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Vol. 13. Issue 4.
Pages 587-604 (July - August 2007)
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Vol. 13. Issue 4.
Pages 587-604 (July - August 2007)
Artigo de Revisão / Revision Article
Open Access
Carcinoma do pulmão de pequenas células – Estado da arte e perspectivas futuras
Small cell lung cancer – State of the art and future perspectives
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Fernando J. Barata1, Ana Filipa Costa1
1 Serviço de Pneumologia. Centro Hospitalar de Coimbra
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Resumo

Em Portugal, o cancro do pulmão é a principal cau-sa de morte entre as neoplasias. Em 2006 são previstos mais de 3500 novos casos, dos quais 20% serão diagnosticados como carcinoma do pulmão de pequenas células (CPPC). Destes, 25% a 30% dos doentes serão estadiados como doença localizada ou regional. Para estes, a opção terapêutica passa pela combinação da radioterapia (50Gy ou 60Gy) diária e quimioterapia. A radioterapia hiperfraccionada, em consequência da sua toxicidade, está limitada a doentes seleccionados.

A combinação etopósido e cisplatina é sinérgica, bem tolerada. É o regimen standard quer na opção concomi-tante com a radioterapia, quer isoladamente na doença disseminada.

Apesar da quimiossensibilidade e radiosensibilidade, o prognóstico global do CPPC é pobre. Há um de-senvolvimento precoce de resistência associado a uma elevada predisposição para a recidiva.

A terapêutica de segunda linha para o CPPC é um problema real e actual. Topotecano é hoje uma op-ção efectiva e bem tolerada no tratamento em segunda linha do CPPC. Há um aumento significativo da sobrevivência mediana versus a terapêutica sintomática. A sua eficácia é comparável ao clássi-co regimen CAV. Mostra boa tolerabilidade mes-mo quando administrado em doentes idosos, com PS=2. Continua a ser bem tolerado e eficaz quando combinado com a radioterapia holocraniana cerebral ou quando administrado num esquema semanal.

Com novas classes de fármacos, como agentes anti-angiogénicos como o bevacizumab, inibidores da tirosina quinase e talidomida, decorrem ensaios avaliando a sua associação com a clássica quimioterapia em doentes com CPPC disseminada.

Rev Port Pneumol 2007; XIII (4): 587-604

Palavras-Chave:
Carcinoma pulmonar de pequenas células
CPPC
cancro do pulmão
topotecano
Abstract

Lung cancer is the leading cause of cancer related death in Portugal. Almost 3500 Portuguese are expected to be diagnosed with lung cancer in 2006; approximately 20% will have small cell lung cancer (SCLC). At presentation, 25% to 30% of patients will have local or regional disease, classified as limited stage disease. The concurrent chemovalidation therapy is the best choice. Once daily thoracic radiation therapy to doses in the range of 50Gy to 60Gy would reflect an accepted standard of care in daily practice. Because of the increase toxicity associated with hyper fractionated radiation, this approach is often limited to select patients. Etoposide plus cisplatin are synergistic, well tolerated and result in equal or superior survival compared with other regimens. This is the standard regimen for concomitant therapy in limited stage and for extensive disease SCLC.

Despite good chemo sensitivity and radio sensitivity, the prognosis of SCLC is very poor because of the early development of resistance and the associated high tendency to recurrence, making second line treatment of SCLC a problem of real medical relevance.

Topotecan now offers an effective and well tolerated mono-substance for second line therapy of recurrent SCLC. There has been a significant increase in median survival for patients with SCLC receiving topotecan plus symptomatic therapy versus symptomatic therapy. The efficacy of this drug is comparable to the efficacy of the three-drug combination CAV. The tolerability can be improved by means of toxicity-adapted dosing. In elderly and in patients with performance status 2, topotecan is also well tolerated and has good efficacy. Initial studies into weekly administration also demonstrate good efficacy. The combination of topotecan with cranial radiotherapy is well tolerated and effective in the treatment of cerebral metastases of SCLC. New classes of agents, such as antiangiogenic agents including bevacizumab, small molecule tyrosine kinase inhibitors and thalidomide are being evaluated with chemotherapy for patients with extensive stage SCLC.

