do not integrate major contributions that have been previously published. Indeed, it has been known for 3 years that anaphylaxis to cetuximab is the result of antidrug IgE antibodies present in patient serum before therapy.2 These IgE antibodies are directed against galactose-α-1, 3-galactose (α3Gal) residues, present in the [...]

Charlotte Parker2012-01-19T10:24:57-07:00January, 2012|Oral Cancer News|

Third Head and Neck Indication for Erbitux

Source: The ASCO Post, January 1, 2012, Volume 3, Issue 1, Matthew Stenger In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.Cetuximab (Erbitux) was recently approved by the FDA for use in combination with platinum-based therapy plus fluorouracil (5-FU) for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.1-3 Cetuximab has prior indications in combination with radiation therapy in locally or regionally advanced squamous cell head and neck cancer and in recurrent or metastatic head and neck cancer that has progressed after platinum-based therapy. It also has indications in colorectal cancer. The most recent approval is based primarily on results of a study conducted outside the United States in 442 patients with metastatic or locally recurrent squamous cell carcinoma of the head and neck who were not suitable for curative treatment with surgery or radiation. The study used a European Union (EU)-approved cetuximab rather than the U.S.-approved cetuximab (Erbitux). Erbitux provides approximately 22% higher exposure than the EU-approved cetuximab; these pharmacokinetic data, together with the results of the study conducted in Europe and other data using Erbitux establish the safety and efficacy of Erbitux at the recommended dose.In this trial, the addition of cetuximab (n = 222) to platinum-based therapy plus 5-FU (n = 220) significantly increased median overall survival from 7.4 to 10.1 months, representing a 20% reduction in risk of death [...]

Oral Cancer Foundation News Team - A2012-01-07T17:15:00-07:00January, 2012|Oral Cancer News|

FDA Approves Cetuximab for Late-Stage Head and Neck Cancer

Source: The Oncology Report The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy. Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy. The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.) Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site. The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy. [...]

Oral Cancer Foundation News Team - A2011-11-09T11:05:16-07:00November, 2011|Oral Cancer News|

US FDA approval for expanded use of Erbitux

Source: www.pharmabiz.com Author: staff The US Food and Drug Administration (FDA) has approved Erbitux (cetuximab), in combination with platinum-based chemotherapy with 5-fluorouracil (CT), for the first-line treatment of recurrent locoregional or metastatic squamous cell carcinoma of the head and neck (SCCHN). The approval, which is based on data from the landmark EXTREME (ErbituX in first-line Treatment of REcurrent or MEtastatic head & neck cancer) trial, makes Erbitux plus CT the first treatment regimen approved in 30 years with extended overall survival in patients with recurrent locoregional or metastatic SCCHN. Erbitux (cetuximab) is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumour cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown that binding of ERBITU Erbitux GFR blocks phosphorylation and activation of receptor-associated kinases, resulting in induction of apoptosis (cell death), inhibition of cell growth, and decreased matrix metalloproteinase and vascular endothelial growth factor production. In vitro, Erbitux can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. In vitro assays and in vivo animal studies have shown that Erbitux inhibits the growth and survival of tumour cells that express the EGFR. No anti-tumour effects of Erbitux were observed in human tumour xenografts lacking EGFR expression. EXTREME, which was previously published in the New England Journal of Medicine, was a phase III open label, randomized, multi-centre, controlled trial. This study was conducted outside the US by [...]

Oral Cancer Foundation News Team - A2011-11-09T06:24:41-07:00November, 2011|Oral Cancer News|

FDA Approves Cetuximab for Metastatic Head and Neck Cancer

Source: MedScape News Today The US Food and Drug Administration (FDA) has approved cetuximab (Erbitux, Bristol-Myers Squibb ) for use in combination with chemotherapy for the treatment of metastatic head and neck cancer. Data show that when combined with cisplatin-based chemotherapy, cetuximab improved overall survival, compared with chemotherapy alone. According to the researchers, this is the first time in 3 decades — since cisplatin was first used in head and neck cancer — that any regimen has improved on its success. The improved survival that was seen after cetuximab was added to the regimen (at a median of 2.7 months) is "therefore notable." Cetuximab was approved in the United States in 2004 for the treatment of epidermal growth-factor receptor–positive late-stage colon cancer in patients who no longer responded to chemotherapy. In 2006, it was approved for use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. This latest approval expands on that to cover metastatic head and neck cancer. The ability of cetuximab "to extend the lives of patients with head and neck cancer is an important tool for oncologists, who often rely on a multitreatment approach for patients," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in a statement." Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have [...]

Oral Cancer Foundation News Team - A2011-11-08T12:00:48-07:00November, 2011|Oral Cancer News|

New Therapies and Prognostic Techniques Highlighted in Head and Neck Cancer

The Asco Post D. Neil Hayes, MD, MPH, of the University of North Carolina at Chapel Hill, described efforts to position the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux) in head and neck cancer treatment. Surprisingly negative results came from the phase III Radiation Therapy Oncology Group (RTOG) 0522 trial (N = 940), which showed no benefit to adding cetuximab to the radiation/cisplatin platform for front-line therapy of advanced head and neck squamous cell carcinoma.1 At 2 years, progression-free survival was approximately 64% in both arms; overall survival was 79.7% with chemoradiation (P = .68) and 82.6% with the addition of cetuximab (P = .17). Rates of locoregional relapse and distant metastases were also similar. Cetuximab increased grade 3/4 mucositis (43% vs 33%;P < .004), in-field skin toxicity (25% vs 15%;P < .001), and out-of-field skin reactions (19% vs 1%;P < .001), but toxicity beyond 90 days was similar between the arms. "RTOG 0522 was the study of the year in head and neck cancer. Unfortunately, it was flat-out negative," Dr. Hayes noted. No differential effect emerged by p16 (HPV status). "While 70% of patients had oropharynx tumors (suggesting HPV positivity), tissue collection was lacking in half the patients. Our ability to make inferences with this amount of missing data is very limited," Dr. Hayes said. Even as a negative study, RTOG 0522 is practice-changing. "Many physicians have been treating with this regimen, assuming this study would be positive," he said. "But we now have no data to support this." Cetuximab Equivalent [...]

