Speculative Studies - Opioid Use & Cancer Growth?

January 2010

Does Morphine Encourage Cancer Growth?

"Some recent scary headlines in the lay press hyped a very preliminary study in lung cancer cell lines, suggesting that use of morphine (or other opioids) in advanced cancer patients may hasten death, and that methylnaltrexone, a peripherally acting opioid antagonist, may retard cancer growth. The news reports cite "growing clinical evidence" of this phenomenon. Unfortunately, the "clinical evidence" cited is barely tenuous and the laboratory studies are very preliminary.

The news reports were based on a press release by the University of Chicago press office. It should be noted that methylnaltrexone, which is currently indicated only for opioid-induced constipation in advanced cancer patients, was developed at the University of Chicago and licensed to a pharmaceutical company.

The press release is based on a presentation at a scientific meeting. Even early research findings by well-regarded scientists must be subjected to peer review through publication in reputable scientific journals; this report is yet to be published.

The research was initiated after a small number of patients in a methylnaltrexone study lived longer than expected. Similarly, a very small number of patients with advanced cancer in an intrathecal analgesic study lived a little longer than expected (but did not reach statistical significance, and it was not a study end-point).

Three small, single-institution clinical studies are mentioned (two of them at the same institution in Ireland). Longevity related to opioid use was not a study question in any of these studies. There are multiple other factors that could have contributed to any perceived survival advantage.

There are several small studies which show that well-managed pain (using aggressive opioid treatment) in end-stage disease does not shorten life and may have a slight survival advantage in some cases (these studies did not address the direct affect of opioids on tumor growth, which is the presumed reason for the observed survival effect).

Opioid analgesics have a long and well-documented track record of relieving pain and dyspnea associated with advanced cancer, reducing suffering, and improving quality of life.

Clinical practice in any arena should not be changed based on the findings of a single study, even one that is well-designed and conducted. The findings from these studies are speculative. From a research perspective they raise interesting questions that suggest hypotheses and form the basis for future laboratory research. Based on results of those future studies, clinical trials can then be designed.

There is some fascinating science at work in this, and it will be prudent to follow its progress in the coming years. However, it would be imprudent, at best, to change current pain management practices with opioid analgesics based on this report. Patients and clinicians need to have the news reports put in perspective."

Thomas Quinn, APRN, MSN
Yale Cancer Center

OTC Medication Recall - Motrin, Benadryl, Rolaids

In consultation with the U.S. Food and Drug Administration (FDA), McNeil Consumer Healthcare has voluntarily recalled certain lot numbers following an investigation of consumer reports of an unusual moldy, musty, or mildew-like odor. The odor was associated with temporary, non-serious gastrointestinal symptoms, including nausea, stomach pain, vomiting, and/or diarrhea.

This recall expands an earlier recall of acetaminophen 100-count bottles with EZ open caps labeled Tylenol Arthritis that began in late 2009. Some of the medications included in this expanded recall are used in the treatment of pain, like:

Children’s Motrin
Children’s Meltaway Tylenol
Benadryl
Extra Strength Tylenol
Regular Strength Tylenol
Motrin IB
Rolaids
St. Joseph Aspirin
Tylenol 8 hour

Specific lot numbers affected by this recall can be found at http://www.mcneilproductrecall.com/
To find if you are in possession of any of the affected products, look on the side of the bottle label for the lot number.

Individuals who may have ANY of these lots in their possession should:
1. Stop taking the medication.
2. Contact your healthcare provider if you have recently taken any of these medications and are experiencing symptoms as listed above or have medically-related questions.
3. Report any adverse reactions to the FDA’s MedWatch Program by:o Fax: 1-800-FDA-0178,o Mail: MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787o Internet:(Medwatch website)
4. Contact McNeil Consumer Healthcare for instructions if you wish to obtain replacement medications or a refund and also to receive information about safe disposal of these products.

The public may direct questions to McNeil Consumer Healthcare or 1-888-222-6036 (Monday-Friday, 8:00 a.m. to 10:00 p.m. Eastern time and Saturday-Sunday 9:00 a.m. to 5:00 p.m. Eastern time).

