BRAIN CANCER Adding Chemotherapy to Radiation Therapy ...€¦ · cannot be cured. “Patients are still not cured of their disease, so we need to do more research and clinical trials,”

President’s Letter .............................................................. 2

Brain Cancer...................................................................... 2

Prostate Cancer................................................................. 4

Gastrointestinal Stromal Tumor...................................... 5

Non-Hodgkin Lymphoma ................................................ 6

Lung Cancer ...................................................................... 8

Cancer Genetics................................................................ 10

Kidney Cancer................................................................... 11

Chemoprevention............................................................. 12

Testicular Cancer .............................................................. 14

Multiple Myeloma ............................................................ 15

CONTENTS

ancer dvancesC Aancer dvancesC ANEWS FROM THE 2004 ASCO ANNUAL MEETING

BRAIN CANCER

Adding Chemotherapy to Radiation Therapy Improves Survival in Patients with GBM

Glioblastoma multiforme (GBM) is a fast-growingprimary brain cancer that is difficult to treat.

The standard treatment for GBM is surgery followedby radiation therapy. However, patients diagnosedwith GBM usually have a poor prognosis (chance ofrecovery). Results of a recent, large, multi-institutionalphase III clinical trial show that treating patientswith radiation and chemotherapy improves both progression-free survival and overall survival in GBM.

“This trial shows, for the first time, thatchemotherapy is effectivein treating this disease,”said lead author RogerStupp, MD, of the Uni-versity Hospital Multi-disciplinary OncologyCenter in Lausanne,Switzerland. “What isalso impressive is that wesaw the same result eventhough patients weretreated in over 80 insti-tutions throughoutEurope, Canada, andAustralia.”

In this study, more than500 patients with GBMwere randomized into two

groups. One groupreceived standard radia-tion therapy, and theother group receivedtemozolomide (TMZ[Temodar] ) during andafter radiation therapy.TMZ is a chemotherapydrug that has shown some promise in treatingrecurrent brain cancer.

After two years of follow-up, the median survival time and progres-sion-free survival was 15months for the patientstreated with both radia-tion and TMZ, and 12months for the patientswho received only radia-

tion. The percentage ofpatients who survived fortwo years or more jumpedfrom 10% in the radiationonly group to 27% in the radiation plus TMZgroup. Overall, this newtreatment appeared safeand well tolerated.

Dr. Stupp cautionedthat although this studywill probably establish anew treatment standard,most people with GBMcannot be cured. “Patientsare still not cured of their disease, so we needto do more research andclinical trials,” he said.(Abstract #0002) ■

This new treatment isnot a cure for GBM, butit can extend patients’lives in a meaningfulway. Many doctors havenot suggested clinicaltrials for these patientsbefore because of howfast these tumors growand spread. Because ofthese positive results,more doctors may con-sider enrolling patientsin clinical trials, whichhelps improve the treat-ment options overall forpeople with GBM.

WHAT THIS MEANSFOR PATIENTS

Information contained in ASCO’s Cancer Advances is not intended asmedical advice or as a substitute for your doctor’s own professionaljudgment; nor does it imply ASCO endorsement of any product orcompany.

2

Dear Friends,

This year ASCO celebrates 40 years of quality cancer care. Since the founding of theSociety in 1964, improving the treatment, prevention, care, and quality of life for each person with cancer has been at the heart of ASCO’s mission. ASCO has enhanced its commitment in recent years by formally expanding its mission to serve not only the informational needs of its members, but also those of its members’ patients.

To support this commitment, ASCO publishes Cancer Advances, a series of consumer information resources designed to help inform people of the latest advances in cancerresearch. Cancer Advances: News from the 2004 ASCO Annual Meeting is designed to provide people living with cancer and their families with the latest information about cancer research, prevention, care, and treatment as presented each year at ASCO’s AnnualMeeting. The information contained in this issue was presented at the 40th Annual Meetingof the American Society of Clinical Oncology held in New Orleans, Louisiana, from June 5to 8, 2004. The theme of the meeting was 40 Years of Quality Cancer Care, reflecting theSociety’s commitment to excellence in the care and treatment of people with cancer overthe past 40 years.

These latest advances will improve the care and treatment of people living with cancer. I hope you find this newsletter helpful in understanding the recent developments that were reported at the 2004 ASCO Annual Meeting. For more information about cancer,please visit ASCO’s People Living With Cancer website (www.plwc.org).

Sincerely,

Margaret Tempero, MDASCO President

A WORD FROM THE PRESIDENT

BRAIN CANCER

Chemotherapy Can Delay Brain Tumor Progression; GeneticDifferences in Brain Tumors Linked to Survival

Anaplastic oligodendrogliomas (AOs) and anaplastic oligoastrocytomas(AOAs) are rare but fast-growing tumors that develop in the brain. The

standard treatment is surgery followed by radiation. Doctors also know thatthese tumors respond to a chemotherapy regimen called PCV (procarbazine,lomustine, and vincristine). This study was done to find out whether giving PCVbefore radiation treatment improved survival in people with AOs and AOAs.

The results showedthat overall survival wasnot different between thepatients who receivedchemotherapy before radi-ation (4.8 years) and thosewho received only radia-

tion (4.5 years). However,the cancer took longer toprogress in the patientswho received both chemo-therapy and radiation (2.6years) compared with thepatients who only received

radiation (1.9 years). Thecombination treatment,though, was more toxicthan radiation alone.

Doctors also collectedtissue samples from thetumors, knowing that in

the past, oligodendro-gliomas with a certaingenetic characteristicresponded better to treatment than tumorswithout it. Interestingly,the patients with oligo-dendrogliomas that hadthis genetic feature livedlonger, regardless of thetreatment they received.

“Oligodendrogliomaswith this genetic signa-ture have a better naturalhistory and response totreatment. Oncologists can learn to use this infor-mation to choose the most

appropriate treatment forthese patients,” said J.Gregory Cairncross, MD, leadauthor andProfessor ofClinicalNeuroscienceand Oncologyat the Uni-versity ofCalgary inCanada.

