role of adjuvant chemotherapy in the treatment of non-small-cell lung cancer

1365Am J Health-Syst Pharm—Vol 62 Jul 1, 2005

THERAPY UPDATE Adjuvant chemotherapy

THERAPY UPDATE

Role of adjuvant chemotherapy in the treatmentof non-small-cell lung cancer

LINDSEY WILHELM AND JILL M. KOLESAR

LINDSEY WILHELM is Pharm.D. degree candidate; and JILL M.KOLESAR, PHARM.D., BCPS, FCCP, is Associate Professor Pharmacy,Pharmacy Practice Division, School of Pharmacy, University of Wis-consin, Madison.

Address correspondence to Dr. Kolesar at the School of Pharmacy,University of Wisconsin, 777 Highland Avenue, Madison, WI 53705

([email protected]).

Copyright © 2005, American Society of Health-System Pharma-cists, Inc. All rights reserved. 1079-2082/05/0701-1365$06.00.

DOI 10.2146/ajhp040529

Purpose. The role of adjuvant chemothera-py in the treatment of non-small-cell lungcancer (NSCLC) is described.Summary. The intrinsic resistance ofNSCLC tumors to chemotherapy necessi-tates the use of complete surgical resectionof the malignant growth as the primarymodality of treatment; however, onlyabout one third of patients are appropriatecandidates for surgical resection. While sev-eral cytotoxic combinations have beenused to treat metastatic NSCLC, no singleregimen is considered the standard of care.Given the poor prognosis of patients withNSCLC, adjuvant chemotherapy has beeninvestigated as a treatment option but hasnot demonstrated a consistent survivalbenefit. Several recent studies have soughtto clarify the role of adjuvant chemothera-py in the treatment of NSCLC: the Big LungTrial, the International Adjuvant Lung Can-cer Trial (IALT), the Adjuvant Lung ProjectItaly trial, and a study of the combination of

uracil and tegafur, which is not yet availablein the United States. The IALT, the largesttrial among the four and sufficiently pow-ered to detect a survival benefit, revealed amodest increase in survival. Complicatingthe issue is the financial cost of adjuvanttherapy, especially in light of the small sur-vival benefit gained.Conclusion. The use of adjuvant chemo-therapy in patients with NSCLC can lead toa modest increase in survival. Platinum-based regimens are the most studied andshould be considered the regimens ofchoice. However, further studies are need-ed to determine the optimal regimen andpatient population that would derive themost benefit from this treatment.

Index terms: Antineoplastic agents; Car-cinoma; Combined therapy; Costs; Eco-nomics; Resistance; Surgery; Tegafur;UracilAm J Health-Syst Pharm. 2005; 62:1365-9

L ung cancer is the leading causeof cancer deaths in both menand women in the United States.

In 2005, an estimated 168,140 pa-tients died of lung cancer—morethan the combined number of deathsfrom colon, prostate, breast, andpancreas cancers.1 Despite major re-search efforts, survival prospects re-main dismally small, and 14% of allpatients with lung cancer are expect-ed to live five years after diagnosis.2

Recent data have demonstrated thata survival benefit may exist with theuse of adjuvant chemotherapy, sug-gesting that adjuvant treatment maybe the new standard of care for non-small-cell lung cancer (NSCLC).

For purposes of treatment, lungcancers are normally classified intotwo main categories: small-cell lungcancer (SCLC), which accounts forapproximately 20% of lung cancers,and NSCLC, which includes the re-maining lung cancers. SCLC is char-acterized by a high growth rate andearly development of widespreadmetastases; thus, it is consideredthe more chemosensitive of the lungcancers, and chemotherapy is usedto treat all stages. NSCLC includes

squamous-cell carcinoma, adeno-carcinoma, and large-cell carcinoma.It develops more slowly and, assuch, is less responsive to cytotoxictreatment.

