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. 2000;2000(2):CD002139.
doi: 10.1002/14651858.CD002139.

Chemotherapy for non-small cell lung cancer

Non-small Cell Lung Cancer Collaborative Group  1
Affiliations

Chemotherapy for non-small cell lung cancer

Non-small Cell Lung Cancer Collaborative Group. Cochrane Database Syst Rev. 2000.

Abstract

Background: The role of chemotherapy in the treatment of patients with non-small cell lung cancer was not clear. A systematic review and quantitative meta-analysis was therefore undertaken to evaluate the available evidence from all relevant randomised trials.

Objectives: To evaluate the effect of cytotoxic chemotherapy on survival in patients with non-small cell lung cancer. To investigate whether or not pre-defined patient sub-groups benefit more or less from chemotherapy.

Search strategy: MEDLINE and CANCERLIT searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists and organisations.

Selection criteria: Trials comparing primary treatments of surgery, surgery + radiotherapy, radical radiotherapy or supportive care versus the same primary treatment, plus chemotherapy were eligible for inclusion provided that they randomised non-small cell lung cancer patients using a method which precluded prior knowledge of treatment assignment.

Data collection and analysis: A quantitative meta-analysis using updated information from individual patients from all available randomised trials was carried out. Data from all patients randomised in all eligible trials were sought directly from those responsible. Updated information on survival, and date of last follow up were obtained, as were details of treatment allocated, date of randomisation, age, sex, histological cell type, stage and performance status. To avoid potential bias, information was requested for all randomised patients including those who had been excluded from the investigators' original analyses. All analyses were done on intention to treat on the endpoint of survival. For trials using cisplatin-based regimens, subgroup analyses by age, sex, histological cell type, tumour stage and performance status were also done.

Main results: Data from 52 trials and 9387 patients were included. The results for modern regimens containing cisplatin favoured chemotherapy in all comparisons and reached conventional levels of significance when used with radical radiotherapy and with supportive care. Trials comparing surgery with surgery plus chemotherapy gave a hazard ratio of 0.87 (13% reduction in the risk of death, equivalent to an absolute benefit of 5% at 5 years). Trials comparing radical radiotherapy with radical radiotherapy plus chemotherapy gave a hazard ratio 0.87 (13% reduction in the risk of death equivalent to an absolute benefit of 4% at 2 years), and trials comparing supportive care with supportive care plus chemotherapy gave a hazard ratio of 0.73 (27% reduction in the risk of death equivalent to a 10% improvement in survival at one year). The essential drugs needed to achieve these effects were not identified. No difference in the size of effect was seen in any subgroup of patients. In all but the radical radiotherapy setting, older trials using long term alkylating agents tended to show a detrimental effect of chemotherapy. This effect reached conventional significance in the adjuvant surgical comparison.

Reviewer's conclusions: At the outset of this meta-analysis there was considerable pessimism about the role of chemotherapy in the treatment of non-small cell lung cancer. These results offer hope of progress and suggest that chemotherapy may have a role in treating this disease.

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Conflict of interest statement