While longer follow-up is needed to learn

whether there are anylonger-term differences intreatment, this study sug-

gests that, inthe future,doctors willbe able to usegenetic mark-ers to assessthe prognosis(chance ofrecovery) ofpatients with

oligodendrogliomas.(Abstract #1500) ■

3

These findings show that treating patients with both radia-tion and chemotherapy keeps the cancer from progressinglonger than treatment with radiation alone. However, thisnew treatment also had more serious side effects and didnot improve overall survival. This doesn’t mean that chemo-therapy is not a good treatment option for this type ofbrain cancer. More research is needed to determine ifother drugs may work better and cause fewer sideeffects, or whether chemotherapy would be more effec-tive if it is given at the same time as radiation therapy.

The second part of the study found a correlationbetween the genetic profile of a brain tumor and patient survival, which may someday help doctors plan individualized treatment.

WHAT THIS MEANS FOR PATIENTS

“Oncologists canlearn to use thisinformation to

choose the mostappropriate

treatment for these patients.”

– J. Gregory Cairncross, MD

Helping patients and their

families find accurate,

timely, and oncologist-

approved information

about cancer.

BRAIN CANCER

New Tumor Marker Affects Prognosis in Glioma

Researchers have discovered a correlation between a tumor protein called epidermal growth factor receptor (EGFR) vIII (“variant three”) and the

prognosis (chance of recovery) of grade 3 and 4 primary brain tumors called gliomas. Primary brain tumors begin in the brain. A grade 4 tumor, also calledglioblastoma, is the fastest-growing brain tumor. Grade 3 tumors are moderatelyaggressive, but may grow as fast as grade 4 tumors in some patients.

In this study, doctorsstudied 63 tumor samplesfrom patients with grade3 tumors. They found thatpatients whose tumor sam-ples had the vIII proteinlived an average of 7.2

months, whereas thepatients whose tumors did not have vIII lived anaverage of 33 months.

Jan Buckner, MD, leadauthor and Professor ofOncology at the Mayo

Clinic College ofMedicine in Rochester,Minn, explained that thisinformation could be usedto identify which grade 3gliomas might grow asquickly as grade 4gliomas. “vIII expression ischaracteristic of glioblas-toma multiforme, the mostaggressive primary braintumor. It is reasonable totreat patients with grade3 tumors and vIII expres-sion as glioblastomapatients.” These resultsconfirm previous findingsthat genetic markers ofglioblastoma in grade 3

tumors are associated witha poor prognosis.

“Eventually, vIII ex-pression may be importantin selecting patients forclinical trial participationand for therapies that target individual mole-cular profiles,” said Dr.Buckner. (Abstract #1508) ■

This study suggests that the presence of a tumor marker called vIII in grade 3 gliomas indicates a fast-growing tumor that should be treated like a grade 4tumor. Previously, doctors determined prognosis andtreatment by looking at how the tumor cells appearedunder the microscope. Now, doctors may be able to useboth the tumor grade and the tumor marker to helpthem better treat people with grade 3 gliomas.


The results of the firststudy showed a 20% sur-vival advantage with anew chemotherapy regi-men of docetaxel and estra-mustine (Estracyte) whencompared with the currentstandard therapy of mitox-antrone (Novantrone) andprednisone in a random-ized, phase III trial of morethan 700 men. In addition,the new combination in-creased the time it tookfor the disease to pro-gress: six months for themen who received doc-etaxel/estramustine, andthree months for the menwho received mitox-antrone/prednisone. For late-stage prostatecancer, an increase of threemonths’ survival time isconsidered significant.The men receiving thedocetaxel/estramustinecombination experiencedmore serious side effects,but the number of treat-ment-related deaths didnot increase.

“The findings showthat docetaxel can effec-tively treat hormone-refractory prostate cancer.Docetaxel-based therapyis now a treatment to

build upon,” said DanielPetrylak, MD, lead authorof the trial and AssociateProfessor of Medicine atColumbia UniversityCollege of Physicians &Surgeons, Director ofGenitourinary OncologyProgram at New YorkPresbyterian Hospital in New York City. (Abstract #0003)

Asecond study of 1,006men with hormone-

refractory prostate cancershowed that docetaxel plusprednisone given everythree weeks improvedoverall survival, reducedprostate-specific antigen(PSA) levels, and improvedpain symptoms. In addi-tion, this treatment hadrelatively few side effects,the most common one beingneutropenia (a low num-ber of white blood cells).

In this study, researcherscompared three drug regi-mens: two different dosesof docetaxel (once a weekvs. once every threeweeks) plus prednisone, or mitoxantrone plusprednisone (given everythree weeks). At a median

follow-up time of 20.7months:

◆ Survival was significant-ly longer for men whoreceived docetaxel onceevery three weeks (18.9months) compared withthose who received docetaxel weekly (17.4months) or mitoxantroneplus prednisone everythree weeks (16.5months).

◆ In men who receiveddocetaxel every threeweeks, 45% had a reduc-tion in their PSA levels,compared with 48% ofthe men who receiveddocetaxel weekly, and32% of the men whoreceived mitoxantroneplus prednisone everythree weeks.

◆ Men who received doc-etaxel every three weeksexperienced greater painrelief (33%) comparedwith those who receivedweekly docetaxel (31%)or mitoxantrone plusprednisone every threeweeks (22%).

“This is the first evi-dence of a survival advan-

4

Two new studies demonstrate that docetaxel (Taxotere) extends survival andrelieves pain in men with prostate cancer that does not respond to hormone

therapy. This type of cancer is called hormone-refractory, or androgen-independent,prostate cancer. Hormone therapy is a primary treatment for prostate cancer, butoften loses its effectiveness over time.

tage with chemotherapyin phase III trials inpatients with hormone-refractory prostate can-cer,” said Mario Eisen-berger, MD, lead authorof this study and R. DaleHughes Professor of On-cology and Urology atJohns Hopkins School ofMedicine in Baltimore,Md. “We have a realchance to finally develop a treatment approach thatis not based primarily onhormonal therapy andmake a real long-termimpact on this disease.” (Abstract #0004) ■

PROSTATE CANCER

Chemotherapy Improves Survival and Quality of Life for Patientswith Hormone-Refractory Prostate Cancer

These two studies demon-strate for the first timethat chemotherapy im-proves survival and re-lieves pain in prostatecancer that no longerresponds to hormones.This type of prostate cancer has been difficultto treat in the past, andnow men with this cancerhave better treatmentoptions. On May 19,2004, the U.S. Food andDrug Administrationapproved docetaxel foruse in combination withprednisone for the treat-ment of metastatic, hor-mone-refractory prostatecancer. Docetaxel-basedchemotherapy will likelybecome the new standardtreatment for men withhormone-refractoryprostate cancer.


of Medicine at HarvardMedical School in Boston,Mass.