The intrinsic resistance of NSCLCtumors to chemotherapy necessitatesthe use of complete surgical resection

of the malignant growths as the pri-mary modality of treatment. Stagingis based on the TNM system, where Trefers to tumor size, N denotesspread of the cancer to local nodes,and M describes the extent of me-tastasis. Generally speaking, patientswith stage I or II disease have the best

1366 Am J Health-Syst Pharm—Vol 62 Jul 1, 2005


chance of cure with surgical resec-tion, depending on tumor size, loca-tion, and the extent of disease.1

Treatment of stage IIIa disease iscontroversial, as surgery, radiation,and chemotherapy may all be used.While patients with stage IV diseaseare not usually surgical candidates,they may still undergo platinum-based chemotherapy, with one-yearsurvival rates of approximately40%.2

Only about one third of patientsare appropriate candidates for surgi-cal resection when diagnosed, andonly half of patients who undergosurgery will live another five years.Treatments directed at eradicatingmicrometastatic disease, includingpostoperative radiation therapy andadjuvant chemotherapy, have beenevaluated as a means to improve thissurvival rate. Although previoustrials failed to show a survival benefitusing either method, recent studiesand meta-analyses have shownmodest but significant improvementwith adjuvant chemotherapy, andmany practitioners now consideradjuvant chemotherapy standardtreatment for NSCLC.

Chemotherapy regimens formetastatic NSCLC

While several cytotoxic combina-tions have been used to treat meta-static NSCLC (Table 1), no singleregimen is considered the standardof care. Compared with best sup-portive care, platinum-based chemo-therapy prolongs survival, improvessymptom control, and providessuperior quality of life for patientswith metastatic disease.2,3 In patientswith advanced, incurable NSCLC,cisplatin-based combinations haveresulted in improved survival rates,and platinum combined with any ofthe newer agents (i.e., vinorelbine,paclitaxel, docetaxel, gemcitabine, oririnotecan) has proven superior toolder platinum-based combina-tions.2 In patients whose diseaseprogresses either during or after

first-line therapy, single-agent doce-taxel and pemetrexed are preferredsecond-line therapies. In fact, peme-trexed has demonstrated comparableefficacy to docetaxel and has a morefavorable adverse-effect profile.2 Fi-nally, oral gefitinib is approved as athird-line treatment for NSCLC thathas progressed either during or aftertreatment with platinum-based regi-mens or docetaxel, though no ran-domized study has demonstratedsuperior survival rates. Gefitinibshould not be used in combinationwith chemotherapy, as the combina-tion offers no better efficacy thanchemotherapy alone. Active regi-mens for metastatic NSCLC are be-ing investigated in the adjuvant set-ting as well.

Adjuvant chemotherapy forNSCLC

Given the poor prognosis ofpatients with NSCLC, adjuvant che-motherapy has been investigated asa treatment option but has notdemonstrated a consistent survivalbenefit, provoking questions aboutthe utility of the treatments withtheir associated toxicities. In 1995,the Non-Small Cell Lung CancerCollaborative Group conducted ameta-analysis of 17 trials comparingsurgery and chemotherapy with sur-gery alone.4 Trials were eligible forinclusion if patient recruitment wasstarted after January 1, 1965, andcompleted by December 31, 1991.The regimens studied includedalkylating agents (mostly cyclophos-

Table 1.Overview of Common Classes of Drugs Used To Treat Non-Small-CellLung Cancer

aEGFR = epidermal growth factor receptor.

Platinums(alkylatingagents)

Taxanes

Vinca alkaloids

Antimetabolites

Topoisomerase Iinhibitors

Podophyllotoxins

EGFR tyrosinekinase inhibitora

Antifolate

Formation of DNA cross-links and bulky adductsinhibits DNA synthesis

Inhibition of tubulindepolymerization hindersDNA, RNA, and proteinsynthesis

Inhibition of microtubuleformation prohibits celldivision

Inhibition of DNApolymerase, obstructsDNA synthesis

Binding to topoisomerase Iresults in single-strandedDNA breaks

Inhibition of topoisomeraseII causes DNA strandbreaks

Inhibition of tyrosinekinases associated withtransmembrane EGFRimpedes cell proliferationand survival

Inhibits folate-dependentpathways necessary forreplication

Cisplatin,carboplatin

Paclitaxel,docetaxel

Vinorelbine,vinblastine

Gemcitabine

Irinotecan,topotecan

Etoposide,teniposide

Gefitinib

Pemetrexed

Nausea andvomiting,nephrotoxicity,neuropathy,tinnitus(cisplatin),myelosuppression(carboplatin)

Myelosuppression

Myelosuppression

Myelosuppression

Myelosuppression,diarrhea(irinotecan)

Myelosuppression

Skin manifestations

Neutropenia, kidneyfailure

Dose-LimitingToxicitiesClass

RepresentativeDrug(s)

