第十届世界肺癌会议（英文

1、Highlights from the Tenth World Conference on lung cancerTracey L, EvansThe oncologist 2004;9:232-238The conference was held in Vancouver, Canadappt made by leeyong1Adjuvant Chemotherapy in non-small-cell lung cancerInternational adjuvant lung cancer trial (IALT) from 1995-2000 1867 pts from 148 cen

2、ters in 33 countries pts undergone complete resection of NSCLC chemotherapy arm vs observation arm 2Chemotherapy used in IALT Adjuvant chemotherapy regimen % of the ptsCisplatin 300-400mg/m2 over 3-4 cycles withetoposidevinovelbinevinblastinvindesine56271163International adjuvant lung cancer trial (

3、IALT)Thoracic radiotherapy was optionalChemotherapy was administered with 60 days35% pts in each arm underwent pneuonectomy and the remainder had lobectomy39% of pts in each arm had stage ,and 46% had scc4International adjuvant lung cancer trial (IALT)74% pts received at least 240mg/m2 of DDP;8% pts

4、 assigned to the chemotherapy arm received no chemotherapyThe lethal treatment-associated toxicity rate in the chemotherapy arm was 0.8%5Outcome data from IALTChemotherapy armControlP valueMedian survival50.8 months44.4 months0.035-year survival rate44.5%40.4%Median disease-free survival40.2 months

5、30.5 months0.0035-year disease-free survival rate39.4%34.3%Lethal toxicity rate0.8%0The overall survival hazard ratio for chemotherapy was 0.86 95% CI=0.76-0.98Absolute 5-year survival benefit of 4.1%Absolute 5-year disease-free survival benefit of 5.1%, and hazard ratio was o.83%6The Big Lung Trial

6、 (BLT)Large, multicenter study in the UKAll pts with NSCLC received primary therapy as determined by stage (surgery, radiation, or BSC)Pts randomized to receive either three 3-weekly cycles of DDP-based chemotherapyDDP/VDS, MMC/IFO/DDP, MMC/VLB/DDP NVB/DDP, or no chemotherapy7The Big Lung Trial (BLT

7、)In the subgroup of pts receiving BSC as their primary modality, there was a statistically significant survival benefit for chemotherapyThere was no benefit to chemotherapy in terms of overall survival or progression-free survivalThe overall survival hazard ratio for chemotherapy was 1.02 (95%CI=0.7

8、7-1.35)8Adjuvant lung project ITALY(ALPI)1209 pts with completely resected NSCLC were randomly assigned to received either MMC, VDS, and DDP every 3 weeks for 3 cycles or no chemotherapy69% of the pts assigned to the chemotherapy arm received all 3 cycles.Stage disease was present in 28%-29% of pts,

9、 while the remainder were stage or stage 9Adjuvant lung project ITALY(ALPI)43% of the pts in each group were schedule to have postoperative radiation therapy, and fewer in the chemotherapy group were able to complete it (65% vs 82%)There was no significant difference in overall survival (OR=o.96, 95

10、% CI=0.81-1.13, p=0.589) between the two groups or progression-free survival (OR=0.89, 95% CI=0.76-1.03, p=0.128)10commentaryOnly 50% of the early-stage pts of NSCLC underwent surgical resection are alive 5 years laterA meta-analysis of postoperative radiotherapy actually showed a survival decrement

11、Individual randomized trials of adjuvant chemotherapy have been suboptimal due to the use of older, less effective chemotherapy regimens, poor chemotherapy compliance, and insufficient power to detect small benefits11commentaryNSCLCCG performed a meta-analysis examining the benefit of adjuvant chemo

12、therapy17 trials were identified that compared surgery and chemotherapy with surgery aloneThere was a nonsignificant trend toward worse survival in the pts who received chemotherapy due primarily to the studies including alkylating agents, which consistently led to worse survival than with surgery a

13、lone (OR=1.15,p=o.oo5)12commentaryAnalysis limited to the 8 trials using DDP-based chemotherapy showed a trend toward better survival in the chemotherapy group that was nearly significant (OR=o.87,p=0.08)Absolute survival benefit of 5% at 5 years13commentaryAt 1867 pts, the IALT study remains the la

14、rgest adjuvant trial presented to dateThe IALT study was large enough to determine that the very small benefits were statistically significantWhy was the IALT study positive while the BLT and ALPI were not?14commentarySize and hazard ratio of overall survival in recent large adjuvant studiesHazard r

15、atio for chemotherapy95% CInNSCLCCG1,394o.870.74-1.02ALPI1,2090.960.81-1.13IALT1,8690.860.76-0.98BLT3811.020.77-1.3515commentarySome point to the better compliance with treatment in the IALT study74% of the pts chemotherapy pts in the IALT study received at least 240mg/m2 of DDPIn the BLT and ALPI,

16、64% and 69% of pts, respectively, received all 3 chemotherapy cycles. There may be a real benefit for adjuvant chemotherapy in NSCLC, but the magnitude of this benefit is likely quite small16commentaryPer IALT data, 25 pts must be treated to convert one person who otherwise would have died from the

