A recent issue of the New England Journal of Medicine includes an article with the bland title Cytarabine Dose for Acute Myeloid Leukemia. AML is an often-curable form of leukemia characterized by rapidly-growing myeloid white blood cells. Cytarabine — what we’d call “Ara-C” on rounds — has been a mainstay of AML treatment for decades.
The new report* covers a fairly large, multicenter, randomized trial of adult patients with AML. The researchers, based in the Netherlands, Switzerland, Belgium and Germany, evaluated 860 patients who received either intermediate or high doses of Ara-C in their initial, induction chemotherapy. According to the journal, “this investigator-sponsored study did not involve any pharmaceutical companies.”
The main finding was that at a median follow-up of 5 years there were no significant differences between the groups in terms of complete remission rates, relapses or overall survival. The high-dose Ara-C offered no clear advantage in any prognostic subgroup, including those with genetic changes that bear a poor risk. Not surprisingly, Grade 3 and 4 (severe) toxicities were more common in the patients who received higher doses of Ara-C. Those patients also had lengthier hospitalizations and prolonged reduction in their blood counts.
Why am I mentioning this report, besides that it hasn’t received any press coverage? First, because the findings might matter to people who have AML and are contemplating treatment options. But mainly it’s an example of how carefully dialing down some chemotherapy doses could reduce health care costs and lessen untoward effects of cancer therapy — in terms of early toxicities and, possibly down the line, fewer secondary malignancies – without compromising long-term outcomes.
*subscription required: N Engl J Med 364: 1027–36 (2011). The free abstract includes some details on the chemo doses.
*This blog post was originally published at Medical Lessons*
Lupus, an autoimmune disease, [recently] turned up on the front page of the Wall Street Journal (WSJ). It cropped up, also, on the first page of the New York Times business section, and elsewhere. Scientific American published a nice online review just now. The reason is that the FDA has approved a new monoclonal antibody for treatment of this condition.
The drug belimumab (Benlysta), targets a molecule called BlyS (B-lymphocyte Stimulator). The newspapers uniformly emphasize that this drug marks some sort of triumph for Human Genome Sciences, a biotech company that first reported on BlyS in the journal Science way back in 1999. BlyS triggers B cells to produce antibodies that in patients with lupus tend to bind and destroy their own cells’ needed machinery, causing various joint, lung, liver, kidney, brain, blood vessel and other sometimes life-threatening problems. So if and when Benlysta works, it probably does so by blocking aberrant autoimmune B-cell activity.
The newspapers don’t give a lot of details on the drug’s effectiveness, except that it appears to help roughly one in 11 patients, and the main benefit may be that some lupus patients on Benlysta can reduce their use of steroids, which have long-term and toxic effects on many organs. The most recent major medical publication on a trial on the drug came out in the Lancet two weeks ago.
Some reported caveats are that the drug has not been adequately tested or approved for patients with severe kidney or neurological manifestations of the disease, and that its activity, marginal as it is, appears to be less in patients of African heritage based on trials completed thus far. Additional trials are in the works.
The drug is expensive, to the updated tune of $35,000 per year. According to the WSJ: “Estimates of how many Americans are affected range from 161,000 to 1.5 million.” (How’s that for a wide ballpark figure? Likely a function of how hard it is to define and establish diagnosis for this disease, which anticipates how hard it will be to measure this drug’s effects — see below.) The same WSJ piece says analysts expect the drug to become a blockbuster, with annual sales eventually topping $1 billion. Read more »
*This blog post was originally published at Medical Lessons*
Maybe you read the other day in The New York Times that the pharmaceutical industry has a problem. Big blockbuster drugs like Lipitor are going off patent and the industry leaders don’t have new blockbusters showing promise to replace them. So the big companies search for little companies with new discoveries and they consider buying them. Industry observers think the days of $5 billion-a-year drugs to lower cholesterol or control diabetes may be past for awhile, and the companies will have smaller hits with new compounds for autoimmune conditions and cancer.