In this small study, 48patients with imatinib-resistant GIST were given

SU11248 (taken as a pillonce a day). Tumors in 26 patients (54%) eitherresponded to this treat-ment or did not progress

5

This risk increases thelonger the treatment con-tinues. GnRH agonistswork by limiting pro-duction of the hormonetestosterone. This type ofhormone therapy is alsocalled androgen depriva-tion therapy (androgensare male sex hormones).

“These results highlightthe importance of osteo-porotic fractures as anadverse effect of androgendeprivation therapy forprostate cancer,” said leadstudy author Matthew R.Smith, MD, PhD, of

Massachusetts GeneralHospital Cancer Centerand Assistant Professor of Medicine at HarvardMedical School in Boston.

In this study, investiga-tors analyzed the Medicareclaims of more than 3800men with non-metastaticprostate cancer who re-ceived GnRH agonists andcompared them with theclaims from more than7700 men who did notreceive these drugs. Theyfound that men who re-ceived GnRH agonist treat-ment were 40% more likely

Continued on page 15

PROSTATE CANCER

Hormone Therapy For Non-Metastatic Prostate Cancer Increases Risk of Bone Fractures

Anew study suggests that men taking a specifictype of hormone therapy, called gonadotropin-

releasing hormone (GnRH) agonists, for prostate cancer are at an increased risk of bone fractures.

Men with prostate cancer who already receive androgendeprivation therapy should talk to their doctor aboutosteoporosis screening and ways to prevent fractures.For example, bisphosphonates have been shown toincrease bone mineral density in men receiving GnRHtreatment for prostate cancer. Men who are consideringhormone therapy are encouraged to talk to their doctorabout the risks and benefits of this therapy.


New Drug Shows Promise in TreatingImatinib-Resistant GIST

Anew drug called SU11248 shrinks or slows theprogression of cancer in patients with gastroin-

testinal stromal tumor (GIST) whose tumors havestopped responding to the standard treatment of imatinib (Gleevec).

GIST is a rare cancer ofthe stomach or intestinaltract that is treatablewith imatinib. However,imatinib eventually stopsworking in about half ofall patients, and the can-cer progresses.

“We’re not replacingimatinib as initial therapy

for GIST, but we need todevelop better therapiesand make their effects lastlonger,” said lead authorGeorge D. Demetri, MD, Director, Center for Sarcoma and BoneOncology at the Dana-Farber Cancer Instituteand Associate Professor

to suffer a fracture than themen who did not receivethis treatment. In addition,men who were on this hor-mone therapy for more thanthree years had a higherrisk of fracture than thosewho took the drugs for oneyear or less.

“We were surprised bythe strength and consisten-

cy of the associationbetween GnRH agonisttreatment and fractures,”said Dr. Smith. “For menwho require androgen-deprivation therapy,screening for osteoporosisand interventions to pre-vent fractures shouldbecome standard care.”(Abstract # 4507) ■

This trial for GIST was a combination phase I/II trial, soresults still need to be verified in a phase III trial. Untilthat research is complete, this drug is only availablethrough clinical trials. For patients with GIST who aredeveloping resistance to imatinib, these results indicatethat SU11248 may delay the progression of this cancerin some patients. Finally, because many cancers havesimilar pathways to GIST, this drug might also be usedto treat or understand other types of cancer.


GASTROINTESTINAL STROMAL TUMOR

6

an improvement in time toprogression, and the effectwas even more robustthan we hoped,” saidHoward Hochster, MD,

lead author ofthe study andProfessor ofMedicine atNew YorkUniversitySchool ofMedicine. Infact, the resultswere so good,

the study was stoppedearly so that all patientscould receive rituximab.

In this phaseIII clinicaltrial, 149patients withstage III or IV follicularand small lymphocyticlymphomareceivedchemotherapy,and 154patientsreceivedchemotherapy followedby rituximab treatment.The chemotherapy regi-men used in this trial was CVP (cyclophos-phamide, vincristine, and prednisone).

After two years, cancer

Monoclonal antibodiesare laboratory-made sub-stances that recognize andattach to specific proteins(called antigens) on the outside oflymphocytes(white bloodcells). Rituxi-mab binds toan antigen onlymphoma cells calledCD20.Researchersthink that this actionhelps the body’s immunesystem destroy the cancercells.

In the first study,researchers found that two years of maintenancetherapy with rituximabincreases the time it takesfor the cancer to progressafter chemotherapy inpatients with advancedindolent lymphoma.Indolent lymphoma is aslow-growing cancer thatinitially responds well totherapy, but eventuallyrecurs in most patients.Maintenance therapy isgiven after chemotherapyto “maintain” a tumor’sresponse to that drug andkeep the cancer fromreturning.

“We had hoped to see

did not progress in 74% of the patients whoreceived rituximab, compared with 42% of the patients who receivedonly chemotherapy. Afterfour years, cancer did notprogress in 58% of thepatients who received rituximab, compared with 34% of the patientsin the other group. Thesedifferences did not appearto be related to tumor cell type (histology), the presence of cancer left behind after chemo-therapy (residual disease),or the amount of cancer inthe patient’s body (tumorburden).

“We hope this willeventually translate into

improved sur-vival in thisdisease. Notreatment to date has shown survivalimprovementin indolentlymphoma,”said Dr.Hochster.Because thesetumors growslowly, Dr.

