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Semin Respir Crit Care Med 2008; 29(3): 302-317
DOI: 10.1055/s-2008-1076750
© Thieme Medical Publishers

Complications of Lung Cancer Treatment

Stephen G. Spiro1 , Jonathan Douse1 , Catherine Read1 , Sam Janes2
  • 1Department of Respiratory Medicine, University College London Hospitals, London, United Kingdom
  • 2Department of Medicine, Centre for Respiratory Research, University College London, London, United Kingdom
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Publication History

Publication Date:
02 June 2008 (online)

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ABSTRACT

In most cases lung cancer is incurable, but treatment is prolonging life for many and sustaining quality of life. Inevitably, disease-related symptoms develop with disease progression, and it can be difficult to differentiate these from treatment-induced complications. This is particularly true for pulmonary complications because tumor progression occurs most frequently in the lungs, and separating the effects of the disease from those induced by treatment (chemotherapy, radiotherapy) is often very difficult. This chapter identifies the main complications around surgical resection of lung cancer, highlighting the importance of expert postoperative care. For palliative treatments such as radiotherapy and chemotherapy, complications are related to the planned intensity of proposed therapy, the performance status of the patients, and patient age. Treatment of the elderly sufferer, now representing almost 50% of new cases, is poorly researched, but therapy-related complications are commoner in those aged over 70 years by ~20% when compared with their younger counterparts. Even during palliative care great attention has to be taken to minimize side effects of commonly used medications.

KEYWORDS

Complications - chemotherapy - radiation therapy - surgery - palliative care

REFERENCES

  • 1 Ries L AG, Eisner M P, Kosary C L et al.. SEER Cancer Statistics review 1975–2000. http://seer.cancer.gov/csr/1975_2000
    Google Scholar
  • 2 Gridelli C, Perrone F, Monfardini S. Lung cancer in the elderly.  Eur J Cancer. 1997;  33 2313-2314
    CrossrefPubMedGoogle Scholar
  • 3 Spiro S G, Gower N H, Evans M T et al.. Recruitment of patients with lung cancer into a randomised clinical trial: experience at two centres.  Thorax. 2000;  55 463-465
    CrossrefPubMedGoogle Scholar
  • 4 Jatoi A, Hillman S, Stella P et al.. Should elderly non-small cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group.  J Clin Oncol. 2005;  23 9113-9119
    CrossrefPubMedGoogle Scholar
  • 5 Martin-Ucar A E, Waller D A, Atkins J L et al.. The beneficial effects of specialist thoracic surgery on the resection rate for non-small cell lung cancer.  Lung Cancer. 2004;  46 227-232
    CrossrefPubMedGoogle Scholar
  • 6 Arozullah A M, Daley J, Henderson W G, Khuri S F. Multifactorial risk index for predicting postoperative respiratory failure in men after major non-cardiac surgery.  Ann Surg. 2000;  232 242-250
    CrossrefPubMedGoogle Scholar
  • 7 Arozullah A M, Khuri S F, Henderson W G, Daley J. Development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery.  Ann Intern Med. 2001;  135 847-857
    CrossrefPubMedGoogle Scholar
  • 8 Rostad H, Strand T-E, Naalsuund A, Talleraas O, Norstein J. Lung cancer surgery: the first 60 days: a population-based study.  Eur J Cardiothorac Surg. 2006;  29 824-828
    CrossrefPubMedGoogle Scholar
  • 9 Bernard A, Deschamps C, Allen M S et al.. Pneumonectomy for malignant disease: factors affecting early morbidity and mortality.  J Thorac Cardiovasc Surg. 2001;  121 1076-1082