Rev Port Pneumol 2007; XIII (4): 587-604

Key-Words:
Small cell lung cancer
lung cancer
topotecan
SCLC
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Bibliografia / Bibliography
[1.]
D. Schottenfeld, J.G. Searle.
The etiology and epidemiology of lung cancer.
Lung Cancer, pp. 3-24
[2.]
J. Ferlay, F. Bray, P. Pisani, D.M. Parkin.
GLOBOCAN 2000 – cancer incidence mortality and prevalence worldwide, IARC Press, (2000),
[3.]
K.M. Dineen, G.A. Silvestri.
The Epidemiology of Lung Cancer.
Malignant Tumors of the Lung, pp. 57-75
[4.]
European Lung White Book – Major Respiratory Diseases – Lung Cancer – European Respiratory Society, 4 (2003), pp. 43-53
[5.]
X. Ma, M.A. Tucker.
Epidemiology of Cancer in Cancer – Principles & Practice of Oncology, 7, pp. 217-226
[6.]
A. Jemal, E.M. Ward, M.J. Thun.
Epidemiology of Cancer in Cancer – Principles & Practice of Oncology, 7, pp. 226-241
[7.]
Registo Oncológico Regional, IPOFG, (1998),
[8.]
F. Levi, F. Luccini, E. Negri, P. Boyle.
Cancer Mortality in Europe 1990-1994 and an overview of trends fron 1955 to 1994.
Eur J Cancer, 35 (1999), pp. 1477-1516
[9.]
M. Kreuzer.
Lung Cancer in Woman – 10th Central European Lung Cancer Conference.
Lung Cancer, 52 (2006), pp. S7-S8
[10.]
N. Gray, L.T. Kozlowski.
More on the regulation of tobacco smoke: how we got here and where next.
Ann Oncol, 14 (2003), pp. 353-357
[11.]
P. Boffetta.
Involuntary smoking and lung cancer.
Scand J. Work Hearth, 28 (2002), pp. 30-40
[12.]
R. Stupp, C. Monnerat, A.T. Turrisi, M.C. Perry.
Small Cell Lung Cancer: state of art and future perspectives.
Lung Cancer, 45 (2004), pp. 105-117
[13.]
F.J. Barata.
Carcinoma Pulmonar de pequenas células – Quimioterapia como tratamento da doença disseminada primária e recidivante.
Rev Port Pneumol, VIII (2002), pp. 341-349
[14.]
A. Spira, D.S. Ettinger.
Multidisciplinary Management of Lung Cancer.
New Engl. J. Med, 350 (2004), pp. 379-392
[15.]
J. Von Pawel, J.H. Schiller, F.A. Shepherd, S.Z. Fields, et al.
Topotecan versus cyclofosfamide, doxorubicin and vincristine for the treatment of recurrent small cell lung cancer.
J Clin Oncol, 17 (1999), pp. 658-667
[16.]
G.A. Masters, O.H. Kyong.
Clinical Presentation of Lung Cancer – Malignant Tumors of the Lung, pp. 119-138
[17.]
M.J.S. Melo.
Clinica e imagem do cancro do pulmão – Tratado de Pneumologia, pp. 1137-1148
[18.]
F.J. Barata.
Diagnóstico e Estadiamento – Tratado de Pneumologia, pp. 1149-1167
[19.]
P. Micke, A. Faldum, T. Metz, et al.
Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer – what limits limited disease?.
Lung Cancer, 37 (2002), pp. 271-276
[20.]
A. Argiris, J.R. Murren.
Staging and Clinical Prognostic Factors for Small Cell Lung Cancer.
Cancer Journal, 7 (2001), pp. 437-447
[21.]
W. Fox, J.G. Scalding.
Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small cell carcinoma.
[22.]
S. Davis, L. Crino, M. Tonato, et al.
A prospective analysis of chemotherapy following surgical resection of clinical stage I-II small cell lung cancer.
Am J Clin Oncol, 16 (1993), pp. 93
[23.]
H.P. Hauber, K.H. Bohuslavizki, C.H. Lund, et al.
Positron Emission tomography in the staging of small cell lung cancer.
Chest, 119 (2001), pp. 950-954
[24.]
J.D. Bradley, F. Dehdashti, M.A. Mintun.
Positron Emission Tomography in Limited Stage Small Cell Lung Cancer: A Prospective Study.
J Clin Oncol, 22 (2004), pp. 3248-3254
[25.]