Hochster estimated thatanother five years of fol-low up might be necessaryto know whether thistherapy increases overallsurvival. (Abstract #6502)

In another trial,researchers found that

adding rituximab tochemotherapy improvessurvival in youngerpatients with low-riskdiffuse large B-cell lym-phoma (DLBCL). DLBCLis the most common typeof non-Hodgkin lym-phoma. The usual treat-ment for DLBCL ischemotherapy based on achemotherapy regimencalled CHOP (cyclophos-phamide, doxorubicin,vincristine, prednisone).Rituximab added tochemotherapy has alreadybeen shown to be an effec-tive treatment in patientsover age 60, so this trialwas designed to learn ifrituximab would have asimilar benefit in youngerpatients with DLBCL.

More than 700 patientsaged 18 to 60 with low-risk DLBCL who had notyet been treated were ran-domized into two groups:half received CHOP-like chemotherapy and the other half receivedCHOP-like chemotherapyand rituximab. Theseresults were observed at15 months:

◆ More patients whoreceived chemotherapyplus rituximab contin-ued to respond to theirtreatment (84%), com-pared with those who

Maintenancetherapy is given after

chemotherapy to “maintain” a

tumor’s response to that drug andkeep the cancerfrom returning.

NON-HODGKIN LYMPHOMA

Adding Immunotherapy to Chemotherapy Benefits Patients With Various Types of NHL

Three new studies suggest that adding rituximab(Rituxan), a monoclonal antibody therapy, to

chemotherapy is an effective treatment for severaltypes of non-Hodgkin lymphoma (NHL).

“We hope this will eventually translate into

improved survival in this disease.No treatment to date has

shown survivalimprovement in indolentlymphoma.”

– Howard Hochster, MD

7

received onlychemotherapy (63%).

◆ Eighty-five percent(85%) of the patientswho received bothchemotherapy and ritux-imab experienced a com-plete remission (CR),compared with 66% ofthe patientswho receivedonly chemo-therapy.

◆ Of thepatientstreated withchemotherapyand ritux-imab, cancerin 6.3% ofthe patients progressed,compared with cancer in17.7% of the patientstreated with chemo-therapy alone.

◆ Overall survival was98.5% in the patientswho received chemo-therapy plus rituximab,and 92% in those whoreceived chemotherapyalone.

Because these younger,low-risk patients startwith a relatively goodprognosis (chance of recov-ery), the investigatorswere surprised that theywere able to improve theresults in these patients.“The combination of aCHOP-like chemotherapywith rituximab has

achieved the best resultsreported ever for youngpatients with low-riskaggressive lymphoma,”said the study’s leadauthor MichaelPfreundschuh, MD,Director of MedicalOncology at SaarlandUniversity Medical

School inHomburg,Germany. Ifdoctors contin-ue to see posi-tive results inthe next sever-al years, Dr.Pfreundschuhspeculates thatlymphoma inthis set of

younger patients could beconsidered curable.(Abstract #6500)

In the third studyinvolving lymphoma,

investigators found thatadding rituximab tochemotherapy can slowthe progression of mantlecell lymphoma (MCL).This subtype of non-Hodgkin lymphoma ismost common in peopleover the age of 60 anddoes not often respond to treatment.

This study included122 patients with newlydiagnosed MCL. Sixtypatients received CHOPand 62 patients receivedCHOP plus rituximab.

◆ Thirty-four percent(34%) of the patientswho received CHOPplus rituximab experi-enced a complete remis-sion (CR) comparedwith only 7% of thepatients who receivedCHOP.

◆ Ninety-four percent(94%) of the patientswho received CHOPplus rituximab experi-enced either aCR or a par-tial remission(PR) comparedwith 75% ofthe peoplewho receivedCHOP alone.

◆ The time until the treat-ment stopped beingeffective was 22 monthsfor the patients takingCHOP plus rituximabcompared with 14

months for the patientsreceiving CHOP alone.

◆ There was no significantdifference in treatment-associated side effects.

“Combining immuno-therapy and chemotherapymay represent the newgold standard for treatingMCL,” said one of thestudy’s lead authors, MartinDreyling, MD, of the Uni-

versity ofMunich inGermany.“Whereas rituximabalone has limited activ-ity againstMCL, com-

bining it with chemother-apy improves treatmenteffectiveness considerablywithout any clinically sig-nificant increase in toxici-ty.” (Abstract #6501) ■

“The combination of a CHOP-like

chemotherapy withrituximab has

achieved the bestresults reported ever for young

patients with low-risk aggressive

lymphoma.”– Michael Pfreundschuh, MD

“Combiningimmunotherapy

and chemotherapymay represent thenew gold standardfor treating MCL.”

– Martin Dreyling, MD

These studies show that adding the monoclonal anti-body therapy rituximab to current therapies is effectivein treating patients of various ages, subtypes, andstages of non-Hodgkin lymphoma (NHL). The first study shows that rituximab is an effective maintenancetherapy for people with indolent NHL. The second studyshows that adding rituximab to chemotherapy improvessurvival in young, low-risk people with DLBCL. Finally,the third study demonstrates that adding rituximab tochemotherapy slows the progression of cancer in peo-ple with MCL. In each case, doctors will continue tostudy the long-term treatment response and sideeffects of rituximab.


8

Gefitinib works byshutting down a proteincalled the epidermalgrowth factor receptor(EGFR), which is why it is called an EGFRinhibitor.

The results showed thatcancer in 19% of the previ-ously untreated patientsresponded to gefitinib,with 6% of patients experiencing a completeresponse, which is whenall signs of cancer disap-pear. In patients who hadalready been treated withother drugs, the cancer

showed a 9% response rate to gefitinib, but therewere no complete respons-es. The median survivalrate was 12 months forthe previously untreatedpatients and 13 months forthose patients who hadbeen previously treatedwith other chemotherapy.

“This trial demonstratesclear, long-lasting activityfor gefitinib in a minorityof patients with BAC, ”said lead author HowardWest, MD, of the SwedishCancer Institute in Seattle,Wash. He suggested that

gefitinib could become anew standard of care forpatients with BAC.

Researchers also foundthat certaingroups ofpatientsresponded dif-ferently to gefi-tinib. For exam-ple, women ongefitinib lived amedian of 19months, com-pared with an average of 8 months in men. Patientswho developed a rash fromgefitinib treatment livedlonger (13 months) thanthose without a rash (5months). Ongoing analysis

of the data also suggeststhat patients who hadnever smoked live longeron gefitinib than former or

current smok-ers. Similarresults havebeen seenpreviously inother EGFRinhibitors.