    CrossrefPubMedGoogle Scholar
  • 10 Harpole D H, Liptay M J, DeCamp M M et al.. Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias.  Ann Thorac Surg. 1996;  61 977-982
    CrossrefPubMedGoogle Scholar
  • 11 Ferguson M K, Reeder L B, Mick R. Optimizing selection of patients for major lung resection.  J Thorac Cardiovasc Surg. 1995;  109 275-283
    CrossrefPubMedGoogle Scholar
  • 12 Yildizeli B, Fadel E, Mussot S et al.. Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer.  Eur J Cardiothorac Surg. 2007;  31 95-102
    CrossrefPubMedGoogle Scholar
  • 13 Van Schil P, Van Meerbeck J, Kramer G et al.. Morbidity and mortality in the surgery arm of EORTC 08941 Trial.  Eur Resp J. 2005;  26 192-197
    PubMedGoogle Scholar
  • 14 Gilligan D, Nicholson M, Smith I et al.. Preoperative chemotherapy in patients with respectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review.  Lancet. 2007;  369 1929-1937
    CrossrefPubMedGoogle Scholar
  • 15 De Pauw R, van Meerbeeck J P. Neoadjuvant chemotherapy in the treatment of non small cell lung cancer.  Curr Opin Oncol. 2007;  19 92-97
    PubMedGoogle Scholar
  • 16 Leo F, Solli P, Veronesi G, Radice D et al.. Does chemotherapy increase the risk of respiratory complications after pneumonectomy?.  J Thorac Cardiovasc Surg. 2006;  132 519-523
    PubMedGoogle Scholar
  • 17 Venuta F, Anile M, Diso D, Ibrahim M. Operative complications and early mortality after induction therapy for lung cancer.  Eur J Cardiothorac Surg. 2007;  31 714-717
    CrossrefPubMedGoogle Scholar
  • 18 Mansour Z, Kochetkova E A, Ducrocq X et al.. Induction chemotherapy does not increase the operative risk of pneumonectomy!.  Eur J Cardiothorac Surg. 2007;  31 181-185
    CrossrefPubMedGoogle Scholar
  • 19 Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group.  BMJ. 1995;  311 899-909
    Google Scholar
  • 20 Arriagada R, Bergman B, Dumant A, Le Chevalier T, Pignon J, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non small-cell lung cancer.  N Engl J Med. 2004;  350 351-360
    CrossrefPubMedGoogle Scholar
  • 21 Waller D, Peake M D, Stephens R J. Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial.  Eur J Cardiothorac Surg. 2004;  26 173-182
    CrossrefPubMedGoogle Scholar
  • 22 Belda J, Calvacanti M, Ferrer M et al.. Bronchial colonisation and postoperative respiratory infections in patients undergoing lung cancer surgery.  Chest. 2005;  Sp; 128(3) 1571-1579
    CrossrefPubMedGoogle Scholar
  • 23 Cabello H, Torres A, Celis R et al.. Bacterial colonisation of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study.  Eur Respir J. 1997;  10 1137-1144
    CrossrefPubMedGoogle Scholar
  • 24 Ioanas M, Angrill J, Baldo X et al.. Bronchial bacterial colonisation in patients with respectable lung cancer.  Eur Respir J. 2002;  19 326-332
    CrossrefPubMedGoogle Scholar
  • 25 Belda J, Cavalcanti M, Ferrer M et al.. Bronchial colonisation and postoperative respiratory infections in patients undergoing lung cancer surgery.  Chest. 2005;  128 1571-1579
    CrossrefPubMedGoogle Scholar
  • 26 Pauwels R A, Buist A S, Calverley P M et al.. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease(GOLD) Workshop summary.  Am J Respir Crit Care Med. 2001;  163 1256-1276
    CrossrefPubMedGoogle Scholar
  • 27 Soler N, Ewig S, Torres A et al.. Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease.  Eur Respir J. 1999;  14 1015-1022
    CrossrefPubMedGoogle Scholar