There is no known conflict of interest

Figures

1.1
1.1. Analysis
Comparison 1 surgery vs surgery + chemotherapy, Outcome 1 survival.
1.2
1.2. Analysis
Comparison 1 surgery vs surgery + chemotherapy, Outcome 2 subgroup for survival ‐ age.
1.3
1.3. Analysis
Comparison 1 surgery vs surgery + chemotherapy, Outcome 3 subgroup for survival ‐ sex.
1.4
1.4. Analysis
Comparison 1 surgery vs surgery + chemotherapy, Outcome 4 subgroup for survival ‐ performance status.
1.5
1.5. Analysis
Comparison 1 surgery vs surgery + chemotherapy, Outcome 5 subgroup for survival ‐ histology.
1.6
1.6. Analysis
Comparison 1 surgery vs surgery + chemotherapy, Outcome 6 subgroup for survival ‐ stage.
2.1
2.1. Analysis
Comparison 2 surgery + radiotherapy vs surgery + radiotherapy + chemotherapy, Outcome 1 survival.
2.2
2.2. Analysis
Comparison 2 surgery + radiotherapy vs surgery + radiotherapy + chemotherapy, Outcome 2 subgroup for survival ‐ age.
2.3
2.3. Analysis
Comparison 2 surgery + radiotherapy vs surgery + radiotherapy + chemotherapy, Outcome 3 subgroup for survival ‐ sex.
2.4
2.4. Analysis
Comparison 2 surgery + radiotherapy vs surgery + radiotherapy + chemotherapy, Outcome 4 subgroup for survival ‐ performance status.
2.5
2.5. Analysis
Comparison 2 surgery + radiotherapy vs surgery + radiotherapy + chemotherapy, Outcome 5 subgroup for survival ‐ histology.
2.6
2.6. Analysis
Comparison 2 surgery + radiotherapy vs surgery + radiotherapy + chemotherapy, Outcome 6 subgroup for survival ‐ stage.
3.1
3.1. Analysis
Comparison 3 radical radiotherapy vs radical radiotherapy + chemotherapy, Outcome 1 survival.
3.2
3.2. Analysis
Comparison 3 radical radiotherapy vs radical radiotherapy + chemotherapy, Outcome 2 subgroup for survival ‐ age.
3.3
3.3. Analysis
Comparison 3 radical radiotherapy vs radical radiotherapy + chemotherapy, Outcome 3 subgroup for survival ‐ sex.
3.4
3.4. Analysis
Comparison 3 radical radiotherapy vs radical radiotherapy + chemotherapy, Outcome 4 subgroup for survival ‐ performance status.
3.5
3.5. Analysis
Comparison 3 radical radiotherapy vs radical radiotherapy + chemotherapy, Outcome 5 subgroup for survival ‐ histology.
3.6
3.6. Analysis
Comparison 3 radical radiotherapy vs radical radiotherapy + chemotherapy, Outcome 6 subgroup for survival ‐ stage.
4.1
4.1. Analysis
Comparison 4 supportive care vs supportive care + chemotherapy, Outcome 1 survival.
4.2
4.2. Analysis
Comparison 4 supportive care vs supportive care + chemotherapy, Outcome 2 subgroup for survival ‐ age.
4.3
4.3. Analysis
Comparison 4 supportive care vs supportive care + chemotherapy, Outcome 3 subgroup for survival ‐ sex.
4.4
4.4. Analysis
Comparison 4 supportive care vs supportive care + chemotherapy, Outcome 4 subgroup for survival ‐ performance status.
4.5
4.5. Analysis
Comparison 4 supportive care vs supportive care + chemotherapy, Outcome 5 subgroup for survival ‐ histology.
4.6
4.6. Analysis
Comparison 4 supportive care vs supportive care + chemotherapy, Outcome 6 subgroup for survival ‐ stage.
5.1
5.1. Analysis
Comparison 5 RT + C vs Rt, Outcome 1 Survival.
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References

