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These data were reported in two separate presentations at the 33rd Annual Congress of the Oncology Nursing Society (ONS). These data confirm that CAPHOSOL is a useful tool to help oncology nurses and other healthcare professionals in the management of OM and related symptoms, particularly in patients with head and neck cancer and those receiving chemotherapy.

One of the two abstracts including this data, ONS Abstract #2757, “Supersaturated Electrolyte Oral Rinse Aids Quality of Life for Head/Neck Chemoradiation Patients” (Haas, ML), was selected by an ONS Expert Panel as one of the Top Ten Best Supportive Care abstracts at the ONS 2008 Congress.

“Oral mucositis is a painful, common side effect experienced by cancer patients receiving chemotherapy and radiation therapy,” commented principal investigator Marilyn L. Haas, PhD, RN, CNS, ANP-C, Nurse Practitioner, Mountain Radiation Oncology, Asheville, N.C. “As layers of epithelial cells in the oral cavity (cells lining the surface of the throat and esophagus) are eroded during therapy, patients often experience severe pain, are more prone to infection and have difficulty eating and swallowing. Our research concludes that CAPHOSOL, a supersaturated electrolyte oral rinse, should be introduced early in the course of cancer therapy for patients at high risk of oral mucositis because it minimizes the onset and severity of symptoms.”

The rate of severe oral mucositis (NCI Clinical OM Grade 3-4) reported by head and neck cancer patients using CAPHOSOL in this study was 11% (Grade 3) and 2% (Grade 4). Historically, the incidence of severe OM in head and neck cancer patients receiving radiation typically ranges from 34% - 56%, depending upon the specific type of treatment.

Relief of Painful Oral Mucositis

Oncologists at 26 sites enrolled 217 patients into this open-label, non-randomized observational study, called the Caphosol Oral Mucositis Follow-up Observational Registry Trial (COMFORT). Patients must have been undergoing chemotherapy and radiation and at high risk of developing OM. Thirty-one percent of the patients had head and neck cancer (HNC), 31 percent had breast cancer, 13 percent had colon cancer, eight percent had lung cancer, six percent had lymphoma and 11 percent had other tumor types. All patients in this study received CAPHOSOL, administered as an oral rinse, four to 10 times daily for an average of six to eight weeks beginning the first day of treatment. Data were reported for 171 of these patients who had completed folow up at the time the data were analyzed for this interim report.

The study showed that 95 percent of the patients reported favorable OM scores as measured by the percentages of patients indicating Grade 0 (no adverse effects or within normal limits), Grade 1 (mild) or Grade 2 (moderate) symptom severity.

The National Cancer Institute (NCI) clinical rating for OM (oral mucositis assessed during a clinical evaluation) of Grade 0 was evident in 61 percent of patients and Grade 1 clinical OM was seen in 20 percent. An NCI functional rating of OM (reflective of how OM affects diet, swallowing, gastrointestinal function and quality of life) of Grades 0 and 1 were reported in 81 percent of patients. Sixty-five percent of patients ranked their dysphagia symptoms (difficulty swallowing) as Grade 0, while 15 percent rated their symptoms as Grade 1. Grade 0 pain was reported by 61 percent of patients and 20 percent assessed their pain as Grade 1.

Out of 112 patients undergoing chemotherapy alone, 78 percent indicated a clinical OM rating of Grade 0 and 79 percent indicated a functional OM rating of Grade 0. Moreover, 23 percent of the 56 patients undergoing radiation therapy alone or in combination with chemotherapy (RT ± chemo) indicated a clinical OM rating of Grade 0, and 34 percent indicated a functional OM rating of Grade 0. With regard to pain 79 percent of patients undergoing chemotherapy alone and 25 percent of RT ± chemo-treated patients rated their pain as Grade 0. For dysphagia, eighty-two percent of chemotherapy-treated patients and 30 percent of those undergoing RT ± chemo treatment reported a dysphagia Grade of 0.

These data confirm that early intervention with Caphosol reduces the occurrence and severity OM, dysphagia and oral pain in patients undergoing chemotherapy, radiation or combination therapy treatments for cancer.

