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Research Update: Vaccine Plus Checkpoint Inhibitor Combos for HPV-related Cancers

Source: MedPage Today
Author: Mark L. Feurst

Two new studies show the profound impact of a combined vaccine and anti-programmed death-1 (PD-1) antibody approach in the treatment of human papilloma virus (HPV)-related cancers.

HPV causes nearly all cervical cancers, as well as most oropharyngeal, anal, penile, vulvar, and vaginal cancers. HPV16 and HPV18 are the leading viral genotypes that increase cancer risk. Given the viral cause of these cancers, immunotherapy has been considered a strong potential approach.

Many patients with the HPV16 and HPV18 subtypes of head and neck squamous cell carcinoma have good outcomes from treatment that includes surgery or chemotherapy and radiation. Although anti-PD-1 therapy is approved for patients who do not respond to treatment or who develop metastatic disease, it benefits only about 15% of patients. The theory, therefore, is that a vaccine could potentially boost the immune systems of patients with HPV-related head and neck cancer, opening the door for better responses to other existing therapies.

Vaccine + Nivolumab in Phase II Study

In the first study, a phase II trial, a tumor-specific vaccine combined with the immune checkpoint inhibitor nivolumab was found to shrink tumors in patients with incurable HPV-related cancers.

“Ours are the first results with this particular approach,” Bonnie Glisson, MD, of the Department of Thoracic Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, told the Reading Room. “The rates of response and survival are approximately double what have been observed with nivolumab given alone to similar patients. These results will lead to larger, randomized clinical trials of this combination.”

Vaccines specific to HPV antigens found on tumors had previously sparked a strong immune response, but had not by themselves been active against established cancers, she noted.

“Vaccines are revving up the immune system, but the immunosuppressive tumor microenvironment probably prevents them from working. Our thinking was that inhibition of programmed death-1 (PD-1) would address one mechanism of immunosuppression, empowering the vaccine-activated T lymphocytes to attack the cancer.”

Glisson and colleagues combined the vaccine ISA101, which targets peptides produced by the strongly cancer-promoting HPV16 genotype of the virus, along with nivolumab, a checkpoint inhibitor that blocks activation of PD-1 on T cells.

The single-arm, single-center clinical trial included 24 patients with incurable HPV-16–positive cancer who were followed for 12.2 months. The vaccine was given subcutaneously on days 1, 22, and 50. A nivolumab dose of 3 mg/kg was given intravenously every 2 weeks beginning on day 8 for up to 1 year. Of the 24 patients with recurrent HPV16-related cancers, 22 had oropharyngeal cancer, one had cervical cancer, and one had anal cancer. The overall response rate was 33% (eight patients), and the median duration of response was 10.3 months. Five of eight patients remain in response, the team reported.

The overall median survival was 17.5 months, progression-free survival was 2.7 months, and 70% of patients survived to 12 months.

Grades 3 to 4 toxicity occurred in two patients (asymptomatic grade 3 transaminase level elevation in one patient and grade 4 lipase elevation in one patient), requiring discontinuation of nivolumab therapy. The researchers observed side effects expected from the two treatments separately, but said they were encouraged to see no sign of synergistic side effects caused by the combination.

“The combination was very well tolerated as opposed to other immunotherapy combinations such as combined blockade of PD-1 and CTLA-4,” Glisson said. “The vaccine did stimulate a strong HPV-specific immune response in peripheral blood T cells, although this was not correlated with response or survival. This suggests that other immune-suppressive factors in the tumor environment are contributing to immune evasion.”

Randomized clinical trials of the vaccine and anti-PD1 combinations for cervical and oropharyngeal cancer are ongoing, she added. “These are promising data that will be confirmed in a randomized trial. Positive results could lead to marketing of the first therapeutic HPV vaccine.”

Vaccine Helps T cells Infiltrate HPV-related Head and Neck Cancer

In the second study, another vaccine was shown to boost antibodies and T cells to help them infiltrate tumors and fight off HPV-related head and neck cancer. This approach might complement PD-1 or programmed death-ligand 1 inhibition in HPV-associated head and neck cancers to improve therapeutic outcomes, explained the study’s lead author, Charu Aggarwal, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania.

“We wanted to know if this vaccine can boost the immune systems of patients with HPV-related head and neck cancer, potentially opening the door for better response rates to other existing therapies. Our findings show that we can.”