References to studies included in this review

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c13 NCCTG 822451 {unpublished data only}
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c14 Buenos Aires {unpublished data only}
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c15 Brussels {unpublished data only}
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c21 Perugia {unpublished data only}
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c22 CALGB 8433 {unpublished data only}
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c23 EORTC 08842 {unpublished data only}
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c24 SWOG 8300 a {unpublished data only}
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ya(surg) <=54 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgical setting.
yb(surg) 55‐59 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgical setting.
yc(surg) 60‐64 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgical setting.
yd(surg) >=65 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgical setting.
ye(surg) male {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the surgical setting.
yf(surg) female {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the surgical setting.
yg(surg) good PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the surgical setting.
yh(surg) poor PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the surgical setting.
yi(surg) adeno {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the surgical setting.
yj(surg) squamous {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the surgical setting.
yk(surg) other {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the surgical setting.
yl(surg) stage I,II {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the surgical setting.
ym(surg) stage III {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the surgical setting.
yn(s+rt) <=54 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgery + RT setting.
yo(s+rt) 55‐59 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgery + RT setting.
yp(s+rt) 60‐64 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgery + RT setting.
yq(s+rt) >=65 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the surgery + RT setting.
yr(s+rt) male {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the surgery + RT setting.
ys(s+rt) female {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the surgery + RT setting.
yt(s+rt) good PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the surgery + RT setting.
yu(s+rt) poor PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the surgery + RT setting.
yv(s+rt) adeno {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the surgery + RT setting.
yw(s+rt) squamous {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the surgery + RT setting.
yx(s+rt) other {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the surgery + RT setting.
yy(s+rt) stage I,II {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the surgery + RT setting.
yz(s+rt) stage III {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the surgery + RT setting.
za(radrt) <=54 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the radical RT setting.
zb(radrt) 55‐59years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the radical RT setting.
zc(radrt) 60‐64years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the radical RT setting.
zd(radrt) >=65 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the radical RT setting.
ze(radrt) male {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the radical RT setting.
zf(radrt) female {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the radical RT setting.
zg(radrt) good PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the radical RT setting.
zh(radrt) poor PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the radical RT setting.
zi(radrt) adeno {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the radical RT setting.
zj(radrt) squamous {unpublished data only}
    1. Subgroup analysis by histolohy for cisplatin‐based trials in the radical RT setting.
zk(radrt) other {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the radical RT setting.
zl(radrt) stage I,II {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the radical RT setting.
zm(radrt) stage III {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the radical RT setting.
zn(sc) <=54 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the supportive care setting.
zo(sc) 55‐59 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the supportive care setting.
zp(sc) 60‐64 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the supportive care setting.
zq(sc) >=65 years {unpublished data only}
    1. Subgroup analysis by age for cisplatin‐based trials in the supportive care setting.
zr(sc) male {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the supportive care setting.
zs(sc) female {unpublished data only}
    1. Subgroup analysis by sex for cisplatin‐based trials in the supportive care setting.
zt(sc) good PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the supportive care setting.
zu(sc) poor PS {unpublished data only}
    1. Subgroup analysis by performance status for cisplatin‐based trials in the supportive care setting.
zv(sc) adeno {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the supportive care setting.
zw(sc) squamous {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the supportive care setting.
zx(sc) other {unpublished data only}
    1. Subgroup analysis by histology for cisplatin‐based trials in the supportive care setting.
zy(sc)non‐metastatic {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the supportive care setting.
zz(sc)metastatic {unpublished data only}
    1. Subgroup analysis by stage for cisplatin‐based trials in the supportive care setting.