Mechanismof Action



phamide and nitrosurea), cisplatin-based combination therapy, and var-ious combinations of uracil–tegafur(UFT). A hazard ratio (HR) of 1.15(95% confidence interval [CI] 1.04–1.27, p = 0.005) was reported for pa-tients treated postoperatively withalkylating agents, suggesting an abso-lute detriment of chemotherapy of4% at two years and 5% at five years.However, subgroup analysis revealedthat patients treated with modern regi-mens containing cisplatin showedmore favorable results than patientstreated with other chemotherapyregimens. When used in combina-tion with radical radiotherapy andsupportive care, patients receivingcisplatin-based regimens did signifi-cantly better than patients on otherregimens. This was evidenced by atrend toward a survival advantage(HR, 0.87; 95% CI, 0.74–1.02;p = 0.08) in trials that used platinum-based therapies.

Several recent studies have soughtto clarify the role of adjuvant chemo-therapy in the treatment of NSCLC.The Big Lung Trial (BLT) was a large,multicenter trial conducted in theUnited Kingdom that sought to de-termine the value of cisplatin-basedchemotherapy for patients of all stag-es of NSCLC.5 A total of 725 patientswere randomized to receive support-ive care alone (n = 361) or supportivecare plus cisplatin-based chemother-apy (n = 364). Patients received pri-mary therapy (surgery or radiation)according to their disease stage andwere randomized to one of two treat-ment groups: cisplatin-based chemo-therapy (cisplatin plus vindesine,mitomycin plus ifosfamide plus cis-platin, mitomycin plus vinblastineplus cisplatin, or vinorelbine pluscisplatin) or best supportive care. Atthe time of analysis, 697 patients(98%) had died, and 31% of patientsdeveloped grade 3 or 4 toxicity. Themost severe treatment-related ad-verse effect was myelosuppression.Other adverse effects included neu-tropenic fever, nausea and vomiting,

and death (n = 6). The median sur-vival was 8.0 months for patients re-ceiving chemotherapy and 5.7months for those receiving best sup-portive care. The overall HR was0.77 (95% CI, 0.66–0.89; p =0.0006), suggesting that adjuvantcisplatin-based chemotherapy pro-longed survival in all stages, ofNSCLC.

The International Adjuvant LungCancer Trial (IALT) studied 1867 pa-tients in 33 countries from 1995 to2000.6 Study participants were ran-domized to receive either adjuvantchemotherapy (n = 932) with one offour regimens (cisplatin plus etopo-side, cisplatin plus vinorelbine, cis-platin plus vinblastine, and cisplatinplus vindesine) or observation (n =935) within 60 days after completesurgical resection of their NSCLC. Ifthe participating center opted forpostoperative radiotherapy, it wasgiven after the completion of chemo-therapy in the chemotherapy group.Disease stages were well representedby patients: stage I, 36.5%; stage II,24.2%; and stage III, 39.3%.

Of patients in the treatmentgroup, 74% received at least 240 mg/m2 of cisplatin; 7.8% received nochemotherapy, mainly becauseof participant refusal. Seven pa-tients (0.8%) died as a result ofchemotherapy-induced toxicity: fivedeaths were attributed to marrowaplasia, one was due to kidney fail-ure, and the other death resultedfrom hyponatremia. Median overallsurvival was 44.4 months in the con-trol group and 50.8 months in thechemotherapy group. The five-yearsurvival rate was 40.4% in the con-trol group and 44.5% in the chemo-therapy group. This yielded a five-year survival benefit of 4.1%, withan overall survival HR for chemo-therapy of 0.86 (95% CI, 0.76–0.98; p< 0.03). To date, this study is thelargest trial published on the subjectand was originally powered to detecta 5% five-year survival benefit with3300 patients. Slow accrual, however,

forced the study to conclude early.Results were consistent acrosschemotherapy treatment regimens,with investigators concluding thatcisplatin-based adjuvant chemother-apy improved survival among pa-tients who had undergone resectionfor NSCLC.