Aggarwal and colleagues conducted a Phase Ib/II safety, tolerability, and immunogenicity study of immunotherapy with MEDI0457, a DNA immunotherapy targeting HPV16/18 E6/E7 with interleukin-12 encoding plasmids. The vaccine was delivered via electroporation to 21 patients. One group of patients received one dose before surgery, followed by three doses after surgery. The second group received four doses following chemotherapy and radiation.

Eighteen of the 21 patients (86%) showed elevated T cell activity that lasted at least 3 months after the final vaccine dose, the team reported. Five tumors were biopsied both before and after one dose of the vaccine, and there was evidence of T cells reacting with antigens contained in the vaccine in all five of these samples. One patient who developed metastatic disease and was treated with anti-PD-1 therapy developed a rapid and durable complete response that has lasted more than 2 years.

“We have not seen that kind of infiltration with just one dose of a vaccine before. These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV,” said Aggarwal, adding that the vaccine was well tolerated, with no serious side effects reported.

“This response suggests that the vaccine may, in some manner, prime the immune system, potentially boosting the effects of subsequent anti-PD-1 therapy,” she explained, noting that a multi-site clinical trial is now open to patients with metastatic HPV-associated head and neck cancer, who will receive a combination of the vaccine with anti-PD-1 therapy.

Previously, the CheckMate-141 trial tested nivolumab in 361 patients with recurrent or metastatic, chemotherapy-refractory squamous cell head and neck cancer, and the results led to FDA approval in that setting. Sixty three of these patients were HPV16-positive, and the overall response rate among this group was 15.9%, with a median overall survival of 9.1 months.

 

November, 2018|Oral Cancer News|

No De-escalation of Therapy for HPV+ Throat Cancer

Source: www.medscape.com
Author: Alexander M. Castellino, PhD

Another trial has shown that de-escalating therapy does not work in patients with good prognosis human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma or throat cancers.

Results from the De-ESCALaTE HPV study show that using the targeted drug cetuximab with radiotherapy does not improve side effects and, more importantly, has worse survival compared with the standard of care — chemotherapy with cisplatin and radiotherapy.

The finding echoes the results from the US National Cancer Institute’s Radiation Therapy Oncology Group (RTOG) 1016 trial, the top-line results of which were released earlier this year, and details of which were presented this week at the American Society of Radiation Oncology (ASTRO) 2018 meeting.

“Do not change your clinical practice of using cisplatin with radiotherapy in these patients,” cautioned Hisham Mehanna, MBChB, PhD, chair of head and neck surgery at the University of Birmingham, United Kingdom, and lead investigator of the De-ESCALaTe study. He presented the results during a presidential session here at the European Society for Medical Oncology (ESMO) 2018 Congress (abstract LBA9).

“Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise — we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV+ should be given cisplatin, and not cetuximab, where possible,” Mehanna said in a statement.

Hope for Fewer Side Effects
Cetuximab with radiation is already approved by the US Food and Drug Administration for use in head and neck cancer, including oropharyngeal cancer, and is an accepted standard of care, especially for patients who cannot tolerate cisplatin.

The hope behind de-escalation of therapy was that this regimen would offer similar efficacy but have fewer side effects than the standard regimen of cisplatin plus radiation.

“The side effects of treatment for patients with head and neck cancers are devastating. They experience loss of speech, loss of taste, and have trouble swallowing,” explained ESMO expert Jean-Pascal Machiels, MD, PhD, head of the department of medical oncology at the Cliniques Universitaires Saint-Luc, Brussels, Belgium.

“With HPV increasing rapidly in the Western world, HPV+ head and neck cancers are typically seen in younger patients who respond well to treatment and live for three to four decades. These patients would like to live without the toxicities associated with treatment,” he added.

“Based on a large study in 2006, many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused fewer side effects,” Mehanna commented. That study showed that for patients with squamous cell carcinoma of the head and neck, treatment with cetuximab and high-dose radiotherapy improved locoregional control and reduced mortality. At the same time, side effects were no worse (N Engl J Med. 2006;354:567-578).

 

OCF NOTE: The foundation’s donors were funders of the RTOG 1016 clinical trial over several years.

HPV vaccine gains support of ADA

Source: Multi Briefs
Date: October 24th, 2018
Author: Tammy Adams

The American Cancer Society estimates there will be more than 50,000 new cases of oral cancer in 2018. And between 70 to 80 percent of these cases will be attributed to the human papillomavirus virus (HPV), a virus that has types associated with oropharyngeal cancer.

These staggering numbers call for action; action the American Dental Society is willing to take. Why? Because the HPV vaccine could prevent the vast majority of these new cases, but compared to other vaccines in the U.S., it is underutilized.