References to studies excluded from this review

Aliev 1985 {published data only}
    1. Aliev BM, Starichkov MS, Mikhina ZP, Petrukhin OD, Bychkov MB. Radiotherapy and combined chemotherapy and radiotherapy of patients with squamous‐cell lung cancer (a randomized study). Voprosy Onkologii 1985;31(10):71‐6. - PubMed
Bergsagel 1972 {published data only}
    1. Bergsagel DE, Jenkin RDT, Pringle JF, White DM, Fetterly JCM, Klaassen DJ. [Lung Cancer: clinical trial of radiotherapy alone vs radiotherapy plus cyclophosphamide]. Cancer 1972;30:621‐627. - PubMed
Blaha 1973 {published data only}
    1. Blaha H, Dierkesmann R, Feuerer W, et al. Adjuvant therapy of non‐small cell bronchial cancer with mopidamol [Adjuvante therapie des nicht‐kleinzellingen bronchialkarzinoms mit mopidamol]. Pneumologie 1973;43:299‐304. - PubMed
Brunner 1971 {published data only}
    1. Brunner KW, Marthaler TH, Muller W. Unfavourable effects of long‐term adjuvant chemotherapy with endoxan in radically operated bronchogenic carcinoma. European Journal of Cancer 1971;7:285‐294. - PubMed
Buyze 1973 {published data only}
    1. Buyze EAC, Nelemans FA. A study of post‐operative cytostatic medication in patients with operable carcinoma of the lung. Arzneim. Forsh (Drug Research) 1973;23(6):860‐862. - PubMed
Byar 1978 {published data only}
    1. Byar D, Kenis Y, Andel JG, et al. Results of a E.O.R.T.C. randomized trial of cyclophosphamide and radiotherapy in inoperable lung cancer: Prognostic factors and treatment results. European Journal of Cancer 1978;14:919‐930. - PubMed
Carr 1972 {published data only}
    1. Carr DT, Childs DS, Lee RE. Radiotherapy plus 5‐FU compared to radiotherapy alone for inoperable and unresectable bronchogenic carcinoma. Cancer 1972;29(2):375‐380. - PubMed
Castberg 1976 {published data only}
    1. Castberg T, Kruse‐Blinkenberg HO. Cancer chemotherapy as a supplement to operation in bronchogenic carcinoma [Cancerkemoterapi som supplement til operation ved bronkogent karcinom]. Ugestr Laeg 1976;138:1449‐1455. - PubMed
Crosbie 1966 {published data only}
    1. Crosbie WA, Kamdar HH, Belcher JR. Controlled trial of vinblastine sulphate in the treatment of cancer of the lung. British Journal of Diseases of the Chest 1966;60:28. - PubMed
Dolton 1970 {published data only}
    1. Dolton EG. Combined surgery and chemotherapy for carcinoma of bronchus. Lancet 1970;Jan 3:40‐41. - PubMed
Durrant 1971 {published data only}
    1. Durrant KR, Ellis F, Black JM, Berry RJ, Ridehalgh FR, Hamilton WS. Comparison of treatment policies in inoperable bronchial carcinoma. Lancet 1971;1(7702):715‐719. - PubMed
Hall 1967 {published data only}
    1. Hall TC, Dederick MM, Chalmers TC, et al. A clinical pharmacologic study of chemotherapy and x‐ray therapy in lung cancer. American Journal of Medicine 1943;2:186‐193. - PubMed
Hansen 1973 {published data only}
    1. Hansen JL. Clinical evaluation of an innoxious antineoplastic agent: Preliminary study of 106 patients treated with or without RSV after pulmonary resection for bronchogenic carcinoma. Cancer Chemotherapy Reports 1973;4(Part 3):261‐264. - PubMed
Helsper 1962 {published data only}
    1. Helsper JT, Sharpe GS. Combination therapy with 5‐fluorouracil and colbalt‐60 for inoperable carcinoma of the lungs. Cancer Chemotherapy Reports 1962;20:103‐105. - PubMed
Holsti 1971 {published data only}
    1. Holsti LR. Adjuvant Chemotherapy. In: Deeley editor(s). Modern Radiotherapy. 222‐240.
Hosley 1962 {published data only}
    1. Hosley HF, Marangoudakis S, Ross CA, Murray WT, Holland JF. Combination radiation‐chemotherapy for bronchogenic carcinoma ‐ pilot study. Cancer Chemotherapy Reports 1962;16:467‐471. - PubMed
Karageorgis 1991 {published data only}
    1. Karageorgis P, Koliarakis N, Paraskevaidis M. NSCLC st. IIIb patients survival after chemotherapy, radiotherapy and combination of the above modalities. Preliminary report. Proceedings of ECCO 1991;6:S180.
Karp {published data only}
    1. Karp DD, Daly BDT, Diehl JT, et al. A pilot study of radiation therapy with or without concomitant cisplatin and etoposide as adjuvant therapy in non‐small cell lung cancer. In: Bernal SD, Hesketh PJ editor(s). Lung Biology in Health and Disease. 58. 1992:325‐334.
