Table of Contents Purpose of This PDQ Summary General Information Cellular Classification Stage Information Treatment Option Overview Limited-Stage Small Cell Lung Cancer
Extensive-Stage Small Cell Lung Cancer Recurrent Small Cell Lung Cancer Get More Information From NCI Changes to This Summary (05/22/2008) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of small cell lung cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information
Note: Separate PDQ summaries on Non-Small Cell Lung Cancer Treatment; Lung Cancer Prevention; and Lung Cancer Screening are also available.
Note: Estimated new cases and deaths from lung cancer (small cell and non-small cell combined) in the United States in 2008:[1]
- New cases: 215,020.
- Deaths: 161,840.
Without treatment, small cell lung cancer (SCLC) has the most aggressive
clinical course of any type of pulmonary tumor, with median survival from
diagnosis of only 2 to 4 months. Compared with other cell types of lung
cancer, SCLC has a greater tendency to be widely disseminated
by the time of diagnosis but is much more responsive to chemotherapy and
radiation therapy.
Because patients with small cell lung cancer tend to develop distant
metastases, localized forms of treatment, such as surgical resection or
radiation therapy, rarely produce long-term survival.[2] With incorporation of
current chemotherapy regimens into the treatment program, however, survival is
unequivocally prolonged, with at least a 4- to 5-fold improvement in median
survival compared with patients who are given no therapy. Furthermore, about
10% of the total population of patients remains free of disease during 2 years
from the start of therapy, the time period during which most relapses occur.
Even these patients, however, are at risk of dying from lung cancer (both small-
and non-small cell types).[3] The overall survival at 5 years is 5% to
10%.[3-5]
Limited-stage disease
At the time of diagnosis, approximately 30% of patients with SCLC will have tumor confined to the hemithorax of origin, the
mediastinum, or the supraclavicular lymph nodes. These patients are designated
as having limited-stage disease, and most 2-year disease-free survivors come
from this group. In limited-stage disease, median survival of 16 to 24 months
with current forms of treatment can reasonably be expected.[6-8] A small
proportion of patients with limited-stage disease may benefit from surgery with
or without adjuvant chemotherapy; these patients have an even better prognosis.
Extensive-stage disease
Patients with tumors that have spread beyond the supraclavicular areas are said
to have extensive-stage disease and have a worse prognosis than patients with
limited-stage disease. Median survival of 6 to 12 months is reported with currently
available therapy, but long-term disease-free survival is rare.
Prognostic factors
The pretreatment prognostic factors that consistently predict for prolonged
survival include good performance status, female gender, and limited-stage
disease.[4,9,10] Patients with involvement of the central nervous system or
liver at the time of diagnosis have a significantly worse outcome.[4,9-11] In
general, patients who are confined to bed tolerate aggressive forms of
treatment poorly, have increased morbidity, and rarely attain 2-year
disease-free survival; however, patients with poor performance status can
often derive significant palliative benefit and prolongation of survival from
treatment.
Regardless of stage, the current prognosis for patients with SCLC is unsatisfactory even though considerable improvements in diagnosis and
therapy have been made during the past 10 to 15 years. All patients
with this type of cancer may appropriately be considered for inclusion in
clinical trials at the time of diagnosis.
Information about ongoing clinical trials is available from the
NCI Web site.
References
-
American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008.
-
Prasad US, Naylor AR, Walker WS, et al.: Long term survival after pulmonary resection for small cell carcinoma of the lung. Thorax 44 (10): 784-7, 1989.
[PUBMED Abstract]
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Johnson BE, Grayson J, Makuch RW, et al.: Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. J Clin Oncol 8 (3): 396-401, 1990.
[PUBMED Abstract]
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Lassen U, Osterlind K, Hansen M, et al.: Long-term survival in small-cell lung cancer: posttreatment characteristics in patients surviving 5 to 18+ years--an analysis of 1,714 consecutive patients. J Clin Oncol 13 (5): 1215-20, 1995.
[PUBMED Abstract]
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Fry WA, Menck HR, Winchester DP: The National Cancer Data Base report on lung cancer. Cancer 77 (9): 1947-55, 1996.
[PUBMED Abstract]
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Murray N, Coy P, Pater JL, et al.: Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11 (2): 336-44, 1993.
[PUBMED Abstract]
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Johnson BE, Bridges JD, Sobczeck M, et al.: Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. J Clin Oncol 14 (3): 806-13, 1996.
[PUBMED Abstract]
-
Turrisi AT 3rd, 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 340 (4): 265-71, 1999.
[PUBMED Abstract]
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Wolf M, Holle R, Hans K, et al.: Analysis of prognostic factors in 766 patients with small cell lung cancer (SCLC): the role of sex as a predictor for survival. Br J Cancer 63 (6): 986-92, 1991.
[PUBMED Abstract]
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Rawson NS, Peto J: An overview of prognostic factors in small cell lung cancer. A report from the Subcommittee for the Management of Lung Cancer of the United Kingdom Coordinating Committee on Cancer Research. Br J Cancer 61 (4): 597-604, 1990.
[PUBMED Abstract]
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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 72 (10): 901-12, 1997.
[PUBMED Abstract]
Back to Top Cellular Classification
Review of pathologic material by an experienced lung cancer pathologist is
important prior to initiating treatment of any patient with small cell lung
cancer (SCLC). The intermediate subtype of SCLC and the more readily
recognized lymphocyte-like or oat cell subtype are equally responsive to
treatment.