The Adjuvant Lung Project Italy(ALPI) trial analyzed 1088 of 1209enrolled patients with previously re-sected NSCLC, 28–29% of whomhad stage III disease, with the re-maining patients having stage I or IIdisease.7 Participants were random-ized to receive either three cycles ofchemotherapy, which consisted ofmitomycin, vindesine, and 100 mg/m2 of cisplatin (n = 606), or no che-motherapy (n = 603). Patients wererandomized, but stratified based oninvestigational center, disease stage,and intention to administer radio-therapy. Postoperative radiotherapywas administered to 43% of patients.No significant difference in overallsurvival or progression-free survivalrates between groups was detectedafter a median follow-up of 64.5months (HR, 0.96 for patients receiv-ing chemotherapy; 95% CI, 0.81–1.13; p = 0.589 and HR, 0.89 for pa-tients in the control group; 95% CI,0.76–1.03; p = 0.128).

Recently, Kato et al.8 conducted arandomized trial of NSCLC adjuvanttherapy with 979 patients with stage Iadenocarcinoma of the lungs. Theonly chemotherapy regimen studiedwas UFT, which is not yet available inthe United States. Tegafur is a pro-drug metabolized to fluorouracil bythe cytochrome P-450 isoenzymesystem, and uracil maximizes serumconcentrations of the active moietyby preventing fluorouracil catabo-lism. In this study, patients withcompletely resected stage I adenocar-cinoma of the lung were randomizedto receive either UFT for two years (n= 491) or no treatment with observa-tion (n = 488). The median durationof follow-up was 73 months. A totalof 482 patients agreed to receive che-

1368 Am J Health-Syst Pharm—Vol 62 Jul 1, 2005


motherapy, and 10 of them devel-oped grade 3 toxicities, including an-orexia, nausea and vomiting, andtransient hepatic enzyme elevations.None had grade 4 toxicities. The reg-imen achieved a five-year overall sur-vival rate of 88% (95% CI, 0.85–0.90), compared with 85% (95% CI,0.82–0.89) in the control group, al-though only patients with Stage IT2N0 disease demonstrated a bene-fit. Investigators concluded that pa-tients who received the combinationchemotherapy survived longer thanthose who received only best sup-portive care (p = 0.04). Also, the fre-quency of death from second prima-ry tumors (SPTs) was slightly lowerin the treatment group, which is con-sistent with an additional benefit ofUFT in the prevention of SPTs. Thestudy design did not provide for con-comitant use of chemotherapy andradiotherapy, a treatment that wasconsistent with poorer outcomes inpast trials.6

Recently, a meta-analysis of cur-rent data concluded that a survivalbenefit exists for adjuvant chemo-therapy in NSCLC. Hotta et al.9 iden-tified trials that were reported afterthe publication of the 1995 meta-analysis. Inclusion criteria werestringent; the analysis limited thestudies to those that randomized pa-tients to surgery followed by chemo-therapy or surgery alone. To mini-mize the influence of radiotherapyon survival benefit, trials primarilydesigned to randomize patients to ei-ther surgery followed by chemother-apy and radiation or surgery plus ra-diation were excluded. Investigatorscalculated HRs using data from 11trials with a total of 5716 patients toevaluate the survival advantage ofadjuvant chemotherapy. An HR of0.872 (95% CI, 0.805–0.944; p =0.001) suggested a statistically signif-icant survival advantage of adjuvantchemotherapy over surgery aloneamong the trials reviewed.

Further examination revealed thatboth cisplatin-based treatments and

therapy with UTF produce a consid-erable survival benefit (HR, 0.891;95% CI, 0.815–0.975; p = 0.012, andHR, 0.799; 95% CI, 0.668–0.957; p =0.015, respectively). Toxicities weregenerally mild and acceptable, withonly 16 treatment-related deaths(0.6%) of 2559 treated patients. Themost common serious adverse effectswere grade 4 neutropenia (14%),grade 4 thrombocytopenia (2%),grade 3 or greater nephrotoxicity(2%), and grade 3 or greater nauseaand vomiting (10%).

The analysis was limited by thefact that its conclusions were basedon abstracted data as opposed to in-dividual patient data, as the latterwould have been more clinically ac-curate. However, its results are animportant contribution, given its uti-lization of current treatment practic-es and data from three times morepatients than the 1995 analysis.

