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VO L . 4 0 , N O. 2 0
Internal Medicine News www.eclinicalpsychia
T he Leading Inde p endent Ne wspaper for the Inter nist—Since 1968 OCTOBER 15, 2007

Combined Insulin


Regimens Often
Become Necessary
Clinical trial shows need for dual therapy.
Cure Worse Than BY MIRIAM E. TUCKER patients with type 2 diabetes
The Disease? Senior Writer who had not achieved desired
Cancer treatments can cause glucose targets with maximally
unbearable skin toxicity. A M S T E R D A M — Most patients tolerated doses of sulfonylureas
with type 2 diabetes who fail to and metformin.
PAGE 14 achieve adequate glucose control At year 1, only 8%-24% of the
In a 63-year-old woman and former smoker, helical CT reveals a with oral agents are likely to need patients achieved a glycated he-
lesion identified as an adenocarcinoma on left lower lobectomy. combination insulin therapy in moglobin level of 6.5% or less.
Brain Protection the long run, Dr. Rury R. Hol- “We’ve seen that you can use
Diet and other lifestyle man said at the annual meeting any of these insulins to improve

CT Not Advised for factors may help ward off

Alzheimer’s disease.
of the European Association for
the Study of Diabetes.
That conclusion was based on
glucose control, but the likeli-
hood of achieving a 6.5% target
is not that great ... and if you’re

Lung Ca Screening the first-year findings from the 3-

year multicenter, open-label
Treating to Target in Type 2 Di-
not successful, you’re likely to
need two insulins,” said Dr. Hol-
man, chief of the Diabetes Trials
abetes (4-T) study. The study is a Unit at the University of Oxford
BY ROBERT FINN pl.]:1S-422S). This edition updates comparison of three insulin (England), during a press briefing
San Francisco Bureau the original version of the guide- treatment strategies—basal, held at the meeting.
lines, published in January 2003. prandial, or biphasic—added to The second and third years of

n a controversial move, the The screening guidelines were oral antidiabetic agents in 708 See Insulin Regimens page 4
American College of Chest developed by a subcommittee
Physicians has formally rec- headed by Dr. Peter B. Bach of
ommended against the use of low-
dose helical CT scanning for gen-
the Memorial Sloan-Kettering
Cancer Center, New York. Al- Gardasil: Cross-Protection
eral lung cancer screening, even in though acknowledging that low-
high-risk populations, except in
the context of clinical trials.
dose CT scanning remains the
most promising of the lung can-
PET Project Extends Potential Benefit
Positron emission
The ACCP also recommended cer screening techniques, the B Y P AT R I C E W E N D L I N G (CIN) grades 2 and 3 or adeno-
against the use of serial chest ra- guideline authors maintain tomography finds additional Chicago Bureau carcinoma in situ (AIS) caused by
diographs and sputum cytologic that—even though the existing lesions in esophageal cancer. HPV 31 or 45, the two most com-
evaluation to screen for the pres- data do suggest that low-dose CT PAGE 36 C H I C A G O — The quadrivalent mon HPV types found in cervical
ence of lung cancer. increases the rate of detection of human papillomavirus vaccine, cancer after HPV 16 and 18.
“The evidence isn’t available early-stage lung cancers—such Gardasil, offers cross-protection Efficacy was 43% against CIN
to show that low-dose CT screen- See Lung Screening page 21 against cancer-causing HPV 2/3 or AIS due to HPV 31, 33, 45,
ing provides a mortality bene- types that are not included in the 52, or 58, the five most common
fit,” Dr. W. Michael Alberts said VITAL SIGNS vaccine, according to data re- types found in cervical cancer af-
in an interview. Dr. Alberts, the ported in a late-breaking poster ter HPV 16 and 18.
chief medical officer of the H. The Majority of Drugs Dispensed in 2006 Were Generic at the annual Interscience Con- Efficacy was 38% for 10 nonva-
Lee Moffitt Cancer Center and 4.5% ference on Antimicrobial Agents ccine oncogenic types (HPV 31,
Research Institute in Tampa, Fla., 9.0% Less expensive and Chemotherapy. 33, 35, 39, 45, 51, 52, 56, 58, or 59),
chaired the ACCP committee Brands with brands with A three-dose regimen of the which cause more than 20% of
that developed the guidelines. generic alternatives generic alternatives human papillomavirus (HPV) cervical cancers worldwide, Dr.
“Because there’s a very real po- by 2009 type 6/11/16/18 vaccine demon- Darron Brown reported on behalf
tential for harm, it’s going to be 11.1% strated 62% efficacy in preventing of the FUTURE Study Group.
important to prove or show a More expensive cervical intraepithelial neoplasia See Gardasil page 2
mortality benefit prior to rec- brands with
ommending screening with a generic alternatives
low-dose CT scan.” 58.0%