This reduction increases the likelihood that patients are able to complete a full course of treatment. The findings were released as part of the 44th annual meeting of the American Society of Clinical Oncology.

“There have been limited studies and anecdotal stories about the effectiveness of calcium plus magnesium in reducing neurotoxicity caused by oxaliplatin,” says Daniel Nikcevich, M.D., Ph.D., an oncologist at St. Mary’s Duluth Clinic in Duluth, Minn., a member of NCCTG and study co-chair.

“We designed a double-blind, placebo-controlled study that confirmed the effectiveness of calcium plus magnesium in reducing debilitating neurological sensitivity associated with oxaliplatin, such as pain in the hands, fingers, feet and toes. In the past, these side effects have caused patients to stop treatment and, therefore, not receive critical therapy.”

Each year in the United States, 150,000 patients are diagnosed with colon cancer, and approximately 50 percent of those develop advanced colon cancer. Oxaliplatin, in combination with other chemotherapy drugs such as 5-fluorouracil (5-FU), has emerged as a standard-of-care of first-line therapy for advanced colon cancer. However, oxaliplatin can cause both acute and chronic cumulative sensory neurological problems including pain, numbness and tingling that can prevent patients from completing treatment.

In the study, 50 of the 102 patients enrolled received intravenous calcium and magnesium along with oxaliplatin-based chemotherapy, while 52 patients received oxaliplatin-based adjuvant chemotherapy for colon cancer and an intravenous placebo. Study results showed that the use of calcium and magnesium infusions before and after oxaliplatin was associated with a significant decrease in the incidence and severity of neurotoxicity, and it also delayed the time to the onset of neurotoxicity on oxaliplatin therapy.

Calcium and magnesium are an easily administered, safe treatment option for oxaliplatin-induced neurotoxicity. “Some initial reports from other studies claimed that the use of calcium and magnesium reduced the activity of oxaliplatin-based chemotherapy,” says Axel Grothey, M.D., an oncologist at Mayo Clinic and study co-chair. “However, we have definitive results from an independent, blinded radiologic review which demonstrates no negative influence of calcium and magnesium on the outcome for oxaliplatin-based chemotherapy.”

“Now that we have shown the effectiveness of calcium and magnesium in reducing oxaliplatin-induced neurotoxicity, a further step may be to evaluate the benefit of calcium and magnesium in reducing neurotoxicity caused by other medications,” says Dr. Nikcevich. “Many other commonly used chemotherapy agents cause neurological sensitivity. By applying our study design, we can test the effectiveness of calcium and magnesium when used with other treatments.”

This study was done as part of a program coordinated by Charles Loprinzi, M.D., a medical oncologist at Mayo Clinic Rochester. The program he leads has conducted more than 50 clinical trials designed to find ways to prevent or treat untoward symptoms related to cancer and cancer therapy. This includes three trials to evaluate ways to treat established neuropathy caused by chemotherapy and three additional studies to try to prevent such toxicity. Additional trials are in development to find other ways to alleviate this toxicity.

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Article adapted by Medical News Today from original press release.
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Other Mayo Clinic researchers participating in the study included Jeff Sloan, Ph.D.; Paul Novotny; and Charles Loprinzi, M.D. They collaborated with John Kugler, M.D., Illinois Oncology Research Associates, Peoria, Ill.; Peter Silberstein, M.D., Missouri Valley Cancer Consortium, Omaha, Neb.; Todor Dentchev, M.D., Altru Health Systems, Grand Forks, N.D.; Donald Wender, M.D., Siouxland Hematology-Oncology, Sioux City, Iowa; and Harold Windschitl, M.D., CentraCare Clinic, St. Cloud, Minn.

NCCTG, a national clinical research group sponsored by the National Cancer Institute, consists of a network of cancer specialists at community clinics, hospitals and medical centers in the United States, Canada and Mexico. NCCTG works with Mayo Clinic to bring the latest cancer research to the community. Find out more about NCCTG (http://ncctg.mayo.edu/) and for available clinical trials, click here).

American Society of Clinical Oncology abstract number: 4009

The ATHENA results will be presented at the late breaking clinical trial session of Heart Rhythm 2008, the Heart Rhythm Society’s 29th Annual Scientific Sessions in San Francisco, USA.

