B Y J O H N Q U A I N , P H O T O G R A P H S B Y V I C T O R S C H R A G E R
turning research into hope
C A N C E R B R E A K T H R O U G H S
The official war on cancer was declared when President Richard
Nixon, in his 1971 State of the Union message, made wiping out the
disease a national goal. The President signed into law the Cancer Act,
earmarking $1.6 billion for research and creating the National Cancer
Institute, now part of the National Institutes of Health (NIH), which
had a reported budget of $4.8 billion last year. Three-plus decades later,
cancer, which encompasses a variety of diseases in which
abnormal cells divide out of control, still kills more than
1,500 Americans a day, according to the American
Cancer Society (ACS). With more than half a million
Americans expected to succumb to the disease this year,
says the ACS, cancer trails only heart disease as the coun-
try’s leading overall cause of death in those 85 and under.
Worldwide, cancer accounts for more than 18,000 deaths
each day, says the International Agency for Research on
Cancer, which adds that between 2000 and 2020, the
number of cancer cases will grow by 50 percent. Further, reports the
NIH, medical treatments of cancer, along with such indirect costs as
loss of productivity, cost the U.S. economy nearly $190 billion in 2004.
I N R O A D S
Still, Christine Jacobs, chairman, president and CEO of THERAGENICS
CORP. (TGX), says she is “overwhelmingly impressed with the inroads
made over the past 15 years.” She points to Hodgkin’s disease, a lym-
phoma and the first cancer that Swarner faced, which now has a five-
year survival rate of 84 percent,meaning that 84 percent of patients are
still alive five years after being diagnosed, says the ACS.
The most recent annual report from the National
Cancer Institute indicated that the incidence of can-
cer decreased 0.5 percent per year between 1991 and
2001, while the death rate from all cancers dropped
1.1 percent annually between 1993 and 2001. Onco-
logists attribute the more encouraging numbers to
early detection and better treatments.
Nevertheless, several cancers stubbornly resist
treatment. For example, the ACS says, 32,000 patients
in the U.S. are diagnosed with pancreatic cancer annually, and nearly
the same number die from the disease in the same time frame.
(See pancreatic cancer section in “The Battle Continues,” page 28.)
S P E C I A L R E P O R T
T WA S A L I F E - C H A N G I N G M O M E N T,”
says Sean Swarner, describing how he felt when he reached the peak of Mount Everest. It’s also the way he
describes the moment he found out he had cancer, when he was 13 years old. Swarner, who says he is the
first two-time cancer survivor to have summited the world’s tallest mountain, is now 29 years old. His story
is a sign of what members of the American Society of Clinical Oncology have recently reported: Rather
than an automatic death sentence, cancer is becoming an increasingly treatable chronic disease.
iC A N C E R - F I G H T I N G C O M P A N I E S A R E U N S H E A T H I N G T H E I R
W E A P O N S T O D E F E A T A L E T H A L F O E .
Lung Cancer page 23
Prostate Cancer 25
Colorectal Cancer 26
Breast Cancer 26
Other Cancers 28
In the Pipeline 29
Spurred by such devastating statistics and inspired by some positive
results, health-care companies say they have renewed the race for treat-
ments to cure a panoply of cancers. The Pharmaceutical Research and
Manufacturers of America estimates that nearly 400 anticancer drugs
were in development in 2003. “Many of these patients are desperate,”
asserts Dr. Daniel Vasella, chairman and CEO of NOVARTIS AG (NVS).
“But that’s what we are here for — to find treatments for patients who
are inadequately treated today and can be better treated tomorrow.”
“Cancer drug discovery is a high-risk business,” confirms Dr.
Richard Connell, PFIZER INC’s
(PFE) executive director of dis-
covery operations antibacteri-
als, immunology and cancer
research. The company esti-
mates it takes 11 to 15 years to
bring a drug through discovery
and development. Vasella adds:
“It now costs about $1.7 billion
to bring a drug to market.”
working in oncology explain
that they require substantial war
chests to develop and test
drugs. For example, SCHERING-
PLOUGH CORP. (SGP) reported
spending 19.4 percent of 2004
revenues on R&D; Vasella says
Novartis spent $3.5 billion, or
about 18.9 percent of net sales,
on pharmaceutical R&D last
year, while ELI LILLY AND CO.