The second edition of the col- 17.4% Generic

lege’s “Diagnosis and Manage- Brands with
ment of Lung Cancer” includes no generic
260 guidelines, three of which in- alternatives
volve lung cancer screening. It
was published as a supplement to Note: Based on the average dispensing rates for Medco clients.
the September 2007 issue of the Source: Medco Health Solutions Inc.
journal Chest (2007;132[sup-
O c t o b e r 1 5 , 2 0 0 7 • w w w. i n t e r n a l m e d i c i n e n e w s . c o m Pulmonary Medicine Clinical Rounds 21

Clinical Trial Data Inadequate have seen a significant improvement in

noninvasive procedures, improvements More Points Covered
Lung Screening from page 1 that are likely to continue if more re-

CT screening fails to reduce the num- ticle (N. Engl. J. Med. 2005;352:2714-20).
search is done in this area.
But for Dr. Len Lichtenfeld, deputy
By the Guidelines
ber of late-stage lung cancers or the risk
of dying from lung cancer. They sug-
gest that this may be because many of
He participates in the International Ear-
ly Lung Cancer Action Program.
Dr. Mulshine acknowledged a lack of
chief medical officer of the American
Cancer Society, “the issue isn’t diagnos-
tic procedures. It’s the morbidity and
I n addition to the three recommendations
on lung cancer screening, the ACCP has
issued 257 recommendations on the pre-
the additional cancers detected are persuasive evidence from double-blind mortality from subsequent surgery that vention, diagnosis, and treatment of lung
small, indolent cancers, which lead to studies showing reduced mortality re- concerns me. ...It’s true that centers for cancer.
unnecessary invasive procedures that lated to lung cancer screening. One excellence report low morbidity and The ACCP classifies its evidence-based
carry a cost in morbidity and mortality. such study may be completed as early mortality rates from their surgery. But guidelines as strong (grade 1) or weak
The subcommittee’s analysis includes as 2009, but possibly not until 2011. experience suggests that, due to many (grade 2) based on a balance of risks, bene-
a theoretical model of the time it takes Data from another study won’t be avail- factors, morbidity and mortality rates are fits, burdens, and costs. The college also
for a given nodule to double in size. able for another 2 years or so after that. higher when these procedures are per- classifies the quality of evidence as high
They estimated that the doubling time “We all hope that the randomized, formed in community settings.” (grade A), moderate (grade B), or low
of lung tumors resulting in deaths is ap- Dr. Mulshine maintained that “from (grade C) based on study design, consisten-
proximately 40-70 days, whereas re- a methodological perspective, indepen- cy of results, and directness of the evidence.
search shows that the doubling time of dent of the merits of screening, [the The recommendations include these


early cancers identified by CT screening guideline’s authors] have just not done points:
ranges from 149 to 813 days. society, or the public in general, or their 씰 The guidelines recommend mind-body
“As best I know, this is the first time association of chest physicians, any par- modalities to reduce anxiety, mood distur-
that anyone has tried to make a public ticular service. ... It’s a somewhat ex- bances, or chronic pain (grade 1B); massage
health policy statement against screening treme, unsupported view that they pro- therapy for anxiety or pain (grade 1C), as
based upon theoretical considerations moted. Screening is a very complex long as it does not involve deep or intense
of nodule doubling time,” said Dr. James issue, associated with enormous promise pressure near cancer lesions or anatomical
L. Mulshine of Rush University Medical but also with many, many undeveloped distortions (grade 2C); and acupuncture for