For the first time in twenty years of clinical drug trials in atrial fibrillation, an investigational medicine, dronedarone, showed a significant decrease in the risk of cardiovascular death by 30% (p=0.03) on top of standard therapy, including rate control and antithrombotic drugs, in patients with atrial fibrillation or atrial flutter. Dronedarone also significantly decreased the risk for arrhythmic death by 45% (p=0.01) and there were numerically less deaths (16%) from any cause in the dronedarone group compared to placebo (p=0.17). First cardiovascular hospitalisation was reduced by 25% (p=0.000000009) in the dronedarone group.

“The ATHENA results have the potential to change the face of atrial fibrillation management. For atrial fibrillation patients, who together with their physicians struggle on a daily basis to manage the dramatic consequences of this complex disease, Multaq®carries hope for patients” said Marc Cluzel, sanofi-aventisSenior Vice President, R&D. “This milestone is indicative of sanofi-aventis’ commitment to bringing innovative therapies to market, and of our ongoing commitment to provide patients, physicians and public health stakeholders with breakthrough medicines in those therapeutic areas where there are major healthcare needs and limited solutions”.

Atrial fibrillation is a major cause of hospitalisation and mortality and affects about 2.5 million people in the United States, as well as 4.5 million people in the European Union and is emerging as a growing public health concern because of the aging of the population. Patients suffering from atrial fibrillation have twice the risk of death, an increased risk of stroke and cardiovascular complications, including congestive heart failure. Furthermore atrial fibrillation considerably impairs patients’ lives, mainly because of their inability to perform normal daily activities due to complaints of palpitations, chest pain, dyspnoea, fatigue or light-headedness, without consideration of the cumbersome and sometime serious constraints imposed by current therapies of atrial fibrillation.

“In atrial fibrillation where treatment morbidity-mortality benefit still needed to be demonstrated, ATHENA is a unique trial using clinically relevant outcomes such as cardiovascular hospitalisation or death as the primary endpoint. In this regard, the trial has clearly achieved these safety and efficacy endpoints,” said Dr Stefan H. Hohnloser, J.W. from the Goethe University, Division of Clinical Electrophysiology, Frankfurt, Germany, who served as co-principal investigator of the ATHENA study. “As a consequence, dronedarone is the first treatment for atrial fibrillation which has been demonstrated to reduce cardiovascular hospitalisation or mortality in patients with AF.”

The most frequently reported adverse events of dronedarone vs placebo induced gastro-intestinal effect (26% vs 22%), skin disorder (10% vs 8%, mainly rash) and increased blood creatinine (4.7% vs 1%). The mechanism of blood creatinine increase (inhibition of creatinine secretion at the renal tubular level) is well defined. Compared to placebo, dronedarone showed low risk of pro-arrhythmia and no excess of hospitalisations for congestive heart failure. There was a similar rate of study drug discontinuation between the two study groups.

“ATHENA is truly a landmark trial, that marks a paradigm change for the management of atrial fibrillation,” said Dr Christopher Cannon, a Senior Investigator in the TIMI Study Group at Brigham and Women’s Hospital, who was not involved in the study. “Atrial fibrillation is a very common disease, and our prior treatment options have been focused only on symptom relief and a hope to not do harm, which has been the problem with prior antiarrhythmic drugs. Now, with a highly significant reduction in death or hospitalisation, as well as a 45% reduction in arrhythmic death or 30% cardiovascular death, dronedarone may become a first line treatment of atrial fibrillation”.

ATHENA, the largest double blind randomised study in patients with atrial fibrillation, was conducted in more than 550 sites in 37 countries and enrolled a total of 4,628 patients. The ATHENA landmark trial is the first morbidity-mortality study as part of the dronedaronephase III clinical development program, which also included five other multinational clinical studies, an initial study in severe cardiac heart failure and a recent decompensationpatients ANDROMEDA, and a total of 4 international studies in atrial fibrillation: EURIDIS/ADONIS, ERATO, and the ongoing DIONYSOS trial.

Based upon this new clinical data, sanofi-aventis plans to submit a registration dossier to the European Medicines Agency (EMEA), and a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) during the 3rd quarter of 2008.