(LLY) reports that the 19.4 per-
cent of its 2004 revenues spent
on R&D amounted to nearly
$52 million each week. BRISTOL-
MYERS SQUIBB CO. (BMY) says
that last year it supported more
than 450 global clinical trials involving about 60,000 patients.
“Two to three decades ago, the success rate for a new drug was
about 14 percent,” Dr. Lester Crawford, acting U.S. Food and Drug
Administration commissioner, indicated in a recent presentation.
Today, a candidate drug entering Phase I trial “is estimated to have
only an 8 percent chance of reaching the market,” he added. Even
more discouraging, the product failure rate at later Phase III clinical
trials is almost 50 percent, he said.
Nevertheless, many health-care and pharmaceutical companies
realized double-digit revenue growth from cancer treatments in
2003, according to LEHMAN BROTHERS HOLDINGS INC. (LEH).
Gleevec, Novartis’ molecularly targeted drug, so far has received
FDA approval for only two relatively rare forms of cancer —
chronic myeloid leukemia and gastrointestinal stromal tumors —
points out Vasella. Still, it generated $1.6 billion in worldwide sales
in 2004, says Novartis.
Among those companies with the largest share of the oncology
pharmaceutical market in 2004,
says Lehman, SANOFI-AVENTIS’
(SNY) revenues increased by
some 23 percent, ASTRAZENECA
PLC’s (AZN) by 32 percent and
Novartis’ by 39 percent. “In
terms of advancing compounds
in our product pipeline and
looking for external opportu-
nities, oncology is an impor-
tant area,” underscores Fred
Hassan, chairman and CEO of
Schering-Plough. (For a list of
new and potential cancer drug
therapies, see “Hope in the
Pipeline,” page 29.)
E A R LY D E T E C T I O N
arly detection has
cantly to increasing
patient survival rates, reports
the National Cancer Institute.
Mammography, for example,
now uses digital technology to
see microscopic tumors previ-
ously undetectable, points out
Wendy Harris, general manager
for oncology at GE Healthcare Technologies, a division of GENERAL
ELECTRIC CORP. (GE). “The sooner you detect it, the greater the
chance of curing it,” she explains, noting that positron-emission
tomography (PET) can image body functions at the molecular
level, while computed tomography (CT) scans capture the body’s
anatomical structure. Harris says GE uses this combination of
scans in its Discovery PET CT systems, which, she adds, are
employed to locate the full extent of a patient’s cancer.
C A N C E R ’S C O S T S T O
T H E U. S. E C O N O M Y,
A C C O R D I N G T O
N AT I O N A L I N S T I T U T E S
OF HEALTH ESTIMATES
B I L L I O N
More sensitive blood tests for cancer indicators include the prostate-
specific antigen test, or PSA, says BECKMAN COULTER INC. (BEC). Using
blood analysis, PSA tests look for an increase in the antigen associated
with enlarged prostates and prostate cancer, the company explains.
Beckman says the free PSA test, which measures the ratio of free-float-
ing to total PSA, can further distinguish prostate cancer from benign
diseases when used as a follow-up to the PSA test in some patients.
Although there is no consensus on when or if cancer will be cured,
researchers and company leaders interviewed for this special report
agree that genetic data and research will play an increasingly important
role in battling the disease. Researchers say they expect not only to
continue uncovering the genetic composition of different cancers but
add that in the not-too-distant future patients might receive detailed
genetic analysis so that treatments can be tailored for a specific patient.
This combination of research on multiple fronts is allowing patients
such as Sean Swarner to achieve new heights, acknowledges the cancer
survivor. Still cancer-free, Swarner says he recently climbed Aconcagua
in Argentina as part of his quest to scale the highest peaks of the seven
continents. Now, he says, he has just three of the peaks left to climb.
he approximately 170,000 people expected to die of lung
cancer in 2005 in the U.S. will represent more than the
number who will die from colon, breast and prostate
cancers combined, says the American Cancer Society.
