Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Look up keyword
Like this
2Activity
0 of .
Results for:
No results containing your search query
P. 1
Magenkrebs - Gastric Cancer

Magenkrebs - Gastric Cancer

Ratings: (0)|Views: 556|Likes:
This editorial discusses the results of a japanese prospective randomized study comparing two groups of patients - surgery alone (gastrectomy including D2 lymphadenectomy) vs surgery and postoperative chemotherapy with S1
This editorial discusses the results of a japanese prospective randomized study comparing two groups of patients - surgery alone (gastrectomy including D2 lymphadenectomy) vs surgery and postoperative chemotherapy with S1

More info:

Published by: Prof Dr Dr Ernst Hanisch on Oct 19, 2011
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

05/22/2012

pdf

text

original

 
Gastric Cancer: Nagoya Is Not New York
John S. Macdonald,
Aptium Oncology, Los Angeles, CA
See accompanying articles doi: 10.1200/JCO.2011.36.5908 and doi: 10.1200/JCO.2011.36.7136
Adenocarcinoma of the stomach and gastroesophageal junctionis a significant problem worldwide, with more than 900,000 casesoccurringyearly.
1
IntheUnitedStates,thisdiseaseoccurredin21,000individualsandresultedinapproximately10,500deathsin2010.
2
Thecurative treatment of gastric cancer is based on surgical gastrectomy.However, after gastrectomy alone, relapse resulting in death frommetastatic disease is relatively common. For this reason, adjunctivetherapies to surgery have been extensively explored in clinical trialsover the last 40 years.
3
Some of these adjunctive therapies have beenacceptedasstandardsofcare.InNorthAmericaandwesternEurope,patients with stages II-IV (M0) disease who have undergone gastrec-tomy benefit in disease-free and overall survival from postoperativechemoradiotherapy.
4,5
In patients identified preoperatively as havingresectablegastriccancer,pre-andpostoperativecytotoxicchemother-apy,
6
a strategy termed perioperative therapy, has been accepted as astandard of care on the basis of results from the Medical ResearchCouncil Adjuvant Gastric Infusional Chemotherapy (MAGIC) trialpublishedin2006byCunninghametal.
6
Manystudiesofpostopera-tive adjuvant chemotherapy 
3
have been carried out in the UnitedStates and Europe, and none of these trials has resulted in a regimenbeingacceptedasastandardofcare.Although gastric cancer is an important cause of morbidity andmortalityintheWesternworld,morbidityanddeathfromthisdiseasearemuchmorecommoninAsia.Forexample,approximately60%of the 900,000 cases occurring worldwide are seen in east Asia.
7
For thisreason, there has been great interest in improving the treatment of stomach cancer in Asia. Asian surgeons have developed carefully plannedsurgicalprotocolsforgastriccancerresection,includingwell-defined systematic nodal dissection (D2 nodal dissection).
8
Thesesurgical procedures have been thought by some to improve the curerate of stomach cancer, but when subjected to phase III trials in theWest, more extensive resection did not result in increased cure ratescompared with less radical surgery.
9
The larger gastric resections (D2gastrectomies) were also associated with more operative morbidity.Although cure rate was not increased with D2 nodal dissection, theprecision of staging was markedly improved
