This Article Abstract Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okuno, S. H. Articles by Jett, J. R. Search for Related Content PubMed PubMed Citation Articles by Okuno, S. H. Articles by Jett, J. R.

Small Cell Lung Cancer: Current Therapy and Promising New Regimens

Mayo Clinic, Rochester, Minnesota, USA

Correspondence: Scott H. Okuno, M.D., Mayo Clinic, Rochester, Minnesota 55905, USA. Telephone: 507-284-2511; Fax: 507-284-1803; e-mail: okuno.scott{at}mayo.edu

	LEARNING OBJECTIVES

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
After completing this course, the reader will be able to:

1. Understand the treatment options for limited versus extensive small cell lung cancer.
   
2. Understand the role of prophylactic cranial irradiation for small cell lung cancer.
   
3. Understand second-line chemotherapy regiments for small cell lung cancer.
   

	ABSTRACT

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
In this review, we cover current therapy and promising new regimens and highlight areas where improvement is needed in the management of small cell lung cancer.

Key Words. Small cell • Lung cancer • Chemotherapy • Radiation

	INTRODUCTION

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
In this review, we cover current therapy and promising new regimens and highlight areas where improvement is needed in the management of small cell lung cancer (SCLC).

SCLC accounts for 15%-20% of all lung cancers in the U.S. This cell type has the strongest association with cigarette smoking and is rarely observed in someone who has never smoked [1]. SCLC is generally staged as limited-stage (LS-SCLC) or extensive-stage disease according to the old Veterans Administration Staging System [2]. Limited-stage disease is confined to one hemithorax, mediastinum, and ipsilateral supraclavicular nodes that can be encompassed within one radiation portal. Extensive stage is any disease that has spread beyond these sites. Malignant pleural effusion or contralateral supraclavicular nodes or contralateral hilar nodes are generally considered to be extensive stage disease [3]. The American Joint Committee on cancer (TNM) system uses the same staging system for SCLC as for non-small cell lung cancer. "Limited disease" corresponds to stages I to IIIA and "extensive disease" to stages IIIB and IV [4].

	TREATMENT OF LIMITED-STAGE SCLC

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
After clinical staging, including a computerized tomography (CT) scan of the chest to include the liver and adrenal gland, bone scan, and CT of the brain, approximately one-third of patients will have limited-stage disease, and they have a response rate of 80%-90% with standard chemotherapy. A complete clinical response can be achieved in 50%-60% of patients. Standard chemotherapy for newly diagnosed SCLC remains etoposide and either cisplatin or carboplatin. Despite activity of several agents in SCLC alone or in combination, etoposide/platinum remains the standard chemotherapy because of its high activity and ease of combining it with thoracic radiation at full systemic doses. Attempts to use alternating noncross-resistant chemotherapy regimens, intensify the dose, or use prolonged maintenance regimens have not consistently shown improved results beyond four to six cycles of etoposide/cisplatin (EP) chemotherapy [5–10]. The addition of thoracic radiation therapy (TRT) has significantly improved the survival in patients with LS-SCLC. SCLC is a radiosensitive tumor. A meta-analysis of trials comparing chemotherapy alone with chemotherapy combined with TRT showed that survival was significantly better with combined modality therapy [11].

Recently, two different cooperative groups randomized patients to once-a-day versus twice-a-day TRT with standard chemotherapy for all patients [12,13]. Turrisi et al. [12] reported the long-term follow-up of patients enrolled in the Eastern Cooperative Oncology Group/Radiation Therapy Oncology Group (ECOG/RTOG) trial (Table 1) and concluded that twice-a-day radiotherapy resulted in a statistically better 5-year survival. All patients received four cycles of EP chemotherapy (two concurrent with radiotherapy), and TRT began on day 1 of treatment. Bonner and associates [13] reported the North Central Cancer Treatment Group (NCCTG) experience and concluded that there was no difference in survival with twice-daily TRT versus once-daily radiotherapy. All patients received identical chemotherapy with six cycles of etoposide and cisplatin (Table 1). Radiotherapy began with cycle four of chemotherapy. What is clear from both of these studies is that median survival is now 18-20 months with concurrent chemotherapy and TRT, and that 40% of patients will be alive at 2 years. The 5-year survival rate (cure rate) is 15%-25%. It is unclear if twice-daily TRT is superior to standard once-daily radiotherapy. Local recurrence is still a problem in over 50% of individuals with doses of TRT less than 50 Gy.

