cisplatin – Page 5 – 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|

Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial

Source: OncologyStat.com TAKE-HOME MESSAGE This randomized, placebo-controlled trial found that weekly palifermin was associated with decreased incidence and duration of severe oral mucositis in patients undergoing postoperative chemoradiotherapy for head and neck cancer. SUMMARY OncologySTAT Editorial Team Combined chemoradiotherapy (CRT) offers improved outcomes after resection of locally advanced head and neck cancer but also increases the risk of oral mucositis, a debilitating and potentially dose-limiting toxicity of locoregional treatment. Palifermin, an analogue of keratinocyte growth factor, is FDA approved to prevent and treat mucositis in patients undergoing high-dose myelotoxic therapy for hematologic malignancies. In this multicenter, randomized, placebo-controlled trial, Henke et al evaluated whether palifermin reduces severe oral mucositis in patients undergoing CRT after surgical resection of locally advanced head and neck cancer. Adult patients receiving postoperative CRT for high-risk stage II to IVB head and neck squamous cell carcinoma and with an ECOG performance status of 0 to 2 were enrolled from 38 centers in Europe, Australia, and Canada. Eligible study patients were stratified by tumor location (oral cavity/oropharynx or hypopharynx/larynx) and residual tumor (R0 [complete resection] or R1 [incomplete resection]). Study patients received a radiation dose of 60 Gy (R0 group) or 66 Gy (R1 group) plus cisplatin 100 mg/m2 on days 1 and 22, with the study drug administered 3 days prior to starting CRT and then weekly for 6 weeks. Patients who underwent radiotherapy after 6 weeks received an additional 100 mg/m2 of cisplatin and study drug. Oral saline rinses, topical anesthetics, feeding tubes, and hematopoietic [...]

Oral Cancer Foundation News Team - A2011-09-20T10:21:43-07:00September, 2011|Oral Cancer News|

New Study Shows that Fatty Acids Reduces Effectiveness of Chemotherapy

Source: Medicalexpress.com Researchers at University Medical Center Utrecht, the Netherlands, have discovered a substance that has an adverse effect on nearly all types of chemotherapy - making cancer cells insensitive to the treatment. Chemotherapy often loses effectiveness over time. It is often unclear how or why this happens. It now appears that chemotherapy is made ineffective by two types of fatty acid that are made by stem cells in the blood. Under the influence of cisplatin chemotherapy, the stem cells secrete these fatty acids that induce resistance to a broad spectrum of chemotherapies. These substances are referred to by researchers as 'PIFAs' which stands for platinum-induced fatty acids. Cisplatin is a type of chemotherapy that is widely used for the treatment of cancer, including cancer of the lungs and ovaries. Tumors under the skin The researchers studied the effect of PIFA's in mice and human cells. The mice studied had tumors under the skin. Under normal conditions, the tumors would decrease in size following the administration of chemotherapy. In the study, after administering the fatty acids to the mice, the tumors were found to be insensitive to chemotherapy. The fatty acids were isolated from the medium in which chemotherapy exposed stem cells were grown. But also stem cells in the blood of patients produce the fatty acids that desensitize tumors to chemotherapy. The fatty acids are also found in commercially-produced fish oil supplements containing omega-3 and omega-6 fatty acids as well as in some algae extracts. In the experiments conducted [...]

Oral Cancer Foundation News Team - A2011-09-13T10:50:40-07:00September, 2011|Oral Cancer News|

Collaboration of major biomedical centers has shown convergence on a cellular process for head and neck cancers

Source: www.rxpgnews.com Author: Broad Institute of MIT and Harvard Powerful new technologies that zoom in on the connections between human genes and diseases have illuminated the landscape of cancer, singling out changes in tumor DNA that drive the development of certain types of malignancies such as melanoma or ovarian cancer. Now several major biomedical centers have collaborated to shine a light on head and neck squamous cell cancer. Their large-scale analysis has revealed a surprising new set of mutations involved in this understudied disease. In back-to-back papers published online July 28 in Science, researchers from the Broad Institute, Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and the University of Texas MD Anderson Cancer Center have confirmed genetic abnormalities previously suspected in head and neck cancer, including defects in the tumor suppressor gene known as p53. But the two teams also found mutations in the NOTCH family of genes, suggesting their role as regulators of an important stage in cell development may be impaired. "This adds a new dimension to head and neck cancer biology that was not on anyone's radar screen before," said Levi A. Garraway, a senior associate member of the Broad Institute, an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, and a senior author of one of the Science papers. "Head and neck cancer is complex and there are many mutations, but we can infer there is a convergence on a cellular process for which we previously did not have [...]