According to a resolution passed recently by the ADA House of Delegates, the ADA urges dentists to support the use and administration of the human papillomavirus virus vaccine, recognizing it as a way to help prevent infection of the types of HPV associated with oropharyngeal cancer.

Resolution 53H-2018 cites recommendations from the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. It states that the vaccination is a “safe and effective intervention to decrease the burden of oral and oropharyngeal HPV infection.”

The policy is the result of a multifaceted ADA council proposal that includes input from the Council on Scientific Affairs, the Council on Advocacy for Access and Prevention and the Council on Dental Practice. A workgroup committed to the HPV issue and led by ADA volunteer members developed an evidence-based background report to help write the policy.

Dr. Paul Eleazer, past chair of the ADA Council on Scientific Affairs, said that he is encouraged to see the ADA “get behind” this growing crisis, referring to the rising number of HPV-associated cancers being reported. “There is incontrovertible evidence that this virus is responsible for the sharp uptick in oropharyngeal cancers, especially in younger patients and young adults,” said Dr. Eleazer.

In 2017, the ADA Council on Scientific Affairs and Center for Evidence-Based Dentistry published “Evidence-based Clinical Practice Guideline for the Evaluation of Potentially Malignant Disorders in the Oral Cavity” to inform dental professionals about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders, in the oral cavity. To view this guideline, visit ADA.org/OralCancer.

To read the full resolution related to the HPV vaccine, members can log in to the Member Center on ADA.org and click on “Committee C—Dental Education, Science and Related Matters” under Reports and Resolutions. It is Resolution 53.

October, 2018|Oral Cancer News|

Lowering Radiation Dose Could Improve QoL, Cut Costs in Oral Ca

Source: MedPage Today, Medpage.com
Date: October 25th, 2018
Author: Elizabeth Hlavinka

SAN ANTONIO — Radiation de-intensification was tied to a quicker rebound in a number of quality of life (QoL) measures and reduced costs for patients with HPV-associated oropharyngeal cancer, a pair of studies found.

With lower doses of radiotherapy (RT), QoL measures including speech, pain, and socialization still generally worsened after treatment, but returned to baseline within 3 to 6 months, reported Kevin Pearlstein, MD, of the University of North Carolina in Chapel Hill.

And more aggressive de-intensification led to a 22% cost reduction for treatment overall ($45,884 versus $57,845 with standard care), with 33% lower costs for RT itself and 50% lower costs for post-treatment care (P=0.01), according to findings presented by Mark Waddle, MD, of the Mayo Clinic in Jacksonville, Florida.

The studies were presented here at the American Society for Radiation Oncology (ASTRO) meeting during a session on improving outcomes while minimizing toxicity in oropharyngeal cancer.

In the research from Pearlstein’s group, patients reported global QoL scores of 81 at baseline (using the 100-point EORTC QLQ-C30 questionnaire, where higher scores connote better health), which dipped to 69 at 3 months post-treatment, then rose to 75 at 6 months. Global QoL scores increased to 82 and 84 by months 12 and 24, respectively.

Common long-term side effects such as sticky saliva, taste, and ability to swallow did not return to baseline within months 3 to 6, but continued to improve between months 12 and 24. Pearlstein noted that swallowing took longer to return to baseline, typically between 1 to 3 years.

“This highlights the possibility that there can be improvement in these symptoms with longer-term follow-up,” he said.

Although oropharynx cancers associated with HPV generally have a more favorable prognosis compared with those that are not, the treatment is similar for both. As a result, these lower-risk patients still typically experience symptoms of dysphagia, dry mouth, and taste changes for upwards of 1 year after treatment, Pearlstein said.

While standard treatments typically include 70 Gy RT along with 100 mg/m2cisplatin, this study investigated whether patients given 60 Gy RT along with weekly 30 mg/m2 doses of cisplatin would result in improved QoL. Cisplatin-intolerant patients were treated with cetuximab, and patients who could not tolerate either did not receive chemotherapy.

The authors also conducted a multivariate analysis that controlled for type of chemotherapy, gender, and age. Those with with worse baseline symptoms of dry mouth, taste, and sticky saliva were more likely to return to baseline function at 12 months (ORs of 1.06, 1.09, and 1.02, respectively). Similar associations for sticky saliva and swallowing were found among patients who underwent unilateral neck RT.