  • 28 Licker M J, Widikker I, Robert J et al.. Operative mortality and respiratory complications after lung resection for cancer: impact of chronic obstructive pulmonary disease and time trends.  Ann Thorac Surg. 2006;  81 1830-1838
    CrossrefPubMedGoogle Scholar
  • 29 Volpino P, Cangemi R, Fiori E et al.. Risk of mortality from cardiovascular and respiratory causes in patients with chronic obstructive pulmonary disease submitted to follow-up after lung resection for non-small cell lung cancer.  J Cardiovasc Surg (Torino). 2007;  48 375-383
    PubMedGoogle Scholar
  • 30 Sonobe M, Nakagawa M, Ichinose M et al.. Analysis of risk factors in bronchopleural fistula after pulmonary resection for primary lung cancer.  Eur J Cardiothorac Surg. 2000;  18 519-523
    CrossrefPubMedGoogle Scholar
  • 31 Deschamps C, Bernard A, Nichols F C et al.. Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence.  Ann Thorac Surg. 2001;  72 243-247
    CrossrefPubMedGoogle Scholar
  • 32 Myrdal G, Valtysdottir M, Lambe M, Stahle E. Quality of life following lung cancer surgery.  Thorax. 2003;  58 194-197
    CrossrefPubMedGoogle Scholar
  • 33 Win T, Sharples L, Wells F C, Ritchie A J, Munday H, Laroche C M. Effect of lung cancer surgery on quality of life.  Thorax. 2005;  60 234-238
    CrossrefPubMedGoogle Scholar
  • 34 Sarna L, Padilla G, Holmes C, Tashkin D, Brecht M L, Evangelista L. Quality of life of long-term survivors of non-small cell ling cancer.  J Clin Oncol. 2002;  20 2920-2929
    CrossrefPubMedGoogle Scholar
  • 35 Tyldesley S, Boyd C, Schulze K, Walker H, Mackillop W J. Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach.  Int J Radiat Oncol Biol Phys. 2001;  49 973-985
    CrossrefPubMedGoogle Scholar
  • 36 Kong F M, Ten Haken R, Eisbruch A, Lawrence T S. Non-small cell lung cancer therapy-related pulmonary toxicity: an update on radiation pneumonitis and fibrosis.  Semin Oncol. 2005;  32(2, Suppl 3) S42-S54
    PubMedGoogle Scholar
  • 37 Lopez Rodriguez M, Cerezo Padellano L. Toxicity associated to radiotherapy treatment in lung cancer patients.  Clin Transl Oncol. 2007;  9 506-512
    PubMedGoogle Scholar
  • 38 Giangreco A, Groot K R, Janes S M. Lung cancer and lung stem cells: strange bedfellows?.  Am J Respir Crit Care Med. 2007;  175 547-553 , Epub 2006 Dec 7
    CrossrefPubMedGoogle Scholar
  • 39 Van der Kogel A J, Ang K K. Complications related to radiotherapy. In: Peckham M, Pinedo H, Veronesi U Oxford Textbook of Oncology. Oxford; Oxford University Press 1995: 2295-2306
    Google Scholar
  • 40 Movsas B, Raffin T A, Epstein A H et al.. Pulmonary radiation injury.  Chest. 1997;  111 1061-1076
    PubMedGoogle Scholar
  • 41 Davis S D, Yankelevitz D F, Henschke C I. Radiation effects on the lung: clinical features, pathology, and imaging findings.  AJR Am J Roentgenol. 1992;  159 1157-1164
    CrossrefPubMedGoogle Scholar
  • 42 Van Houtte P, Mornex P. Radiotherapy of non-small-cell and small-cell and SCLC. In: Spiro SG Carcinoma of the Lung. European Respiratory Monograph, Vol 1. Leeds, UK; Maney Publishers 1995: 241-268
    Google Scholar
  • 43 Bate D, Guttemann R J. Changes in the lung and pleura following 2-million volt therapy for carcinoma of the breast.  Radiology. 1957;  69 372-382
    PubMedGoogle Scholar
  • 44 Ross W M. Radiotherapeutic and radiological aspects of radiation fibrosis of the lungs.  Thorax. 1956;  11 241-246
    PubMedGoogle Scholar
  • 45 Libshitz H I, Southard M E. Complications of radiation therapy: the thorax.  Semin Roentgenol. 1974;  9 41-49
    PubMedGoogle Scholar
  • 46 Roswit B, White D C. Severe radiation injuries of the lung.  AJR Am J Roentgenol. 1977;  129 127-136
    PubMedGoogle Scholar
