Promising drug that can kill all solid tumor cancers

Source: www.nextbigfuture.com Author: Brian Wang Above – The City of Hope-developed small molecule AOH1996 targets a cancerous variant of the protein PCNA. In its mutated form, PCNA is critical in DNA replication and repair of all expanding tumors. Here we see untreated cancer cells (left) and cancer cells treated with AOH1996 (right) undergoing programmed cell death (violet). (Photo credit: City of Hope) Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, today published a new study explaining how they took a protein once thought to be too challenging for targeted therapy, proliferating cell nuclear antigen (PCNA), and developed a targeted chemotherapy that appears to annihilate all solid tumors in preclinical research. As the scientists continue to investigate the foundational mechanisms that make this cancer-stopping pill work in animal models, they note that there is an ongoing Phase 1 clinical trial testing the City of Hope-developed therapeutic in humans. Most targeted therapies focus on a single pathway, which enables wily cancer to mutate and eventually become resistant, said Linda Malkas, Ph.D., professor in City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology. However, the cancer-killing pill Malkas has been developing over the past two decades, AOH1996, targets a cancerous variant of PCNA, a protein that in its mutated form is critical in DNA replication and repair of all expanding tumors. “PCNA is like a major airline terminal hub containing [...]

Radiation alone may suffice for some nasopharyngeal cancer

Source: www.medpagetoday.com Author: Ed Susman, Contributing Writer, MedPage Today In selected patients with nasopharyngeal carcinoma, radiation alone may do as much against the disease as the combination of radiation and chemotherapy but with fewer adverse effects, researchers suggested here. About 90% of patients who received radiation alone achieved failure-free survival at 3 years versus 91.9% of patients treated with both radiation and chemotherapy (P=0.86; non-inferiority P<0.001), reported Jun Ma, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China. In his virtual oral presentation at the annual meeting of the American Society of Clinical Oncology, Ma also reported that 98.2% of patients treated with radiation alone survived to 3 years compared with 98.6% of patients who got both radiation and chemotherapy (P=0.30). The multifaceted subgroup analysis almost entirely favored treatment with alone. There was no difference in distant metastasis-free survival (95% in both arms) or local-regional recurrence-free survival, with both arms hovering in the 90-92% level. And patients treated with both therapeutic modes paid a price in adverse events (AEs), Ma reported, noting that grade 3 to 4 mucositis was observed in 18.9% of patients on chemoradiation but in just 9.7% of those on radiation therapy alone. A similar story in AEs was observed for leukopenia, neutropenia, nausea (0.6% vs 13% grade 3-4), vomiting (1.2% vs 14.8%), anorexia (4.8% vs 29%), and weight loss. That differential in AEs was reflected in quality of life measurements, with better scores in the radiation-only group as far as their global health status, [...]

Docetaxel plus radiation new standard of care in cisplatin-ineligible head and neck cancer

Source: www.healio.com Author: Devin McLaughlin Perspective author: Marshall Posner, MD Docetaxel prolonged DFS (disease free survival) and OS (overall survival) when added to radiation for cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma, according to study results presented at ASCO Annual Meeting. The addition of docetaxel also did not appear to worsen quality of life at 6 months, researchers concluded. “This now represents the new reference standard of care for cisplatin-ineligible patients planned for chemoradiotherapy,” Vanita Noronha, MD, of the department of medical oncology at Tata Memorial Center in Mumbai, India, said during a presentation. Background and methods Docetaxel has shown promise in phase 1 and phase 2 studies among patients unsuitable for cisplatin — a standard therapy in chemoradiation for locally advanced HNSCC, according to Noronha. However, limited prospective data exist in this setting. The open-label, randomized phase 3 study by Noronha and colleagues examined docetaxel as a radiosensitizer among 356 cisplatin-ineligible patients with locally advanced HNSCC set for treatment with radical or adjuvant chemoradiation. Researchers randomly assigned patients to radiation alone (n = 176) or with concurrent docetaxel dosed at 15 mg/m2 weekly for up to seven cycles (n = 180). Patients in the docetaxel group received a median six cycles of the treatment. The radiotherapy-alone and combination therapy groups had similar baseline characteristics, including median age (63 years vs. 61 years), ECOG performance status (59.7% vs. 50.6%) and reasons for cisplatin ineligibility (low creatinine clearance, 26.7% vs. 26.1%; hearing loss, 42.6% vs. 45%; ECOG [...]