	TREATMENT OF EXTENSIVE-STAGE SCLC

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

Two cooperative oncology groups carried out randomized prospective trials evaluating CAV versus EP versus alternating CAV and EP [8,16]. These trials showed similar survival on all three arms for extensive-stage patients. The myelosuppression and other toxicity associated with the CAV regimen were greater, and subsequently, EP was adopted as standard therapy in the U.S.

Subsequently, trials have been performed looking at a variety of combination chemotherapeutic agents against extensive-stage SCLC. The CAE regimen (cyclophosphamide, doxorubicin, and etoposide) has been a commonly used regimen in European trials. The other commonly used regimens are etoposide and carboplatin (EC); etoposide, ifosfamide, and cisplatin (VIP); and ifosfamide, carboplatin, and etoposide (ICE). The median survival with all these regimens is in the 8-10 month range with 2-year survival of 10% or less [14]. No regimen has been shown to be superior to EP or EC until the recently reported Japanese trial of CPT-11 and cisplatin (see below).

	NEW AGENTS

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
In the 1990s, a number of promising new agents entered into clinical trials. Paclitaxel was tested by the ECOG and NCCTG in previously untreated SCLC with response rates of 34% and 68%, respectively, demonstrating activity of this agent in previously untreated SCLC [17,18].

The ECOG evaluated topotecan at a dose of 2.0 mg/m² daily for 5 days in untreated SCLC and observed a response rate of 39% [19]. Japanese investigators have evaluated CPT-11, another topoisomerase I inhibitor, and demonstrated activity of this agent against SCLC [20]. Recently, in a trial at the University of Pittsburgh, the combination of topotecan and paclitaxel was evaluated in untreated extensive-disease SCLC patients. With the doses given, patients required G-CSF support. It is unclear, as discussed previously, whether there is an additional benefit of the dose intensity achieved with CSFs. Twenty-nine patients were enrolled in the study, and 28 patients were evaluable. There were 17 major responses (six complete responses [CR] and 11 partial responses [PR]) for a response rate of 60% [21]. The median survival time was 54 weeks with 1- and 2-year survival rates of 50% and 15%, respectively. Toxicity was predictable and was primarily myelosuppression.

At the American Society of Clinical Oncology (ASCO) 2000 meeting, the Cancer and Leukemia Group B reported the results of their phase II trial of topotecan and paclitaxel with G-CSF support. They administered the paclitaxel by 3-hour infusion on day 1 followed by topotecan daily for 5 days [22]. They treated 34 evaluable patients and had one CR and 22 PRs for an overall response rate of 68%. The median survival time was 9.4 months and the estimated 1-year survival was 26%. They concluded that the combination of paclitaxel and topotecan was no better than standard therapy.

Also at the ASCO 2000 meeting, the NCCTG reported the results of their trial of alternating chemotherapy with paclitaxel/topotecan and etoposide/cisplatin. Of 46 evaluable patients, there was a major response in 76% [23]. The median survival time was 10.5 months and the 1-year survival was 38%. While these results were good, they were not obviously superior to standard therapy.

The ECOG reported a phase III trial for extensive-stage SCLC patients. All patients received four cycles of etoposide and cisplatin and then were randomized to observation alone or further treatment with four cycles of single-agent topotecan. Survival was essentially identical in the two groups, with median survivals of 8.9 months (observation) and 9.3 months (topotecan). Quality of life was not significantly improved with topotecan, and toxicity was considerably greater [24].

The most exciting recent report on SCLC was the report by Noda et al. [20]. This Japan Clinical Oncology Group phase III trial compared CPT-11 and cisplatin (CP) with EP in extensive-stage disease patients. The overall response rates were 89% and 67%, respectively. The median survival time and 1-year survival rate with CP were 420 days and 60% versus 300 days and 40% with EP (p = 0.005). Myelosuppression was somewhat greater following EP (p = 0.01), and grade 3/4 diarrhea was greater after CP (p = 0.0001). A confirmatory phase III trial is being planned by the Southwest Oncology Group.