“One obvious limitation is that we don’t have a direct comparison with standard intensity chemotherapy/radiotherapy,” Pearlstein said. “However, when we view these findings in the context of what we already know for patients with head and neck cancer, we do feel our findings suggest that patients who receive de-intensified chemotherapy/radiotherapy may benefit from faster return to baseline quality of life, continue improvement in symptoms over time, and less long-term morbidity.”

To conduct the study, the researchers collected data from two de-intensification phase II trials that took place from 2012 to 2017. A total of 126 patients were included, a majority of which were ages 60 and over (53%) and were non-smokers (63%). Patients were followed for an average of 25 months.

Cost of Treatment

De-intensification of radiation may also benefit these patients by decreasing total treatment costs, according to an analysis of a prospective phase II study.

“Several studies have or are investigating de-escalation of treatment to reduce toxicity while maintaining outcomes,” Waddle said during his presentation. “However, those studies haven’t investigated the cost of care that may be associated with de-escalation of treatment.”

He reported that the median cost was $17,309 for RT among those who received de-escalated doses compared with $28,161 with standard treatment (P<0.0001). The per-patient costs were $797 versus $933 per month, respectively, in the first 6 months after treatment and $518 versus $611 in the 16 to 24 months after treatment.

Among the post-treatment savings, gastrointestinal-related costs were 79% lower (P<0.01), hospitalization costs were 40% lower, and emergency department visit costs were 90% lower.

This study obtained data from the MC1273 trial, in which 68 patients received aggressive de-escalated doses of RT (30-36 Gy), and then compared the costs to 84 patients treated with standard of care (60-66 Gy). The average patient age was 58.5 years and the majority of them were white men.

October, 2018|Oral Cancer News|

Long-term implant failure in patients treated for oral cancer by external radiotherapy: a retrospective monocentric study

Source: Journal of Oral Medicine and oral Surgery, JOMOS
Date: October 10th, 2018
Authors: Aline Desoutter, Sophie Deneuve, Sophie-Charlotte Condamin and Anne-Gaëlle Chaux-Bodard

Abstract

Introduction: The placement of dental implants in irradiated bone has allowed functional rehabilitation for many oral cancer patients. Nonetheless, there is only few data about implant failure in irradiated tissues and their consequences. This retrospective study aims to highlight the rate and circumstances of implant failure.

Material and method: Patients treated with external radiotherapy for oral carcinoma and who received dental implants were included. Patients reconstructed with free bone flaps were excluded.

Results: Eighteen patients were included. Forty implants were placed between 2004 and 2007, 8 failed, of whom one osteoradionecrosis was observed. Time interval between radiotherapy and implantation was 44.6 (6–182) months. Mean dose was 51.8 (50–66) Gy.

Discussion: In the series, the implant failure rate is 20%, which corroborates the literature’s data. Failures occur more often for doses over 50 Gy. The placement of dental implant in irradiated bone leads to soft tissue complications but also increases the risk of osteoradionecrosis. The recent reimbursement of dental implants in oral cancer patients by the National Social Health system will probably increase the indications. Multidisciplinary staffs should be aware of benefit/risk ratio for each patient.

Introduction

Dental implants in patients treated for upper aerodigestive tract (UADT) cancers have facilitated the functional and aesthetic rehabilitation of patients whose postoperative anatomy did not allow for the placement of conventional prostheses. Several studies have been conducted and the success rates have varied from 62.5% to over 90% [1]. These success rates would be similar to those found in a healthy patient’s mandible, which is reported to be 92.6% [2]. However, there is little information regarding the types of failures that occur with these implants, as well as the consequences and circumstances surrounding their occurrence, especially when the radiation dose at the implant site is >40 Gy. Indeed, most of the published studies are case studies in which there is great heterogeneity in the initial tumor sites and in the radiation doses received at the implant site. It is therefore difficult to precisely determine the failure risk in patients who have received large radiation doses in the oral area. The expected complications are mainly peri-implantitis, loss of implants, and even osteoradionecrosis (ORN) [3]. The aim of this study was to highlight long-term implant failures in patients who were treated with radiotherapy for oral cancer and to observe the circumstances and consequences of these failures.

Material and methods

The clinical records of oral cancer patients treated between 2004 and 2007 by radiotherapy (exclusively or not) and who received implants were reviewed. In the interest of maintaining the homogeneity of the study sample, patients treated with a microanastomosis fibula flap were excluded.

