CEL-SCI gets Israeli nod to commence phase III trial of multikine in head and neck cancer

Source: www.pharmabiz.com Author: staff CEL-SCI Corporation announced that the State of Israel's Ministry of Health has given approval to begin enrolment of subjects for a phase III clinical trial of Multikine in Israel. Israel is one of nine countries to participate in this global phase III trial. The phase III trial will be conducted in approximately 48 clinical centres. CEL-SCI's partner Teva Pharmaceutical Industries will be conducting the trial at three clinical centers in Israel. The phase III trial started in the United States in late December 2010 and is expected to commence in other countries around the world within the next 30-60 days. Multikine is the company's flagship immuno-therapy developed as a first-line standard of care in treating head and neck cancer. CEL-SCI's phase III clinical trial is an open-label, randomized, controlled, multi-centre study designed to determine if Multikine administered prior to current standard of care (surgery plus radiotherapy or surgery plus concurrent chemo radiotherapy) in previously untreated subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate (Head and Neck cancer) will result in an increased overall rate of survival, versus the subjects treated with standard of care only. CEL-SCI's 880 patient phase III trial is expected to be the largest clinical study of head and neck cancer ever conducted. It is also the first trial in which immunotherapy will be administered before any other traditional means of care are attempted. This is significant because conventional cancer therapy weakens the immune system and likely compromises the [...]

DNA repair biomarker profiling of head and neck vancer: Ku80 rxpression predicts locoregional failure and death following radiotherapy

Source: American Association for Cancer Research Abstract Purpose: Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes. Experimental Design: Archival HNSCC tumor specimens were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort. Results: Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy. The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a nine-fold greater risk of death at two years. Conclusions: Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment. Clin Cancer Res; [...]

Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer.

Source: HighWire- Stanford University In this retrospective investigation we analyzed outcome and toxicity after intensity-modulated reirradiation of recurrent head and neck cancer. METHODS: Thirty-eight patients with local recurrent head and neck cancer were evaluated. The median dose of initial radiotherapy was 61 Gy. Reirradiation was carried out with step-and-shoot intensity-modulated radiotherapy (median dose: 49 Gy). RESULTS: Median overall survival was 17 months, and the 1- and 2-year overall survival rates were 63% and 34%. The 1- and 2-year local control rates were 57% and 53%. Distant spread occurred in 34%, and reirradiation induced considerable late toxicity in 21% of the patients. Thirty-two percent showed increased xerostomia after reirradiation. The risk for xerostomia was significantly higher for cumulative mean doses of ?45 Gy to parotid glands. Considering median cumulative maximum doses of 53 Gy to the spinal cord and 63 Gy to the brainstem, no late toxicities were observed. CONCLUSIONS: Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer is feasible with acceptable toxicity and yields encouraging rates of local control and overall survival. � 2011 Wiley Periodicals, Inc. Head Neck, 2011.

2011-02-09T11:45:36-07:00February, 2011|Oral Cancer News|

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

Source: www.thelancet.com Authors: Dr Christopher M Nutting FRCR et al. Background: Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods: We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1—4, N0—3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings: 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0—59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in [...]

2011-02-04T12:18:59-07:00February, 2011|Oral Cancer News|

Reducing xerostomia through advanced technology

Source: The Lancet Oncology Radiation-related xerostomia has been the most significant and disabling side-effect of radiotherapy for head and neck cancer for more than 50 years. With the PARSPORT trial, reported in The Lancet Oncology, the largest and best designed of several randomised trials focusing on xerostomia, radiation oncologists and their partners in physics and dosimetry should take pride that significant progress has been made. Before the introduction of intensity-modulated radiotherapy (IMRT), more than 80% of survivors experienced substantial dry mouth syndrome and associated effects on dental health, swallowing, taste, and quality of life. By contrast, Nutting and colleagues report about 25% of 2-year survivors had significant clinician-rated xerostomia. Taken together with two randomised trials of IMRT for nasopharyngeal cancer, there is now compelling evidence of the power of advanced technology in reducing toxicity from head and neck radiotherapy. Can even better use of technology help us to further reduce xerostomia? The parotid glands provide watery saliva during eating, which is largely replaceable by consuming more water or lubricants. The submandibular, sublingual, and minor salivary glands provide mucinous saliva, associated with the resting sense of moisture and dry mouth symptoms. Future work should systematically explore the prioritisation of different components of the salivary gland system. A clinical benefit from sparing the submandibular glands may be seen, beyond that seen by sparing the parotid glands. The mean dose delivered to the minor salivary glands within the oral cavity has also been reported to be a significant factor in patient-reported xerostomia. Further possibilities include gland repair [...]

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

The Lancet Oncology, Early Online Publication, 13 January 2011 Dr Christopher M Nutting FRCR a b , James P Morden MSc b, Kevin J Harrington FRCR a b, Teresa Guerrero Urbano PhD c, Shreerang A Bhide FRCR a, Catharine Clark PhD d, Elizabeth A Miles MPhil e, Aisha B Miah FRCR a, Kate Newbold FRCR a, MaryAnne Tanay MSc a, Fawzi Adab FRCR f, Sarah J Jefferies FRCR g, Christopher Scrase FRCR h, Beng K Yap FRCR i, Roger P A'Hern MSc b, Mark A Sydenham BSc b, Marie Emson BSc b, Emma Hall PhD b, on behalf of the PARSPORT trial management group† Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1—4, N0—3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomization was by computer-generated permuted blocks and was stratified by centre and tumor site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by [...]