Some 13 percent of all lung cancer cases are small-cell lung cancer
(SCLC), also known as oat-cell carcinoma, explains the Society,
which notes that most diagnosed SCLC cases involve a spreading of
the disease. Because non-small-cell lung cancer (NSCLC), which the
Society estimates makes up the other 87 percent of diag-
noses, tends to be less widespread at the time of diagnoses
and progresses somewhat more slowly, doctors say they
have more treatment options, and researchers say they see
a larger window of opportunity.
An early hope for a targeted therapy to treat NSCLC is
Iressa,researchers point out.Iressa,which the FDA approved
for use as a last resort in NSCLC patients in 2003, inhibits
the epidermal growth factor receptor (EGFR) affecting
tyrosine kinase, an enzyme involved in the signaling path-
ways in cells, reports its developer, ASTRAZENECA PLC (AZN). EGFR is
present in many cancers, the company says, including lung cancer.
According to research published in both the New England Journal
of Medicine and Science, patients who have a strong positive response to
Iressa appear to have a mutation in their EGFR. Unfortunately,
AstraZeneca recently reported, a larger study with more than 1,600
patients indicated that the drug did not improve overall survival rates.
The company says it is analyzing trial data to determine what role,
if any, EGFR status and its mutation played in the trial results.
GENENTECH INC.’s (DNA) and OSI Pharmaceuticals’ lung cancer
drug Tarceva also inhibits EGFR growth and stops cell division, says
Myrtle Potter, Genentech president of commercial operations. The
FDA put Tarceva on a fast-track development program for review, and
the drug was approved in December 2004 for NSCLC
patients, says Potter. According to Genentech, Tarceva has
also been shown to improve survival rates among pancre-
atic cancer patients, and the company and its partner hope
to apply for expanded FDA approval this year.
Pharmaceutical houses are also developing new chemo-
therapies that allow them to target cancer cells without
harming surrounding healthy cells. ELI LILLY AND CO. (LLY)
says its Alimta, which is approved for treatment of NSCLC
and malignant pleural mesothelioma, simultaneously blocks
three separate enzyme targets important to cancer cell growth and
division. Edmundo Muniz, vice president, global oncology at Lilly,
reports that Alimta is the first and only drug approved for treating
malignant pleural mesothelioma, which, he explains, is a relatively rare
form of cancer associated mainly with asbestos exposure.
stopping cell growth
L U N G C A N C E R
T A R G E T E D T H E R A P I E S R E P R E S E N T A W I N D O W O F O P P O R T U N I T Y .
breakthrough: A P O P T O S I S
Most normal cells are programmed to die, a process called apoptosis, explain
scientists, so that healthy cells can replace them. In contrast, according to oncolo-
gists, malignant cells evade normal apoptosis and continue to survive, increasing the
size and spread of a cancer. ABBOTT LABORATORIES (ABT) says it has discovered
some promising compounds in the laboratory. The compounds mimic proteins
that promote apoptosis in the body that may take particular aim at lung cancer.
Sidney Taurel, president, chairman and CEO of Lilly, says:“We now
offer two leading therapies for the most common and significant forms
of cancer: Gemzar for lung, breast and pancreatic cancer; and Alimta
for lung and mesothelioma cancer. This solid foundation of cancer
therapy marks our commitment to patients with cancer, and we build
upon that foundation with continued research and innovation.”
Meanwhile, one approach of ABBOTT LABORATORIES (ABT) in-
volves apoptosis, explains Dr. Stephen Fesik, divisional vice president
for cancer research. Normal cell death, he points out, is often short-
circuited in cancer cells by an increase in proteins, such as Bcl-2.
“We’ve discovered inhibitors to the Bcl-2 family of proteins to pro-
mote programmed cell death,”says Fesik, who notes Abbott has some
promising compounds in the lab that mimic proteins that promote
apoptosis in the body.