Dr. Westthought theseresults were

interesting, but explainedthat more research neededto be done to understandwhy different groups ofpatients respond different-ly to the same treatment.(Abstract #7014) ■

Bronchioalveolar cell carcinoma (BAC) is a rare type of non-small cell lung cancer (NSCLC) that is most

common in younger, non-smoking women. The number of people diagnosed with BAC increases each year. Inthe largest prospective trial to date of 138 patients withadvanced BAC, researchers found that a drug called gefi-tinib (Iressa) produced a positive response, especially inpatients who had not received any prior treatment.

For reasons not yet understood,

women, non-smokers, andpatients who

develop a rashsurvive longer on

this therapy.

Drug Shows Activity in Advanced BAC

LUNG CANCER

These results add to existing data showing that gefitiniband drugs that target the EGFR pathway are effective intreating people with BAC. For reasons not yet under-stood, women, nonsmokers, and patients who developa rash survive longer on this therapy.


U.S. and Japanese Patients With NSCLC Respond Differently to Chemotherapy

Anew study shows that paclitaxel (Taxol) is moreeffective but also more toxic in Japanese patients

with advanced stage non-small cell lung cancer(NSCLC) than in U.S. patients. Non-small cell lungcancer is the most common type of lung cancer.

To address differencesin study results from coun-try to country, doctorsfrom the Japanese FourArm Cooperative Study(FACS) and the South-west Oncology Group

(SWOG) in the UnitedStates designed separate,parallel phase III trials forthe treatment of NSCLC.One group of patients ineach trial received thesame treatment—a combi-

nation of paclitaxel andcarboplatin. Because thedose of paclitaxel the pa-tients received was basedon previous phase I stud-ies, the Japanese patientsreceived 200 mg/m2 andthe American patientsreceived 225 mg/m2.

The study found thatthe characteristics of thepatients (such as age, ratioof men to women, stage,

and type of cancer) en-rolled in Japan were sta-tistically identical to thoseof the patients enrolled inthe United States. But,the response to treatmentwas different. After oneyear of treatment, 51% ofthe Japanese patients wereliving, compared with37% of the Americanpatients. The Japanesepatients were also 2.5

9

times more likely to expe-rience severe neutropenia(low white blood cellcount) and almost fivetimes more likely to expe-rience neutropenia accom-panied by a fever thanU.S. patients.

“Results of a cancerclinical trial performed inone part of the world maynot necessarily hold truefor populations in anotherregion,” said lead authorDavid Gandara, MD,

Director of ClinicalResearch at the Universityof California, DavisCancer Center andProfessor of Medicine atthe University ofCalifornia, Davis Schoolof Medicine. “Comparedto the relatively homoge-nous population in Japan,the United States is verydiverse. When we exam-ine studies, we have totake these population-related differences into

treatment information

coping strategies

resources for caregivers

clinical trials

techniques to manage

side effects

the latest cancer news

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consideration.”Dr. Gandara and his

fellow researchers thinkthat genetic differences inthe way people’s bodiesbreak down drugs may

explain these results, andthat this effect may bewhy the response to can-cer treatments varies indifferent parts of theworld. (Abstract #7007) ■

The study demonstrates that people from differentcountries can have different responses to treatment,such as chemotherapy, than patients in the UnitedStates. This result may help doctors interpret clinical trial results from countries outside the United States.


Chemotherapy After Surgery Improves Survival inPatients with Early Lung Cancer

Anew study shows that giving chemotherapy aftersurgery (adjuvant chemotherapy) results in a

significant survival advantage in people with stage IBnon-small cell lung cancer (NSCLC).

Stage IB NSCLCdescribes a small to medi-um-sized tumor that hasnot spread to the lymphnodes. This type of lungcancer is currently treatedwith surgery. The purposeof this study was to learnwhether chemotherapyafter surgery helped peo-ple with stage IB NSCLClive longer, because the

results of previous studieshave been conflicting.

In this study, researchersrandomly assigned 344patients with stage IBNSCLC to receive pacli-taxel (Taxol) and carbo-platin (Paraplatin) aftersurgery or surgery alone.After four years, 71% ofthe patients who receivedchemotherapy were liv-

ing, compared with 51%of the patients who onlyhad the surgery. Thismeans that adjuvantchemotherapy lowered therisk of death by 38%. Infact, the results were soclear that the trial wasstopped early so that allpatients could receiveadjuvant chemotherapy.

“These figures willhopefully translate into animprovement in the curerate in early stage lungcancer,” said lead investi-gator Gary Strauss, MD,MPH, of Rhode IslandHospital and BrownMedical School in Provi-dence. He hopes thatthese results are convinc-ing enough to change howpatients with high-risk,early stage lung cancer aretreated. (Abstract #7019) ■

This study shows that adjuvant chemotherapy (chemo-therapy after surgery) improves survival in a specificgroup of people with early stage NSCLC. More researchis needed to know whether adjuvant chemotherapycould help people with operable, stage II cancers.


10

In this study, doctorstreated 147 patients withradiation and either cis-platin (Platinol) or carbo-platin (Paraplatin) andrecorded the gastrointesti-nal (GI) side effects, suchas nausea, vomiting, andinflammation or irritationof the esophagus

(esophagitis). They alsoanalyzed each patient’sERCC1 gene.

The investigators foundthat 30% of the patientswho experienced moreintense side effects had avariation in the ERCC1gene. In comparison, only14% of patients without

this genetic variation expe-rienced serious side effects.

“Our study raises inter-esting questions that willneed to be validated in

prospective trials beforethe results can be used inpatient care,” said leadinvestigator Rebecca Suk,

Continued on page 13

Genetic Variation Is Associated With Treatment-Related Side Effects

Anew study finds an increased risk of severe digestive side effects in patients with a specific

genetic variation who were treated with radiation andplatinum-based chemotherapy for non-small cell lungcancer (NSCLC).

Anew study found an association between the quality of life of patients withmetastatic colorectal cancer and variations in a set of genes called folate

genes. The results of this study suggest that doctors may be able to identify and provide relief to those patients who are more at risk of certain side effectsassociated with cancer.

