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C A N C E R B R E A K T H R O U G H S
turning research into hope
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
S P E C I A L R E P O R T
C A N C E R - F I G H T I N G
W E A P O N S T O
C O M P A N I E S
The official war on cancer was declared when President Richard
D E F E A T
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,
A R E
U N S H E A T H I N G
L E T H A L F O E.
T H E I R
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.
Still, Christine Jacobs, chairman, president and CEO of THERAGENICS
CORP. (TGX), says she is “overwhelmingly impressed with the inroads
earmarking $1.6 billion for research and creating the National Cancer made over the past 15 years.” She points to Hodgkin’s disease, a lym-
Institute, now part of the National Institutes of Health (NIH), which phoma and the first cancer that Swarner faced, which now has a five-
had a reported budget of $4.8 billion last year. Three-plus decades later, year survival rate of 84 percent, meaning that 84 percent of patients are
cancer, which encompasses a variety of diseases in which still alive five years after being diagnosed, says the ACS.
abnormal cells divide out of control, still kills more than The most recent annual report from the National
1,500 Americans a day, according to the American Cancer Institute indicated that the incidence of can-
Cancer Society (ACS). With more than half a million Lung Cancer page 23 cer decreased 0.5 percent per year between 1991 and
Americans expected to succumb to the disease this year, Leukemia 24 2001, while the death rate from all cancers dropped
Prostate Cancer 25
says the ACS, cancer trails only heart disease as the coun- 1.1 percent annually between 1993 and 2001. Onco-
Colorectal Cancer 26
try’s leading overall cause of death in those 85 and under. logists attribute the more encouraging numbers to
Breast Cancer 26
Worldwide, cancer accounts for more than 18,000 deaths Other Cancers 28 early detection and better treatments.
each day, says the International Agency for Research on In the Pipeline 29 Nevertheless, several cancers stubbornly resist
Cancer, which adds that between 2000 and 2020, the treatment. For example, the ACS says, 32,000 patients
number of cancer cases will grow by 50 percent. Further, reports the in the U.S. are diagnosed with pancreatic cancer annually, and nearly
NIH, medical treatments of cancer, along with such indirect costs as the same number die from the disease in the same time frame.
loss of productivity, cost the U.S. economy nearly $190 billion in 2004. (See pancreatic cancer section in “The Battle Continues,” page 28.)
Spurred by such devastating statistics and inspired by some positive Nevertheless, many health-care and pharmaceutical companies
results, health-care companies say they have renewed the race for treat- realized double-digit revenue growth from cancer treatments in
ments to cure a panoply of cancers. The Pharmaceutical Research and 2003, according to LEHMAN BROTHERS HOLDINGS INC. (LEH).
Manufacturers of America estimates that nearly 400 anticancer drugs Gleevec, Novartis’ molecularly targeted drug, so far has received
were in development in 2003. “Many of these patients are desperate,” FDA approval for only two relatively rare forms of cancer —
asserts Dr. Daniel Vasella, chairman and CEO of NOVARTIS AG (NVS). chronic myeloid leukemia and gastrointestinal stromal tumors —
“But that’s what we are here for — to find treatments for patients who points out Vasella. Still, it generated $1.6 billion in worldwide sales
are inadequately treated today and can be better treated tomorrow.” in 2004, says Novartis.
“Cancer drug discovery is a high-risk business,” confirms Dr. Among those companies with the largest share of the oncology
Richard Connell, PFIZER INC ’s pharmaceutical market in 2004,
(PFE) executive director of dis- says Lehman, SANOFI-AVENTIS ’
covery operations antibacteri- (SNY) revenues increased by
als, immunology and cancer some 23 percent, ASTRAZENECA
research. The company esti- PLC ’s (AZN) by 32 percent and
mates it takes 11 to 15 years to Novartis’ by 39 percent. “In
bring a drug through discovery terms of advancing compounds
and development. Vasella adds: in our product pipeline and
“It now costs about $1.7 billion looking for external opportu-
to bring a drug to market.” nities, oncology is an impor-
Consequently, companies tant area,” underscores Fred
working in oncology explain Hassan, chairman and CEO of
that they require substantial war Schering-Plough. (For a list of
chests to develop and test new and potential cancer drug
drugs. For example, SCHERING- therapies, see “Hope in the
PLOUGH CORP. (SGP) reported Pipeline,” page 29.)