Karrer 1978 {published data only}
    1. Karrer K, Prindun N, Denck H. Chemotherapy as an adjuvant to surgery in lung cancer. Cancer Chemotherapy and Pharmacology 1978;1:145‐159. - PubMed
Kaung 1974 {published data only}
    1. Kaung DT, Wolf J, Hyde L, Zelen M. [Preliminary report on the treatment of nonresectable cancer of the lung]. Cancer Chemotherapy Reports 1974;58(Part 1):359‐364. - PubMed
NCCTG852451 {unpublished data only}
    1. NCCTG. Phase III randomized comparison of surgical adjuvant combination chemotherapy with CAP (CTX/ADR/CDDR) vs observation in patients with totally resected stage I, II or III.
Newman 1985 {published data only}
    1. Newman CE, Cox R, Ford CHJ, Johnson JR, Jones DR, Wheaton M. Reduced survival with radiotherapy and razoxane compared with radiotherapy alone for inoperable lung cancer in a randomised double‐blind trial. British Journal of Cancer 1985;51:731‐732. - PMC - PubMed
Okawa 1992 {published data only}
    1. Okawa T, Hashimoto S, Niibe H, et al. Effect of sizofiran (SPG) combined with radiotherapy on non‐small cell lung cancer (NSCLC), results of a prospective randomized controlled study, cooperative study on SPG lung cancer. Proceedings of the American Society of Clinical Oncology 1992;11:288.
Osterlind 1985 {published data only}
    1. Osterlind K. Hansen M. Hansen HH. Dombernowsky P. Controlled trial of RSV, herbs or placebo as adjuvants to complete resection of squamous cell lung cancer. European Journal of Surgical Oncology 1985;11(4):349‐351. - PubMed
Petrovic 1978 {published data only}
    1. Petrovich Z, Ohanian M, Cox J. [Clinical research on the treatment of locally advanced lung cancer. Final report of VALG protocol 13 limited]. Cancer 1978;42:1129‐1134. - PubMed
Pirogov 1976 {published data only}
    1. Pirogov AI, Traktenburg AKh. Results and prospects for combined surgery and antitumour chemotherapy for lung cancer. Cancer Treatment Reports 1976;60(10):1489‐1491. - PubMed
Privitera 1987 {published data only}
    1. Privitera G, Ciottoli GB, Patanè C, et al. Phase II double‐blind randomized study of lonidamine and radiotherapy in epidermoid carcinoma of the lung. Radiotherapy and Oncology 1987;10:285‐90. - PubMed
Scheer 1974 {published data only}
    1. Scheer AC, Wilson RF, Kalisher L. Combined radiotherapy and hydroxyurea in the management of lung cancer. Clinical Radiology 1974;25:415‐418. - PubMed
Selawry 1977 {published data only}
    1. Selawry O, Krant M, Scotto J, et al. Methotrexate compared with placebo in lung cancer. Cancer 1977;40:4‐8. - PubMed
Slack 1970 {published data only}
    1. Slack NH. Bronchogenic carcinoma: nitrogen mustard as a surgical adjuvant and factors influencing survival. University surgical adjuvant lung project. Cancer 25;5:987‐1002. - PubMed
Spatti 1985 {published data only}
    1. Spatti G, Regazzoni M, Koronel R, Zecchini AM, Palo G. Adjuvant treatment with melphalan in ovarian carcinoma with no residual disease following surgery. Tumori 1987;73:157‐162. - PubMed
Spittle 1980 {published data only}
    1. Spittle M, Newton KA, White W, et al. Razoxane as a radiopotentiator for lung cancer.. Second World Conference on Lung Cancer, Copenhagen. 1980; Vol. 220.
Vincent 1975 {published data only}
    1. Vincent RG, Pickren JW, Fergen TB, Takita H. Evaluation of methotrexate in the treatment of bronchogenic carcinoma. Cancer 1975;36:873‐880. - PubMed
Wils 1984 {published data only}
    1. Wils JA, Utama I, Naus A, Verschueren TA. Phase II randomized trial of radiotherapy alone vs the sequential use of chemotherapy and radiotherapy in stage II non‐small cell lung cancer. Phase II trial of chemotherapy alone in stage IV non‐small cell lung cancer. European Journal of Clinical Oncology 1984;20(7):911‐914. - PubMed
Wingfield 1970 {published data only}
    1. Wingfield HV. Combined surgery and chemotherapy for carcinoma of the bronchus. Lancet 1970;1(7644):470‐471. - PubMed
Wolf 1991 {published data only}
    1. Wolf K, Havemann K, Hans K, et al. Radiotherapy versus chemotherapy followed by radiotherapy in inoperable limited stage non‐small cell lung cancer (NSCLC). Lung Cancer 1991;7s:A611.