The following information was extracted from the case records: tumor location, tumor stage, and type of treatment received, the duration between radiotherapy and implantation, the type of implants placed, the surgical and operative protocol, the patient’s medical history (excluding oncology) as well as any implant or peri-implant clinical events and their time of occurrence. Failure was defined as loss of implant osseointegration resulting in implant loss or removal. Surgical and implant loading failures were considered. Statistical analysis was performed using XLSTAT® software (Microsoft).

Results

Eighteen patients, consisting of 14 males (77%) and four females (13%) were eventually included. The mean age at the time of implant placement was 57.5 years (range: 42–78 years).

The initial tumor locations, the initial tumor stage, and the treatments received are presented in Table I.

Table I : Population studied: sites, tumor stages, and treatments received.
Table II : Implant failures as a function of the radiation dose received, initial tumor site, and failure onset delay.

Discussion

Cervicofacial radiation is one of the primary causes of implant loss [1,4] regardless of whether it is administered early or late [5]. Several failure factors specific to implant placement in irradiated areas have been identified; these include the duration after radiotherapy and the radiation dose received.

For successful implantation, the minimum time after radiotherapy before implantation should be 6–12 months [6]. A delay of >12 months would improve implant success rates [7]. In the current study, a minimum period of 6 months was selected after the multidisciplinary consultation with the surgical oncologists and radiotherapists. After excluding the two patients who were treated several years ago, missed their follow-up, and then reappeared for prosthetic rehabilitation, the average implantation time after radiotherapy in our study was 20.37 months (range: 6–49 months). One study [8] showed that the failures are less severe in patients receiving implants a later stage of oncological treatment (17.1% failure rate for intraoperative implants versus 4.6% for those placed postoperatively). Of course, the idea of early rehabilitation encourages the surgical team to perform implantation along with tumor removal, before additional treatments are administered. Although this technique has the advantage of decreasing treatment duration, it is not always feasible because of the constraints of tumor management.

The radiation dose received at the implant site is also a major cause of implant failure, with doses <50 Gy being more favorable [9,10]. Animal studies and literature reviews show that the implant failure rate is directly correlated with the radiation dose received [9,10]. In the study, implant sites that received estimated doses >55 Gy had failure (mean: 59.33 Gy). In fact, all implant failures occurred in patients who received treatment for cancer involving the anterior aspect of the floor of the mouth. The therapeutic target was therefore very close to the implant site, and the dose administered at the implant site was close to the therapeutic dose delivered.

The biggest challenge consists in evaluating the radiation dose received at the implantation site. In most studies, the initial tumor sites involved all the UADTs, including the oropharynx, with low radiation doses of about 30 Gy at the symphyseal and parasymphyseal level. It therefore seems more appropriate to limit the evaluation of failure rates to patients treated for cancer of the oral cavity, as the radiation doses at the implant site are therefore more homogeneous. In published studies, only a few authors [11] highlight the antecedents or lack thereof of radiation, with irradiated tissue implants having osseointegration rates of 83% at 5 years.

Long-term implant survival rates reported by the previous clinical studies are nonhomogeneous, with values of 72.8% at 10 years [9], 24% at 5 years [10], or 72% at 8 years [11]; however, these values support the results of our present study. Thus, Wagner [12] reports a 5-year osseointegration rate of 97.5% and at 10 years of 72.8%, whereas other authors report success rates of 48.3% [3]. Another study reports complications in 41.5% patients [13].

Seven out of eight failures encountered in the series began with peri-implantitis. Werkmeister [14] observed a soft-tissue complication rate of 28.6% in irradiated areas versus 8.3% in nonirradiated areas. These complications can be explained in part by the small amount of keratinized gingiva, along with the predisposing factors of radiotherapy-related sensitization and dry mouth. The occurrence of peri-implantitis should be carefully monitored to avoid ORN [15].

An increased loss of marginal bone was reported by many authors, with 2–9 mm variations for a period of 3 years after implant surgery [16]. According to Tanaka [17], early failures are more frequent. In the studies, all failures occurred >1 year after implant placement.

In the present series, a case of loss of osseointegration resulted in extensive ORN at a rate of 2.5%. Treatment of ORN required a subsequent free vascularized bone transfer reconstruction. This patient had been treated for a mouth floor lesion in the past and had received a postoperative radiation dose of 64 Gy (See Patient 3, Tab. I). This implant failed 1 year previously, and a reimplantation was proposed because of the impossibility of prosthetic rehabilitation without bone anchorage. Thus, there were two interventions on adjacent parasymphyseal mandibular bone sites. The patient had reverted to smoking regularly despite tobacco counseling. The risk of triggering ORN following implant placement was estimated to be 1.6%–5% [9,16,18,19]. Some authors advocate the use of hyperbaric oxygen therapy before and after implantation to stimulate or optimize healing and decrease ORN risk [20,21]. Others believe that the risk/benefit/cost ratio is not sufficiently favorable. More recently, the use of low-intensity pulsed ultrasound to increase healing capacity has been advocated [22]. Animal studies are currently underway [23].