  • 47 Bachman A L, Macken K. Pleural effusions following supervoltage radiation for breast carcinoma.  Radiology. 1959;  72 699-709
    PubMedGoogle Scholar
  • 48 Libshitz H I, Shuman L S. Radiation-induced pulmonary change: CT findings.  J Comput Assist Tomogr. 1984;  8 15-19
    PubMedGoogle Scholar
  • 49 Glazer H S, Lee J KT, Levitt R G et al.. Radiation fibrosis: differentiation from recurrent tumor by MR imaging.  Radiology. 1985;  156 721-726
    PubMedGoogle Scholar
  • 50 Kataoka M, Kawamura M, Itho H et al.. Ga-67 citrate scintigraphy for the early detection of radiation pneumonitis.  Clin Nucl Med. 1992;  17 27-31
    PubMedGoogle Scholar
  • 51 Watchie J, Coleman C N, Raffin T A et al.. Minimal long-term cardiopulmonary dysfunction following treatment for Hodgkin's disease.  Int J Radiat Oncol Biol Phys. 1987;  13 517-524
    PubMedGoogle Scholar
  • 52 Lokich J J, Brass H, Eberly F E et al.. The pulmonary effect of mantle irradiation in patients with Hodgkin's disease.  Radiology. 1973;  108 397-402
    PubMedGoogle Scholar
  • 53 Uitterhoeve A L, Koolen M G, van Os R M et al.. Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with non-small cell lung cancer.  Radiat Oncol. 2007;  2 27
    CrossrefPubMedGoogle Scholar
  • 54 Onishi H, Kuriyama K, Yamaguchi M et al.. Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: a good local response but no good survival due to radiation pneumonitis.  Lung Cancer. 2003;  40 79-84
    CrossrefPubMedGoogle Scholar
  • 55 Kouroussis C, Mavroudis D, Kakolyris S et al.. High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in patients with non-small cell lung cancer: results of a dose-finding study.  Lung Cancer. 2004;  44 363-368
    CrossrefPubMedGoogle Scholar
  • 56 Nagata Y, Matsuo Y, Takayama K et al.. Current status of stereotactic body radiotherapy for lung cancer.  Int J Clin Oncol. 2007;  12 3-7 , Epub 2007 Feb 25
    CrossrefPubMedGoogle Scholar
  • 57 Li X, Zhang P, Mah D, Gewanter R, Kutcher G. Novel lung IMRT planning algorithms with nonuniform dose delivery strategy to account for respiratory motion.  Med Phys. 2006;  33 3390-3398
    CrossrefPubMedGoogle Scholar
  • 58 Liu R, Buatti J M, Howes T L, Dill J, Modrick J M, Meeks S L. Optimal number of beams for stereotactic body radiotherapy of lung and liver lesions.  Int J Radiat Oncol Biol Phys. 2006;  66 906-912 , Epub 2006 Aug 14
    PubMedGoogle Scholar
  • 59 Rancati T, Ceresoli G L, Gagliardi G, Schipani S, Cattaneo G M. Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study.  Radiother Oncol. 2003;  67 275-283
    CrossrefPubMedGoogle Scholar
  • 60 Jenkins P, D'Amico K, Benstead K, Elyan S. Radiation pneumonitis following treatment of non-small-cell lung cancer with continuous hyperfractionated accelerated radiotherapy(CHART).  Int J Radiat Oncol Biol Phyl. 2003;  56 360-366
    PubMedGoogle Scholar
  • 61 Yorke E D, Jackson A, Rosenzweig K E et al.. Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy.  Int J Radiat Oncol Biol Phys. 2002;  54 329-339
    PubMedGoogle Scholar
  • 62 Fu X L, Huang H, Bentel G et al.. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V(30) and transforming growth factor beta.  Int J Radiat Oncol Biol Phys. 2001;  50 899-908
    CrossrefPubMedGoogle Scholar
  • 63 Gross N J. Pulmonary effects of radiation therapy.  Ann Intern Med. 1977;  86 81-92
    PubMedGoogle Scholar
  • 64 Wang J Y, Chen K Y, Wang J et al.. Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis.  Int J Radiat Oncol Biol Phys. 2002;  54 735-741
    CrossrefPubMedGoogle Scholar
  • 65 Rubin O, Casarett G W. Clinical Radiation Pathology. Philadelphia; WB Saunders 1968: 423-470