“Patients diagnosedwith cancer are affectedby their condition in dif-ferent ways. These resultssuggest that a patient’sgenetic structure may playa role in determining thequality of life after a diag-nosis of cancer,” said JeffSloan, PhD, of the MayoClinic in Rochester, Minn.

In this study, 494 patients with metastaticcolon cancer providedDNA samples and com-pleted a quality of lifequestionnaire before theyreceived chemotherapy. By

collecting this informationbefore treatment, the re-searchers could explorethe relationship betweengenetic profile and qualityof life without the influ-ence of side effects fromthe treatment.

The researchers thenanalyzed three folate genescalled DPYD, MTHFR, andTYMS, which are knownto be associated with aperson’s health. One interesting result is thatpatients with two variantforms of the DPYD geneexperienced less fatigue

Patients’ Quality of Life May be Linked to Genetic Structure

than patients with theregular form of the gene.

“We want cancerpatients to have the bestquality of life possible,”said Dr. Sloan. “If we canidentify cancer patientswho have a genetic predis-position to fatigue, stress,or other quality of lifedeficits, we can interveneearly to help them dealwith these issues.”

Dr. Sloan and his col-leagues will continue toinvestigate genes that mayaffect quality of life, withthe goal of developing

clinical interventions toimprove the quality of cancer patients’ lives. Forexample, patients who arelikely to experience fatiguecould be offered sleeptherapy, counseling, orexercise. (Abstract #0005) ■

CANCER GENETICS

This is the first study to find a relationshipbetween patients’ qualityof life and their genesthat is not dependent on the treatment theyreceive. In the future,doctors hope that theycan analyze a patient’sgenes to anticipatewhich patients will bene-fit the most from qualityof life interventions.


Doctors are starting to understand why people have dif-ferent reactions or responses to cancer treatment, andone of these reasons appears to be genetic. Once moreof these studies are done in larger groups of people,doctors may someday be able to select treatment plansaccording to a patient’s genes. This individual approachto cancer treatment, though, is still many years away.


11

In the first study, John Hainsworth, MD,Director of ClinicalResearch at the SarahCannon Cancer Center inNashville, Tenn, and col-leagues gave 62 patientswith RCC a combinationof bevacizumab (Avastin)and erlotinib (Tarceva).Of the first 40 patientswho were treated, cancerin 25% of the patientsshowed a partial responseat eight weeks, and thecancer progressed in only12% of the patients. Inaddition, the cancer did not get worse for six months in 71% ofpatients. Usually, doctors only see a 5%response to treatmentwith the standard thera-py—either interleukin-2or interferon.

Dr. Hainsworth cau-tioned that these resultsare still preliminary. “Ifthese results are verifiedin larger trials, this treat-ment may emerge as thefirst well-tolerated regi-men for people with renal cancer.”

These drugs are specifi-cally designed to act on

new approach in using targeted therapy. “Com-bining these targetedagents is the future of cancer treatment,” said Dr. Hainsworth. The U.S. Food and DrugAdministration recentlyapproved bevacizumab,but erlotinib is still anexperimental drug and isonly available throughclinical trials at this time.(Abstract #4502)

In the second study, 63patients with metastatic

RCC received a newchemotherapy pill calledSU011248. The cancershowed a partial responsein nearly a quarter of thepatients. Six months aftertreatment, the cancer wasstill not growing in 14 ofthose patients. At thispoint in the study, thenew drug appears safe

KIDNEY CANCER

First Time Drugs Show Promise in Treating Metastatic Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most commonkind of kidney cancer. Unfortunately, most cases

are not diagnosed until the cancer has spread to otherparts of the body (metastasized), which means thatpatients with metastatic RCC usually have limitedtreatment options. Two new studies demonstrate thatmetastatic RCC responds to new drugs that targetmultiple, specific pathways in cancer cells.

For the first time, there appears to be safer, more effec-tive treatment options on the horizon for RCC. How-ever, both studies, while promising, are small, phase IIclinical trials, so investigators will need to comparethese new drugs with the current standard therapy inphase III trials before these drugs become available out-side of a clinical trial. So far, these results suggest twonew ways of treating metastatic RCC. Both studies sup-port the idea that blocking multiple molecular pathwaysin cancer cells is a reasonable approach in treatingmetastatic RCC and possibly other advanced cancers.


proteins important to the cancer process.Researchers think thaterlotinib blocks an enzymecalled the epidermalgrowth factor receptortyrosine kinase, whichregulates cancer cellgrowth. Bevacizumab is a monoclonal antibodythat blocks the activity of a protein called vascu-lar endothelial growthfactor, which helps thetumor form new bloodvessels in a process calledangiogenesis.

Interestingly, these twodrugs block differentpathways in the cancercell, and may lead to a

and well tolerated, al-though patients experi-enced mild to moderatefatigue and gastrointesti-nal problems.

“During the past 15years, I have conductedmany studies for renal cancer, but none of themshowed this degree ofactivity as a single agent,”said Robert J. Motzer,MD, the study’s leadauthor and AttendingPhysician at MemorialSloan-Kettering CancerCenter in New York City.“SU011248 clearly showsactivity, is relatively welltolerated, and it’s a pillthat patients can take athome.”

Researchers think thatSU011248 blocks severaldifferent targets in cancercells, including those necessary for cancer cellgrowth and new bloodvessel formation (angio-genesis). SU011248 stillneeds to be tested in phaseIII clinical trials to confirmthese findings.

“This is a very excitingdrug for possible use inthe treatment of renal cancer,” added Dr. Mot-zer. “The disease has beenconsidered ‘the unbeatablecancer,’ with resistance toall forms of chemotherapyand only a small propor-tion of patients respondingto immunotherapies for a limited time.” (Abstract # 4500) ■

12

Astudy of more than 5,000 postmenopausal womenwith osteoporosis shows that raloxifene (Evista),

a drug used to treat bone loss, also lowers a woman’srisk of estrogen receptor (ER) positive invasive breastcancer. These findings mark eight years of follow-upwithout any new safety concerns.