Fesik says Abbott applies a research technique to the discovery
of Bcl-2 family of inhibitors called structure activity relationships
by nuclear magnetic resonance, or SAR by NMR. The technique, he
explains, involves the screening of molecules to find fragments that
scientists can assemble into full-size molecules to bind to a drug
target. According to Abbott, SAR by NMR helps its scientists build
new molecules that could not be built before. Such cell sleuthing is
a daunting task, admits Fesik. “Different kinds of cells have differ-
ent Bcl-2 proteins, and some cells have different amounts of differ-
ent Bcl-2 proteins,” he says. “This is a hard problem,” underlines
Fesik, “but we’re making significant progress and trying our best.”
ancers of the blood and immune systems are where oncol-
ogists say the most promising targeted drug therapies first
appeared. Researchers point to Gleevec, widely regarded as
one of the first targeted drugs designed to stop a specific
form of cancer — chronic myelogenous leukemia, or CML. NOVARTIS
AG (NVS) says Gleevec blocks the protein Bcr-Abl, which triggers run-
away growth of abnormal white blood cells in CML patients.
The American Cancer Society reports that 68 percent of Gleevec
patients in one clinical trial had no detectable leukemia after 14
months, compared with 7 percent who received once-standard treat-
ment of chemotherapy and interferon. Such results led Novartis Chair-
man and CEO Daniel Vasella to call Gleevec the “magic cancer bullet.”
David Epstein, head of Oncology and Specialty Medicines at
Novartis Oncology, reports the company began preparing to produce
the drug, which the FDA approved in 2001, before clinical trials were
completed.“But if we only did the sure thing, patients would have had
to wait for this lifesaving drug,” he notes.
Gleevec also inhibits c-kit, says Epstein, who notes that c-kit is
involved in driving the growth of gastrointestinal stromal tumors, or
GISTs. The usually fatal GIST, reports Novartis, was previously treated
only by surgery. The FDA approved Gleevec for patients with c-kit-
positive GIST in 2002, and recent data shows that median survival for
GIST patients taking Gleevec still has not been reached with 34 months
of followup, says Epstein.
enzymes in the blood
L E U K E M I A A N D L Y M P H O M A
A M A G I C B U L L E T A I M E D AT L E U K E M I A M AY O F F E R H O P E A G A I N S T O T H E R C A N C E R S .
NOVARTIS AG (NVS), the developer of the
molecularly targeted anticancer drug
Gleevec, reports that it spends almost 19
percent of net pharmaceutical sales on
R&D. A Gleevec timeline follows:
a path to market
SOURCE: NOVARTIS AG
1985 Scientists isolate inhibitors of the Bcr-Abl oncogene.
early Researchers identify Bcr-Abl gene as a cause of chronic
1990s myelogenous leukemia (CML) in experiments with mice.
1992 Novartis becomes involved, synthesizing STI571.
1994 The company launches the first in-vitro studies to gauge
STI571’s effect on cancer cells.
1997 The company develops a pill form of STI571.
1998 April— Phase I clinical trials begin for CML patients in
chronic phase after failure of interferon-alpha therapy.
September— Phase I trial reveals positive results.
1999 July— Novartis starts mass production of STI571.
October— Phase II trials are launched to assess the drug’s
effectiveness in a larger population.
2000 June— Novartis debuts expanded-access program, reaching
7,000 patients in 32 countries.
July— FDA grants fast-track designation to STI571.
2001 February— Novartis files New Drug Application with the
FDA for the drug, now known as Gleevec.
May— Gleevec receives FDA approval for treating CML.
2004 Long-term efficacy and safety demonstrated in newly diag-
nosed CML patients, with 91 percent survival at 42 months
and low risk of relapse. Median survival for gastrointestinal
stromal patients still not reached with 34 months of followup.
BRISTOL-MYERS SQUIBB CO. (BMY) reports it is working on a com-
pound for CML patients who develop a resistance to Gleevec. Phase I
trials on BMS-354825 indicated 31 of 36 patients responded after
becoming resistant to Gleevec, say the study’s leaders. Novartis says it is
also working on AMN107 for Gleevec-resistant patients.