    Google Scholar
  • 66 Bennett D E, Million R R, Ackerman L V. Bilateral radiation pneumonitis: a complication of the radiotherapy of bronchogenic carcinoma.  Cancer. 1969;  23 1001-1018
    PubMedGoogle Scholar
  • 67 Coggle J E, Lambert B E, Moores S R. Radiation effects in the lung.  Environ Health Perspect. 1986;  70 261-291
    PubMedGoogle Scholar
  • 68 Crestani B, Valeyre D, Roden S et al.. Bronchiolitis obliterans organising pneumonia syndrome primed by radiation therapy to the breast.  Am J Respir Crit Care Med. 1998;  158 1929-1935
    CrossrefPubMedGoogle Scholar
  • 69 Martin C, Romero S, Sanchez-Paya J et al.. Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation.  Eur Respir J. 1999;  13 727-732
    CrossrefPubMedGoogle Scholar
  • 70 Braakhuis B J, Tabor M P, Kummer J A et al.. A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications.  Cancer Res. 2003;  63 1727-1730
    PubMedGoogle Scholar
  • 71 Johnson B E, Cortazar P, Chute J P. Second lung cancers in patients successfully treated for lung cancer.  Semin Oncol. 1997;  24 492-499
    PubMedGoogle Scholar
  • 72 Van Bodegom P C, Wagenaar S S, Corrin B et al.. Second primary lung cancer: Importance of long term follow up.  Thorax. 1989;  44 788-793
    PubMedGoogle Scholar
  • 73 Sugimura H, Watanabe S, Tsugane S et al.. Case-control study on histologically determined multiple primary lung cancer.  J Natl Cancer Inst. 1987;  79 435-441
    PubMedGoogle Scholar
  • 74 Mathisen D J, Jensik R J, Faber L P, Kittle C F. Survival following resection for second and third primary lung cancers.  J Thorac Cardiovasc Surg. 1984;  88 502-510
    CrossrefPubMedGoogle Scholar
  • 75 Deschamps C, Pairolero P C, Trastek V F, Payne W S. Multiple primary lung cancers: results of surgical treatment.  Ann Thorac Cardiovasc Surg. 1990;  99 769-777 discussion 777-778
    CrossrefPubMedGoogle Scholar
  • 76 Tucker M A, Coleman C N, Cox R S et al.. Risk of second cancers after treatment for Hodgkin's disease.  N Engl J Med. 1988;  318 76-81
    PubMedGoogle Scholar
  • 77 Kirova Y M, Feuilhade F, Calitchi E et al.. Radiation-induced sarcoma after breast cancer: apropos of 8 cases and review of the literature.  Cancer Radiother. 1998;  2 381-386
    PubMedGoogle Scholar
  • 78 Van der Kogel A J. Radiation response and tolerance of normal tissues. In: Steel GG Basic Clinical Radiobiology. London, UK; Arnold 1997: 30-39
    Google Scholar
  • 79 Stewart J R, Fajardo L F. Radiation-induced heart disease: an update.  Prog Cardiovasc Dis. 1984;  27 173-194
    PubMedGoogle Scholar
  • 80 Schultz-Hector S. Heart. In: Scherer E, Streffer C, Trott KR Radiopathology of Organs and Tissues. Berlin; Springer-Verlag 1991: 347-368
    Google Scholar
  • 81 Brosius F C, Waller B F, Roberts W L. Analysis of 16 young (aged 15–33 years) necropsy patients who received over 3500 rads to the heart.  Am J Med. 1981;  70 519-530
    CrossrefPubMedGoogle Scholar
  • 82 PORT Meta-analysis Trialists Group . Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials.  Lancet. 1998;  352 257-263
    CrossrefPubMedGoogle Scholar
  • 83 Dautzenberg B, Arriagada R, Chammard A B et al.. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma.  Cancer. 1999;  86 265-273
    CrossrefPubMedGoogle Scholar
  • 84 Van der Kogel A J, Ang K K. Complications related to radiotherapy. In: Peckham M, Pinedo H, Veronesi U Oxford Textbook of Oncology. Oxford; Oxford University Press 1995: 2295-2306
    Google Scholar