Conclusion

It is widely accepted that the use of implant techniques in cancer patients is sometimes essential to ensure functional prosthetic rehabilitation. This retrospective study, which was conducted on patients who had specifically received oral radiotherapy, confirmed that it was a reliable therapeutic treatment for radiation doses of 45–50 Gy. However, the small number of patients in this study prevents the extrapolation of results to larger populations, considering the significant morbidity and lower success rate than patients who were not irradiated. Thus, the inherent risk of a past history of radiotherapy must be taken into account. The use of software like Dentalmaps® [24] allows a better evaluation of the doses received at potential implantation sites. This software is based on the automatic segmentation and delineation of the dental zones, making it possible to estimate the dose received at different points of the dental arch to the nearest 2-Gy fraction. However, the software is expensive, the work is laborious, and this device cannot be routinely used. Considering that health organizations are responsible for the cost management of implants in patients with cancer of UADT, there will be a definite increase in the indications for implantation [25]. It is up to the members present at the multidisciplinary consultation meetings to evaluate the benefit/risk ratio on a case-by-case basis.

October, 2018|Oral Cancer News|

AN E-CIGARETTE COMPANY PUT VIAGRA AND CIALIS IN ITS VAPING LIQUIDS, AND THE FDA IS NOT PLEASED

Source: newsweek.com
Date: 10/13/18
Author: Kelly Wynne

A vape company, HelloCig Electronic Technology Co., has included Viagra and Cialis in its liquids, and has raised the ire of the Food and Drug Administration.

One liquid was called e-Cialis, a popular erectile dysfunction drug, and was displayed with photos of the real product, according to Ars Technica. A weight loss drug, whose brand was banned in Europe, was allegedly adapted into the liquid form as well, though FDA testing proved it instead contained the erectile dysfunction medication found in Viagra.

The FDA sent a warning letter to HelloCig on Thursday. It urged the company to make the necessary changes to properly market their products and asked they comply with FDA regulations to continue selling any type of drug.

HelloCig alleged they responded to the FDA in a statement sent to USA Today Saturday. “Our aim is to fully comply with all FDA regulations, both in letter and spirit,” the statement read.

The FDA also released a statement, written by FDA Commissioner Scott Gottlieb, on the illegal sale of these liquids on Thursday. “There are no e-liquid products approved to contain prescription drugs or any other medications that require a doctor’s supervision,” the statement read. “Prescription drugs are carefully evaluated and labeled to reflect the risks of the medications and their potential interactions with other medicines, and vaping active drug ingredients is an ineffective route of delivery and can be dangerous.”

Gottlieb considers the e-cigarette usage among teenagers an epidemic, he clarified in a statement last month. “E-cigs have become an almost ubiquitous—and dangerous—trend among teens,” he wrote. “The disturbing and accelerating trajectory of use we’re seeing in youth, and the resulting path to addiction, must end. It’s simply not tolerable. I’ll be clear. The FDA won’t tolerate a whole generation of young people becoming addicted to nicotine as a tradeoff for enabling adults to have unfettered access to these same products.”

HelloCig is based in China but sells vaping products in America. The brand carries over 150 flavors of e-liquid among other products like “e-herbs, e-healthcare and e-beverages smoke liquid.”

October, 2018|Oral Cancer News|

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

The U.S. Food and Drug Administration today approved a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years. Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

“Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. ”The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing.”

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

October, 2018|Oral Cancer News|

Vaccine, anti-PD1 drug show promise against incurable HPV-related cancers

A tumor-specific vaccine combined with an immune checkpoint inhibitor shrank tumors in one third of patients with incurable cancer related to the human papilloma virus (HPV) in a phase II clinical trial led by investigators at The University of Texas MD Anderson Cancer Center and reported in JAMA Oncology.

“That encouraging response rate is about twice the rate produced by PD1 checkpoint inhibitors in previous clinical trials, so these results will lead to larger, randomized clinical trials of this combination,” said principal investigator Bonnie Glisson, M.D., professor of Thoracic/Head and Neck Medical Oncology and Abell-Hanger Foundation Distinguished Professor at MD Anderson.