	PROPHYLACTIC CRANIAL IRRADIATION

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
Prophylactic cranial irradiation (PCI) is one of the most controversial areas in the treatment of SCLC. If a patient achieves a complete remission, then there is a 50% chance of developing cranial metastasis within the next 2 years [25]. Small randomized trials have shown that patients who receive PCI have a significantly lower rate of central nervous system metastases than those who do not receive PCI [26]. There have also been reports in the literature of neurocognitive abnormalities and neurologic sequelae, such as ataxia, that have developed as a result of PCI [27]. Recently, a meta-analysis was performed of seven randomized trials of PCI versus no PCI of patients in complete remission. The authors observed a beneficial effect after PCI, with a 5.4% greater absolute survival at 3 years [28]. The major questions raised by the meta-analysis concern the optimal dose and sequencing of PCI. Advocates of PCI point out two trials in Europe that prospectively performed neuropsychiatric testing in patients on randomized trials of PCI or no PCI. They did not observe any significant differences in neuropsychologic symptoms, cortico-atrophy, or ventricular dilatation as evaluated by CT [29,30]. Detractors argue that these trials were suboptimal and that more data are needed. In practice, experts vary in their recommendation on the use of PCI.

	SECOND-LINE THERAPY

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
When patients relapse after initial therapy, the median survival time is generally 3-4 months. The longer the patients have been in remission, the more likely they are to respond to second-line therapy. In patients who have been off treatment for 6 months or more, it is reasonable to retreat them with the same initial agents that achieved the first remission. The chance of a second response is approximately 50%. If a patient has not been treated with a platinum-based regimen, then second-line therapy should include a platinum regimen, such as EC or EP.

A number of clinical trials have evaluated topotecan as second-line therapy in patients with relapsed SCLC. If patients had responded to initial therapy and had been off chemotherapy for 3 months or longer, then their response to second-line topotecan was approximately 25%-35% [31]. Recently, topotecan was approved by the U.S. Food and Drug Administration for second-line treatment of SCLC. If a patient relapses while on therapy or has been off therapy fewer than 2-3 months, his response to topotecan or any other chemotherapy regimen is generally <10% [32].

There are multiple single-agent studies demonstrating activity for recurrent SCLC with response rates ranging from 11%-40% [33–38]. These agents include irinotecan, docetaxel, paclitaxel, topotecan, vinorelbine, and carboplatin. Unfortunately, the duration of response is short, averaging up to 30 weeks.

Combination chemotherapy generally yields improved overall response rates compared with single-agent therapy, but the duration of response is still short. The NCCTG is currently conducting a second-line therapy trial for progressive or relapsed SCLC. Patients receive topotecan (1.25 mg/m²) daily for 3 days and paclitaxel (200 mg/m² over 3 hours) on day 3. G-CSF support is not used for the initial cycle.

In summary, patients with extensive-stage SCLC have a 75%-85% response rate to initial chemotherapy. The median survival time is 8-9 months, the 2-year survival is <10%, and there are virtually no 5-year survivors. A recent review by the National Cancer Institute-Navy was unable to substantiate any improvement in survival with SCLC since the mid-1970s [39]. New agent therapies are desperately needed for the treatment against SCLC.

	ACKNOWLEDGMENT

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 
S.H.O. receives an honorarium from GlaxoSmithKline. J.R.J. receives a research grant from GlaxoSmithKline.

Presented in part at the Mayo Clinic's 11th Annual Hematology/Oncology Reviews, State-of-the-Art Treatment of Hematology/Oncology Treatments, Amelia Island, Florida, August 16-19, 2001.

	REFERENCES

Top Learning Objectives Abstract Introduction Treatment of Limited-Stage SCLC Treatment of Extensive-Stage... New Agents Prophylactic Cranial Irradiation Second-Line Therapy References

 