When I saw my oncologist for a checkup yesterday — the news was good — we chatted about the article and the trend toward “niche science.” We welcomed it. We didn’t think — from our perspective — the world needed yet another drug to lower cholesterol. We need unique products to fight illnesses that remain daunting, some where there are no effective drugs at all. For example, my daughter has suffered for years from what seems to be an autoimmune condition called eosinophilic gastroenteritis (EGID). Her stomach gets inflamed with her own eosinophil cells. They would normally be marshaled to fight a parasite in her GI tract but in this case, there’s nothing to attack. So the cells make trouble on the lining of the stomach and cause pain and scarring. Right now, there’s no “magic bullet” to turn off these cells. My hope is some pharma scientists will come up with something to fill this unmet need.
In the waiting room before I saw my doctor at the cancer center in Seattle I overheard a woman on the phone speaking about her husband’s new diagnosis of pancreatic cancer. I was sitting at a patient education computer station nearby. When she was finished I introduced myself and showed her some webpages to give her education and hope: pancan.org and our Patient Power programs about the disease. She was grateful. I did tell her — and she already knew — that there was no miracle drug for pancreatic cancer and that it was a usually-fatal condition. But that there were exceptions and, hopefully, her husband would be one. Of course, wouldn’t an effective medicine be best? Read more »
*This blog post was originally published at Andrew's Blog*
Ear infections used to be a devastating problem. In 1932, acute otitis media (AOM) and its suppurative complications accounted for 27 percent of all pediatric admissions to Bellevue Hospital. Since the introduction of antibiotics, it has become a much less serious problem. For decades it was taken for granted that all children with AOM should be given antibiotics, not only to treat the disease itself but to prevent complications like mastoiditis and meningitis.
In the 1980s, that consensus began to change. We realized that as many as 80 percent of uncomplicated ear infections resolve without treatment in three days. Many infections are caused by viruses that don’t respond to antibiotics. Overuse of antibiotics leads to the emergence of resistant strains of bacteria. Antibiotics cause side effects. A new strategy of watchful waiting was developed.
Current Medical Guidelines
In 2004, the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) collaborated to issue evidence-based guidelines based on a review of the published evidence. Something was lost in the transmission: The guidelines have been over-simplified and misrepresented, so it’s useful to look at what they actually said. There were six parts:
1. Criteria were specified for accurate diagnosis.
- History of acute onset of signs and symptoms
- Presence of middle ear effusion (ear drum bulging, lack of mobility, air-fluid level)
- Signs and symptoms of middle ear inflammation: Either red ear drum or ear pain interfering with normal activity or sleep
They stressed that AOM must be distinguished from otitis media with effusion (OME). OME is more common, occurs with the common cold, can be a precursor or a consequence of AOM, and is not an indication for antibiotic treatment. Read more »
*This blog post was originally published at Science-Based Medicine*
New clinical trials and published research are giving us information on how to improve health in elderly patients. Here are some brief points from the Cleveland Journal of Medicine that were surprising to me:
— Each year 30 percent of people age 65 or older fall and sustain serious injuries so preventing falls and fractures is important. Vitamin D prevents both falls and fractures, but mega doses of Vitamin D (50,000 mg) might cause more falls. A better dose is 1,000mg a day in people who consume a low-calcium diet.
— Exercise boosts the effect of influenza vaccine.
— The benefits of dialysis in older patients is uncertain, as it does not improve function in people over age 80. We don’t even know if it improves survival. Older patients who receive dialysis for kidney failure had a decline in function (eating, bed mobility, ambulation, toileting, hygiene, and dressing) after starting treatment.
— Colinesterase inhibitors (Aricept, Razadyne and Exelon) are commonly used to treat Alzheimer disease, but they all can have serious side effects. Syncope (fainting), hip fractures, slow heart rate, and the need for permanent pacemaker insertion were more frequent in people taking these drugs. The benefits of these drugs on cognition is modest.
— A new drug called Pradaxa (dabigatran) will likely prove to be safer than Coumadin (warfarin). Over two million adults have atrial fibrillation and the median age is 75. The blood thinner warfarin is critical for prevention of strokes but it caries a high risk of bleeding and drug levels have to be monitored frequently. Dabigatran will probably replace warfarin, but it will probably also be a lot more expensive.
As I often say, medicine and science are constantly changing and evolving. As new evidence comes forth, physicians and patients need to re-evaluate they way we do things.
*This blog post was originally published at EverythingHealth*