Oral Cancer Foundation News Team - A2011-10-18T09:58:29-07:00October, 2011|Oral Cancer News|

Researchers find potential new therapeutic strategy for head and neck cancer

Source: www.uab.edu Author: Beena Thannickal Shih-Hsin (Eddy) Yang, M.D., Ph.D., an assistant professor in the UAB Department of Radiation Oncology and associate scientist in the experimental therapeutics program at the UAB Comprehensive Cancer Center, found a way to prevent head and neck cancer cells from repairing damage to DNA as they grow. The findings, published by the Public Library of Science, showed that using the drug cetuximab can induce a DNA repair defect in head and neck cancer cells, and subsequently render the tumors susceptible to PARP inhibitors, which block enzymes that repair some types of DNA damage. This method prevents cancer cells from repairing the damage to the DNA as they grow, ultimately leading to cancer inhibition. Poly ADP-ribose polymerases, or PARPs, are enzymes that repair some types of damage done to DNA. If they are inhibited, a backup repair pathway is initiated. Cetuximab, which inhibits the epidermal growth factor receptor signaling pathway of cancer cells, blocks this backup pathway and thus induces cancer cell death. “The novelty of this finding is that we use targeted agents like cetuximab, in combination with a PARP inhibitor, ABT-888, both of which have already been tested to be safe in humans, to selectively kill tumors defective in DNA repair while potentially minimizing side effects,” says Yang. Cetuximab was pioneered by James Bonner, M.D., chair of the UAB Department of Radiation Oncology, in a landmark multi-institutional clinical trial in head and neck cancer patients. Because head and neck cancers are frequently aggressive, outcomes [...]

Oral Cancer Foundation News Team - A2011-09-23T16:29:08-07:00September, 2011|Oral Cancer News|

Cancer drug resistance strategy uncovered

Source: Cancer Research UK Author: Staff Friday 9 September 2011- US scientists have identified a way in which cancer cells can become resistant to the cancer drug cetuximab (Erbitux), and suggest that treatments that are already available might be able to overcome this resistance. Researchers from the Dana-Farber Cancer Institute in Boston, US, have been studying why some patients only experience short-term benefits with cetuximab, or none at all. Cetuximab is an antibody that interferes with cancer cell growth. It can be given in combination with chemotherapy to patients with bowel cancer or head and neck cancer. Until now, scientists didn't know why some cancers failed to respond to the drug, or initially responded but then became resistant. The new study, published in Science Translational Medicine, found that in some of the drug-resistant cells, a protein known as ErbB2 (also known as HER2/neu) was sending 'grow' signals. These were bypassing the 'stop growing' signals caused by the drug. Pasi Janne, the study's co-senior author, said: "ErbB2 activates a critical signalling pathway that is not normally blocked by cetuximab, and in this way subverts cetuximab's function. "Because ErbB2 isn't affected by cetuximab, this is an easy way for cancers to become resistant to the drug." The researchers suggest that combining cetuximab with already available ErbB2 inhibitors such as trastuzumab (Herceptin) could produce an effective therapy to tackle cancers that previously showed resistance to cetuximab. Henry Scowcroft, science information manager at Cancer Research UK, said: "Unfortunately, patients's tumours can become resistant to treatment, and understanding why this happens is a [...]

Charlotte Parker2011-09-09T12:20:44-07:00September, 2011|Oral Cancer News|

Strategy to conquer cancer drug resistance uncovered

Source: info.cancerresearchuk.org Author: staff US scientists have identified a way in which cancer cells can become resistant to the cancer drug cetuximab (Erbitux), and suggest that treatments that are already available might be able to overcome this resistance. Researchers from the Dana-Farber Cancer Institute in Boston, US, have been studying why some patients only experience short-term benefits with cetuximab, or none at all. Cetuximab is an antibody that interferes with cancer cell growth. It can be given in combination with chemotherapy to patients with bowel cancer or head and neck cancer. Until now, scientists didn't know why some cancers failed to respond to the drug, or initially responded but then became resistant. The new study, published in Science Translational Medicine, found that in some of the drug-resistant cells, a protein known as ErbB2 (also known as HER2/neu) was sending 'grow' signals. These were bypassing the 'stop growing' signals caused by the drug. Pasi Janne, the study's co-senior author, said: "ErbB2 activates a critical signalling pathway that is not normally blocked by cetuximab, and in this way subverts cetuximab's function. "Because ErbB2 isn't affected by cetuximab, this is an easy way for cancers to become resistant to the drug." The researchers suggest that combining cetuximab with already available ErbB2 inhibitors such as trastuzumab (Herceptin) could produce an effective therapy to tackle cancers that previously showed resistance to cetuximab. Henry Scowcroft, science information manager at Cancer Research UK, said: "Unfortunately, patients's tumours can become resistant to treatment, and understanding why this happens is a major [...]

Oral Cancer Foundation News Team - A2011-09-09T05:32:14-07:00September, 2011|Oral Cancer News|