Researchers are also looking to treat lymphoma, notes the National
Cancer Institute. “One of the more intriguing new molecules is a PKC
beta inhibitor, called enzastaurin, being developed for glioblastoma,
non-Hodgkin’s lymphoma and other cancers,” says Edmundo Muniz,
vice president, global oncology at ELI LILLY AND CO. (LLY). Enzastaurin,
which, he explains, tries to block the formation of new blood vessels, is
in Phase II trials. The company hopes to apply for regulatory approval
by the end of the decade, says Charles Golden, executive vice president
and CFO of Eli Lilly. Also, SANOFI-AVENTIS (SNY) says its vascular
endothelial growth factor Trap drug compound is currently in early
Phase I clinical trials for non-Hodgkin’s lymphoma patients.
oe Torre reports he’s had it. So have Rudolph Giuliani,
Colin Powell and Michael Milken. According to the
National Cancer Institute, prostate cancer is the second-
most lethal cancer killer among men. However, as these
and other patients can attest, the picture has improved significantly.
“The advancements and attention brought to the disease by
these celebrities are helping us move toward making it a disease
that is no longer a devastating diagnosis,” says Christine Jacobs,
chairman, president and CEO of THERAGENICS CORP. (TGX),
a maker of radioactive implantable devices used to treat
prostate cancer. According to the American Cancer Society,
the overall five-year survival rate has increased to about 98
percent today from just 67 percent 20 years ago.
An increasingly common treatment against pros-
tate cancers that have not yet spread is brachytherapy,
according to data presented at an Advanced Prostate
Brachytherapy Conference last year. Doctors insert
small radioactive “seeds” about the size of a grain
of rice into the prostate, explains Jacobs. With
brachytherapy, she says doctors can apply a higher
dose of radiation directly to a tumor without harm-
ing adjacent healthy tissue. The treatment is about as suc-
cessful as surgery and offers a quicker recovery, she adds.
Noting the tiny seeds have a tendency to move within the tissue and
stray from their intended target, Dr. John DeFord, vice president of sci-
ence and technology at C.R. BARD INC. (BCR), says Bard encapsulates
Theragenics’ radioactive seeds within a polymer sleeve. The procedure,
he explains,connects multiple seeds like the cars of a train,reducing the
chances that the seeds will migrate before doing their work.
Richard Levy, chairman and CEO of VARIAN MEDICAL SYSTEMS INC.
(VAR), notes the position of the prostate changes with bladder and rec-
tal fullness. Three-dimensional conformal radiation therapy has been
used since the 1980s because it can adapt the shape of the radiation
beam to that of the tumor, says Levy, reducing the amount of radiation
that accidentally hits normal tissue. Using sophisticated linear
accelerators, such as those in Varian’s ClinacTM and TrilogyTM
lines, he explains, doctors can target thousands of pencil-thin
radiation beams on a tumor.
Levy says new computer programs let physicians view real-
time images of a patient’s anatomy so they can precisely plan
and deliver treatments with either brachytherapy or radio-
therapies.“The holy grail is to give more dosage to tumors
and less to healthy tissue,” says Levy. Varian’s linear accel-
erators, he says, let doctors compensate for respiratory
motion to target tumors and even small metastases.
For cancers progressing beyond the prostate or for
patients who don’t respond to standard therapies,
“we’ve focused on drugs that are better tolerated and
may prevent further tumor growth,” says Dr. Jeffrey
Leiden, president and COO of ABBOTT LABORATORIES’
(ABT) pharmaceutical products group. He says several drugs
in Abbott’s pipeline, including Xinlay, have “the potential to revolu-
tionize cancer treatment.” Xinlay blocks activation of the receptor for
endothelin, a protein thought to help spread cancer cells, he explains.
The key to successful treatment, however, say all the researchers,
is early detection. “It comes down to doing your homework,” con-
cludes Jacobs.“And for God’s sake, ask for the screening test. Prostate
cancer does not have to be a death sentence.”
moving to a chronic state
P R O S T A T E C A N C E R
N E W R A D I O A C T I V E T R E AT M E N T S A R E Z E R O I N G I N O N T U M O R S .
nly 39 percent of colorectal cancer cases are diagnosed
at the localized stage, according to the American Cancer
Society. For cancers that spread only to nearby organs,
about two-thirds of patients survive for five years, esti-
mates the organization, but adds the survival rate plummets to 10
percent if colorectal cancer spreads to distant parts of the body.