M.P. Dearing, S.M. Steinberg, R. Phelps, et al.
Outcome of patients with small cell lung cancer – effect of changes in staging procedures and imaging technology on prognostic factors over 14 years.
J Clin Oncol, 8 (1990), pp. 1042-1049
[26.]
D. Spiegelman, L.H. Maurer, J.H. Ware, et al.
Prognostic factors in small cell carcinoma of the lung: an analysis of 1521 patients.
J Clin Oncol, 7 (1989), pp. 344-354
[27.]
M. Paesmans, J.P. Scullier, J. Leconte, et al.
Prognostic factors for patients with small cell carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.
Cancer, 89 (2000), pp. 523-533
[28.]
E. Quoix, A. Pirohit, M. Faller-Beau, et al.
Comparative Prognostic Value of Lactate Dehydrogenase and Neuron Specific Enolase in Small Cell Lung Cancer Patients treated with platinum based Chemotherapy.
Lung Cancer, 30 (2000), pp. 127-134
[29.]
K. Osterlink.
LDH or NSE or LDH and NSE as pre-treatment prognostic factors in small cell lung cancer? A Commentary.
Lung Cancer, 30 (2000), pp. 51-55
[30.]
F.H. Blackhall, M. Pintilie, M. Michael, et al.
Expression and prognostic significance of kit, protein kinase B and mitogen activated protein kinase in patients with small cell lung cancer.
Clin Cancer Res, 9 (2003), pp. 2241-2247
[31.]
B. Martin, M. Paesmans, T. Berghmans, et al.
Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of literature with meta-analysis.
Br J Cancer, 89 (2003), pp. 55-64
[32.]
J.P. Pingnon, R. Arriagada, D. Ihde, et al.
A Meta-analysis of thoracic radiotherapy for small cell lung cancer.
N Eng J Med, 327 (1992), pp. 16-18
[33.]
D.B. Fried, D.L. Morris, C. Poole, et al.
Systemic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited stage small cell lung cancer.
J Clin Oncol, 22 (2004), pp. 4785-4793
[34.]
A.T. Turrisi, K. Kim, R. Blum, et al.
Twice daily compared with once daily thoracic radiotherapy in limited small cell lung cancer treated concurrently with cisplatin and etoposide.
N Eng J Med, 340 (1999), pp. 265-271
[35.]
S.E. Schild, J.A. Bonner, T.G. Shanahan, et al.
Long term results of a phase III trial comparing once daily radiotherapy with twice daily radiotherapy in limited stage small cell lung cancer.
J Radiat Oncol Biol, 59 (2004), pp. 943-951
[36.]
A.W. Blackstock, J.A. Bogart, C. Matthews, et al.
Split course versus continuous thoracic radiation therapy for limited stage small cell lung cancer: Final Report of a randomized phase III trial.
Clin Lung Cancer, 6 (2005), pp. 287-292
[37.]
J.J. Urbanic, A.W. Blackstock.
Radiotherapy for patients with Limited Stage Small Cell Lung Cancer – Educational Book, American Society Clinical Oncology, (2006),
[38.]
A. Auperin, R. Arriagada, J.P. Pignon, et al.
Prophylatic cranial irradiation for patients with limited small cell lung cancer in complete remission.
N Eng J Med, 341 (1999), pp. 476-484
[39.]
D.S. Ettinger, D.M. Finfelstein, et al.
A Randomized comparision of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive stage small cell lung cancer: a phase III study of Eastern Cooperative Oncology Group.
J Clin Oncol, 8 (1990), pp. 230-240
[40.]
J. Von Pawel.
The role of topotecan in treating small cell lung cancer: second line treatment.
Lung Cancer, 41 (2003), pp. S3-S8
[41.]
K. Noda, Y. Nishiwaki, M. Kawahara, S. Negoro, T. Su-giura, et al.
Irinotecan plus cisplatin compared with eto-poside plus cisplatin for extensive small cell lung cancer.
N Eng J Med, 346 (2002), pp. 85-91