Johnson & Johnson expands voluntary recall of Tylenol Arthritis Pain caplets

Johnson & Johnson, the makers of Tylenol Arthritis Pain caplets, is expanding a voluntary recall of the product because of consumer complaints of a strange, moldy smell that has caused nausea and other ailments. The health care company, based in New Brunswick, N.J., is now recalling all 100-count bottles of the arthritis caplets with the red E-Z Open Cap. Last month, Johnson & Johnson recalled five lots of the pain medicine after consumers complained of a mildew-like odor from the pills that produced nausea, vomiting, stomach pain and diarrhea.

The pills’ musty odor comes from trace amounts of a chemical known as 2, 4, 6-tribromoanisole, according to the company, which is believed to be from the breakdown of another chemical in wooden pallets used to transport and store the drugs.

To date, the health complaints have been “temporary and nonserious,” according to a press release by McNeil Consumer Health Care, the division of J&J that sells Tylenol, although the health effects of the chemical have not been studied.Johnson & Johnson will move production of the caplets to a new facility and return the product to the market by January.

Consumers are advised to stop using the product and call the company at (888) 222-6036 for a refund. Additional information on the recall can be found online at Tylenol's Web site.

Managing Your Pain: How to Use Prescription Drugs Without Becoming Addicted

While the stories of current and former prescription opioid addicts are frightening, chronic pain experts note that addiction is relatively rare and that these drugs do offer benefits when they are properly prescribed and used. And there is certainly a need for them. Be smart if you take prescription opioids—and find alternative forms of relief

Posted October 26, 2009
Michael Jackson's death has brought renewed attention to prescription drug abuse, which has long been a problem for everyday Americans as well as pill-popping celebrities. About 48 million people, or 20 percent of Americans over age 12, have taken prescription medications—often, the painkillers called opioids—for nonmedical reasons, according to the National Institute on Drug Abuse, and seniors are particularly vulnerable since they often juggle many medications. Those prescription opioids cause more drug overdose deaths than heroin and cocaine combined, according to the Drug Enforcement Administration. (Drowsiness, respiratory depression and arrest, nausea, confusion, constipation, sedation, unconsciousness, and coma are among the potential health consequences of abusing the drugs.) Meantime, painkiller-related admissions to state-licensed treatment centers are on the rise, according to a March report.

Michele Braa-Heidner, 47, started taking prescription painkillers in 1995, when she had her wisdom teeth removed. Soon after, she developed a painful spinal condition for which she needed several surgeries—and more medications. The drugs relieved the pain and "made me feel really good," she says. Soon, she found that she couldn't get through the day without them. "You're almost chasing that first high, [but] you never get it anymore unless you take a huge amount," she says.

But while the stories of current and former prescription opioid addicts are frightening, chronic pain experts note that addiction is relatively rare and that these drugs do offer benefits when they are properly prescribed and used. And there is certainly a need for them. More than a quarter of Americans age 20 or older—more than 76 million people—say they've experienced pain that lasted longer than 24 hours, according to the American Pain Foundation, and 42 percent of those sufferers have endured pain lasting longer than a year. For many of these people, prescription opioids like the oxycodone (commonly sold as OxyContin) and hydrocodone (sold most popularly as Vicodin) used by Braa-Heidner, as well as meperidine (sold as Demerol) and others, are very helpful. "I think the fear can be a huge barrier to proper pain control," says Paul Christo, director of the multidisciplinary pain fellowship program at the Johns Hopkins University School of Medicine. So how should you approach using a pain medication to get the relief you need without getting hooked?

First, experts say it's best to stick with one doctor to coordinate your care; that way, she will keep tabs on all the pain medications you're taking. She may also be looking for signs of abuse. Pain specialists can monitor pill use and do urine drug testing to ward off addiction in their patients. They may also require patients to sign treatment agreements that give the doctor permission to take certain steps if he or she suspects addiction—including talking to family members about suspected abuse, says Howard Heit, a pain management and addiction medicine specialist based in Fairfax, Va.

And there are other systemic measures in place to help curb abuse. By July of this year, 40 states had passed legislation to start prescription drug monitoring programs to keep tabs on when, where, and for whom controlled substances, including opioids, are dispensed. There's even a push to fund a federal program, approved by Congress but never put into action, to monitor opioid prescriptions from state to state. Meantime, after being prompted by the Food and Drug Administration, drug companies are trying to do their part to ease the problem by reformulating drugs to make them more difficult to abuse. An FDA advisory panel recently recommended approving a new formulation of OxyContin that would reduce the amount of medication released when tablets are crushed or chewed—common methods used by abusers to boost the impact of the drug. (The FDA typically follows the advice of its expert panels.)