10
when compared withthe less rigorous nodal dissections commonly performed in theUnitedStates.
4,5
Asmightbeexpected,therehasbeenmuchinterestinevaluatingadjuvanttherapyinAsia.Inthisissueof 
 JCO
,Sasakoetal
11
reportthe5-year results of a phase III trial of adjuvant chemotherapy in morethan1,000Japanesepatientswithresectedgastriccancer.Thisclinicaltrial, known as Adjuvant Chemotherapy Trial of TS-1 for GastricCancer (ACTS-GC), evaluated the oral fluoro-pyrimidine S-1 in pa-tientswithresectedstageII/IIIstomachcancer.
12
Thisagenthasbeenshown to potentially improve on the efficacy of oral fluorinated py-rimidines by combining the antineoplastic agent with two biologicmodulatorsaimedatreducingboweltoxicityandincreasingtheanti-tumorefficacyofthefluoro-pyrimidine.The ACTS-GC trial enrolled 1,034 patients with stages II-IIIresected gastric carcinoma. Patients all underwent D2 gastrectomiesandthenwererandomlyallocatedto1yearofS-1therapyortosurgeralone. The results of ACTS-GC reporting 3-year survivals were firstpublished in
New England Journal of Medicine
in November 2007.
13
Eighty percent of S-1 patients were alive at 3 years after gastrectomy versus 70% of surgery-only patients. These survival differences werehighly statistically significant and raised provocative questions notonlyabouttheactivityofadjuvantchemotherapyingastriccancer,butalsoaboutpotentialdifferencesbetweenstomachcancerinAsiacom-paredwiththesametumorhistologyintheWest.To Western oncologists, there are several striking findingsconcerning the ACTS-GC study and its outcomes. First, this phaseIII clinical trial is well designed and well powered. It is a prospec-tively randomized trial of oral therapy with S-1 monotherapy inpatients who underwent D2 gastrectomy versus patients who un-derwent D2 gastrectomy with no adjuvant therapy. There were1,034 patients randomly allocated on ACTS-GC, providing a sta-tistical power to easily detect clinically important differences. Thefact that monotherapy with S-1 was the treatment arm is unusualto oncologists in north America and western Europe, who gener-ally use combination chemotherapy in advanced stomach cancerand assume that an active multidrug regimen would be the mostlikely candidate for success as adjuvant therapy. The most strikingfinding of ACTS-GC is the survival outcome in both the treatmentand control arms. Table 1 compares the 5-year survival outcomesof the US Southwest Oncology Group Coordinated Intergrouptrial(INT0116)ofpostoperativechemoradiationandtheUKperi-operative chemotherapy trial (MAGIC) with the outcomes of ACTS-GC. As can be seen, the ACTS-GC results are strikingly better both for treatment (72% 5-year survival) and for thesurgery-onlycontrols(61%5-yearsurvival)thantheMAGICperi-operative chemotherapy results (36% and 23%, respectively) andINT0116 (43% and 28%, respectively). Western oncologists areparticularly impressed with how well the patients treated withsurgery only do. One could argue that the Japanese patients hadlower stage disease at gastrectomy and therefore had better prog-noses than the patients included in INT0116 and MAGIC. In thatregard,Table2showsthatACTS-GCpatientshadsomewhatmore
 J
OURNAL OF
C
LINICAL
O
NCOLOGY
E D I T O R I A L S
© 2011 by American Society of Clinical Oncology
1
Journal of Clinical Oncology,
Vol 29, 2011
 