spending 19.4 percent of 2004
revenues on R&D; Vasella says E A R LY D E T E C T I O N
Novartis spent $3.5 billion, or arly detection has
about 18.9 percent of net sales, contributed signifi-
on pharmaceutical R&D last cantly to increasing
year, while ELI LILLY AND CO. patient survival rates, reports
(LLY) reports that the 19.4 per- the National Cancer Institute.
cent of its 2004 revenues spent C A N C E R ’S C O S T S T O Mammography, for example,
T H E U. S. E C O N O M Y,
on R&D amounted to nearly ACCORDING TO now uses digital technology to
$52 million each week. BRISTOL- N AT I O N A L I N S T I T U T E S see microscopic tumors previ-
O F H E A LT H E S T I M AT E S
MYERS SQUIBB CO. (BMY) says BILLION ously undetectable, points out
that last year it supported more Wendy Harris, general manager
than 450 global clinical trials involving about 60,000 patients. for oncology at GE Healthcare Technologies, a division of GENERAL
“Two to three decades ago, the success rate for a new drug was ELECTRIC CORP. (GE). “The sooner you detect it, the greater the
about 14 percent,” Dr. Lester Crawford, acting U.S. Food and Drug chance of curing it,” she explains, noting that positron-emission
Administration commissioner, indicated in a recent presentation. tomography (PET) can image body functions at the molecular
S T Y L I N G B Y S H E L LY C O O N
Today, a candidate drug entering Phase I trial “is estimated to have level, while computed tomography (CT) scans capture the body’s
only an 8 percent chance of reaching the market,” he added. Even anatomical structure. Harris says GE uses this combination of
more discouraging, the product failure rate at later Phase III clinical scans in its Discovery PET CT systems, which, she adds, are
trials is almost 50 percent, he said. employed to locate the full extent of a patient’s cancer.
More sensitive blood tests for cancer indicators include the prostate-
specific antigen test, or PSA, says BECKMAN COULTER INC. (BEC). Using breakthrough: APOPTOSIS
blood analysis, PSA tests look for an increase in the antigen associated Most normal cells are programmed to die, a process called apoptosis, explain
with enlarged prostates and prostate cancer, the company explains. scientists, so that healthy cells can replace them. In contrast, according to oncolo-
Beckman says the free PSA test, which measures the ratio of free-float- 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
ing to total PSA, can further distinguish prostate cancer from benign
some promising compounds in the laboratory. The compounds mimic proteins
diseases when used as a follow-up to the PSA test in some patients. that promote apoptosis in the body that may take particular aim at lung cancer.
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 This combination of research on multiple fronts is allowing patients
role in battling the disease. Researchers say they expect not only to such as Sean Swarner to achieve new heights, acknowledges the cancer
continue uncovering the genetic composition of different cancers but survivor. Still cancer-free, Swarner says he recently climbed Aconcagua
add that in the not-too-distant future patients might receive detailed in Argentina as part of his quest to scale the highest peaks of the seven
genetic analysis so that treatments can be tailored for a specific patient. continents. Now, he says, he has just three of the peaks left to climb.
L U N G C A N C E R
stopping cell growth
TA 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.
he approximately 170,000 people expected to die of lung AstraZeneca recently reported, a larger study with more than 1,600
cancer in 2005 in the U.S. will represent more than the patients indicated that the drug did not improve overall survival rates.
number who will die from colon, breast and prostate The company says it is analyzing trial data to determine what role,
cancers combined, says the American Cancer Society. if any, EGFR status and its mutation played in the trial results.
