Monthly Archives: October 2006

Genmab begins trial of cancer combination therapy

  • 10/26/2006
  • USA
  • staff
  • www.pharmaceutical-business-review.com

Danish biotech firm Genmab has initiated a phase I/II study of HuMax-EGFr in combination with chemo-radiation as first line treatment of head and neck cancer.

The study will include a total of 36 patients with advanced squamous cell carcinoma of the head and neck.

The objective of the study is to investigate the safety and efficacy of HuMax-EGFr in combination with chemo-radiation as first line treatment of patients with advanced head and neck cancer.

“We welcome the expansion of the HuMax-EGFr program, which we hope will benefit earlier stage patients,” said Lisa Drakeman, CEO of Genmab.

The study consists of an initial dose-escalation part and a subsequent parallel group design. In the dose-escalation part of the study, three dose levels of HuMax-EGFr will be tested in combination with conventional fractionated radiotherapy and cisplatin. The safety of the dose levels will then be evaluated before dosing is continued at the next level.

In the following parallel group design part of the study, HuMax-EGFr will be tested in combination with cisplatin and three different regimes of accelerated radiotherapy.

October, 2006|Archive|

Saving salivary glands from the collateral damage of radiation therapy

  • 10/30/2006
  • Seoul, Korea
  • staff
  • EurekAlert.com

Researchers have shown that targeted overexpression of heat shock protein 25 prevents radiation-induced damage to salivary glands, a common consequence of treatment for head and neck cancer. The related report by Lee et al., “Radioprotective effect of HSP25 on submandibular glands of rats,” appears in the November issue of The American Journal of Pathology.

Patients with head and neck cancer often receive radiation therapy as part of their treatment. However, the salivary glands, which frequently reside within the irradiation field, can become damaged at the same time. The resulting salivary dysfunction may involve dry mouth, oral infections, dental caries, and difficulty eating, some of which persist long after treatment ends, even permanently.

Dr. Yun-Sil Lee and colleagues examined whether salivary glands could be protected by heat shock proteins (HSPs), which are expressed by cells in an effort to counteract environmental stressors such as heat, hypoxia, and ionizing radiation. Using adenoviral vectors, the researchers specifically overexpressed HSP25 and HSP70i in submandibular salivary glands of rats. Rat salivary glands were then irradiated and monitored for radiation-induced changes.

In treated rats, HSP25 protected salivary gland function by maintaining gland weight, salivary flow rate, and salivary fluid composition, whereas HSP70i significantly protected only salivary flow rate. When specific damage to the glands was assessed, HSP25 and HSP70i both greatly diminished scarring, nuclear damage, and cell death (apoptosis), but HSP70i was slightly less effective. Finally, HSP25 and HSP70i preserved expression of aquaporin 5, which is important for water transport in salivary glands.

It is interesting to note that the results with HSP25 were similar to those observed with amifostine, an FDA-approved radioprotective drug. However, differences did exist: only amifostine protected all components of salivary fluid from change, but HSP25 afforded better protection from apoptosis than amifostine.

These results demonstrate the radioprotective effects of both heat shock proteins, with HSP25 providing the stronger defense. Thus, HSP25 delivery may represent a novel means of preventing the collateral damage associated with radiation therapy.

October, 2006|Archive|

Miconazole Lauriad Bioadhesive Buccal Tablets (Loramyc) for Oropharyngeal Candidiasis in France

  • 10/30/2006
  • web resource, no city listed
  • Yael Waknine
  • Medscape.com

On October 13, the French regulatory authority Agence Francaise de Sécurité Sanitaire des Produits de Santé (AFSSAPS) approved miconazole Lauriad 50-mg bioadhesive buccal tablets (Loramyc, made by BioAlliance Pharma SA) for the treatment of oropharyngeal candidiasis in immunodepressed patients, particularly those with head and neck cancers who have undergone radiotherapy and those infected with HIV.

Miconazole Lauriad is designed with proprietary technology (Lauriad) that ensures an early and extended release of the active component at the site of infection, maintaining therapeutic levels of the drug (saliva concentration > 1 µg/mL) while reducing the risk for drug interactions and systemic effects. In contrast with other topical treatments such as gels, rinses, or lozenges that require multiple daily dosing, the product is applied once daily on the upper gum.

According to a company news release, approval of miconazole Lauriad was based on data from 2 European phase 3 clinical trials. The first of these was conducted in 25 HIV-positive patients at 11 clinical sites in France. Results showed clear evidence of efficacy (success rates at day 7 and 15 were 89.5% and 94.7%, respectively) and the study was therefore terminated early.