[42.]
N. Hanna, L. Einhorn, A. Sandler, et al.
Randomized, phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) as treatment for chemotherapy naïve patients with extensive disease small cell lung cancer.
J.Clin. Oncol, 23 (2005), pp. 622s
[43.]
H. Okamoto, K. Watanabe, H. Kunikane, et al.
Randomized phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor risk patients with extensive disease small cell lung cancer.
J Clin Oncol, 23 (2005), pp. 623S
[44.]
A. Ardizzoni, A. Favaretto, L. Boni, et al.
Platinun-eto-poside chemotherapy in elderly patients with small cell lung cancer.
J Clin Oncol, 23 (2005), pp. 569-575
[45.]
J. Sculier, T. Bergman, C. Castaigne, et al.
Maintenance chemotherapy for small cell lung cancer. A critical review of the literature.
Lung Cancer, 19 (1998), pp. 141-151
[46.]
W. Schutte.
Chemotherapy as treatment of primary and recurrent small cell lung cancer.
Lung Cancer, S99 (2001), pp. 107
[47.]
J.R. Eckardt.
Second Line Treatment of Small Cell Lung Cancer.
[48.]
B.J. Roth, D.H. Johnson, L.H. Einhorn, et al.
Randomized study of cyclophosphamide, doxorubicin and vincristine versus etoposide and cisplatin versus alternating of these two regimens in extensive small cell lung cancer.
J Clin Oncol, 10 (1992), pp. 282-291
[49.]
G. Giaconne.
Second line chemotherapy in small cell lung cancer.
Lung Cancer, 5 (1989), pp. 207-213
[50.]
H.A. Burris, A.R. Hanauske, R.K. Johnson, et al.
Activity of Topotecan, a new topoisomerase I inibitor, against human tumor colony forming units.
J Nat Cancer Inst, 84 (1992), pp. 1816-1820
[51.]
F.A. Greco.
Topotecan as first line therapy for small cell lung cancer.
Lung Cancer, 41 (2003), pp. S9-S16
[52.]
A. Ardizonni, H. Hansen, T. Gamucci, et al.
Topotecan, a new active drug in the second line treatment of small cell lung cancer. A phase II study in patients with refractory and sensitive disease.
J. Clin. Oncol, 15 (1997), pp. 2090-2096
[53.]
A. Cesano, S.R. Lane, R. Poulin, et al.
Stabilization of disease as a useful predictor of survival following second line chemotherapy in small cell lung cancer and ovarian cancer patients.
Int J Oncol, 15 (1999), pp. 1233-1238
[54.]
C. Hui Huang, J. Treat, et al.
New advances in Lung Cancer Chemotherapy: Topotecan anda the Role of To-poisomerases I Inibitors.
Oncology, 61 (2001), pp. 14-24
[55.]
R. Huber, M. Reck, H. Gosse, et al.
Reduced toxicity with adjusted topotecan therapy is not associated with decreased efficacy. A multicenter phase II trial in recurrent small cell lung cancer.
Ann Oncol, 20 (2005),
[56.]
D. Mavroudis, K. Veslemes, C. Kouroussis, et al.
Cis-platin-etposide alternating with topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II trial.
Lung Cancer, 38 (2002), pp. 59-63
[57.]
E. Felip, R. Rosell, M. Domine, et al.
Sequencial dosedense paclitaxel followed by topotecan in untreated extensive disease small cell lung cancer: a Spanish Lung Cancer Group phase II study.
Ann Oncol, 14 (2003), pp. 1549-1554
[58.]
D.J. Steward.
Foreword. New Directions for topotecan in Lung Cancer Treatment.
[59.]
J. Treat.
Weekly topotecan in the management of lung cancer.
Lung Cancer, 41 (2003), pp. S27-S31
[60.]
J.R. Eckardt.
Emerging Role of Weekly Topotecan in Recurrent Small Cell Lung Cancer.
The Oncologist, 9 (2004), pp. 25-32
[61.]
V.K. Kasturi, J.R. Eckardt, F.A. Greco.
A preliminary retrospective analysis of weekly topotecan in recurrent small cell lung cancer.