 
Copyright 2011 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on October 19, 2011. For personal use only. No other uses without permission.Copyright © 2011 American Society of Clinical Oncology. All rights reserved.
 
favorable T stage (45% T3/4
64% for MAGIC and 68% forINT0116). However, for the strong negative prognostic factor of lymph node metastases,
5
one may see that ACTS-GC patients hadmore frequent nodal metastases (89%) than patients in MAGIC(72%)andINT0116(85%).ItappearsfromexaminingTstageandnodal dissemination that there are no marked prognostic dispari-ties that could explain the excellent outcomes in both treated andcontrol patients in ACTS-GC.The patients on the MAGIC trial were identified preoperatively andmaywellhaveimplicitdifferencesinprognosticfactorscomparedwithpatientsidentifiedaftergastrectomy.PatientsinACTS-GCwereidentifiedaftergastrectomy,aswerethepatientsforINT0116.There-fore it makes sense to carefully investigate the patients in these twostudies to look for reasons that may explain the striking outcomedifferences between the two trials. It is not fruitful to attempt tocompare outcomes differences between ACTS-GC and INT0116by pathologic stage because INT0116 accrued patients in the early to mid 1990s using an American Joint Committee on Cancerstaging schema quite different form the current sixth-editionUnion for International Cancer Control/American Joint Commit-tee on Cancer used in ACTS-GC.Tables 3 and 4 examine 5-year survival rates in INT0116(Table 3) and ACTS-GC (Table 4). It is instructive to look at thesurgery-onlypatientsinthesetwotables.Forexample,inINT0116,T3patients,havea20%survival.InACTS-GC,T3patientsurvivalsvary from a high of 70.8% (stage II) to a low of 42.7% (stage IIIB).Likewise, in patients with advanced nodal metastases (stage IIIB),ACTS-GC survival is 40.1%. In INT0116 the roughly comparablegroup is patients with four or more nodal metastases. The survivalofthisgroup(Table3)isonly17%.TheconclusionthatonedrawsfromthesedataisthattheACTS-GCpatientsdobetter,sometimesmarkedly better, stage for stage than the North American patientsenrolled onto INT0116. The inescapable conclusion is that thepatient populations in these two studies are different and that theoutcomes of adjuvant therapy cannot be generalized from onepopulation to the other.Why do Japanese patients have superior outcomes with re-sectable gastric cancer? As discussed above, it does not seem to berelated to earlier stage at diagnosis. Could it be “better” surgery?There is no question that the consistent use of D2 resection im-proves the precision of staging,
10
but randomized Western studieshave not shown an overall survival benefit.
9
It has been recognizedfor a number of years that there are disparities in the uses andoutcomes of gastric cancer chemotherapy between Europe/NorthAmerica and Asia.
14
There may be differences in the toxicity/efficacyprofileofS-1betweenAsianandNorthAmericanpatients.Tolerable doses may be lower as a result of higher folate levels inNorth American populations and genetic differences
15
in drugmetabolismbetweenWesternandAsianpopulations.Thesediffer-ences make the application of the same regimens of treatment inthe two populations even more complex.Finally,howshouldtheclinicianlookattheACTS-CCresults?First, this is a high-quality, well-designed and executed trial. Sec-ond, S-1 is a highly effective adjuvant therapy that may be admin-istered with modest toxicity in the Japanese study population. S-1should be considered a standard of care for such patients. Third,the S-1 therapy as used in ACTS-GC cannot be considered appli-cable to patients with gastric cancer in the West for the reasonsmentioned in this editorial. There is no doubt that there are differ-ences between adenocarcinomas of the stomach in Japan andNorth America. Finding out precisely what these differences arewill hopefully allow us to enhance the outlook for gastric cancerpatients throughout the world.
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
Table 1.
Five-Year Survival RatesStudy Surgery (%)Chemoradiotherapy/ Chemotherapy (%)INT0116 28 43MAGIC 23 36ACTS-GC 61 72Abbreviations: ACTS-GC, Adjuvant Chemotherapy Trial of TS-1 for GastricCancer; INT0116, Intergroup 0116; MAGIC, Medical Research CouncilAdjuvant Gastric Infusional Chemotherapy.
Table 2.
Patient CharacteristicsCharacteristic INT0116 MAGIC ACTS-GCNo. of patients 554 503 1,034T3/T4, % 68 64 45Node positive, % 85 72 89Abbreviations: ACTS-GC, Adjuvant Chemotherapy Trial of TS-1 for GastricCancer; INT0116, Intergroup 0116; MAGIC, Medical Research CouncilAdjuvant Gastric Infusional Chemotherapy.
Table 3.
INT0116 5-Year Survival Estimates by T Stage and Nodal StatusCharacteristic Chemoradiotherapy (%) Surgery Only (%)Nodal statusN0 60 44N1-3 50 37N
4 30 17StageT1-2 56 38T3 38 20
Table 4.
UICCC/AJCC Sixth Edition: Survival Outcomes in ACTS-GC5-Year SurvivalStage S-1 Surgery Only (%)II (T2N1, T3N0) 83.4 70.8IIIA (T2N2, T3N1) 68.9 56.7IIIB (T3N2) 43.7 40.1IV (T4N1) 45.1 42.7Abbreviations: ACTS-GC, Adjuvant Chemotherapy Trial of TS-1 for GastricCancer; AJCC, American Joint Committee on Cancer; UICC, Union forInternational Cancer Control.
John S. Macdonald
2
© 2011 by American Society of Clinical Oncology
J
OURNAL OF
C
LINICAL
O
NCOLOGY
Downloaded from jco.ascopubs.org on October 19, 2011. For personal use only. No other uses without permission.Copyright © 2011 American Society of Clinical Oncology. All rights reserved.

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->