  • 85 Macbeth F R, Wheldon T E, Girling D J et al.. Radiation myelopathy: estimates of risk in 1048 patients in three randomised trials of palliative radiotherapy for non-small cell lung cancer. The Medical Research Council Lung Cancer Working Party.  Clin Oncol (R Coll Radiol). 1996;  8 176-181
    CrossrefPubMedGoogle Scholar
  • 86 Cullen M H, Billingham L J, Woodroffe C M et al.. Mitomycin, ifosfamide and cisplatin in unresectable non-small cell lung cancer: Effects on survival and quality of life.  J Clin Oncol. 1999;  17 3188-3194
    PubMedGoogle Scholar
  • 87 Spiro S G, Rudd R M, Souhami R L et al.. Chemotherapy versus best supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life.  Thorax. 2004;  59 828-836
    CrossrefPubMedGoogle Scholar
  • 88 Schiller J H, Harrington D, Belani C P et al.. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer.  N Engl J Med. 2002;  346 92-98
    CrossrefPubMedGoogle Scholar
  • 89 Rudd R M, Gower N H, Spiro S G et al.. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small cell lung cancer: a phase III randomised study of the London Lung Cancer Group.  J Clin Oncol. 2005;  23 142-153
    CrossrefPubMedGoogle Scholar
  • 90 Dimitroulis J, Stathopoulos G P. Evolution of non small cell lung cancer chemotherapy [review].  Oncol Rep. 2005;  13 923-930
    PubMedGoogle Scholar
  • 91 Ruckdeschel J C, Finkelstein D M, Mason B A et al.. Chemotherapy for metastatic non-small-cell bronchogenic carcinoma: EST 2575, generation V–a randomized comparison of four cisplatin-containing regimens.  J Clin Oncol. 1985;  3 72-79
    PubMedGoogle Scholar
  • 92 Gridelli C, Ardizzoni A, Le Chevalier T et al.. Treatment of advanced non-small cell lung cancer patients with ECOG performance status 2: results of an European Expert Panel.  Ann Oncol. 2004;  15 419-426
    CrossrefPubMedGoogle Scholar
  • 93 Georgoulias V, Papadakis E, Alexopoulos A et al.. Platinum-based and non-platinum based chemotherapy in advanced non-small cell lung cancer: a randomised multicentre trial.  Lancet. 2001;  357 1478-1484
    CrossrefPubMedGoogle Scholar
  • 94 Kosmidis P, Mylonakis N, Nicolaides C et al.. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small cell lung cancer: a phase III randomised trial.  J Clin Oncol. 2002;  20 3578-3585
    CrossrefPubMedGoogle Scholar
  • 95 Alberola V, Camps C, Provencio M et al.. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small cell lung cancer: a Spanish Lung Cancer Group phase III randomised trial.  J Clin Oncol. 2003;  21 3207-3213
    CrossrefPubMedGoogle Scholar
  • 96 Gridelli C, Gallo C, Shepherd F A et al.. Gemcitabine plus vinorelbine compared to cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada-Clinical Trials Group.  J Clin Oncol. 2003;  21 3025-3034
    CrossrefPubMedGoogle Scholar
  • 97 Gridelli C, Langer C, Maione P, Rossi A, Schild S E. Lung cancer in the elderly.  J Clin Oncol. 2007;  25 1898-1907
    CrossrefPubMedGoogle Scholar
  • 98 Elderly Lung Cancer Vinorelbine Italian Study Group . Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small cell lung cancer.  J Natl Cancer Inst. 1999;  91 66-72
    CrossrefPubMedGoogle Scholar
  • 99 Cullen M, Steven N, Billingham L et al.. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas.  N Engl J Med. 2005;  353 988-998
    CrossrefPubMedGoogle Scholar
  • 100 Morittu L, Earl H M, Souhami R L et al.. Patients at risk of chemotherapy-associated toxicity in small cell lung cancer.  Br J Cancer. 1989;  59 801-804
    PubMedGoogle Scholar
  • 101 Carnes P, White D A. Drugs and the lungs. In: Albert RK, Spiro SG, Jett JR Clinical Respiratory Medicine. 3rd ed. Philadelphia; Elsevier 2008
    Google Scholar