Raloxifene is a type ofdrug called a SERM(selective estrogen recep-tor modulator), whichmeans it acts like a naturalestrogen in some ways. Itis currently used for theprevention and treatmentof osteoporosis.Osteoporosis is a condi-tion marked by a decreasein bone size and strength.Postmenopausal women

are at greater risk ofdeveloping this conditionbecause their bodies stopproducing the estrogenhormone, which helpsprotect against bone loss.

The CORE (Con-tinuing Outcomes Rele-vant to Evista) trial is afollow-up to the MORE(Multiple Outcomes OfRaloxifene) trial. In theMORE trial, doctors

compared raloxifene withno treatment (a placebo)over a four-year period ina large group of women.They found that the inci-dence of invasive breastcancer was reduced by72% in women receivingraloxifene.

In the CORE trial,researchers continued tofollow the women whowere part of the MOREtrial for four more years tolearn whether raloxifenecontinues to lower theincidence of breast cancerin postmenopausalwomen.

The CORE trial re-sults showed that womenwho received raloxifenereduced their risk of inva-sive breast cancer by 59%during years four througheight. The magnitude of

the risk reduction duringthe second four-year peri-od was similar to thatseen during the first fouryears. When the results ofthe CORE trial are com-bined with the results ofthe MORE trial, womentaking raloxifene reducedtheir incidence of ER-positive invasive breastcancer by 66% over theeight-year period.

“These data add to theexisting body of informa-tion that SERMs are anapproach by which breastcancer incidence can bereduced,” said SilvanaMartino, DO, of theCancer Institute MedicalGroup and John WayneCancer Institute in SantaMonica, Calif, and leadauthor of this study.(Abstract #1000) ■

Raloxifene Continues to Lower Incidence of Invasive Breast Cancer in Postmenopausal Women

CHEMOPREVENTION

These data suggest that women can take raloxifene foras long as eight years to reduce their risk of ER-positivebreast cancer without serious side effects. These find-ings also support other data showing that SERMs canreduce the incidence of ER-positive breast cancer.

Although raloxifene is approved for the prevention andtreatment of osteoporosis, it is not approved to reduce a woman’s risk of breast cancer. At this time, doctors donot recommend that women take raloxifene to reducetheir risk of breast cancer outside of a clinical trial set-ting. Finally, it should be noted that his study was notdesigned to address the effect of raloxifene on ER-negative breast cancer.


LIVE CHATS ON PLWCLog on to PLWC for Live Chats with Leading Cancer ExpertsLIVE CHATS ON PLWC

2004 PLWC LIVE CHAT SERIES SCHEDULE2:00 – 3:00 PM ET

June 10: Advances in Cancer Research: Newsfrom the ASCO 2004 Annual Meeting

July 28: Hematologic Cancers (Leukemia,Lymphoma, and Myeloma)

August 18: Nutrition Before, During, and After Cancer Treatment

September 13: Cancers in Men

September 21: Complementary and AlternativeMedicine and Cancer

October 15: Breast Cancer

November 12: Lung Cancer

November 17: Coping with Cancer During the Holidays

13

Anew study from the University of Michigan andCHS National Cancer Control Center in Israel

suggests that statins may be protective against colorectal cancer.

Statins are a group ofwidely-prescribed drugsthat lower cholesterol.Previous studies have asso-ciated statin use with areduction of colorectalcancer risk. Colorectalcancer is the second lead-ing cause of cancer deathin both men and women

in the United States, sec-ond only to lung cancer.

In this case-controlstudy, researchers com-pared the use of statins in1,608 Israeli patients whowere diagnosed withcolon cancer and 1,734Israelis who did notdevelop colorectal cancer.

The researchers confirmedthe use of statins from prescription records.

They found that peoplewho took statins were51% less likely to developcolorectal cancer thanthose who did not reporttaking statins. This pro-tective effect was still significant even afterresearchers adjusted forother known risk factorsof colorectal cancer.

“While the study’sresults provide a com-pelling rationale for moreresearch, it is too early torecommend that patientstake statins to reduce theirrisk of colorectal cancer,”said Stephen Gruber,MD, PhD, senior investi-gator of the study, of theUniversity of Michigan inAnn Arbor.

Other types of choles-

terol-lowering drugs, suchas fibrates, did not appearto protect against coloncancer. “We found thatthe protective effect oflipid lowering agents was restricted to statins,”said Dr. Gruber.(Abstract #0001) ■

Cholesterol-Lowering Statin Drugs May Reduce Risk of Colorectal Cancer

At this time, statins arenot approved for reduc-ing the risk of colorectalcancer. People shouldnot take statins toreduce their risk of colorectal cancer. Theresults of this study willlikely lead to random-ized, controlled clinicaltrials that test whetherstatins can be used toprevent or treat cancer.


MD, of HarvardUniversity in Boston,Mass. “However, as welearn more about howgenetic differences affecttreatment outcomes forlung cancer, we hope toone day be able to selecttreatment based on indi-viduals’ genetic profiles.”

Chemotherapy andradiation cause DNA dam-

age in both healthy andcancerous tissues. Inpatients with a functionalERCC1 gene, the damageis repaired in the healthytissue. The researchershypothesized that in thepatients with an alterationin the ERCC1 gene, thedamage cannot berepaired, and as a result,these patients experiencemore severe side effects.(Abstract #2014) ■

Continued from page 10

CANCER GENETICS (Continued)

New ASCO Patient Guide Available

Hormone Therapy for Advanced Prostate Cancerdescribes the clinical recommendations for the management of men with metastatic, recurrent, or progressive (advanced) prostate cancer.

This patient guide addresses topics such as

• What is advanced prostate cancer

• The role of hormones and hormone therapy inadvanced prostate cancer

• When to begin hormone therapy

• The role of nonsteroidal anti-androgen treatment

• The use of combined androgen blockade treatment

• What to ask your doctor about hormone therapy

• Where to find the original ASCO guideline

To order, please call 1-888-651-3038 or access it onlineat ASCO’s People Living With Cancer website(www.plwc.org).

ASCO PATIENT GUIDES

14

Stage I seminoma is an early stage, slow-growingtype of testicular cancer. The standard treatment is

usually removal of the cancerous testicle (orchiectomy),followed by adjuvant radiation therapy. However,patients who receive radiation therapy also tend tohave a higher risk of developing a second cancer inanother organ 10 to 20 years later.