Oral Cancer Foundation News Team - A2011-08-02T11:40:36-07:00August, 2011|Oral Cancer News|

Palifermin reduces severe mucositis in head and neck cancer

Source: http://www.medscape.com/ Author: Janis C. Kelly Palifermin (Kepivance), which is currently approved for preventing mucositis associated with total-body irradiation and stem-cell transplantation in hematologic malignancies, also prevents oral mucositis in patients with head and neck cancer undergoing radiation and chemotherapy, according to 2 randomized trials published online June 13 in the Journal of Clinical Oncology. Michael Henke, MD, who led both studies, told Medscape Medical News that "this shows for the first time that radiation-induced mucositis can be ameliorated — and this in a phase 2/3 design!" Dr. Henke is from the Department of Radiation Oncology at University Clinic in Freiburg, Germany. The multicenter studies included researchers from Austria, France, Germany, Hungary, Italy, Poland, Spain, the United Kingdom, and the United States. The first study was a double-blind randomized placebo-controlled trial of 186 patients with stage II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Treatment included radiation, 60 or 66 Gy, after complete or incomplete resection, delivered at 2 Gy per fraction and 5 fractions per week. Treatment also included cisplatin 100 mg/m2 on days 1 and 22 (and on day 43 with incomplete resection). Patients were randomized to weekly palifermin 120 μg/kg or placebo from 3 days before and throughout radiochemotherapy. The primary end point was the incidence of severe oral mucositis (World Health Organization [WHO] grades 3 to 4). Palifermin reduced oral mucositis incidence to 51% (41 of 92), compared with 67% (63 of 94) with placebo (P = .027), shortened median mucositis from [...]

Oral Cancer Foundation News Team - A2011-07-03T09:08:28-07:00July, 2011|Oral Cancer News|

Larynx preservation studies should consider treatment impact

Source: www.internalmedicinenews.com Author: Sara Freeman, Internal Medicine News Digital Network Almost one-quarter of patients who had been given induction chemotherapy before radiotherapy for head and neck cancer experienced long-term swallowing difficulties, with another 15% experiencing voice disabilities that correlated with the mobility of the vocal cords. Long-term data from the GORTEC (Groupe Oncologie Radiothérapie Tête et Cou) 2000-01 larynx preservation trial also show that approximately two-thirds of long-term head and neck cancer survivors experienced severe problems with sticky saliva and dry mouth, which were in turn linked to nutritional problems. These findings, reported May 9 at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference, further confirm that studies looking at the effects of chemoradiotherapy on the larynx in head and neck cancer need to consider prospective assessment of laryngeal function, rather than just looking at anatomical preservation, according to a French radiation oncologist. Dr. Gilles Calais of the Centre Hôpitalier Régional et Universitaire de Tours (France) presented data from a prospective analysis of 61 patients who had participated in the original 213-patient GORTEC 2000-01 trial. He also presented updated results from the trial using a recently developed composite end point. "Larynx preservation can be achieved for most of our [head and neck] patients by using three different strategies: induction chemotherapy, concomitant [chemoradiotherapy], or alternating chemoradiotherapy," Dr. Calais observed. Indeed, larynx preservation is a possibility in approximately 80% of patients, he said. However, anatomical preservation does not mean that laryngeal function is maintained, especially with respect to the ability [...]

Oral Cancer Foundation News Team - A2011-05-21T14:31:34-07:00May, 2011|Oral Cancer News|

Turmeric makes head, neck cancer treatment more effective

Source: www.dailyindia.com Author: staff Researchers at the University of Michigan Comprehensive Cancer Center have found that a compound derived from curcumin helps cells overcome the treatment failure of head and neck cancer. Curcumin is the principal curcuminoid of the popular Indian spice turmeric. When researchers added a curcumin-based compound, called FLLL32, to head and neck cancer cell lines, they were able to cut the dose of the chemotherapy drug cisplatin by four while still killing tumor cells equally as well as the higher dose of cisplatin without FLLL32. "This work opens the possibility of using lower, less toxic doses of cisplatin to achieve an equivalent or enhanced tumor kill. Typically, when cells become resistant to cisplatin, we have to give increasingly higher doses. But this drug is so toxic that patients who survive treatment often experience long-term side effects from the treatment," said senior author Thomas Carey, professor of otolaryngology and pharmacology at the U-M Medical School. That tumors become resistant to cisplatin is a major reason why head and neck cancer patients frequently see their cancer return or spread. It also plays a big role in why five-year survival for head and neck cancer has not improved in the past three decades. In the current study, researchers compared varying doses of cisplatin alone with varying doses of cisplatin plus FLLL32 against two sets of head and neck cancer cells: one line that was sensitive to cisplatin and one line that was resistant. They found that FLLL32 decreased the activation [...]

