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  • 1. 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
  • 2. 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 . inside: Lung Cancer page 23 Leukemia 24 Prostate Cancer 25 Colorectal Cancer 26 Breast Cancer 26 Other Cancers 28 In the Pipeline 29
  • 3. 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.” Consequently, companies 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 contributed signifi- 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. cancerbreakthroughs 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 $190 STYLINGBYSHELLYCOON E
  • 4. 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 T 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.
  • 5. 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 C 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 . cancerbreakthroughs 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.
  • 6. 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 J 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 .
  • 7. 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. O 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- blocking hormones B 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 . cancerbreakthroughs 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 $1.7 beyond chemotherapy
  • 8. 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
  • 9. 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 following treatment. 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 T 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 . cancerbreakthroughs 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 11-15 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
  • 10. Pfizer says its SU11248 also inhibits protein receptors associated with the spread of kidney cancer. A report given at the 2004 American Society of Clinical Oncology meeting indicated that 33 percent of patients in one clinical trial responded, and SU11248 appeared to sta- bilize the disease in 40 percent of patients in another trial. SU11248, which could emerge from clinical trials this year, also targets a protein blocked by NOVARTIS AG’s (NVS) Gleevec, and may help patients suf- fering with gastrointestinal stromal tumors, says Pfizer. Bladder cancer may involve some of the same cell types as kidney cancer, according to researchers. Bristol-Myers Squibb says its vinflu- nine, aimed at bladder cancer, is currently in Phase III trials in Europe. C E R V I C A L C A N C E R A cancer that researchers say they may be close to wiping out is cervical cancer. That’s because they say they have identified the primary risk factor: the human papilloma virus (HPV). MERCK & CO. INC. (MRK) announced that it hopes to file an application with the FDA this year for approval of a vaccine against the four primary HPV viruses. Merck reports that in its latest trial, the vaccine, now in Phase III clinical trials, contains the same components as one that tested 94 percent effective in protecting women against at least one of the viruses over a four-year period. Meanwhile, GLAXOSMITHKLINE PLC (GSK) reports that it is also engaged in Phase III clinical trials for a vaccine designed to pre- vent two types of HPV infection. The company says it could file for drug approval in Europe as early as 2006. Researchers from both companies note that to be effective the vaccines need to be administered to young women before the onset of sexual activity. But analysts say the news is promising. S K I N C A N C E R Skin cancer accounts for more than half of all reported cases of cancer today in the U.S., says the National Cancer Institute. Most are of the non-life-threatening nonmelanoma type, says the Institute. The more dangerous melanoma accounts for only about 4 percent of all inci- dences of skin cancer, but since 1981 its incidence has been increasing by about 3 percent per year, the American Cancer Society reports. Although it is usually curable in its early stages, notes the Society, melanoma is more likely than most other cancers to metastasize. If that happens, melanoma is usually fatal, says the Society. Several companies say they are exploring treatments to slow or attack the disease. Pharmaceutical companies say they are devoting a huge share of their R&D war chests to potential cancer killers. A sampling of some drugs currently in trials that the companies say they consider the most promising follows: Xinlay Lupron ABT-510 ABT-751 ZD6474 AZD2171 ZD4054 AZD0530 AZD6244 BAY 43-9006 BAY 57-9352 BMS-354825 Vinflunine Ixabepilone MDX-010 Erbitux LY335979 Enzastaurin Avastin Tarceva Omnitarg PRO1762 485232 786034 Cervarix 715992 Ethynylcytidine Lapatinib Hycamtin Navelbine Nelarabine Gardasil SAHA EMD7200 L-BLP25 Mitumomab Cilengitide PTK787 AMN107 LBQ707 EPO906 Gleevec SU11248 AG-13736 CI-1033 VEGF Trap Tirapazamine SR 31747 Uvidem Sarasar Temodar PEG-Intron Abbott Laboratories (ABT) AstraZeneca PLC (AZN) Bayer AG (BAY) Bristol-Myers Squibb Co. (BMY) Eli Lilly and Co. (LLY) Genentech Inc. (DNA) GlaxoSmith- Kline PLC (GSK) Merck & Co. Inc. (MRK) Novartis AG (NVS) Pfizer Inc (PFE) Sanofi-Aventis (SNY) Schering-Plough Corp. (SGP) Prostate, kidney, ovarian, brain and lung Prostate Lymphoma Breast, colorectal and lung Thyroid Breast, colon and kidney Prostate Breast and colon Breast, colon, lung, pancreatic and skin Kidney, liver and melanoma Solid tumor Chronic myelogenous leukemia, solid tumor Bladder, breast, lung and ovarian Breast Melanoma Head, neck and lung Various Non-Hodgkin’s lymphoma and brain Various Lung and pancreatic Breast, lung, ovarian and prostate Pancreatic and prostate Melanoma and kidney Solid tumor Cervical Lung Solid tumor Breast, bladder, gastric, head, lung and neck Lung and ovarian Breast, lung and solid tumor Leukemia and lymphoma Cervical Lymphoma Gastric, cervical and non-small-cell lung Lung Lung Brain Colon and rectal Chronic myelogenous leukemia Solid tumor Ovarian and lung Brain Kidney and GIST Pancreatic Ovarian and breast Non-Hodgkin’s lymphoma Head and neck Prostate Melanoma Leukemia and a variety of solid tumors Glioblastoma multiforme (form of brain cancer) Melanoma footnotes for the chart 1 Phase III for prostate; Phase II for kidney, ovarian, brain and lung, 2 Phase III for kidney; Phase II for liver and melanoma, initiating Phase III. 3 Phase II for chronic myelogenous leukemia; Phase I for solid tumor. 4 Approved for late-stage colorectal; Phase III for head, neck and lung. 5 Approved for colorectal; Phase III for breast, lung, kidney, ovarian, prostate and pancreatic. 6 Approved in 2004 for lung; Phase III for pancreatic. hope in the pipeline III, II1 III II II II I II I I III2 I II, I3 III III III III4 II II III5 III6 II I II II III II II III III III III III II II II III I III I II II II III II II I III II II II FILED III COMPANY DRUG TYPES OF CANCERS PHASE SOURCE: RESPECTIVE COMPANIES >> nyse M A G A Z I N E IS PUBLISHED BY THE NEW YORK STOCK EXCHANGE IN CONJUNCTION WITH TIME INC. CUSTOM PUBLISHING. © 2005 NEW YORK STOCK EXCHANGE, INC. ALL RIGHTS RESERVED.

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