The second study was a comparative, multicenter, randomized study in 306 French and North African patients with head and neck cancer treated by radiotherapy and presenting with candidiasis and low saliva levels (dry mouth). Results at day 14 confirmed the noninferiority of the miconazole Lauriad 50-mg tablet applied once daily compared with miconazole 125-mg oral gel applied 4 times daily.

According to the news release, miconazole Lauriad is currently being evaluated in a pivotal phase 3 US clinical trial with the objective of pursuing its approval by the Food and Drug Administration. Also, the same technology is being used to develop a second product (acyclovir Lauriad) for the treatment of oral herpes.

October, 2006|Archive|

Successful recovery of esophageal patency in 2 patients with complete obstruction by using combined antegrade retrograde dilation procedure, needle knife, and EUS needle

  • 10/28/2006
  • Pennsylvania, PA
  • Matthew T Moyer et al.
  • Gastrointest Endosc, November 1, 2006; 64(5): 789-792

BACKGROUND:
Esophageal occlusion is typically caused by cancer or postradiation changes; it is difficult to treat, with poor surgical outcomes. The combined antegrade retrograde dilation (CARD) method has been used to endoscopically restore the esophageal lumen after complete occlusion by cancer or postradiation changes, with good preliminary results. Reproducing this technique and improving its speed and convenience would be advances in treating this difficult clinical problem.

Objective:
A demonstration of 2 alternative endoscopic techniques for treating complete esophageal obstructions.

Design:
The CARD method was performed in 2 patients with unresectable cancer and complete esophageal occlusion. In the first patient, a needle knife was used to cut through the obstruction, instead of removing it piecemeal with biopsy forceps before over-the-wire dilation. In the second patient, an EUS needle was used to cross a particularly long obstruction, which allowed subsequent dilation and recanalization.

Setting:
A tertiary referral center.

Patients:
Two patients with complete esophageal obstruction secondary to head and neck cancer, with associated radiation therapy.

Results:
In both cases, this method resulted in successful recanalization of the occluded lumen in a relatively short amount of time, without complications.

Limitations: The small number of patients in this series.

Conclusions:
The CARD needle-knife method may be a safe, effective, and efficient approach to complete esophageal occlusion. In addition, the CARD-EUS needle method may be an preferable technique to cross long obstructions quickly; however, more experience will be required.

Authors:
Matthew T Moyer1, Brendan C Stack Jr.2, and Abraham Mathew1

Authors’ affiliations:
1. Division of Gastroenterology and Hepatology, Pennsylvania State University Hospital, Hershey Medical Center, Hershey, Pennsylvania
2. Department of Otolaryngology, University of Arkansas Medical Center, Little Rock, Arkansas (Dr Stack), USA

October, 2006|Archive|

Does clinical and radiological response predict complete tumor control in N2-N3 squamous cell head and neck cancer after non-operative management of the neck?

  • 10/28/2006
  • Belgium
  • D Dequanter et al.
  • Acta Otolaryngol, December 1, 2006; 126(11): 1225-8

Background:
We retrospectively reviewed the outcome of 28 patients with N2-N3 disease treated initially with chemotherapy and radiotherapy.

Patients and methods:
A neck dissection was performed for all patients with residual disease in the neck.

Results:
A CCRR in the neck was achieved in 25 of 28 patients. The remaining three patients with residual neck mass underwent a salvage neck dissection: the pathological examination confirmed the persistence of tumoral disease. No regional failure was observed in these three patients. In 25 patients considered to have CCRR in the neck, 5 patients (20%) developed regional recurrence. Successful salvage approach was not possible for any of these patients.

Conclusion:
A complete clinical and radiological response observed following chemotherapy and radiotherapy is not predictive of the absence of residual disease. Moreover, salvage neck surgery does not always seem to be an effective strategy. Consequently, early neck dissection should be advised for patients with complete clinical and radiological response (CCRR) after chemoradiotherapy for tumors with N2-N3 disease.

Authors:
D Dequanter, P Lothaire, A Awada, Y Lalami, T Hien Nguyen, M Lemort, L Vandevelde, and G Andry

Authors’ affiliation:
Institut Jules Bordet, Bruxelles, Belgium.

October, 2006|Archive|

Prevention and early detection of oral and pharyngeal cancer in veterans

  • 10/28/2006
  • Seoul, Korea
  • HY Kim et al.
  • Oral Surg Oral Med Oral Pathol Oral Radiol Endod, November 1, 2006; 102(5): 625-31

Objectives:
To assess knowledge of oral and pharyngeal cancer (OPC) clinical signs and risk factors, the association between the risk factors and OPC, and the experience with OPC screening between newly diagnosed OPC patients and controls among a population of veterans in North Carolina.