1. Wu AH, Henderson BE, Thomas DC et al. Secular trends in histologic types of lung cancer. J Natl Cancer Inst 1986;77:53–56.
2. Mountain CF. Clinical biology of small cell carcinoma: relationship to surgical therapy. Semin Oncol 1978;5:272–279.[Medline]
3. American Joint Committee on Cancer. Lung cancer. In: Beahrs OH, Henson DE, Huttner RVP et al., eds. Manual for Staging of Cancer, Fourth Edition. Philadelphia: JB Lippincott, 1995:115.
4. Wittekind CH, Henson DE, Hutter RVP et al., eds. TNM Supplement. A Commentary on Uniform Use, Second Edition. New York: Wiley-Liss, 2001:43.
5. Johnson DH, Einhorn LH, Birch R et al. A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 1987;5:1731–1738.[Abstract/Free Full Text]
6. Ihde DC, Mulshine JL, Kramer BS et al. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small cell lung cancer. J Clin Oncol 1994;17:2022–2034.
7. Evans WK, Feld R, Murray N et al. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer. A multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med 1987;107:451–458.
8. Roth BJ, Johnson DH, Einhorn LH et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alteration of these two regimens in extensive small cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 1992;10:282–291.[Abstract]
9. Giaccone G, Dalesio O, McVie GJ et al. Maintenance chemotherapy in small-cell lung cancer: long-term results of a randomized trial. European Organisation for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 1993;11:1230–1240.[Abstract/Free Full Text]
10. Spiro SG, Souhami RL, Geddes DM et al. Duration of chemotherapy in small cell lung cancer: a cancer research campaign trial. Br J Cancer 1989;59:578–583.[Medline]
11. Pignon JP, Arriagada R, Ihde DC et al. A meta-analysis of thoracic radiotherapy for small cell lung cancer. N Engl J Med 1992;327:1618–1624.[Abstract]
12. Turrisi 3rd AT, Kim K, Blum R et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340:265–271.[Abstract/Free Full Text]
13. Bonner JA, Sloan JA, Shanahan TG et al. Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small cell lung carcinoma. J Clin Oncol 1999;17:2681–2691.[Abstract/Free Full Text]
14. Ihde DC, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, Fifth Edition. Philadelphia: Lippincott-Raven, 1997:911-918.
15. Evans WK, Osoba D, Feld R et al. Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer. J Clin Oncol 1985;3:65–71.[Abstract]
16. Fukuoka M, Furuse K, Saijo N et al. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small cell lung cancer. J Natl Cancer Inst 1991;83:855–861.[Abstract/Free Full Text]
17. Ettinger DS, Finkelstein DM, Sarma RP et al. Phase II study of paclitaxel in patients with extensive-disease small cell lung cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 1995;13:1430–1435.[Abstract]
18. Kirschling RJ, Grill JP, Marks RS et al. Paclitaxel and G-CSF in previously untreated patients with extensive stage small cell lung cancer: a phase II study of the North Central Cancer Treatment Group. Am J Clin Oncol 1999;22:517–522.[CrossRef][Medline]
19. Schiller JH, Kim KM, Hutson P et al. Phase II study of topotecan in patients with extensive-stage small cell carcinoma of the lung: an Eastern Cooperative Oncology Group trial. J Clin Oncol 1996;14:2345–2352.[Abstract]
20. Noda K, Nishiwaki Y, Kawahara M et al. Randomized phase III study of irinotecan (CPT-11) and cisplatin versus etoposide and cisplatin in extensive disease small cell lung cancer: Japan Clinical Oncology Group study 9511. Proc Am Soc Clin Oncol 2000;19:483a.
21. Jacobs SA, Jett JR, Belani CP et al. Topotecan and paclitaxel, an active couplet in untreated extensive disease small cell lung cancer. Proc Am Soc Clin Oncol 1999;18:471a.
22. Lynch TJ, Herndon JE, Lyss AP et al. Paclitaxel plus topotecan plus G-CSF for previously untreated extensive small cell lung cancer: preliminary analysis of CALGB 9430. Proc Am Soc Clin Oncol 2000;19:1922a.
23. Jett J, Hatfield A, Bauman M et al. Phase II trial of topotecan and paclitaxel with G-CSF support alternating with etoposide and cisplatin in previously untreated extensive stage small cell lung cancer. Proc Am Soc Clin Oncol 2000;19:1921a.
24. Johnson DH, Adak S, Cella DF et al. Topotecan vs observation following cisplatin plus etoposide in extensive-stage small cell lung cancer (E7593): a phase III trial of ECOG. Proc Am Soc Clin Oncol 2000;19:482a.
25. Komaki R, Cox JD, Whitson W. Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation. Cancer Treat Rep 1981;65:811–814.[Medline]
26. Kristjansen PEG, Hansen HH. Prophylactic cranial irradiation in small cell lung cancer: an update. Lung Cancer 1995;12(suppl 3):S23–S40.
27. Johnson BE, Becker B, Goff 2nd WB et al. Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2- to 10-year survivors of small cell lung cancer. J Clin Oncol 1985;3:1659–1667.[Abstract/Free Full Text]
28. Auperin A, Arriagada R, Pignon JP et al. Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341:475–484.
29. Arriagada R, Le Chevalier T, Borie F et al. Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission. J Natl Cancer Inst 1995;87:183–190.[Abstract/Free Full Text]
30. Gregor A, Cull A, Stephens RJ et al. Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicenter randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organisation for Research and Treatment of Cancer (EORTC). Eur J Cancer 1997;33:1752–1758.
31. Ardizzoni A, Hansen H, Dombernowsky P et al. Topotecan, a new active drug in second-line treatment of small cell lung cancer: a phase II study in patients with refractory and sensitive disease. J Clin Oncol 1997;15:2090–2096.[Abstract/Free Full Text]
32. von Pawel J, Schiller JH, Shepherd FA et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17:658–667.[Abstract/Free Full Text]
33. De Vore R, Blanke C, Denham C et al. Phase II study of irinotecan (CPT-11) in patients with previously treated small-cell lung cancer (SCLC). Proc Am Soc Clin Oncol 1998;17:451a.
34. Smyth JF, Smith IE, Sessa C et al. Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur J Cancer 1994;30A:1058–1060.[CrossRef]
35. Smit EF, Fokkema E, Biesma B et al. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer 1998;77:347–351.[Medline]
36. Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C et al. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group. Eur J Cancer 1993;29A:1720–1722.
37. Groen HJ, Smit EF, Haaxma-Reiche H et al. Carboplatin as second line treatment for recurrent or progressive brain metastases from small cell lung cancer. Eur J Cancer 1993;29A:1696–1699.[CrossRef]
38. Perez-Soler R, Glisson BS, Lee JS et al. Treatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan. J Clin Oncol 1996;14:2785–2790.[Abstract/Free Full Text]
39. Chute JP, Venzon DJ, Hankins L et al. Outcome of patients with small cell lung cancer during 20 years of clinical research at the US National Cancer Institute. Mayo Clin Proc 1997;72:901–912.[Abstract]