  • 102 Ramanathan R K, Reddy V V, Holbert J M, Belani C P. Pulmonary infiltrates following administration of paclitaxel.  Chest. 1996;  110 289-292
    CrossrefPubMedGoogle Scholar
  • 103 Bonomi P, Faber L P, Warren W et al.. Postoperative bronchopulmonary complications in stage III lung cancer patients treated with preoperative paclitaxel-containing chemotherapy and concurrent radiation.  Semin Oncol. 1997;  24(4 Suppl 12) S12-123-S12-129
    PubMedGoogle Scholar
  • 104 Dimopoulou I, Efstathiou E, Samakovli A et al.. A prospective study on lung toxicity in patients treated with gemcitabine and carboplatin: clinical, radiological and functional assessment.  Ann Oncol. 2004;  15 1250-1255
    CrossrefPubMedGoogle Scholar
  • 105 Carron P L, Cousin L, Caps T et al.. Gemcitabine-associated diffuse alveolar hemorrhage.  Intensive Care Med. 2001;  27 1554
    CrossrefPubMedGoogle Scholar
  • 106 Vansteenkiste J F, Bomans P, Verbeken E K et al.. Fatal pulmonary veno-occlusive disease possibly related to gemcitabine.  Lung Cancer. 2001;  31 83-85
    CrossrefPubMedGoogle Scholar
  • 107 Forsythe B, Faulkner K. Clinical experience with gefitinib (Iressa,ZD1839): an overview of safety and tolerability.  Lung Cancer. 2003;  41(Suppl 2) S70-S71
    PubMedGoogle Scholar
  • 108 Gurjal A, An T, Valdivieso M, Kalemkerian G P. Etoposide-induced pulmonary toxicity.  Lung Cancer. 1999;  26 109-112
    CrossrefPubMedGoogle Scholar
  • 109 Inoue A, Saijo Y, Maemondo M et al.. Severe acute interstitial pneumonia and gefitinib.  Lancet. 2003;  361 137-139
    CrossrefPubMedGoogle Scholar
  • 110 Shepherd F A, Rodrigues Pereira J, Ciuleanu T et al.. Erlotinib in previously treated non–small-cell lung cancer.  N Engl J Med. 2005;  353 123-132
    CrossrefPubMedGoogle Scholar
  • 111 Tassinari D, Sartori S, Gianni L et al.. Is acute dyspnoea a rare side effect of vinorelbine?.  Ann Oncol. 1997;  8 503-504
    PubMedGoogle Scholar
  • 112 Verweij J, van Zanten T, Souren T et al.. Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis.  Cancer. 1987;  60 756-761
    CrossrefPubMedGoogle Scholar
  • 113 Rivera M P, Kris M G, Gralla R J, White D A. Syndrome of acute dyspnea related to combined mitomycin plus vinca alkaloid chemotherapy.  Am J Clin Oncol. 1995;  18 245-250
    PubMedGoogle Scholar
  • 114 Raderer M, Kornek G, Hejna M et al.. Acute pulmonary toxicity associated with high-dose vinorelbine and mitomycin C.  Ann Oncol. 1996;  7 973-975
    PubMedGoogle Scholar
  • 115 Chang A YC, Kuebler J P, Pandya K J et al.. Pulmonary toxicity induced by mitomycin C is highly responsive to glucocorticoids.  Cancer. 1986;  57 2285-2290
    CrossrefPubMedGoogle Scholar
  • 116 Torra R, Poch E, Torras A et al.. Pulmonary hemorrhage as a clinical manifestation of hemolytic-uremic syndrome associated with mitomycin C therapy.  Chemotherapy. 1993;  39 453-456
    PubMedGoogle Scholar
  • 117 Castro M, Veeder M H, Mailliard J A, Tazelaar H D, Jett J R. A prospective study of pulmonary function in patients receiving mitomycin.  Chest. 1996;  109 939-944
    PubMedGoogle Scholar
  • 118 Soares M, Darmon M, Salluh J IF et al.. Prognosis of lung cancer patients with life – threatening complications.  Chest. 2007;  131 840-846
    CrossrefPubMedGoogle Scholar
  • 119 http://www.who.int/cancer/palliative/en/ WHO guidelines: Cancer pain relief. 2nd ed. Geneva; World Health Organisation 1996
    Google Scholar
  • 120 Donnelly S, Walsh D. The symptoms of advanced cancer.  Semin Oncol. 1995;  22(2, Suppl 3) 67-72
    PubMedGoogle Scholar
  • 121 McCaffrey M, Beebe A. Pain: Clinical Manual for Nursing Practice. St. Louis; CV Mosby 1989
    Google Scholar