Proceeding ASCO, 23 (2004), pp. 7359
[62.]
F.A. Greco, Ha Burris III, D.A. Yardley, et al.
Phase II tria of weekly topotecan in the second line treatment of small lung cancer.
Lung Cancer, 41 (2003), pp. S237
[63.]
U. Seifart, K. Jensen, J. Ukena, et al.
Randomized phase II study comparing topotecan/cisplatin administration for 5 days versus 3 days in the treatment of extensive stage small cell lung cancer (SCLC).
Lung Cancer, 48 (2005), pp. 415-422
[64.]
J. Treat, H.H. Chao, S.R. Lane, et al.
Topotecan in the treatment of Relapsed Small Cell Lung Cancer Patients with Poor Performance Status.
The Oncologist, 9 (2004), pp. 173-181
[65.]
R.J. Gralla.
Quality-of-life Considerations in Patients with advanced Lung Cancer: Effect of Topotecan on Symptom Palliation and Quality of Life.
The Oncologist, 9 (2004), pp. 14-24
[66.]
D.K. Armstrong, D. Spriggs, J. Levin, S. Lane, et al.
He-matologic Safety and Tolerability of Topotecan in Recurrent Ovarian Cancer and Small Cell Lung Cancer: An integrated Analysis.
The Oncologist, 10 (2005), pp. 686-694
[67.]
M. O’Brian, H. Tsekov, T. Ciuleanu, et al.
Survival benefit of oral topotecan plus supportive care versus supportive care alone in relapsed, resistant SCLC.
Lung Cancer, 49 (2005), pp. S54
[68.]
G. Frasci, G. Nicollela, P. Cornella, et al.
A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte colony stimulating factor support for patients with extensive disease small cell lung cancer.
Br J Cancer, 4 (2001), pp. 1166-1171
[69.]
G.P. Stathopoulos, C.H. Christodoulou, D. Skarlos, et al.
Second line chemotherapy in small cell lung cancer in a modified administration of topotecan combined with paclitaxel: a phase II study.
Cancer Chemother Pharmacol, (2005),
[70.]
J. Eckhardt, J. Von Pawel, G. Manikhas, et al.
Comparable activity with oral topotecan/cisplatin and IV etoposide/cisplatin as treatment for chemotherapy patients with extensive disease small cell lung cancer. Final results.
J Clin Oncol, 22 (2005), pp. 621s
[71.]
F. Grossi, et al.
The role of systemic chemotherapy in the treatment of brain metastases from small cell lung cancer.
Clinical Reviews in Oncology/Hematology, 37 (2001), pp. 61-67
[72.]
A. Korfel, et al.
Response to topotecan of symptomatic brain metastases of small cell lung cancer also after whole brain irradiation. A Multicentre phase II study.
European Journal of Cancer, 38 (2002), pp. 1724-1729
[73.]
E.T. Wong, A. Berkenblit.
The role of Topotecan in the treatment of Brain Metastases.
The Oncologist, 9 (2004), pp. 68-79
[74.]
F.A. Shepherd, P.J. Rodrigues, T. Ciuleanu, et al.
Erloti-nib in previously treated non small cell lung cancer.
N Engl J Med, 353 (2005), pp. 123-132
[75.]
D.H. Johnson, L. Fehrenbacher, W.F. Novotny, et al.
Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non small cell lung cancer.
J Clin Oncol, 22 (2004), pp. 2184-2191
[76.]
B.E. Jonson.
Potentially effective targeted agents for patients with small cell lung cancer.
Educational Book, pp. 449-451
[77.]
S. Singhal, J. Mehta, R. Desikan, et al.
Antitumor activity of thalidomide in refractory multiple myeloma.
N Engl J Med, 341 (1999), pp. 1565-1571
[78.]
C.M. Rudin, M. Kozloff, et al.
Phase I study og G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin/etoposide in SCLC.
J Clin Oncol, 22 (2004), pp. 1110-1117
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