Some 13 percent of all lung cancer cases are small-cell lung cancer GENENTECH INC. ’s (DNA) and OSI Pharmaceuticals’ lung cancer
(SCLC), also known as oat-cell carcinoma, explains the Society, drug Tarceva also inhibits EGFR growth and stops cell division, says
which notes that most diagnosed SCLC cases involve a spreading of Myrtle Potter, Genentech president of commercial operations. The
the disease. Because non-small-cell lung cancer (NSCLC), which the FDA put Tarceva on a fast-track development program for review, and
Society estimates makes up the other 87 percent of diag- the drug was approved in December 2004 for NSCLC
noses, tends to be less widespread at the time of diagnoses patients, says Potter. According to Genentech, Tarceva has
and progresses somewhat more slowly, doctors say they also been shown to improve survival rates among pancre-
have more treatment options, and researchers say they see atic cancer patients, and the company and its partner hope
a larger window of opportunity. to apply for expanded FDA approval this year.
An early hope for a targeted therapy to treat NSCLC is Pharmaceutical houses are also developing new chemo-
Iressa, researchers point out. Iressa, which the FDA approved therapies that allow them to target cancer cells without
for use as a last resort in NSCLC patients in 2003, inhibits harming surrounding healthy cells. ELI LILLY AND CO. (LLY)
the epidermal growth factor receptor (EGFR) affecting says its Alimta, which is approved for treatment of NSCLC
tyrosine kinase, an enzyme involved in the signaling path- and malignant pleural mesothelioma, simultaneously blocks
ways in cells, reports its developer, ASTRAZENECA PLC (AZN). EGFR is three separate enzyme targets important to cancer cell growth and
present in many cancers, the company says, including lung cancer. division. Edmundo Muniz, vice president, global oncology at Lilly,
According to research published in both the New England Journal reports that Alimta is the first and only drug approved for treating
of Medicine and Science, patients who have a strong positive response to malignant pleural mesothelioma, which, he explains, is a relatively rare
Iressa appear to have a mutation in their EGFR. Unfortunately, form of cancer associated mainly with asbestos exposure.
Sidney Taurel, president, chairman and CEO of Lilly, says: “We now
offer two leading therapies for the most common and significant forms a path to market
of cancer: Gemzar for lung, breast and pancreatic cancer; and Alimta NOVARTIS AG (NVS), the developer of the
for lung and mesothelioma cancer. This solid foundation of cancer molecularly targeted anticancer drug
Gleevec, reports that it spends almost 19
therapy marks our commitment to patients with cancer, and we build
percent of net pharmaceutical sales on
upon that foundation with continued research and innovation.” R&D. A Gleevec timeline follows:
Meanwhile, one approach of ABBOTT LABORATORIES (ABT) in-
1985 Scientists isolate inhibitors of the Bcr-Abl oncogene.
volves apoptosis, explains Dr. Stephen Fesik, divisional vice president
early Researchers identify Bcr-Abl gene as a cause of chronic
for cancer research. Normal cell death, he points out, is often short- 1990s myelogenous leukemia (CML) in experiments with mice.
circuited in cancer cells by an increase in proteins, such as Bcl-2. 1992 Novartis becomes involved, synthesizing STI571.
“We’ve discovered inhibitors to the Bcl-2 family of proteins to pro- 1994 The company launches the first in-vitro studies to gauge
STI571’s effect on cancer cells.
mote programmed cell death,” says Fesik, who notes Abbott has some
1997 The company develops a pill form of STI571.
promising compounds in the lab that mimic proteins that promote
apoptosis in the body. 1998 April — Phase I clinical trials begin for CML patients in
chronic phase after failure of interferon-alpha therapy.
Fesik says Abbott applies a research technique to the discovery September— Phase I trial reveals positive results.
of Bcl-2 family of inhibitors called structure activity relationships 1999 July— Novartis starts mass production of STI571.
October— Phase II trials are launched to assess the drug’s
by nuclear magnetic resonance, or SAR by NMR. The technique, he effectiveness in a larger population.
explains, involves the screening of molecules to find fragments that 2000 June— Novartis debuts expanded-access program, reaching
scientists can assemble into full-size molecules to bind to a drug 7,000 patients in 32 countries.
July — FDA grants fast-track designation to STI571.
target. According to Abbott, SAR by NMR helps its scientists build
2001 February— Novartis files New Drug Application with the
new molecules that could not be built before. Such cell sleuthing is FDA for the drug, now known as Gleevec.