Treatment paradigms are shifting for locally advanced HPV-positive head and neck cancers

Source: www.onclive.com Authors: Kaveh Zakeri, MD, MAS, Nancy Y. Lee, MD The standard of care for patients with locally advanced head and neck squamous cell carcinomas does not substantially differ according to human papillomavirus (HPV) status in the National Comprehensive Cancer Network guidelines.1 Resectable tumors can be treated with surgery followed by adjuvant therapy. Alternatively, definitive chemoradiation therapy with cisplatin is the other dominant treatment paradigm. Incidence of HPV-associated oropharyngeal squamous cell carcinoma has increased rapidly and is associated with higher overall survival (OS) compared with cancers caused by smoking and alcohol.2,3 Given the unique biology of HPV-associated oropharyngeal disease, a separate staging system was developed for these tumors.4 HPV-associated oropharyngeal cancers are more radiosensitive and chemosensitive than cancers caused by smoking and alcohol, yet the traditional treatment paradigms—including high doses of radiation and chemotherapy—were developed prior to the epidemic of HPV-associated disease. De-escalation of therapy has been proposed for HPV-associated oropharyngeal cancer based on data demonstrating high OS and progression-free survival (PFS).5 De-escalation of therapy has been investigated for both definitive surgical and chemoradiation therapy paradigms. Most de-escalated approaches focus on selecting patients according to clinical features, such as disease stage and smoking status, whereas personalized de-escalation reduces treatment intensity for patients according to treatment response. Transoral Robotic Surgery Followed by Adjuvant Radiotherapy Transoral robotic surgery (TORS) is a minimally invasive approach that reduces morbidity compared with traditional, open surgery for patients with oropharyngeal cancers. TORS is a standard of care option for patients with resectable tonsil or base [...]

2021-11-23T08:16:08-07:00November, 2021|Oral Cancer News|

Checkpoint inhibitors whiff in head and neck cancer trials

Source: www.medpagetoday.com Author: Charles Bankhead Three different checkpoint inhibitors missed the primary endpoints in separate randomized trials of head and neck cancer. In one trial, adding avelumab (Bavencio) to standard treatment did not significantly improve progression-free survival (PFS) in cisplatin-eligible or ineligible patients with locally advanced head and neck squamous cell carcinoma (HNSCC). In another trial, the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) did not improve overall survival (OS) as first-line treatment for recurrent/metastatic HNSCC. Both trials were reported during the European Society for Medical Oncology (ESMO) virtual meeting. Although subgroup analyses suggested benefits for certain patients, neither study should influence clinical practice at this point, said ESMO invited discussant Amanda Psyrri, MD, of the University of Athens in Greece. In the avelumab study, known as GORTEC-REACH, results in cisplatin-eligible patients were consistent with those of the previously reported JAVELIN trial with avelumab, said Psyrri. A signal of benefit was evident in cisplatin-ineligible patients but did not achieve statistical significance. With regard to the CheckMate 651 trial of nivolumab and ipilimumab, Psyrri said, "Combined PD-1 and CTLA-4 inhibition does not appear to be an effective strategy in recurrent/metastatic HNSCC. Future research efforts may identify predictive biomarkers for response to anti-PD-1 and anti-CTLA-4 combinations in HNSCC." Additionally, a smaller trial of pembrolizumab (Keytruda) showed no significant improvement in OS versus chemotherapy for platinum-treated relapsed/metastatic nasopharyngeal carcinoma. GORTEC-REACH This trial evolved from evidence of potential synergy with PD-1/L1 inhibition, cetuximab (Erbitux), and radiotherapy, said Jean Bourhis, MD, of University Hospital Center [...]

2021-09-24T06:54:20-07:00September, 2021|Oral Cancer News|

Chemotherapy and radiation therapy issues: What audiologists need to know

Source: journals.lww.com Author: A. Croutch, Carl AuD With hearing loss, tinnitus, and imbalance as among the numerous side-effects of cancer treatment,1 audiologists play a critical role in monitoring patients receiving chemotherapy and radiation therapy. Sensorineural hearing loss (SNHL) attributed to chemotherapy and radiation therapy is usually permanent, making audiometric monitoring essential to detect its early occurrence.2 Cisplatin, carboplatin & radiation therapy Chemotherapy is used to treat cancer, control the growth and spread of cancer cells, and ease cancer symptoms. Cisplatin and carboplatin are two common antineoplastic agents used to treat testicular, ovarian, breast, esophageal, lung, and head and neck cancers among others. Besides hearing loss, these can cause other side effects including kidney, gastrointestinal disorders, allergic reactions, decreased immunity to infections, and hemorrhaging. Cisplatin was first found to have cytotoxic properties in the 1960s, and in 1978 was the first platinum compound approved by the FDA for cancer treatment.3 On the other hand, carboplatin is less potent than cisplatin and does have fewer side effects, especially on kidney problems.3 Both drugs work by interfering with DNA repair mechanisms causing DNA damage and inducing apoptosis in cancer cells. Cancerous cells cannot limit cell division as do normal cells. Normal cells cease dividing when they encounter similar cells whereas cancerous cells do not. The effectiveness of chemotherapy is determined by its ability to damage the RNA or DNA that gives the cell instructions to copy itself. The cells will die if they are unable to divide. The more quickly they are dividing, [...]