To treat cells that have metastasized beyond the main
tumor mass, doctors say they often follow surgery with
chemotherapy or chemotherapy plus radiotherapy.
SANOFI-AVENTIS (SNY) says its chemotherapy drug
Eloxatin, injected along with other medicines, pre-
vents recurrence in patients with early-stage cancer.
However, the company says, its effect on long-term
survival is not known because patients in these stud-
ies need to be followed longer.Eloxatin has been shown
to shrink cancers in some patients in whom the cancer
had already spread to distant organs, says Sanofi-Aventis.
In 2004, the FDA reported approval of two monoclonal antibody
treatments for cancer that spreads outside the colon. Normally, a per-
son’s immune system produces antibodies to fight foreign invaders
such as bacteria or viruses, according to scientists. One monoclonal
antibody treatment is Erbitux (Cetuximab), codeveloped by BRISTOL-
MYERS SQUIBB CO. (BMY) and ImClone Systems Inc., says Peter R.
Dolan, Bristol-Myers’ chairman and CEO. The drug “is initially indi-
cated to treat advanced colorectal cancer, a disease that has few options
when the patient is unresponsive or doesn’t tolerate other treatments.”
Erbitux, which was launched in 2004, slows cancer growth by targeting
the epidermal growth factor receptor protein, present in 77 percent of
colon cancers, estimates Bristol-Myers. The drug is also being tested
with other medications to treat pancreatic, head and neck
and non-small-cell lung cancers, says the company.
GENENTECH INC.’s (DNA) recently FDA-approved
therapeutic antibody Avastin binds to a substance
released by tumors called vascular endothelial
growth factor, notes Susan Desmond-Hellmann,
president of product development. Genentech says
the drug, used with chemotherapy, increased sur-
vival rates of metastatic colon cancer patients by five
months. Avastin may help in other cancers, Desmond-
Hellmann adds. “Our broad development program includes
seeking extensions to treat multiple tumor types.”
NOVARTIS AG (NVS) reports that its PTK787 slows the growth and
spread of tumor blood vessels. In early trials, the company says, the
monoclonal antibody shrank tumors in colon cancer patients when
used with chemotherapy. First Phase III results, being developed with
SCHERING AG (SHR), are expected by mid-year.
C O L O R E C T A L C A N C E R
W I T H N E W M O N O C L O N A L A N T I B O D Y D R U G S, S C I E N T I S T S A R E G E T T I N G S P E C I F I C .
reast cancer offers a bad news/good news scenario
that is now tipping more to the good news side, says
Dr. Clifford Hudis, chief of breast cancer medicine
service and associate attending physician at the
Memorial Sloan-Kettering Cancer Center in New York City. “The
population, in the U.S. at least, has gotten older and larger, so the
total number of [breast cancer] cases has done nothing but go up,”
he acknowledges.“Yet the absolute number of women who have died
of breast cancer has been dropping for 13 years.” The reason, accord-
ing to Hudis, is that earlier detection and new therapies allow
women to live longer without recurrence, or even to survive with
an active form of the disease.
Because most breast cancers grow in response to abnormal
levels of estrogen, explains Hudis, doctors often prescribe an estro-
B R E A S T C A N C E R
E S T R O G E N T H E R A P I E S A N D D R U G C O M B I N AT I O N S H AV E U P P E D T H E S U R V I VA L R AT E .
B I L L I O N
T H E C O S T O F
B R I N G I N G A D R U G
TO M A R K E T,
E S T I M A T E S
N OVA RT I S
gen blocker for women who have been treated for early-stage breast
cancer. ASTRAZENECA PLC (AZN) describes its tamoxifen drug,
brand name Nolvadex, as the world’s largest-selling breast cancer
treatment in terms of revenues, saying it has racked up more than
10 million patient-years of use since the company developed it
more than 30 years ago.
The problem? AstraZeneca says that although studies have indi-
cated that taking tamoxifen after initial breast cancer treatment
reduces the chances that the cancer will return, some women suffer
serious side effects, and more than 30 percent experience relapses
despite taking it. Further, according to the company, clinical trials
have shown that tamoxifen use must be stopped after five years.