References to ongoing studies

Ancona {unpublished data only}
    1. Gasparini S, Zuccatosta L, Massei V. Lonidamine and chemotherapy plus lonidamine vs the best supportive care in the treatment of advanced non‐small cell lung cancer.
ANITA {unpublished data only}
    1. Adjuvant Navelbine International Trialist Association (ANITA). Phase III randomized trial of adjuvant chemotherapy following curative resection for non‐small cell lung cancer.
BLT {published and unpublished data}
    1. MRC CTU. Phase III randomized study of cisplatin‐based chemotherapy in patients with non‐small cell lung cancer.
CAN NCIC BR10 {published and unpublished data}
    1. NCIC Clinical Trials Group. Phase III randomized study of adjuvant chemotherapy with VNB/CDDP vs no adjuvant chemotherapy for completely resected non‐small cell lung cancer.
CLB 9633 {published and unpublished data}
    1. Cancer and Leukemia Group B. Phase III randomized study of carboplatin / paclitaxel vs no adjuvant chemotherapy after resection of stage IB non‐small cell lung cancer.
CNR ALPI {published and unpublished data}
    1. Consiglio Nazinale Ricerche, Italy / EORTC. Phase III randomized study of adjuvant MVP vs no adjuvant chemotherapy (with or without adjuvant radiotherapy) for radically resected stage I/II/IIIa non‐small cell lung cancer.
CRC‐TU‐LU3001 {published and unpublished data}
    1. Cullen MH, Billingham LJ, Woodroffe CM, et al. Mitomycin, Ifosphamide, and Cisplatin in unresectable non‐small cell lung cancer: effect on survival and quality of live. Journal of Clinical Oncology 1999;17:3188‐3194. - PubMed
CRC‐TU‐LU3002 {published data only}
    1. Cullen MH, Billingham LJ, Woodroffe CM, et al. Mitomycin, Ifosphamide, and Cisplatin in unresectable non‐small cell lung cancer: effect on survival and quality of live. Journal of Clinical Oncology 1999;17:3188‐3194. - PubMed
EORTC 08922 {published and unpublished data}
    1. EORTC. Phase III randomised trial of adjuvant MICE (Mesna/IFF/CBDCA/VP‐16) or EP (VP‐16/CDDP) vs no adjuvant therapy in patients with completely resected stage I/II/IIIa non‐small cell lung cancer containing the activated oncogene K‐ras.
FRE IALT {published and unpublished data}
    1. Institut Gustave Roussy. Phase III randomized study of adjuvant chemotherapy following curative resection for non‐small cell lung cancer.
GAP {published data only}
    1. Clerici M, Barni S, Cantaluppi G, et al. Adjuvant chemotherapy in non‐small cell lung cancer: a randomised trial. European Journal of Cancer 1991;27(Suppl 2):S173.
Helsing {published and unpublished data}
    1. Helsing M, Bergman B, Thaning L, Hero U. Quality of life and survival in patients with advanced non‐small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. European Journal of Cancer 1998;34(7):1036‐1044. - PubMed
Ichinose 1991 {published data only}
    1. Ichinose Y, Hara N, Ohta M, Motohiro A, Kuda T, Aso H. Postoperative adjuvant chemotherapy in non‐small cell lung cancer: Prognostic value of DNA ploidy and postrecurrent survival. Journal of Surgical Oncology 1991;46:15‐20. - PubMed
Kim 1993 {published data only}
    1. Kim NK, Yang SH, Im YH, et al. A phase III randomized comparison of neoadjuvant chemotherapy with cisplatin, etoposide and vinblastine plus radiation vs. radiation alone in stage III non‐small cell lung cancer. Proceeding of the American Society for Clinical Oncology 1993;12:330.
NCCTG‐822451 {published data only}
    1. North Central Cancer Treatment Group. Phase III randomized comparison of surgical adjuvant combination chemotherapy with CAP vs observation in patients with totally resected stage I, II or III non‐small cell lung cancer.
RICUM {published data only}
    1. Ayoub J, Duranceau A, Lorange G, et al. Effectiveness of adjuvant chemotherapy in operable non‐small cell lung cancer. In: Salmon SE editor(s). Adjuvant therapy of cancer. New York: and Stratton, 1987:157‐164.
RTOG 8808 {unpublished data only}
    1. Sause WT, Scott C, Taylor S, et al. Radiation Therapy Oncology Group (RTOG) 88‐08 and Eastern Cooperative Oncology Group (ECOG) 4588: Preliminary results of a phase III trial in regionally advanced unresectable non‐small cell lung cancer. Journal of the National Cancer Institute 1995;87:198‐205. - PubMed
TELCVIS 1999 {published data only}
    1. The Elderly Lung Cancer Vinorelbine Italian Study. Effects of Vinorelbine on quality of live and survival of elderly patients with advanced non‐small celllung cancer. Journal of the National Cancer Institute 1999;91:66‐72. - PubMed
Thongprasert 1999 {published and unpublished data}
    1. Thongprasert S, Sanguanmitra P, Juthapan W, Clinch J. Relationship between quality of live and clinical outcomes in advanced non‐small cell lung cancer: best supportive care (BSC) versus BSC plus chemotherapy. Lung Cancer 1999;24:17‐24. - PubMed

Additional references

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Holmes 1991
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Kaplan 1958
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Parkin 1993
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Rankin 1986
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Rudd 1991
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Slevin 1990
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Squires 1993
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References to other published versions of this review

NSCLCCG 1995
    1. Non‐small Cell Lung Cancer Collaborative Group. Chemotherapy in non‐small cell lung cancer: a meta‐analysis using updated data on individual patients from 52 randomised clinical trials. British Medical Journal 1995;311:899‐909. - PMC - PubMed

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