May — Gleevec receives FDA approval for treating CML.
a daunting task, admits Fesik. “Different kinds of cells have differ-
2004 Long-term efficacy and safety demonstrated in newly diag-
ent Bcl-2 proteins, and some cells have different amounts of differ- nosed CML patients, with 91 percent survival at 42 months
ent Bcl-2 proteins,” he says. “This is a hard problem,” underlines and low risk of relapse. Median survival for gastrointestinal
stromal patients still not reached with 34 months of followup.
Fesik, “but we’re making significant progress and trying our best.”
SOURCE: NOVARTIS AG
L E U K E M I A A N D L Y M P H O M A
enzymes in the blood
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 A Y 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 .
ancers of the blood and immune systems are where oncol- David Epstein, head of Oncology and Specialty Medicines at
ogists say the most promising targeted drug therapies first Novartis Oncology, reports the company began preparing to produce
appeared. Researchers point to Gleevec, widely regarded as the drug, which the FDA approved in 2001, before clinical trials were
one of the first targeted drugs designed to stop a specific completed. “But if we only did the sure thing, patients would have had
form of cancer — chronic myelogenous leukemia, or CML. NOVARTIS to wait for this lifesaving drug,” he notes.
AG (NVS) says Gleevec blocks the protein Bcr-Abl, which triggers run- Gleevec also inhibits c-kit, says Epstein, who notes that c-kit is
away growth of abnormal white blood cells in CML patients. involved in driving the growth of gastrointestinal stromal tumors, or
The American Cancer Society reports that 68 percent of Gleevec GISTs. The usually fatal GIST, reports Novartis, was previously treated
patients in one clinical trial had no detectable leukemia after 14 only by surgery. The FDA approved Gleevec for patients with c-kit-
months, compared with 7 percent who received once-standard treat- positive GIST in 2002, and recent data shows that median survival for
ment of chemotherapy and interferon. Such results led Novartis Chair- GIST patients taking Gleevec still has not been reached with 34 months
man and CEO Daniel Vasella to call Gleevec the “magic cancer bullet.” of followup, says Epstein.
BRISTOL-MYERS SQUIBB CO. (BMY) reports it is working on a com- non-Hodgkin’s lymphoma and other cancers,” says Edmundo Muniz,
pound for CML patients who develop a resistance to Gleevec. Phase I vice president, global oncology at ELI LILLY AND CO. (LLY). Enzastaurin,
trials on BMS-354825 indicated 31 of 36 patients responded after which, he explains, tries to block the formation of new blood vessels, is
becoming resistant to Gleevec, say the study’s leaders. Novartis says it is in Phase II trials. The company hopes to apply for regulatory approval
also working on AMN107 for Gleevec-resistant patients. by the end of the decade, says Charles Golden, executive vice president
Researchers are also looking to treat lymphoma, notes the National and CFO of Eli Lilly. Also, SANOFI-AVENTIS (SNY) says its vascular
Cancer Institute. “One of the more intriguing new molecules is a PKC endothelial growth factor Trap drug compound is currently in early
beta inhibitor, called enzastaurin, being developed for glioblastoma, Phase I clinical trials for non-Hodgkin’s lymphoma patients.
P R O S T A T E C A N C E R
moving to a chronic state
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 .
oe Torre reports he’s had it. So have Rudolph Giuliani, Richard Levy, chairman and CEO of VARIAN MEDICAL SYSTEMS INC.
Colin Powell and Michael Milken. According to the (VAR), notes the position of the prostate changes with bladder and rec-
National Cancer Institute, prostate cancer is the second- tal fullness. Three-dimensional conformal radiation therapy has been
most lethal cancer killer among men. However, as these used since the 1980s because it can adapt the shape of the radiation
and other patients can attest, the picture has improved significantly. beam to that of the tumor, says Levy, reducing the amount of radiation
“The advancements and attention brought to the disease by that accidentally hits normal tissue. Using sophisticated linear
these celebrities are helping us move toward making it a disease accelerators, such as those in Varian’s ClinacTM and TrilogyTM
that is no longer a devastating diagnosis,” says Christine Jacobs, lines, he explains, doctors can target thousands of pencil-thin
chairman, president and CEO of THERAGENICS CORP. (TGX), radiation beams on a tumor.