In the past few years, doctors say they are turning to a new class
of hormonal therapy when the tamoxifen option is no longer
viable. PFIZER INC (PFE) reports it has come out with Aromasin, a
hormone inactivator that binds to the aromatase enzyme so it can
no longer produce estrogen. A study published in the New England
Journal of Medicine last March indicated that breast cancer
patients who switched to Aromasin after a few years of taking
tamoxifen saw a 32 percent reduction in the risk of the disease’s
recurrence after three years, compared with those
who continued on tamoxifen.
Studies suggest that aromatase inhibitors may
ultimately replace tamoxifen as a standard treatment
for postmenopausal patients, say oncologists. For
example, NOVARTIS AG’s (NVS) aromatase inhibitor,
Femara, cut the recurrence of breast cancer so dra-
matically that one trial was halted early to allow all
women in the trial to receive the drug, says Novartis.
A more recent 8,000-patient study compared
Femara head-to-head with tamoxifen, where the
new drug showed a 19 percent reduction in risk of
occurrence in the adjuvant setting, says Novartis.
Even more striking, notes the company, was a 27
percent reduction in the risk of cancer spreading to
other parts of the body.
Another study recently published in the
medical journal The Lancet reported that
Arimidex, AstraZeneca’s aromatase inhib-
itor, might prevent some 70 percent to 80
percent of the most common types of
breast cancers that occur in women after
menopause. By comparison, tamoxifen is
believed to prevent cancer from recurring
in 50 percent of such cases, according to the
journal. For cases where breast cancer returns after use of tamox-
ifen, says AstraZeneca, patients can turn to its alternative estrogen-
receptor blocker, called Faslodex, which also was recently approved.
Additional targeted therapies are also on the horizon, point out
scientists. Herceptin, for example, a therapeutic antibody treatment,
is the only immune therapy currently available for HER2-positive
breast cancer, explains its developer, GENENTECH INC. (DNA). The
company says Herceptin delivers an HER2/neu antibody that locks
onto a particular protein that is overexpressed by
about one in four types of breast cancer cells to pre-
vent them from receiving growth signals. The
American Cancer Society reports that Herceptin
shrinks some breast-cancer metastases and causes
fewer side effects than other drugs.
In many cases, combinations of drugs may dis-
rupt several cancer cell pathways at once, according
to Hudis. For example, a monoclonal antibody
medication could be used in conjunction with a
drug that inhibits epidermal growth factor recep-
tors, or EGFRs, which are overexpressed in many
cancers, he notes.
One such promising drug, according to oncolo-
gists, is GLAXOSMITHKLINE PLC’s (GSK) Lapatinib,
which the company says is a HER2/neu inhibitor
similar to Herceptin, as well as an EGFR inhibitor,
resembling AstraZeneca’s lung cancer drug
Iressa. In earlier trials, Lapatinib, currently in
clinical Phase III trials, had halted or stabi-
lized breast cancer in some women whose
disease had progressed under Herceptin,
according to GlaxoSmithKline. The company
indicates that it anticipates filing for FDA
approval later this year.
For a cancer to metastasize, scientists say, the body produces an extensive net-
work of new blood vessels to feed oxygen and nutrients to tumors, a process called
angiogenesis. Using anti-angiogenesis drugs such as Avastin, GENENTECH INC.
(DNA) says it hopes to block the formation of new blood vessels, which in turn
could cause tumors to grow more slowly — or even shrink and die. Angiogenesis
inhibitors could be extremely useful in treating cancers, such as brain cancers,
that are difficult to reach using surgery, say scientists. According to the National
Cancer Institute, researchers are evaluating angiogenesis inhibitors to treat a vari-
ety of cancers, from breast to stomach.
breakthrough: A N G I O G E N E S I S I N H I B I T O R S
P A N C R E A T I C C A N C E R
oday pancreatic cancer is the fourth
leading cause of cancer death, accord-
ing to the American Cancer Society.