Vaccines specific to HPV antigens found on tumors had previously sparked a strong immune response, but had not, by themselves, been active against established cancers, Glisson said.

“Vaccines are revving up the immune system, but the immunosuppressive tumor microenvironment probably prevents them from working,” Glisson said. “Our thinking was that inhibition of PD-1 would address one mechanism of immunosuppression, empowering the vaccine-activated T lymphocytes to attack the cancer.”

The team combined the vaccine ISA101, which targets important peptides produced by the strongly cancer-promoting HPV16 genotype of the virus, along with nivolumab, a checkpoint inhibitor that blocks activation of PD-1 on T cells.

Of the 24 patients with recurrent HPV16-related cancers, 22 had oropharyngeal (back of the throat) cancer, one had cervical cancer and one had anal cancer.

  • Eight (33 percent) had a tumor response, two were complete. All eight had oropharyngeal cancer. Median duration of response was 10.3 months.
  • Overall median survival was 17.5 months, progression-free survival was 2.7 months and 70 percent of patients survived to 12 months.
  • Five of the eight responders remain in response.

“The median survival of 17.5 months for these patients is promising and provides further support for randomized trials testing the contribution of ISA101 to PD-1 inhibition,” Glisson said.

HPV causes nearly all cervical cancers, and most oropharyngeal, anal, penile, vulvar and vaginal cancers. HPV16 and HPV18 are the leading viral genotypes that increase cancer risk. Given the viral cause of these cancers, immunotherapy has been considered a strong potential approach. The researchers note that three previous clinical trials of PD1 inhibitors alone for recurrent HPV-related cancers yielded response rates ranging from 16 to 22 percent.

Two patients had grade 3 or 4 side effects—elevated enzyme levels—that required them to discontinue nivolumab. Glisson said the team observed side effects expected from the two treatments separately, but the researchers were encouraged to see no sign of synergistic side effects caused by the combination.

“That’s important as we develop rational combination immunotherapy,” Glisson said. This clinical trial was among the first to combine vaccination with PD1 inhibition.

Randomized clinical trials of the vaccine and anti-PD1 combination for cervical and oropharyngeal cancer are being organized.

The single-arm trial was an investigator-initiated effort originated at MD Anderson, Glisson noted.

September, 2018|Oral Cancer News|

OCF’s Tobacco Cessation Spokesperson and Bradley Cooper’s Stunt Double Rides in Pendleton

You won’t find Cody Kiser at this year’s NFR, but you will find him working as a stuntman in the 2014 blockerbuster hit “American Sniper” starring Bradley Cooper.

The biographical war drama was directed by Clint Eastwood, and told the story of U.S. Navy Seal Chris Kyle.

Kiser, who rode Saturn Rocket for a 75.5-point score Friday at the Pendleton Round-Up, stepped in for Bradley during the scene that shows Kyle riding broncs during his rodeo days before he joined the Navy.

“That was the coolest thing I have ever done,” Kiser said. “I got to hang out for a day with Clint Eastwood and Bradley Cooper. Clint told me I looked a lot like Bradley. They said they wished they had me for the whole movie.”

A friend of Kiser’s who does stunt work in California put Kiser in touch with the people from the movie.

“They needed a bareback rider who had a certain look,” he said. “They had me and a saddle bronc rider, but he couldn’t ride bareback very well, so the job was mine.”

Kiser, 27, said he was living in Texas near where Kyle was shot in 2013, and that he had a friend working at the Rough Creek Ranch-Lodge in Erath County, Texas, where Kyle was shot.

“It’s such a small world,” he said.

Kiser earned a nice paycheck for his work, but said playing Kyle, even in a stunt role, was an honor.

“To be a part of that was unreal,” he said.

September, 2018|OCF In The News|

New Book: Vaccines Have Always Had Haters

Date: 09/23/18
Source: National Public Radio
Author: Susan Brink

Vaccinations have saved millions, maybe billions, of lives, says Michael Kinch, associate vice chancellor and director of the Center for Research Innovation in Business at Washington University in St. Louis. Those routine shots every child is expected to get can fill parents with hope that they’re protecting their children from serious diseases.

But vaccines also inspire fear that something could go terribly wrong. That’s why Kinch’s new book is aptly named: Between Hope and Fear: A History of Vaccines and Human Immunity.

He wrote it, he says, to present the science behind vaccines and to highlight the fallacy of anti-vaccine movements. NPR talked with Kinch about vaccines. This interview has been edited for clarity and length.