Study limitationsIALT, as the largest trial on the

subject to date, was best powered toshow a survival benefit. A 4.1%greater five-year overall survival rate(p < 0.03) and a 5.1% greater five-year disease-free survival rate (p <0.003) were associated with the use ofadjuvant chemotherapy.6 BLT andALPI, by comparison, enrolled 725and 1209 patients, respectively.5,7 Pa-tients enrolled in these two studieswere able to complete only three cy-cles of treatment. The compliancerate was 64% in the BLT and 69% inthe ALPI. IALT and the UFT trialdemonstrated moderately bettercompliance rates: 74% of IALT’s pa-tients received at least 240 mg/m2 ofcisplatin, and UFT complianceranged from 80% at 6 months (95%CI, 0.77–0.84) to 61% at 24 months(95% CI, 0.57–0.66). However, theoptimal dose of cisplatin per cyclewas controversial in IALT; investiga-tors set a broad dosing range (80–120mg/m2 for three or four cycles),which allowed some flexibility whenassessing compliance. Compliance in

the UFT trial was confined to patientreports of self-administration, amethodology that has inherent accu-racy limitations. Finally, IALT’sstudy population included a largerpercentage of patients with stage IIIdisease (39%) than either the ALPIor BLT (28–29% and 25–27%, re-spectively), which could explain thediscrepant results. Patients withmore advanced NSCLC may receivegreater benefit from adjuvant che-motherapy than those with stage I orII disease, so IALT’s more advancedpopulation could have contributedto its capacity to show a smalltreatment-related survival benefit.

Overall, the majority of clinicaltrials and two meta-analyses havedemonstrated consistent, small im-provements in survival for cisplatin-based adjuvant therapy of NSCLC,with acceptable levels of toxicity.

There is no consensus opinion re-garding the most appropriate che-motherapeutic regimen for the adju-vant treatment of NSCLC. However,a recent Canadian trial studied adju-vant vinorelbine and cisplatin incompletely resected stage 1b and IINSCLC, with endpoints that includ-ed overall survival, recurrence-freesurvival (RFS), quality of life, andtoxicity.10 Between 1994 and 2001,482 patients were randomized to re-ceive four cycles of vinorelbine (25mg/m2 weekly for 16 weeks) plus cis-platin (50 mg/m2 for days 1 and 8every 4 weeks) or follow-up alone.Patients were stratified by nodal sta-tus (N0 versus N1) and ras mutationstatus (present, absent, or un-known). The investigators foundthat median overall survival was con-siderably longer in patients receivingchemotherapy (94 months versus 73months) (HR, 0.69; p = 0.011). Pa-tients in the control group did notreach RFS, while patients treatedwith chemotherapy had an RFS of46.7 months (p = 0.0003). The five-year survival rate was 69% in patientstreated with chemotherapy and 54%for patients in the control group.



Toxicities included grade 4 febrileneutropenia (7%), fatigue (77%),nausea (76%), anorexia (53%), vom-iting (46%), sensory neuropathy(45%), and constipation (44%). Todate, this is the only randomizedclinical trial to demonstrate that ad-juvant treatment with a third-generation platinum-based doubletprolongs overall survival and RFS inearly-stage NSCLC. Preliminary datafrom a recent trial of adjuvant che-motherapy with paclitaxel and car-boplatin showed significantly im-proved survival rates for a uniformpopulation (stage Ib NSCLC) receiv-ing a carboplatin-based regimen.11

Clinical implicationsWhile most experts agree that ad-

juvant chemotherapy for resectedNSCLC provides a modest survivalbenefit, they disagree about whetherthe practice should become the stan-dard of care. The consensus opinionis that patients with an Eastern Co-operative Oncology Group score of0–1 should be offered chemotherapy,but with a careful explanation of ex-pected survival benefits and associat-ed toxicities of chemotherapy. Inother words, individual patient char-acteristics have a major influence onthe decision to undertake a treat-ment in which benefits are quitesmall, but potential toxicities may besevere. The IALT investigators re-ported that 1 of every 125 patientswho received chemotherapy diedfrom treatment-associated toxicitieswithin six months of surgery. How-ever, patients who have a terminalrelapse after surgical resection andchoose best supportive care for treat-ment will often live another one totwo years. Interpreted another way,one life was preserved for five yearswhen 25 patients were treated duringIALT; presumably, the other 24 pa-tients endured chemotherapy and itsassociated adverse effects withoutany survival advantage.6

The financial cost of adjuvanttreatment, with its small survival

benefit, is another consideration inthe dilemma about whether to im-plement adjuvant chemotherapy asthe standard of care for NSCLC. In2003, the National Institutes ofHealth estimated that the overall costof cancer was $189.5 billion, of which$64.2 billion was spent on directmedical costs (the total of all expen-ditures), $16.3 billion for indirectmorbidity costs (the cost of lost pro-ductivity due to illness), and $109billion for indirect mortality costs(the cost of lost productivity due topremature death).1 Further compli-cating the cost dilemma are the esti-mated 16% of Americans under age65 years who do not have health in-surance coverage, one third of whomrely on Medicare coverage alone.