Study Design:
A case-control study with 31 OPC cases and 30 frequency-matched controls recruited from 2003 to 2004. Bivariate analysis using chi-square statistics and multivariate logistic regression was implemented to estimate the association with OPC.

Results:
Only 34% of respondents knew 1 clinical sign and 4 or 5 risk factors for OPC. The lifetime accumulation of tobacco had a significant relationship with OPC (>20 pack-years; OR, 3.2; 95% CI, 1.01-10.3). Many respondents had not had an oral cancer examination within 3 years, mostly through ignorance. Most VA OPC patients were diagnosed by physicians, rather than by dentists.

Conclusions:
A considerable knowledge deficit on OPC was found among North Carolina veterans. Use of tobacco was a risk factor for OPC in this population.

Authors:
HY Kim, JR Elter, TG Francis, and LL Patton

Authors’ affiliation:
Dental Research Institute, Seoul National University, Seoul, Korea

October, 2006|Archive|

Identification of a Gene Signature for Rapid Screening of Oral Squamous Cell Carcinoma

  • 10/28/2006
  • Philadelphia, PA
  • Amy F Ziober et al.
  • Clin. Cancer Res., October 15, 2006; 12(20): 5960-5971

Purpose:
Oral cancer is a major health problem worldwide and in the U.S. The 5-year survival rate for oral cancer has not improved significantly over the past 20 years and remains at approximately 50%. Patients diagnosed at an early stage of the disease typically have an 80% chance for cure and functional outcome, however, most patients are identified when the cancer is advanced. Thus, a convenient and an accurate way to detect oral cancer early will decrease patient morbidity and mortality. The ability to noninvasively monitor oral cancer onset, progression, and treatment outcomes requires two prerequisites: identification of specific biomarkers for oral cancers as well as noninvasive access to and monitoring of these biomarkers that could be conducted at the point of care (i.e., practitioner’s or dentist’s office) by minimally trained personnel.

Experimental Design:
Here, we show that DNA microarray gene expression profiling of matched tumor and normal specimens can identify distinct anatomic site expression patterns and a highly significant gene signature distinguishing normal from oral squamous cell carcinoma (OSCC) tissue.

Results:
Using a supervised learning algorithm, we generated a 25-gene signature for OSCC that can classify normal and OSCC specimens. This 25-gene molecular predictor was 96% accurate on cross-validation, averaging 87% accuracy using three independent validation test sets and failing to predict non-oral tumors.

Conclusion:
Identification and validation of this tissue-specific 25-gene molecular predictor in this report is our first step towards developing a new, noninvasive, microfluidic-based diagnostic technology for mass screening, diagnosis, and treatment of pre-OSCC and OSCC.

Authors:
Amy F Ziober, Kirtesh R Patel, Faizan Alawi, Phyllis Gimotty, Randall S Weber, Michael M Feldman, Ara A Chalian, Gregory S Weinstein, Jennifer Hunt, and Barry L Ziober

Authors’ affiliations:
Departments of Otorhinolaryngology-Head and Neck Surgery, Pathology and Laboratory Medicine, Department of Pathology, School of Dental Medicine, and Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Health System, Philadelphia, Pennsylvania

October, 2006|Archive|

Detecting oral cancer: a new technique and case reports

  • 10/28/2006
  • Seattle, WA
  • JC Kois and E Truelove
  • Dent Today, October 1, 2006; 25(10): 94, 96-7

The VELscope is an important aid in patient assessment, and when added to a well-thought out clinical assessment process that takes into consideration the age of the patient and risk factors that include tobacco, alcohol, and immunologic status, it increases the clinician’s ability to detect oral changes that may represent premalignant or malignant cellular transformation.

False positive findings are possible in the presence of highly inflamed lesions, and it is possible that use of the scope alone may result in failure to detect regions of dysplasia, but it has been our experience that use of the VELscope improves clinical decision making about the nature of oral lesions and aids in decisions to biopsy regions of concern.

Where tissue changes are generalized or cover significant areas of the mouth, use of the scope has allowed us to identify the best region for biopsy. As with all clinical diagnostic activities, no single system or process is enough, and all clinicians are advised to use good clinical practice to assess patients and to recall and biopsy lesions that do not resolve within a predetermined time frame.