Currently, one promising pancreat-
ic cancer treatment is a chemotherapy drug called
Gemzar, says its maker, ELI LILLY AND CO. (LLY). The
company notes that nearly eight out of every 10
patients with pancreatic cancer receive Gemzar. The
drug interferes with the processes of DNA produc-
tion and can slow or stop tumor growth, explains the
company. Gemzar has been approved since 1996 for treating
advanced pancreatic cancer and is now being tested with BRISTOL-
MYERS SQUIBB CO.’s (BMY) Erbitux to see if survival rates can be
improved, say the companies.
The experimental kidney cancer drug Bay 43-9006 may have an
even more pronounced effect on pancreatic cancer, according to BAYER
AG (BAY). In addition to inhibiting blood vessel growth, the company
explains, the drug also impedes signals produced by a gene mutation
called RAS. Some 90 percent of pancreatic cancers
carry this mutation, according to the company.
Similarly, a compound known as AG-13736, now
in Phase II testing, reports PFIZER INC (PFE), showed
via magnetic resonance imaging that tumors shrank
B R A I N C A N C E R
A clinical trial conducted by the European
Organization for Research and Treatment of Cancer
and the National Cancer Institute of Canada in
spring 2004 reported for the first time that adding a chemotherapy
drug to standard radiation treatment significantly increased
survival rates for patients suffering from an aggressive form of brain
cancer called glioblastoma multiforme, or GBM. For example, in the
chemotherapy study, close to 30 percent of patients with GBM who
received a combination of SCHERING-PLOUGH CORP.’s (SGP) Temodar
chemotherapy drug and radiation therapy survived for two years or
more, compared with only 10 percent of patients who received radi-
ation therapy alone, according to the company.
“Until now there have been few treatment options for glioblastoma
patients,” Dr. Gregory Cairncross, one of the study’s primary investiga-
tors and professor and head of the department of clinical neurosciences
at the University of Calgary in Alberta, said in a presentation.
K I D N E Y C A N C E R
Doctors call kidney tumors highly vascularized, meaning they
require many new blood vessels to survive. Several companies
report that they are currently trying to develop ways to disrupt the
formation of new blood vessels. In a Phase II study by Bayer and
Onyx Pharmaceuticals, investigators reported tumor shrinkage or
disease stabilization at 12 weeks in 70 percent of the 202 study par-
ticipants with kidney cancer who received an investigational com-
pound called Bay 43-9006. This compound, says Bayer, is currently
undergoing Phase III investigation for the treatment of advanced
kidney cancer. The two companies, says Bayer, also intend to initiate
additional Phase III and Phase II trials in other tumor types, includ-
ing melanoma and hepatocellular carcinoma (liver cancer).
the battle continues
A D D I T I O N A L C A N C E R S
M A N Y T R E AT M E N T S C A N B E N E F I T PAT I E N T S S U F F E R I N G F R O M A VA R I E T Y O F C A N C E R S .
Pharmaceutical companies say they are designing treatments to interrupt a specific
element of a cancer-cell life cycle while leaving normal cells untouched. Such
gene-based and protein-based therapies have fewer side effects and can be
extremely effective in treating specific forms of cancer, say researchers.
An example of a molecularly targeted drug is NOVARTIS AG’s (NVS) Gleevec,
which, according to the company, shuts off the protein that causes cells to
become cancerous and multiply. So far Novartis says the orange pill stops only
two relatively rare forms of cancer — chronic myelogenous leukemia and gas-
trointestinal stromal tumors — but many oncologists say they also view it as a
sign of what gene-based research can do in the future.
Researchers also hope to block cancer-specific proteins that allow runaway cell
division. For example, scientists say they have already identified the epidermal growth
factor (EGFR) as spurring the growth of solid tumor cancers, which could apply to can-
cers of the lung, breast, prostate, colon, ovary, head and neck. New drugs that target
EGFR receptors in different ways include BRISTOL-MYERS SQUIBB CO.’s (BMY) Erbitux
(a monoclonal antibody used against colon cancer) and ASTRAZENECA PLC’s (AZN)
Iressa (a small-molecule inhibitor used to treat lung cancer).
breakthrough: TA R G E T E D D R U G S
T H E T I M E I T
TA K E S T O B R I N G
A D R U G T O
M A R K E T,
E S T I M AT E S
P F I Z E R I N C
Y E A R S