The body of evidence points to-ward platinum-based chemotherapyas the standard of care for adjuvanttreatment. The National Cancer In-stitute of Canada Clinical TrialsGroup study provides strong evi-dence to support the use of the studyregimen of four cycles of vinorelbineat 25 mg/m2 weekly for 16 weeks withcisplatin 50 mg/m2 on days 1 and8 every 4 weeks.10 However, the sameconcerns about severe treatment-related adverse effects apply; thestudy attributes the death of threepatients to treatment-related toxicity.

Further study is needed to conclu-sively determine which stage of dis-ease will most benefit from chemo-therapy and which specific regimensare most effective. Standard therapyfor NSCLC has been based on earlierstudies and does not yet achieve sig-nificant outcomes. Thus, participa-tion in clinical trials represents state-of-the-art treatment for NSCLC andshould be encouraged while investi-gators continue to search for newand better treatments that result insubstantial survival benefits.

ConclusionThe use of adjuvant chemothera-

py in patients with NSCLC can leadto a modest increase in survival.

Platinum-based regimens are themost studied and should be consid-ered the regimens of choice. Howev-er, further studies are needed to de-termine the optimal regimen andpatient population that would derivethe most benefit from this treatment.

References1. Jemal A, Murray T, Ward E et al. Cancer

statistics, 2005. CA Cancer J Clin. 2005;55:10-30.

2. National Comprehensive Cancer Net-work. Non-small cell lung cancer. Clini-cal practice guidelines in oncology v2.2005. www.nccn.org/professionals/physician_gls/PDF/nscl.pdf (accessed2005 Mar 29).

3. Lynch TJ Jr. Lung cancer highlights. On-cologist. 2000; 5:274-9.

4. Non-Small Cell Lung Cancer Collabora-tive Group. Chemotherapy in non-smallcell lung cancer: a meta-analysis usingupdated data on individual patients from52 randomised clinical trials. BMJ. 1995;311:899-909.

5. Spiro SG, Rudd RM, Souhami RL et al.Chemotherapy vs supportive care in ad-vanced nonsmall cell lung cancer: im-proved survival without detriment toquality of life. Thorax. 2004; 59:828-36.

6. Arriagada R, Bergman B, Dunant A et al.Cisplatin-based adjuvant chemotherapyin patients with completely resected non-small-cell lung cancer. N Engl J Med.2004; 350:351-60.

7. Scagliotti GV, Fossati R, Torri V et al.Randomized study of adjuvant chemo-therapy for completely resected stage I, II,or IIIA non-small cell lung cancer. J NatlCancer Inst. 2003; 95:1453-61.

8. Kato H, Ichinose Y, Ohta M et al. A ran-domized trial of adjuvant chemotherapywith uracil-tegafur for adenocarcinomaof the lung. N Engl J Med. 2004; 350:1713-21.

9. Hotta K, Matsuo K, Ueoka H et al. Role ofadjuvant chemotherapy in patients withresected non-small-cell lung cancer: re-appraisal with a meta-analysis of ran-domized controlled trials. J Clin Oncol.2004; 22:3860-7.

10. Winton TL, Livingston R, Johnson D etal., for the National Cancer Institute ofCanada Clinical Trials Group. A prospec-tive randomised trial of adjuvant vinorel-bine (VIN) and cisplatin (CIS) in com-pletely resected stage 1B and II nonsmall cell lung cancer (NSCLC) inter-group JBR. J Clin Oncol. 2004; 22:A7018.Abstract.

11. Strauss GM, Herndon J, Maddaus MA etal. Randomized clinical trial of adjuvantchemotherapy with paclitaxel and carbo-platin following resection in stage IBnon-small cell lung cancer (NSCLC): re-port of cancer and leukemia group B(CALGB) protocol 9633. J Clin Oncol.2004; 22:A7019. Abstract.

role of adjuvant chemotherapy in the treatment of non-small-cell lung cancer

Documents