The first attempts to control smallpox go back at least 1,000 years and didn’t involve vaccines. Can you describe those attempts?

Smallpox was probably killing a half a million people a year in Europe alone. The medical community had adopted a practice called nasal insufflation. You could take a little bit of the material from a smallpox scab, turn it into a powder and have a child snort it into the nose. Or you could intentionally scrape the skin and put material from a smallpox pustule under the skin of a healthy individual. That was called variolation. Those procedures caused smallpox, and people got sick. But far fewer of them died because most people would get a less virulent form of disease than if they were infected through exposure to a smallpox patient. Those who survived were then immune to smallpox.

How do you suppose people even thought of doing those disgusting things with scabs and pus?

You have to make assumptions. Maybe someone who was caring for a person with smallpox got a cut, and the cut got infected with pus from the patient. Then the caretaker noticed that afterward, they were immune to smallpox infection.

Variolation and nasal insufflation worked reasonably well, but they were not vaccines. What is a vaccine?

A vaccine is an intentional procedure using killed or weakened germs to trigger an immune response. The exposure to the virus or bacteria allows your body’s defenses to work, clearing the germs from the body. With the next exposure to those germs, the body is ready to fight off infection. Vaccines are generally delivered in an injection in the muscle, because the vaccine stays in place long enough for the immune system to detect and fight it.

The development of the smallpox vaccine was a breakthrough by Edward Jenner in 1796. What did science learn from the smallpox vaccine?

It took about a century for all the lessons to be learned. The smallpox vaccine made people understand that, once you identify a pathogen, you can kill or weaken it. Inoculating people with those weakened or killed forms alerts their immune systems but without causing disease, without causing harm. But first, pathogens had to be identified. A whole slew of discoveries happened from the 1880s through the early 20th century. People discovered anthrax bacteria, discovered measles, mumps, rubella viruses, discovered diphtheria, pertussis and tetanus. Then scientists could weaken or kill the germs and create vaccines.

Which vaccines does the world most need now?

The two holy grails are an AIDS vaccine and a universal influenza vaccine. AIDS has proven particularly challenging because the virus mutates very rapidly, and AIDS has found really good ways to circumvent an immune response. And the influenza virus changes constantly. It kills 30,000 to 40,000 Americans a year, and every few generations, there’s a pandemic. Exactly 100 years ago, we had the Spanish flu that wiped out tens of millions of people.

There are others. The current scourge of the world is malaria. The organism that causes it can change and thus hide from a vaccine. New pathogens always arise, and with global warming they’re working their way north, where they haven’t been seen before.

The current anti-vaccination movement fears that vaccinations are linked to autism, though the original study suggesting the link has been roundly discredited. Were there always “anti-vaxers” throughout history?

The anti-vax movement is actually older than vaccines. There was a well-established anti-variolation movement when people were using scabs and pus to try to prevent smallpox. Lady Mary Wortley Montagu was the wife of the British ambassador to the Ottoman Empire and a progressive thinker. She strong-armed the embassy physician to perform variolation on her four-year-old son in 1715, but her husband was opposed to it and she had to do it behind his back.

For virtually any vaccine you can name, there was an anti-vax movement around it. An 1802 cartoon was titled “The Wonderful Effects of the New Inoculation.” It was a spoof, reflecting widespread fear and showing people sprouting cow’s heads and horns and tails after being vaccinated against smallpox. (Note: Smallpox vaccine was made with cowpox virus, which rendered people immune to both cowpox and smallpox.)

Have there been scientifically valid reasons for people to fear vaccines?

There have been mistakes. When Dr. Jonas Salk announced his polio vaccine in 1955, bells were rung around the country to celebrate. But as people started getting immunized, Cutter Laboratories, which manufactured the vaccine in California, didn’t properly prepare the vaccine. A lot of kids were unintentionally infected with polio, and the incident created a lot of fear. (According to the National Institutes of Health, 40,000 cases of polio were caused by 200,000 vaccinations from the bad batch; 10 children died and 40 were left with varying degrees of paralysis).

Vaccines aren’t perfect. But there’s no substance in the world, including water and oxygen, that is entirely safe.

Why did you write this book now?

I saw that things were getting worse. It’s becoming more expensive to develop vaccines and less profitable. We haven’t developed a novel vaccine in decades. Pharmaceutical companies are abandoning vaccines. The anti-vax movement, I would argue, is stronger than ever. They’re highly organized, highly motivated and well-funded.

September, 2018|Oral Cancer News|