a maker of radioactive implantable devices used to treat Levy says new computer programs let physicians view real-
prostate cancer. According to the American Cancer Society, time images of a patient’s anatomy so they can precisely plan
the overall five-year survival rate has increased to about 98 and deliver treatments with either brachytherapy or radio-
percent today from just 67 percent 20 years ago. therapies. “The holy grail is to give more dosage to tumors
An increasingly common treatment against pros- and less to healthy tissue,” says Levy. Varian’s linear accel-
tate cancers that have not yet spread is brachytherapy, erators, he says, let doctors compensate for respiratory
according to data presented at an Advanced Prostate motion to target tumors and even small metastases.
Brachytherapy Conference last year. Doctors insert For cancers progressing beyond the prostate or for
small radioactive “seeds” about the size of a grain patients who don’t respond to standard therapies,
of rice into the prostate, explains Jacobs. With “we’ve focused on drugs that are better tolerated and
brachytherapy, she says doctors can apply a higher may prevent further tumor growth,” says Dr. Jeffrey
dose of radiation directly to a tumor without harm- Leiden, president and COO of ABBOTT LABORATORIES ’
ing adjacent healthy tissue. The treatment is about as suc- (ABT) pharmaceutical products group. He says several drugs
cessful as surgery and offers a quicker recovery, she adds. in Abbott’s pipeline, including Xinlay, have “the potential to revolu-
Noting the tiny seeds have a tendency to move within the tissue and tionize cancer treatment.” Xinlay blocks activation of the receptor for
stray from their intended target, Dr. John DeFord, vice president of sci- endothelin, a protein thought to help spread cancer cells, he explains.
ence and technology at C.R. BARD INC. (BCR), says Bard encapsulates The key to successful treatment, however, say all the researchers,
Theragenics’ radioactive seeds within a polymer sleeve. The procedure, is early detection. “It comes down to doing your homework,” con-
he explains, connects multiple seeds like the cars of a train, reducing the cludes Jacobs. “And for God’s sake, ask for the screening test. Prostate
chances that the seeds will migrate before doing their work. cancer does not have to be a death sentence.”
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 .
nly 39 percent of colorectal cancer cases are diagnosed Dolan, Bristol-Myers’ chairman and CEO. The drug “is initially indi-
at the localized stage, according to the American Cancer cated to treat advanced colorectal cancer, a disease that has few options
Society. For cancers that spread only to nearby organs, when the patient is unresponsive or doesn’t tolerate other treatments.”
about two-thirds of patients survive for five years, esti- Erbitux, which was launched in 2004, slows cancer growth by targeting
mates the organization, but adds the survival rate plummets to 10 the epidermal growth factor receptor protein, present in 77 percent of
percent if colorectal cancer spreads to distant parts of the body. colon cancers, estimates Bristol-Myers. The drug is also being tested
To treat cells that have metastasized beyond the main with other medications to treat pancreatic, head and neck
tumor mass, doctors say they often follow surgery with and non-small-cell lung cancers, says the company.
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.
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,
THE COST OF
However, the company says, its effect on long-term BRINGING A DRUG president of product development. Genentech says
survival is not known because patients in these stud- T O M A R K E T, the drug, used with chemotherapy, increased sur-
E S T I M AT E S
ies need to be followed longer. Eloxatin has been shown N OV A R T I S vival rates of metastatic colon cancer patients by five
to shrink cancers in some patients in whom the cancer months. Avastin may help in other cancers, Desmond-
had already spread to distant organs, says Sanofi-Aventis. Hellmann adds. “Our broad development program includes
In 2004, the FDA reported approval of two monoclonal antibody seeking extensions to treat multiple tumor types.”
treatments for cancer that spreads outside the colon. Normally, a per- NOVARTIS AG (NVS) reports that its PTK787 slows the growth and
son’s immune system produces antibodies to fight foreign invaders spread of tumor blood vessels. In early trials, the company says, the
such as bacteria or viruses, according to scientists. One monoclonal monoclonal antibody shrank tumors in colon cancer patients when
antibody treatment is Erbitux (Cetuximab), codeveloped by BRISTOL- used with chemotherapy. First Phase III results, being developed with
MYERS SQUIBB CO. (BMY) and ImClone Systems Inc., says Peter R. SCHERING AG (SHR), are expected by mid-year.