Results of a newEuropean study show thatone course of chemothera-py treatment with carbo-platin (Paraplatin) is aseffective as radiation therapy, and is associatedwith a lower risk of a second cancer in the near

term. In men who are atrisk of developing cancerin the remaining testicle,this research suggests thatthe use of chemotherapymay allow doctors to preserve the remainingtesticle.

Doctors randomlyassigned 904 patientswith stage I seminoma toreceive radiation after sur-gery, and 543 patients toreceive a single dose ofcarboplatin after surgery.After two years of follow-up, the researchers foundthat cancer did not returnin 98.1% of patients whoreceived carboplatin treat-ment, compared with97.2% of the patients whoreceived radiation treat-ment. These numberswere also similar afterthree years of follow-up.To date, one man whoreceived carboplatin hasdeveloped a tumor in theremaining testicle, com-pared with seven menwho received radiationtherapy.

“This large, randomizedtrial establishes after 20years of research and

uncertainty that one shotcarboplatin in the shortterm is as safe as radia-tion, is less toxic, andmight open theway to usingchemotherapyfor testis con-servation,” saidlead author R.Timothy Oliver,MD, Sir Max-well Professorin Oncology at Barts and The LondonQueen Mary’sSchool ofMedicine inGreat Britain.

Another advantage isthat patients only needone chemotherapy treat-ment instead of threeweeks of radiation thera-py, which is more conven-ient for the patient and

results in a shorter recov-ery time. Because thesepatients have only beenfollowed for two or

three years,researchers do not yetknow thelong-termeffects of thistherapy.

“Thoughneedinglonger fol-low-up andlarger num-bers to besure, thissurprisingfinding is

the first hint that ulti-mately research may makeit possible for testis con-servation to be as routineas breast conservation,”said Dr. Oliver. (Abstract #4517) ■

Single Dose of Chemotherapy May Lead to Testis Preservation in Men with Seminoma

TESTICULAR CANCER

Although testicular cancer is curable, men may experi-ence second cancers or other long-term effects fromradiation therapy. Because many men who develop testicular cancer are young, the possibility of long-termside effects is a significant issue. These data may introduce adjuvant chemotherapy as the new standardtreatment for stage I seminoma, but the long-term risksof this treatment are not known at this time. Adjuvantchemotherapy also appears to be safer and more con-venient for patients than adjuvant radiation therapy. The study did not evaluate this treatment in men withtesticular nonseminomas.


“Though needinglonger follow-up

and larger numbers to be sure, this

surprising finding is the first hint that ultimately

research may make it possible for

testis conservation to be as routine

as breastconservation.”

– R. Timothy Oliver, MD

Advanced Lung

Cancer Treatment

Bisphosphonates

for Breast Cancer

Bisphosphonates for

Multiple Myeloma

Epoetin Treatment

Follow-Up Care for

Breast Cancer

Follow-Up Care for

Colorectal Cancer

Preventing and Treating

Nausea and Vomiting

Caused by Cancer

Treatment

Understanding Tumor

Markers in Breast and

Colorectal Cancer

ASCO Patient GuidesASCO Patient Guides

15

Results of a phase III clinical trial show that borte-zomib (Velcade) improves patient survival and

slows the progression of multiple myeloma that hascome back after initial treatment (relapsed).

Bortezomib also appearsto cause fewer side effectsin patients than a currentstandard treatment, dex-amethasone.

In this study, doctorscompared bortezomib todexamethasone in 669people with relapsed mul-tiple myeloma. At theinterim analysis, borte-zomib delayed cancer pro-gression by 5.7 months,compared with 3.6months for dexamethasone.

Survival also appeared tobe better in the patientstaking bortezomib, withfewer deaths in thisgroup. The results were sosignificant that the studyinvestigators stopped thetrial early so all patientscould receive bortezomib.

In addition, the patientswho received bortezomibexperienced fewer seriousinfections (6.7%) than thepatients who receiveddexamethasone (10.6%).

“These results confirmthe activity in patientswith relapsed multiplemyeloma,” said lead authorPaul Richardson, MD, ofthe Dana-Farber CancerInstitute in Boston, Mass.“Compared to dexametha-

sone, bortezomib hadsuperior time to progres-sion and less toxicity.”Doctors will continue tomonitor the safety andeffectiveness of borte-zomib in these patients.(Abstract #6511) ■

MULTIPLE MYELOMA

New Drug Delays Cancer Progression in Patients With Relapsed Multiple Myeloma

While these results are preliminary, they support thefindings of an earlier phase II trial of bortezomib inpatients with multiple myeloma, which prompted theU.S. Food and Drug Administration to approve borte-zomib for the treatment of multiple myeloma in 2003.Because of this study, bortezomib may become a standard treatment option for relapsed multiple myeloma and may be studied as a therapy for patients with earlier stage multiple myeloma.


for six months or more.Tumors in six of thepatients (13%) showed a partial response. Theresearchers also analyzedgenes from the tumor sam-ples and found that certainmutations, or changes, in agene called KIT were asso-ciated with responses to

SU11248. These studiesare important because theymay help researchersunderstand how this newdrug works.

Researchers think thatSU11248 blocks severalenzymes, called kinases,which are believed to beinvolved in cancer cellgrowth. “There is evi-dence that SU11248 shuts

Continued from page 5

GASTROINTESTINAL STROMAL TUMOR (Continued)

down several switches incancer cells, while ima-tinib only shuts down afew,” said Dr. Demetri. “It may be possible thatseveral switches need tobe shut off in order for apatient to derive the mostclinical benefit.”

Although GIST is arare cancer, the pathwaysinvolved in the develop-

ment and spread of thiscancer are similar to thosein other cancers. “Studiesof SU11248 in GIST give us the foothold in thedoor of cancer,” said Dr.Demetri. He believes thatknowing how this drugworks could be helpful inunderstanding some of themore common cancers.(Abstract #3001) ■

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BRAIN CANCER Adding Chemotherapy to Radiation Therapy ...€¦ · cannot be cured. “Patients are still not cured of their disease, so we need to do more research and clinical trials,”