  • 122 Corner J. Innovative approaches in symptom management.  Eur J Cancer Care (Engl). 1995;  4 145-146
    CrossrefPubMedGoogle Scholar
  • 123 Cooley M E. Symptoms in adults with lung cancer: a systematic research review.  J Pain Symptom Manage. 2000;  19 137-153
    CrossrefPubMedGoogle Scholar
  • 124 O'Driscoll M, Corner J, Bailey C. The experience of breathlessness in lung cancer.  Eur J Cancer Care (Engl). 1999;  8 37-43
    CrossrefPubMedGoogle Scholar
  • 125 Smith E L, Hann D M, Ahles T A et al.. Dyspnea, anxiety, body consciousness and quality of life in patients with lung cancer.  J Pain Symptom Manage. 2001;  21 323-329
    CrossrefPubMedGoogle Scholar
  • 126 Muers M F. Opioids for dyspnoea.  Thorax. 2002;  57 922-923
    CrossrefPubMedGoogle Scholar
  • 127 Lai Y L, Chan C W, Lopez V. Perceptions of dyspnea and helpful interventions during the advanced stage of lung cancer: Chinese patients' perspectives.  Cancer Nurs. 2007;  30 E1-E8
    PubMedGoogle Scholar
  • 128 Hately J, Laurence V, Scott A, Baker R, Thomas P. Breathlessness clinics within specialist palliative care settings can improve the quality of life and functional capacity of patients with lung cancer.  Palliat Med. 2003;  17 410-417
    CrossrefPubMedGoogle Scholar
  • 129 Corner J, Plant H, A'Hern R, Bailey C. Non-pharmacological intervention for breathlessness in lung cancer.  Palliat Med. 1996;  10 299-305
    CrossrefPubMedGoogle Scholar
  • 130 Dorman S, Byrne A, Edwards A. Which measurement scales should we use to measure breathlessness in palliative care? A systematic review.  Palliat Med. 2007;  21 177-191 , Epub 2007 Mar 15
    CrossrefPubMedGoogle Scholar
  • 131 Levin D N, Cleeland C S, Dar R. Public attitudes toward cancer pain.  Cancer. 1985;  56 2337-2339
    CrossrefPubMedGoogle Scholar
  • 132 Hoffman A J, Given B A, von Eye A, Gift A G, Given C W. Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer.  Oncol Nurs Forum. 2007;  34 785-792
    CrossrefPubMedGoogle Scholar
  • 133 World Health Organization. .WHO's Pain Relief Ladder. http://www.who.int/cancer/palliative/painladder/en/index.html Accessed April 1, 2008
    Google Scholar
  • 134 Larue F, Colleau S M, Brasseur L et al.. Multicentre study of cancer pain and its treatment in France.  BMJ. 1995;  310 1034-1037
    PubMedGoogle Scholar
  • 135 Brown J, Thorpe H, Napp V et al.. Assessment of quality of life in the supportive care setting of the big lung trial in non-small-cell lung cancer.  J Clin Oncol. 2005;  23(30) 7417-7427
    CrossrefPubMedGoogle Scholar
  • 136 Lin H R, Bauer-Wu S M. Psycho-spiritual well-being in patients with advanced cancer: an integrative review of the literature.  J Adv Nurs. 2003;  44 69-80
    CrossrefPubMedGoogle Scholar
  • 137 Sand L, Strang P. Existential loneliness in a palliative home care setting.  J Palliat Med. 2006;  9 1376-1387
    CrossrefPubMedGoogle Scholar
  • 138 Osse B HP, Vernooij-Dassen M JFJ, Schadé E, Grol R PTM. The problems experienced by patients with cancer and their needs for palliative care.  Support Care Cancer. 2005;  13 722-732
    PubMedGoogle Scholar
  • 139 Henoch I, Bergman B, Gustafsson M, Gaston-Johansson F, Danielson E. The impact of symptoms, coping capacity, and social support on quality of life experience over time in patients with lung cancer.  J Pain Symptom Manage. 2007;  34 370-379
    CrossrefPubMedGoogle Scholar

Stephen G SpiroM.D. 

Department of Respiratory Medicine, University College London Hospitals

Grafton Way, London WC1E 6AU, UK

Email: stephen.spiro@uclh.nhs.org

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