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 A V E U P P E D T H E S U R V I V A L R AT E .
reast cancer offers a bad news/good news scenario he acknowledges. “Yet the absolute number of women who have died
that is now tipping more to the good news side, says of breast cancer has been dropping for 13 years.” The reason, accord-
Dr. Clifford Hudis, chief of breast cancer medicine ing to Hudis, is that earlier detection and new therapies allow
service and associate attending physician at the women to live longer without recurrence, or even to survive with
Memorial Sloan-Kettering Cancer Center in New York City. “The an active form of the disease.
population, in the U.S. at least, has gotten older and larger, so the Because most breast cancers grow in response to abnormal
total number of [breast cancer] cases has done nothing but go up,” levels of estrogen, explains Hudis, doctors often prescribe an estro-
gen blocker for women who have been treated for early-stage breast journal. For cases where breast cancer returns after use of tamox-
cancer. ASTRAZENECA PLC (AZN) describes its tamoxifen drug, ifen, says AstraZeneca, patients can turn to its alternative estrogen-
brand name Nolvadex, as the world’s largest-selling breast cancer receptor blocker, called Faslodex, which also was recently approved.
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. breakthrough: ANGIOGENESIS INHIBITORS
The problem? AstraZeneca says that although studies have indi- 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
cated that taking tamoxifen after initial breast cancer treatment
angiogenesis. Using anti-angiogenesis drugs such as Avastin, GENENTECH INC.
reduces the chances that the cancer will return, some women suffer (DNA) says it hopes to block the formation of new blood vessels, which in turn
serious side effects, and more than 30 percent experience relapses could cause tumors to grow more slowly — or even shrink and die. Angiogenesis
despite taking it. Further, according to the company, clinical trials inhibitors could be extremely useful in treating cancers, such as brain cancers,
have shown that tamoxifen use must be stopped after five years. that are difficult to reach using surgery, say scientists. According to the National
Cancer Institute, researchers are evaluating angiogenesis inhibitors to treat a vari-
In the past few years, doctors say they are turning to a new class
ety of cancers, from breast to stomach.
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 Additional targeted therapies are also on the horizon, point out
no longer produce estrogen. A study published in the New England scientists. Herceptin, for example, a therapeutic antibody treatment,
Journal of Medicine last March indicated that breast cancer is the only immune therapy currently available for HER2-positive
patients who switched to Aromasin after a few years of taking breast cancer, explains its developer, GENENTECH INC. (DNA). The
tamoxifen saw a 32 percent reduction in the risk of the disease’s company says Herceptin delivers an HER2/neu antibody that locks
recurrence after three years, compared with those onto a particular protein that is overexpressed by
who continued on tamoxifen. about one in four types of breast cancer cells to pre-
Studies suggest that aromatase inhibitors may vent them from receiving growth signals. The
ultimately replace tamoxifen as a standard treatment American Cancer Society reports that Herceptin
for postmenopausal patients, say oncologists. For shrinks some breast-cancer metastases and causes
example, NOVARTIS AG ’s (NVS) aromatase inhibitor, fewer side effects than other drugs.
Femara, cut the recurrence of breast cancer so dra- In many cases, combinations of drugs may dis-
matically that one trial was halted early to allow all rupt several cancer cell pathways at once, according
women in the trial to receive the drug, says Novartis. to Hudis. For example, a monoclonal antibody
A more recent 8,000-patient study compared medication could be used in conjunction with a
Femara head-to-head with tamoxifen, where the drug that inhibits epidermal growth factor recep-
new drug showed a 19 percent reduction in risk of tors, or EGFRs, which are overexpressed in many
occurrence in the adjuvant setting, says Novartis. cancers, he notes.