This article has been cited by other articles:

				A. R. Shoemaker, M. J. Mitten, J. Adickes, S. Ackler, M. Refici, D. Ferguson, A. Oleksijew, J. M. O'Connor, B. Wang, D. J. Frost, et al. Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models Clin. Cancer Res., June 1, 2008; 14(11): 3268 - 3277. [Abstract] [Full Text] [PDF]

				J. R. Eckardt, J. von Pawel, J.-L. Pujol, Z. Papai, E. Quoix, A. Ardizzoni, R. Poulin, A. J. Preston, G. Dane, and G. Ross Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer J. Clin. Oncol., May 20, 2007; 25(15): 2086 - 2092. [Abstract] [Full Text] [PDF]

				S. K. Tahir, X. Yang, M. G. Anderson, S. E. Morgan-Lappe, A. V. Sarthy, J. Chen, R. B. Warner, S.-C. Ng, S. W. Fesik, S. W. Elmore, et al. Influence of Bcl-2 Family Members on the Cellular Response of Small-Cell Lung Cancer Cell Lines to ABT-737 Cancer Res., February 1, 2007; 67(3): 1176 - 1183. [Abstract] [Full Text] [PDF]

				A. Ardizzoni Topotecan in the Treatment of Recurrent Small Cell Lung Cancer: An Update Oncologist, December 1, 2004; 9(suppl_6): 4 - 13. [Abstract] [Full Text] [PDF]

				J. R. Eckardt Emerging Role of Weekly Topotecan in Recurrent Small Cell Lung Cancer Oncologist, December 1, 2004; 9(suppl_6): 25 - 32. [Abstract] [Full Text] [PDF]

				D. J. Stewart Topotecan in the First-Line Treatment of Small Cell Lung Cancer Oncologist, December 1, 2004; 9(suppl_6): 33 - 42. [Abstract] [Full Text] [PDF]

				R. E. Merritt, A. Mahtabifard, R. E. Yamada, R. G. Crystal, and R. J. Korst Cisplatin augments cytotoxic T-lymphocyte-mediated antitumor immunity in poorly immunogenic murine lung cancer J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1609 - 1617. [Abstract] [Full Text] [PDF]

				G. M.M. Videtic, L. W. Stitt, A. R. Dar, W. I. Kocha, A. T. Tomiak, P. T. Truong, M. D. Vincent, and E. W. Yu Continued Cigarette Smoking by Patients Receiving Concurrent Chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer Is Associated With Decreased Survival J. Clin. Oncol., April 15, 2003; 21(8): 1544 - 1549. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okuno, S. H. Articles by Jett, J. R. Search for Related Content PubMed PubMed Citation Articles by Okuno, S. H. Articles by Jett, J. R.