Center, Chicago, in an interview. “This aspects. And they really did not educate poorly controlled pain or for side effects
is a totally unvalidated tool, and really their people about the critical issues.” such as neuropathy or xerostomia (grade
not the grist for evidence-based analysis.” He prefers the position of the U.S. 1A) and for nausea and vomiting (grade 1B).
“The recommendations weren’t Preventive Services Task Force, which 씰 In terms of lung cancer chemopreven-
based on that at all,” Dr. Bach respond- Helical CT offers a closer view of the states that there is insufficient evidence tion, the guidelines recommend against sup-
ed in an interview. Instead, he said, the adenocarcinoma shown on p. 1. to recommend for or against lung can- plementation with β-carotene, vitamin D,
model was intended to provide one cer screening. retinoids, N-acetylcysteine, and aspirin
possible explanation for the fact that controlled trials will show a mortality “The American Cancer Society does (grade 1A). Even for individuals at risk of
studies have so far failed to demon- benefit,” Dr. Alberts said. “We’d like to not recommend routine CT screening lung cancer or with a history of lung can-
strate that screening results in demon- have that outcome, at which time maybe for lung cancer at this time,” Dr. Lich- cer, there are insufficient data to recom-
strable improvements in mortality. low-dose CT scanning should be recom- tenfeld noted in an interview. “Under- mend any agent—either alone or in combi-
Dr. Mulshine said that some studies mended. But at this time, the evidence is standing that some people will nonethe- nation—for chemoprevention, except in the
were omitted from the analysis unfairly, not available, and there is potential evi- less want to proceed with screening, context of a clinical trial (grade 1B).
and that the guideline authors interpret- dence that it may be harmful. As a result, they should have a careful discussion 씰 Regarding palliative care, patients should
ed other studies selectively. He is we can’t in all good conscience recom- with their doctor regarding the poten- be reassured that pain can be treated safely
on the board of directors of the Lung mend CT scanning at this point.” tial risks that could result.” and effectively, and all patients should be
Cancer Alliance (www.lungcancer But Dr. Mulshine noted that while According to Dr. Mulshine, several questioned regularly about their pain (grade, which is spearheading op- waiting for results from those random- factors should enter into a decision on 1A). Patients with mild to moderate pain
position to the new screening guidelines. ized trials, 160,000 Americans die every screening, such as the patient’s medical should be managed first with aceta-
Since 2006, the nonprofit alliance has re- year from lung cancer, in part because and family history, his or her smoking minophen or an NSAID, and then with an
ceived $160,000 in grants from General most lung cancer is not diagnosed un- history, and even whether the screening opioid when pain becomes more severe
Electric Co., which makes CT scanners, til stage III or IV. And he cited data would be done at a center of excellence (grade 1B). Those with pain unresponsive to
and grants from other sources. Dr. Mul- showing that morbidity and mortality or at a local freestanding screening clin- standard methods should be referred to a
shine, who has published extensively on from diagnostic procedures conducted ic. For current smokers, the dialogue specialized pain clinic or a palliative care
his lung cancer screening research, was as a result of screening are low in “cen- should include advice and assistance in consultant (grade 1C).
coauthor of an influential 2005 review ar- ters of excellence.” Also, the last 5 years smoking cessation. ■

BRCA1 Predicted Poor Outcomes in Lung Cancer Patients

BY ERIK GOLDMAN BRCA1 had independent prognostic value. pressing tumor, Dr. Rosell reported at the Alexander Eggermont, president of the
Contributing Writer Patients in the uppermost quartile of conference, which was sponsored by the newly formed ECCO organization, said, “If
BRCA1 expression showed much greater Federation of European Cancer Societies. this will be validated in future studies, it will
B A R C E L O N A — Overexpression of resistance to cisplatin-based treatment reg- He and his colleagues obtained very really change the landscape of diagnostic
BRCA1, one of the genes associated with imens, and were twice as likely to die consistent findings in a validation cohort of testing and treatment decision making.
aggressive breast cancer, also predicts cis- within 3 years, compared with those in the 58 patients. They will publish a retrospec- “Genetic profiling is showing us how
platin resistance, faster recurrence, and re- lowest quartile. Median time to recur- tive analysis late this year, and they are de- differently tumors can behave, though
duced survival in people with non–small rence was 22 months among the high veloping a prospective trial to validate and they may look the same histologically,” Dr.
cell lung cancers, Dr. Rafael Rosell said at BRCA1 expressors, and median survival quantify the predictive value of BRCA1 ex- Eggermont added. “We’re moving away
the 14th European Cancer Conference. was 29 months. Among those in the low- pression for clinical decision making. from one-size-fits-all treatment. In this
Dr. Rosell and colleagues at the Catalan est quartile, the majority was still alive and BRCA1 plays a central role in repair of case, perhaps some patients can be spared
Institute of Oncology have identified nine disease free after 3 years. DNA damage. Several earlier studies have treatment with cisplatin, which would be
genes, all involved in the process of DNA The data suggest that only 30% of the shown that low levels of BRCA1 expres- unlikely to work for them.”
repair, that may have value in predicting high expressors would still be alive at 40 sion correlate well with cisplatin sensitiv- Dr. Rosell expects a long debate before
the behavior and treatment responsiveness months after surgery, while 70% of the low ity, while increased BRCA expression is as- practices change. Because cisplatin has
of lung tumors. By far the biggest red flag expressors would survive. By 60 months, sociated with treatment resistance. been the standard of care for non–small
is BRCA1. the probability of survival drops to about “These findings could have significant cell lung cancer for so long, he explained,
The investigators assessed expression 20% for those with high-BRCA1 primary therapeutic impact,” Dr. Rosell said. “Per- and because nearly all of the clinical trials
of these nine genes in tumor tissue ob- tumors, but remains around 60% for the haps those patients with high-BRCA1–ex- for these cancers are cisplatin-based, there
tained from 126 people with stage IA-IIIA low expressors. Overall, having a high- pressing tumors should just bypass cis- will likely be a fair amount of resistance to
squamous cell carcinoma or adenocarci- BRCA1–expressing tumor doubled the platin altogether, and go directly to anything that challenges the preeminence
noma. Overall, 42% of patients had stage hazard ratio for recurrence and mortality, taxane-based therapies.” of the drug or suggests that some patients
IB tumors and 26% had stage II. Only compared with having a low-BRCA1–ex- Commenting on the findings, Dr. would be better off without it. ■