If your pain isn't improving, talk to your physician. It's a bad idea to take medications that haven't been prescribed for you, so don't be tempted to use pills intended for a friend or relative. Instead, see if a different medication or dosing schedule might make things better, and be sure to consider alternative ways of managing pain that might work instead of or in tandem with powerful opioids.

Experts say that injections of steroids or other medications, nerve blocks that interrupt pain signals, physical therapy, and psychological interventions such as cognitive behavioral therapy, biofeedback, and guided imagery, as well as other relaxation techniques can all be beneficial. Acupuncture is another option. It's thought to ease pain by raising the level of endorphins—the body's natural pain relievers—in the body, Christo says. "They are released when the body experiences pain, when you sprain your ankle, cut your finger—in response to injury." The therapy may work for some but isn't a cure-all; a review of 13 studies published in January in the British Medical Journal found that acupuncture offered only a small level of relief for people with low-back pain, migraines, knee osteoarthritis, and postoperative pain.

And while it may sound counterintuitive, people with chronic pain should try to get exercise, both for the same health reasons as everyone else and, specifically, to avoid muscle atrophy. A 2005 study published in the Annals of Internal Medicine found that a supervised, individually tailored exercise program may help both ease pain and improve function. A physical therapist or personal trainer can help.

If you are using prescription opioids, be aware of the different states that your body may experience. Tolerance occurs when the body adjusts to one dosage and needs increasingly more medication over time to achieve the same result. (This also applies to side effects, so if opioids make you itch, for instance, that feeling may go away as your body adjusts.) People should not be overly concerned about developing tolerance to pain medications, because it's a part of taking the drugs, experts say. Users can also experience physical dependence, causing withdrawal symptoms such as diarrhea, perspiration, and abdominal cramping when they abruptly stop taking the medication. It can occur after as few as two days of continuous use; to reduce symptoms, physicians can help you taper off the dosage, says Christo.

Addiction is far more serious. It involves compulsive use of the drug, continued use despite harm to a person or loved ones, and cravings for the substance. Not everyone who takes the medicine will get hooked, even with years of use, and there's no sure way to predict who will. Wonder if you have a problem? The hallmarks of addiction are an inability to keep up with work, school, or family matters as a result of drug abuse, and an inability (or refusal) to stop despite those consequences, says Scott Fishman, professor and chief of pain medicine at the University of California-Davis School of Medicine.

If you suspect that you or a family member might have developed an addiction to prescription opioids, contact a doctor (a personal physician or a local addiction medicine specialist). Some physicians prescribe the medication buprenorphine—a narcotic sold under the brand name Suboxone that makes it easier to withdraw from prescription opioids—for outpatient use. This is not a do-it-yourself project; this medication can also be abused and needs to be used under a doctor's supervision. And be sure there's a plan for ending its use. For more severe cases, people may be referred to treatment centers, which offer detox and treatment.

Patients admitted to the Betty Ford Center in Rancho Mirage, Calif., are first put on buprenorphine, then weaned off the drug quickly. "The drug is only a step to facilitate recovery," says Garrett O'Connor, president of the Betty Ford Institute, the nonprofit arm of the treatment center. Traditional 12-step programs are also necessary, he says, because a "major part of recovery is doing work on character defects and lifestyle problems [such as] grandiosity, antisocial activity, cheating, lying, being unaccountable and irresponsible. They're the things that have to be examined and then put into reverse," says O'Connor.

As for Braa-Heidner, she's stopped using the drugs that got her in trouble. She soon plans to start, with the help of her psychiatrist, slowly tapering off Suboxone. The drug "has helped me in regards to normalizing my life and getting me out of the ups and downs of taking pain meds every four hours, so I am grateful for that," she says. "I am feeling quite good about my life right now, and I am looking forward to succeeding at healing myself and getting off of Suboxone." It's time to put all the drugs aside.

U.S.News & World Report
J. W. P.