Oral Cancer Foundation News Team - A2011-05-21T14:13:55-07:00May, 2011|Oral Cancer News|

A compound found in a common Indian spice boosts effectiveness of head and neck cancer treatment

Source: Science Blog A primary reason that head and neck cancer treatments fail is the tumor cells become resistant to chemotherapy drugs. Now, researchers at the University of Michigan Comprehensive Cancer Center have found that a compound derived from the Indian spice curcumin can help cells overcome that resistance. When researchers added a curcumin-based compound, called FLLL32, to head and neck cancer cell lines, they were able to cut the dose of the chemotherapy drug cisplatin by four while still killing tumor cells equally as well as the higher dose of cisplatin without FLLL32. The study appears this week in the Archives of Otolaryngology — Head and Neck Surgery. “This work opens the possibility of using lower, less toxic doses of cisplatin to achieve an equivalent or enhanced tumor kill. Typically, when cells become resistant to cisplatin, we have to give increasingly higher doses. But this drug is so toxic that patients who survive treatment often experience long-term side effects from the treatment,” says senior study author Thomas Carey, Ph.D., professor of otolaryngology and pharmacology at the U-M Medical School and co-director of the Head and Neck Oncology Program at the U-M Comprehensive Cancer Center. That tumors become resistant to cisplatin is a major reason why head and neck cancer patients frequently see their cancer return or spread. It also plays a big role in why five-year survival for head and neck cancer has not improved in the past three decades. FLLL32 is designed to sensitize cancer cells at a [...]

Oral Cancer Foundation News Team - A2011-05-20T10:07:30-07:00May, 2011|Oral Cancer News|

Sensitization of Head and Neck Cancer to Cisplatin Through the Use of a Novel Curcumin Analog

Source: EthiconEndo-Surgery.com Objective To determine whether a novel small molecule inhibitor derived from curcumin (FLLL32) that targets signal transducer and activator of transcription (STAT) 3 would induce cytotoxic effects in STAT3-dependent head and neck squamous cell cancer (HNSCC) cells and would sensitize tumors to cisplatin. Design Basic science. Two HNSCC cell lines, UM-SCC-29 and UM-SCC-74B, were characterized for cisplatin [cis-diammineplatinum(II) dichloride] sensitivity. Baseline expression of STAT3 and other apoptosis proteins was determined. The FLLL32 50% inhibitory concentration (IC50) dose was determined for each cell line, and the effect of FLLL32 treatment on the expression of phosphorylated STAT3 and other key proteins was elucidated. The antitumor efficacy of cisplatin, FLLL32, and combination treatment was measured. The proportion of apoptotic cells after cisplatin, FLLL32, or combination therapy was determined. Results The UM-SCC-29 cell line is cisplatin resistant, and the UM-SCC-74B cell line is cisplatin sensitive. Both cell lines express STAT3, phosphorylated STAT3 (pSTAT3), and key apoptotic proteins. FLLL32 downregulates the active form of STAT3, pSTAT3, in HNSCC cells and induces a potent antitumor effect. FLLL32, alone or with cisplatin, increases the proportion of apoptotic cells. FLLL32 sensitized cisplatin-resistant cancer cells, achieving an equivalent tumor kill with a 4-fold lower dose of cisplatin. Conclusions FLLL32 monotherapy induces a potent antitumor effect and sensitizes cancer cells to cisplatin, permitting an equivalent or improved antitumor effect at lower doses of cisplatin. Our results suggest that FLLL32 acts by inhibiting STAT3 phosphorylation, reduced survival signaling, increased susceptibility to apoptosis, and sensitization to cisplatin.

Oral Cancer Foundation News Team - A2011-05-17T11:21:32-07:00May, 2011|Oral Cancer News|

HPV and EGFR are hottest topics in head and neck cancer

Source: www.medscape.com Author: Zosia Chustecka The hottest topic in head and neck cancers is the role of human papillomavirus (HPV) in the disease, although there is also a lot interest in treatment with EGRF inhibitors, especially the second-generation products, according to an expert here at the European Society for Therapeutic Radiology and Oncology 11th Biennial Conference. HPV has only been associated with head and neck cancer in the last few years, but it is now clear that patients who are positive for the virus have a better prognosis, said Cai Grau, MD, DMSC, professor of oncology at Aarhus University Hospital, Denmark. He chaired a session during which both hot topics were discussed. "These patients have a better prognosis, irrespective of treatment, and their risk of a second cancer is virtually zero," added session participant Lisa Licitra, MD, medical oncologist at the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, Italy. However, there is a difference between patients in the United States and those in Europe with regard to risk, she told meeting attendees. For American patterns, Dr. Licitra cited the analysis published last year in the New England Journal of Medicine (2010;363:24-35), which reported a risk model for death from oropharyngeal squamous cell carcinoma on the basis of HPV status, pack-years of tobacco smoking, and tumor and nodal stage. In this 266-patient cohort, 43% were low risk, 30% were intermediate risk, and 27% were high risk. Dr. Licitra reported that when she performed the same analysis [...]

Oral Cancer Foundation News Team - A2011-05-17T06:56:01-07:00May, 2011|Oral Cancer News|