Three-drug combination shows long-lasting survival benefit in head and neck cancer patients

Source: www.medicalnewstoday.com Author: staff Adding a third drug (docetaxel) to a standard two-drug initial chemotherapy regimen significantly improves the long-term survival of patients with head and neck cancer, reducing the likelihood of dying by 26% over 6 years. The long-term results of the TAX 324 trial published Online First in The Lancet Oncology, confirm that this three-drug regimen should become the standard of care for patients who are suitable for induction therapy. Every year, cancers of the head and neck are diagnosed in more than 40 000 people in the USA. Standard treatment for these patients involves combining radiotherapy and chemotherapy with or without surgery, and the addition of induction chemotherapy has been shown to prolong survival. However, the best ways of combining these treatments remains unclear. In recent years, cisplatin plus fluorouracil (PF) has become a standard induction chemotherapy combination and has been shown to significantly prolong survival. The TAX 324 trial was designed to establish whether the addition of docetaxel to initial chemotherapy with cisplatin and fluorouracil (PF) might help patients with locally advanced head and neck cancer live longer. Between May 1999 and December 2003, 501 patients were recruited from 55 centres across the USA, Canada, Argentina, and Europe. In 2007, initial results (minimum follow-up 2 years) showed that induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) significantly improved survival compared with PF. To establish the durability of this survival benefit, Jochen Lorch from the Dana-Farber Cancer Institute, Boston, USA and colleagues evaluated the long-term follow-up of [...]

Radiation aids local control of head and neck mucosal melanoma

Source: www.oncolink.org ( from Reuters Health Information) Author: staff Radiotherapy after surgery for head and neck mucosal melanoma (HNMM) can help prevent local spread of the disease, according to a retrospective study from France. The study covered 160 patients treated over 28 years at 13 centers in the Groupe d'Etude des Tumeurs de la Tete et du Cou (GETTEC). It's the largest analysis to date of this rare cancer, according to lead author Dr. Adil Benlyazid of the Claudius Regaud Institute in Toulouse and colleagues. HNMM accounts for 3% of melanoma cases and 0.4% to 10% of melanomas of the head and neck, the researchers said in the December Archives of Otolaryngology and Head and Neck Surgery. Treatment typically involves surgery with or without postoperative radiotherapy, or radiotherapy alone if surgery is not feasible. Previous studies involving fewer subjects (i.e., 59 and 69 patients) found a benefit to adjuvant radiotherapy, but "there remains great skepticism, mostly among head and neck surgeons," according to Dr. Benlyazid and colleagues. Between 1980 and 2008, 82 HNMM patients had surgery at the GETTEC hospitals, and another 78 had surgery followed by radiotherapy. There was a nonsignificant trend toward more locally advanced tumor stage in patients who had adjuvant radiation. Overall and relapse-free survival didn't differ between the two groups. But the radiotherapy patients were significantly less likely to have locoregional recurrence as a first event, with a five-year cumulative rate of 55.6% with surgery alone vs 29.9% with surgery plus radiotherapy. After adjustment for [...]

Predicting the Prognosis of Oral Squamous Cell Carcinoma After First Recurrence

Source: Archives of Otolaryngology- Head and Neck Surgery Objectives To describe the clinicopathologic features of oral squamous cell carcinoma in patients who develop locoregional recurrence of disease, to identify factors that predict prognosis in the subset of patients treated with salvage surgery, and to determine the adjusted effect of time to recurrence. Design Cohort study. Setting A head and neck cancer institute in Sydney, New South Wales, Australia. Patients A total of 77 patients who underwent salvage surgery for oral squamous cell carcinoma that had been treated initially by surgery, radiotherapy, or surgery with postoperative radiotherapy. Main Outcome Measures Univariable and multivariable analysis of clinical and pathologic risk factors. Results Median time to recurrence from initial treatment was 7.5 months (range, 0.9-143.9 mo), with 86% of recurrences occurring within the first 24 months. Surgical salvage was attempted in 77 patients who had experienced recurrence at the primary site (n = 39), ipsilateral neck (n = 27), and contralateral neck (n = 11). Time to recurrence, initial treatment modality, and site of failure were independent prognostic variables. Conclusions The relationship of these prognostic variables displays a dynamic interaction. Initial combined-modality treatment and shorter time to recurrence were associated with worse outcome, while the effect of site of recurrence (local vs regional) was dependent on an interaction with the time to recurrence. The result of this interaction was that local recurrence was worse for those who experienced it early (eg, <6 mo after the initial treatment) and nodal recurrence was worse for those who experienced it late (eg, [...]

2010-12-22T11:11:20-07:00December, 2010|Oral Cancer News|

My dog saved my life, says Sunderland man

Source: Sunderland Echo By: Katy Wheeler John and Pauline Douglas were devastated when their dog Diesel had to be put down after developing cancer of the neck. But it was the late bull mastiff’s symptoms which helped John, 39, realise that he too had the disease. The dad-of-four, of Tunstall Bank, noticed a lump in his neck in February. And despite the fact he was told by doctors to rule out cancer, John’s experience with Diesel’s disease convinced him something was seriously wrong – and he pushed for further tests. His instincts were proved correct and John was diagnosed with cancer, which had spread to his neck, in April – just a week before his wedding day to wife Pauline, 41. John said: “Because of my age, the fact I don’t smoke and because I am a moderate drinker, I was told not to worry about cancer and that it was just an infection. “But what happened to Diesel set alarm bells ringing. “He had the same kind of lump in his neck that would swell up and down. We were told his wasn’t cancer to start with and it was only found late on. “Even though I was told by a specialist that I didn’t fit the criteria for cancer, the doubt was still niggling and I made such a song and dance that more tests were done.” As a result of John’s persistence, one of his tonsils was removed and a biopsy revealed the cancer, which had spread [...]

2017-03-29T19:08:21-07:00December, 2010|Oral Cancer News|
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