2021-09-09T06:48:49-07:00September, 2021|Oral Cancer News|

Calls grow for treatment deintensification of HPV-positive OPC

Source: ww.pharmacytimes.com Author: Bryan Fitzgerald, PharmD, BCOP Health-System Edition, July 2021, Volume 10, Issue 4 Oropharyngeal cancer (OPC) is a type of head and neck cancer that affects structures in the back of the throat, including the base of the tongue, the posterior pharynx, the soft palate, and the tonsils.1 In the United States, rates of OPC are increasing each year, with an estimated 54,010 new cases in 2021.2 Well-established risk factors include alcohol abuse; exposure to tobacco, including chewing tobacco, cigarettes, and pipes; and infection with human papillomavirus (HPV). With an estimated 43 million infections in 2018, HPV is the most common sexually transmitted infection in the United States.3 HPV infection is causally linked with cancers of the anogenital region, including anal, cervical, penile, vaginal, and vulvar cancers. When HPV is spread orally, infections can also lead to the development of OPC. In the United States, more than 70% of OPC cases are caused by HPV.4 HPV is a group of more than 100 viruses, including certain high-risk strains associated with the development of cancer. The HPV-16 strain is responsible for causing the majority of HPV-positive (HPV+) OPC cases, with HPV-18, HPV-33, and HPV-35 also contributing, albeit significantly less than HPV-16.1 In these high-risk HPV strains, the viral genome encodes several oncogenic proteins that inhibit tumor suppressor proteins, leading to chromosomal instability and malignancy in infected cells. HPV+ OPC is considered a genetically distinct form of OPC. Compared with HPV-negative (HPC–) OPC cases, HPV+ OPC is associated with a [...]

‘On the rise:’ Immunotherapy options for head and neck cancer

Source: www.curetoday.com Author: Kristie L. Kahl On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future. Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore. “I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series. On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments. How have genomics and targeted therapies played a role in head and neck cancer treatment? Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very [...]

On treating advanced head and neck cancer without cisplatin – an oncology grand rounds discussion

Source: www.medpagetoday.com Author: Mark L. Fuerst An oncology grand rounds discussion with Sachin Jhawar, MD. Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous set of diseases with different features and treatment recommendations. Physicians face challenges in initial treatment decision-making and response assessments, including the changing role of surgery, the incorporation of human papilloma and Epstein Barr virus status, as well as the potential for treatment de-escalation using patient-related and tumor-related factors. A recent "Oncology Grand Rounds" article in the Journal of Clinical Oncology provides an overview of treating advanced HNSCC when cisplatin is not an option, including concurrent chemotherapy, cetuximab, targeted therapy, and immunotherapy. In the following interview, the paper's lead author, Sachin Jhawar, MD, of Ohio State University Comprehensive Cancer Center in Columbus, reviews the main issues. What is the focus of the article? Jhawar: We focused on patients with locally advanced disease who would be receiving definitive non-surgical treatment when possible treatment with concurrent cisplatin, delivered either every 3 weeks or weekly, is always the preferred treatment. We specifically wanted to delve into the subset of patients who we would not recommend to receive cisplatin because of age or comorbidities. This could be concurrent chemotherapy (carboplatin/paclitaxel), concurrent cetuximab, and altered or standard fractionation radiation schedules without systemic therapy, as well as when to consider immunotherapy and palliative radiation for those with recurrent or metastatic disease. There is also a great deal of institutional preference involved. At our institution, we prefer concurrent carboplatin/paclitaxel in patients who cannot [...]

Experts release new guidelines for studies into most effective treatments for HPV-positive throat cancer

Source: en.brinkwire.com Author: provided by University of Birmingham, United Kingdom Heightened caution is needed when considering de-escalation trials for patients with Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC), to ensure minimal harm to patients, new guidelines from a group of international head and neck cancer experts have suggested. HPV-positive oropharyngeal cancer is a cancer of the throat caused by the human papillomavirus—a common, but symptomless group of sexually transmitted viruses. Instances of many throat and neck cancers have declined as smoking rates have fallen, whereas HPV-positive OPC has increased, largely affecting younger patients. The standard course of treatment for this disease is a combination of cisplatin (a common chemotherapy drug) and radiotherapy. The younger age of the patient population, significantly improved prognosis, and relatively minimal morbidities caused by the standard treatment pathway have led to the popularisation of the concept of treatment de-escalation as a way to improve the quality of life of patients by reducing dosage or frequency of treatment. These new recommendations, published today in the Journal of Clinical Oncology have been created by the Head and Neck Cancer International Group, a group of experts from nineteen countries, led by the University of Birmingham, UK. The guidelines have been prompted by the recent results of the first three randomised de-escalation trials which suggested a clear detriment in survival when cisplatin is omitted or substituted to minimise side effects. After a review of available HPV-positive OPC literature, the guidelines recommend an overall need for caution when considering de-escalation options, even [...]

Go to Top