Even more striking, notes the company, was a 27 One such promising drug, according to oncolo-
percent reduction in the risk of cancer spreading to gists, is GLAXOSMITHKLINE PLC ’s (GSK) Lapatinib,
other parts of the body. which the company says is a HER2/neu inhibitor
Another study recently published in the similar to Herceptin, as well as an EGFR inhibitor,
medical journal The Lancet reported that resembling AstraZeneca’s lung cancer drug
Arimidex, AstraZeneca’s aromatase inhib- Iressa. In earlier trials, Lapatinib, currently in
itor, might prevent some 70 percent to 80 clinical Phase III trials, had halted or stabi-
percent of the most common types of lized breast cancer in some women whose
breast cancers that occur in women after disease had progressed under Herceptin,
menopause. By comparison, tamoxifen is according to GlaxoSmithKline. The company
believed to prevent cancer from recurring indicates that it anticipates filing for FDA
in 50 percent of such cases, according to the approval later this year.
A D D I T I O N A L C A N C E R S
the battle continues
M A N Y T R E AT M E N T S C A N B E N E F I T P AT I E N T S S U F F E R I N G F R O M A V A R I E T Y O F C A N C E R S .
PANCREATIC CANCER called RAS. Some 90 percent of pancreatic cancers
oday pancreatic cancer is the fourth
leading cause of cancer death, accord-
ing to the American Cancer Society.
Currently, one promising pancreat-
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
ic cancer treatment is a chemotherapy drug called THE TIME IT
Gemzar, says its maker, ELI LILLY AND CO. (LLY). The TA K E S T O B R I N G
A DRUG TO
company notes that nearly eight out of every 10 BRAIN CANCER
M A R K E T,
patients with pancreatic cancer receive Gemzar. The E S T I M AT E S A clinical trial conducted by the European
drug interferes with the processes of DNA produc- PFIZER INC Organization for Research and Treatment of Cancer
tion and can slow or stop tumor growth, explains the and the National Cancer Institute of Canada in
company. Gemzar has been approved since 1996 for treating spring 2004 reported for the first time that adding a chemotherapy
advanced pancreatic cancer and is now being tested with BRISTOL- drug to standard radiation treatment significantly increased
MYERS SQUIBB CO.’s (BMY) Erbitux to see if survival rates can be survival rates for patients suffering from an aggressive form of brain
improved, say the companies. 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
breakthrough: TA R G E T E D D R U G S chemotherapy drug and radiation therapy survived for two years or
Pharmaceutical companies say they are designing treatments to interrupt a specific more, compared with only 10 percent of patients who received radi-
element of a cancer-cell life cycle while leaving normal cells untouched. Such ation therapy alone, according to the company.
gene-based and protein-based therapies have fewer side effects and can be
“Until now there have been few treatment options for glioblastoma
extremely effective in treating specific forms of cancer, say researchers.
patients,” Dr. Gregory Cairncross, one of the study’s primary investiga-
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 tors and professor and head of the department of clinical neurosciences
become cancerous and multiply. So far Novartis says the orange pill stops only at the University of Calgary in Alberta, said in a presentation.
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 Doctors call kidney tumors highly vascularized, meaning they
division. For example, scientists say they have already identified the epidermal growth require many new blood vessels to survive. Several companies
factor (EGFR) as spurring the growth of solid tumor cancers, which could apply to can- report that they are currently trying to develop ways to disrupt the
cers of the lung, breast, prostate, colon, ovary, head and neck. New drugs that target
formation of new blood vessels. In a Phase II study by Bayer and
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) Onyx Pharmaceuticals, investigators reported tumor shrinkage or
Iressa (a small-molecule inhibitor used to treat lung cancer). 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
The experimental kidney cancer drug Bay 43-9006 may have an undergoing Phase III investigation for the treatment of advanced
even more pronounced effect on pancreatic cancer, according to BAYER kidney cancer. The two companies, says Bayer, also intend to initiate
AG (BAY). In addition to inhibiting blood vessel growth, the company additional Phase III and Phase II trials in other tumor types, includ-
explains, the drug also impedes signals produced by a gene mutation ing melanoma and hepatocellular carcinoma (liver cancer).