17、disease into a 5-year survivorOne of every 125 pts treated experience lethal toxicity with the IALT regimens, and those pts die within 6 months of surgery, whereas pts who die of relapse usually live 1-2 year beyond surgical resection.17commentaryLung cancer pts are not the same as breast cancer or

18、colon cancer ptsLung cancer pts frequently have significant additional comorbidities that can complicate chemotherapy administration, and the chemotherapeutic regimens are usually more difficultThere is at least some indication that DDP may be a better drug than carboplatin in NSCLC 18commentaryShou

19、ld adjuvant chemotherapy for resected NSCLC become the standard of care?It depends on whom you you askOnly the most fit pts should be offered adjuvant chemotherapyGiven the current state of the evidence, pts performance must factor strongly in the decision to administer19Second-Line Chemotherapy In

20、Advanced NSCLC Spanish Lung Cancer Group (SLCG) phase trial in which 259 pts who had prior chemotherapy for advanced NSCLC were randomized to receive either the traditional method of second-line docetaxel administration or a weekly regimen of docetaxelPrimary end point was 1 year survival, and secon

21、dary end points included OS, TTP, RR, toxicity profile, and QOL 20Second-Line Chemotherapy In Advanced NSCLCComparison of every-3-weeks versus weekly docetaxelDocetaxel 75mg/m2every 3 weeksDocetaxel 36mg/m2weeklyP valueResponse rate8%5%NSTTP2.7 months2.9 monthsNS1-year survival rate29.2%21.8%NSMedia

22、n survival7.1 months5.4 monthso.o421Second-Line Chemotherapy In Advanced NSCLCThe rates of grade 3/4/5 toxicities were similar in both armMore neutropenia, leukopenia, alopecia, and hepatic toxicity in the every-3-weeks armMore diarrhea, mucositis, and dyspnea in the weekly armThere was no differenc

23、e in quality-of-life measurements between the two armsComparison of every-3-weeks versus weekly docetaxel22Second-Line Chemotherapy In Advanced NSCLCRegimens in pemetrexed versus docetaxel study Pemetrexed: 500mg/m2 iv every 3 weeks folic acid: 350-1,000g daily and vitB12 1mg 1/9ws Dexamethasone: 4

24、mg bid d -1,0,+1OrDocetaxel: 75mg/m2 iv every 3 weeks Dexamethasone: 8mg twice a day on days -1,0,+1 Pemetrexed versus Docetaxel23Second-Line Chemotherapy In Advanced NSCLCEfficacy of pemetrexed versus docetaxelMedian survivalHazard ratio (95% CI)Pemetrexed (n=283)Docetaxel (n=288)1-year survival ra

25、teTime to progressionHazard ratio (95% CI)Response rate8.3 months7.9 monthso.99(0.8-1.2)29.7%29.7%2.9 months2.9 months0.97(0.8-1.2)9.1%8.8%24Second-Line Chemotherapy In Advanced NSCLCGrade toxicity of pts of pemetrexed versus docexelPemetrxedn=285DocetaxelN=276P valueNeutropeniaNeutropenia feverThro

26、mbcytopeniaNeuropathy (grade 2-4)Hospitalization due to Fever and neutropenia5%2%2%3%2%40%13%1%8%16%0.00010.0001o.1160.0140.000125commentaryWeekly regimens appear better tolerated, and assumption has been that they are likely similar in efficacy to the every-3-weeks regimensSpanish study demonstrate

27、d that there was a trend toward a higher 1-year survival rate in the every-3-weeks arm, and it is hard to ignore the statistically different overall survival rate favoring the every-3-weeks docetaxel arm, with a 1.7 month longer median survival time and a p value of 0.04 The every-3-weeks schedule o

28、f choice, according to the study26commentaryWeekly regimens may be reasonable for pts in whom the toxicity pro the every-3-weeks schedule is not desirableIt now appear that pemetrexed has efficacy similar to that of docetaxel in the second-line treatment of advanced NSCLCThe toxicity pro pemetrexed

29、is much better than that of the traditional method of docetaxel administration.Vitamin supplementation is critical to minimizing toxicity from pemetrexed27Second-Line Chemotherapy In Advanced NSCLCIrresa was approved by the FDA in the May 2003 for the treatment of advanced NSCLC in the setting of pr

30、ogressive disease following platinum-based chemotherapy and docetaxelIn Japan, Interstitial pneumonitis has been reported in 2% of the pts, and 0.7% of the pts experienced fatal pneumonitisOf the pts outside Japan, o.33% developed pneumonitis and 0.1% developed fatal pneumonitisEAP in the US, pneumo

31、nitis occurred in 0.36% of pts and fatal pneumonitis occurred in 0.06% Gefitinib (Irresa)Safety and Tolerability28Second-Line Chemotherapy In Advanced NSCLCGefitinib (Irresa)Pts with BAC and never smokePts with either non-smoker or BAC histology Pts who were smoker with non-BAC histologyRRMST55%14 months26%9 months6%4 months Pts with nonadenocacinoma0Memorial Sloan-Kettering Cancer Center29Second-Line Chemotherapy In Advanced NSCLCNone of the molecular markers (EGFR ERK p-Akt PTEN Her-2 P27 P53 k-Ras) were significant predictors of responseBetter performance status