Lesions that are VELscope-positive and absorb light need to be followed with particular caution, and if they do not resolve within a 2-week period, then further assessment and biopsy are generally advised. It is much better to occasionally sample tissue that turns out to be benign than to fail to diagnose dysplastic or malignant lesions. In our fight to protect patients from cancer, the VELscope improves our odds for early detection, hopefully resulting in fewer deaths from oral cancer

Authors’ affiliation:
Graduate Restorative Program, University of Washington, USA

October, 2006|Archive|

Identification of a Gene Signature for Rapid Screening of Oral Squamous Cell Carcinoma

  • 10/25/2006
  • Philadelphia, PA
  • Amy F. Ziober et al
  • Clinical Cancer Research Vol. 12, 5960-5971, October 15, 2006

Purpose:
Oral cancer is a major health problem worldwide and in the U.S. The 5-year survival rate for oral cancer has not improved significantly over the past 20 years and remains at 50%. Patients diagnosed at an early stage of the disease typically have an 80% chance for cure and functional outcome, however, most patients are identified when the cancer is advanced. Thus, a convenient and an accurate way to detect oral cancer early will decrease patient morbidity and mortality. The ability to noninvasively monitor oral cancer onset, progression, and treatment outcomes requires two prerequisites: identification of specific biomarkers for oral cancers as well as noninvasive access to and monitoring of these biomarkers that could be conducted at the point of care (i.e., practitioner’s or dentist’s office) by minimally trained personnel.

Experimental Design:
Here, we show that DNA microarray gene expression profiling of matched tumor and normal specimens can identify distinct anatomic site expression patterns and a highly significant gene signature distinguishing normal from oral squamous cell carcinoma (OSCC) tissue.

Results:
Using a supervised learning algorithm, we generated a 25-gene signature for OSCC that can classify normal and OSCC specimens. This 25-gene molecular predictor was 96% accurate on cross-validation, averaging 87% accuracy using three independent validation test sets and failing to predict non–oral tumors.

Conclusion:
Identification and validation of this tissue-specific 25-gene molecular predictor in this report is our first step towards developing a new, noninvasive, microfluidic-based diagnostic technology for mass screening, diagnosis, and treatment of pre-OSCC and OSCC.

Authors:
Amy F. Ziober1, Kirtesh R. Patel1, Faizan Alawi3, Phyllis Gimotty4, Randall S. Weber6, Michael M. Feldman2, Ara A. Chalian1, Gregory S. Weinstein1, Jennifer Hunt5 and Barry L. Ziober1

Authors’ affiliations:
Departments of
1 Otorhinolaryngology-Head and Neck Surgery,
2 Pathology and Laboratory Medicine,
3 Department of Pathology, School of Dental Medicine, and
4 Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Health System, Philadelphia, Pennsylvania;
5 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and
6 Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas

October, 2006|Archive|

Nasopharyngeal Carcinoma Incidence Higher in Young Blacks Than Whites

  • 10/24/2006
  • Marietta, GA
  • Will Boggs, MD
  • CancerPage.com

Blacks under 20 years face higher rates of nasopharyngeal carcinoma (NPC) than do whites and even Asians, according to a report in the October Archives of Otolaryngology–Head and Neck Surgery.

“NPC in the U.S. is not a disease affecting only Asians,” Luke M. Richey from University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina told Reuters Health. “NPC is a relatively rare neoplasm, and in younger age groups, it occurs in blacks at a rate more than twice that of whites.”

Richey and colleagues used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) tumor registry to investigate incidence and survival rates for cases of NPC in blacks, whites, and Asians younger than 30 years between 1973 and 2002.

Among individuals under age 20 years, NPC incidence rates ranged from 1.61 per million for blacks to 0.95 per million for Asians and 0.61 per million for whites, the authors report.

In the age 20 to 29 group, incidence rates were much higher for Asians (7.18/million) than for blacks (1.87/million) and whites (0.96/million), the results indicate.

Survival rates in younger patients diagnosed with NPC did not differ significantly among blacks, whites, and Asians, the report indicates.

“The higher incidence of NPC in young blacks in the U.S. has multiple causes,” Richey said. “Genetic and/or environmental factors lead to cellular or immune alterations, which in the setting of EBV viral infection, give rise to NPC.”

“As we accumulate longer follow-up in national and regional cancer databases, we will be able to further investigate NPC epidemiology and make comparisons between demographic groups,” Richey concluded.

Source:
Arch Otolaryngol Head Neck Surg 2006;132:1035-1040.

October, 2006|Archive|