The current classification of subtypes of SCLC is:[1]
- Small cell carcinoma.
- Mixed small cell/large cell carcinoma.
- Combined small cell carcinoma (i.e., SCLC combined with
neoplastic squamous and/or glandular components).
Neuroendocrine carcinomas of the lung represent a spectrum of disease. At one
extreme is SCLC, which has a poor prognosis. At the other
extreme are bronchial carcinoids, which have an excellent prognosis after surgical
excision.[2] Between these extremes is an unusual entity called
well-differentiated neuroendocrine carcinoma of the lung.[3] It has been
referred to as malignant carcinoid, metastasizing bronchial adenoma,
pleomorphic carcinoid, nonbenign carcinoid tumor, and atypical carcinoid. Like
SCLC, it occurs primarily in cigarette smokers, but it
metastasizes less frequently. The 5-year survival rate is more than 50% in
some series, and surgical cure appears possible in most stage I patients.
Careful diagnosis is important, however, since the differential pathologic
diagnosis from SCLC may be difficult.
References
-
Hirsch FR, Matthews MJ, Aisner S, et al.: Histopathologic classification of small cell lung cancer. Changing concepts and terminology. Cancer 62 (5): 973-7, 1988.
[PUBMED Abstract]
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Harpole DH Jr, Feldman JM, Buchanan S, et al.: Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg 54 (1): 50-4; discussion 54-5, 1992.
[PUBMED Abstract]
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Lequaglie C, Patriarca C, Cataldo I, et al.: Prognosis of resected well-differentiated neuroendocrine carcinoma of the lung. Chest 100 (4): 1053-6, 1991.
[PUBMED Abstract]
Back to Top Stage Information
Staging procedures are important in distinguishing patients who have disease
limited to their thorax from those who have distant metastases. Determining
the stage of cancer by nonsurgical means allows a better assessment of
prognosis and identifies sites of tumor that can be evaluated for response.
Also, the choice of treatment is usually influenced by stage, particularly when
chest radiation therapy or surgical excision is added to chemotherapy for patients
with limited-stage disease. Staging procedures commonly used to document
distant metastases include bone marrow examination, computed tomographic (CT) or
magnetic resonance imaging scans of the brain, CT scans
of the chest and the abdomen, and radionuclide bone scans.
Because occult or overt metastatic disease is present at diagnosis in most
patients, survival is usually not affected by small differences in the amount
of locoregional tumor involvement. The detailed TNM staging system
developed for lung cancer by the American Joint Committee on Cancer is
not commonly employed in patients with small cell lung cancer (SCLC). (Refer to the PDQ
summary on Non-Small Cell Lung Cancer Treatment for more information.) A simple two-stage system developed by the Veterans
Administration Lung Cancer Study Group is more commonly used for staging SCLC patients.
Limited-stage disease
Limited-stage SCLC means tumor confined to the hemithorax of
origin, the mediastinum, and the supraclavicular nodes, which can be
encompassed within a tolerable radiation therapy port. No
universally accepted definition of this term is available, and patients with pleural
effusion, massive pulmonary tumor, and contralateral supraclavicular nodes have
been both included within and excluded from limited stage by various groups.
Extensive-stage disease
Extensive-stage SCLC means tumor that is too widespread to be
included within the definition of limited-stage disease above. Patients with
distant metastases (M1) are always considered to have extensive-stage
disease.[1,2]
References
-
Ihde D, Souhami B, Comis R, et al.: Small cell lung cancer. Lung Cancer 17 (Suppl 1): S19-21, 1997.
[PUBMED Abstract]
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Mountain CF: Revisions in the International System for Staging Lung Cancer. Chest 111 (6): 1710-7, 1997.
[PUBMED Abstract]
Back to Top Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
The majority of patients with small cell lung cancer (SCLC) die of their tumor despite
the best available treatment. Most of the improvements in the survival of
patients with SCLC are attributable to clinical trials that
have attempted to improve on the best available and most accepted therapy. Patient
entry into such studies is highly desirable.
Treatments under clinical evaluation in SCLC include studies
of the timing of thoracic radiation therapy (for patients with limited-stage
disease) and studies evaluating the role of surgery for stage I patients in conjunction
with varying drug doses in current regimens, using different schedules of
chemotherapeutic agents, and using new drug regimens composed of standard and
new agents.[1] Information about ongoing clinical trials is available from the
NCI Web site.
Chemotherapy improves the survival of patients with limited-stage or extensive-stage SCLC, but it is curative in only a minority of patients.[1,2] Prospective randomized trials have not demonstrated a consistent survival
advantage for patients treated with higher doses of chemotherapy.[3,4] One
retrospective review of chemotherapy trials did not show consistent evidence
for improved response rates or survival with more dose-intensive chemotherapy
regimens.[5][Level of evidence: 1iiA] Even chemotherapy of the intensity used
in autologous bone marrow transplant regimens has not clearly been shown to
improve survival in patients with SCLC.[6] An intergroup study that
compared the combination of dose-intensive cisplatin, vincristine, doxorubicin,
and etoposide with standard doses of cyclophosphamide, doxorubicin,
vincristine/etoposide, and cisplatin found that the more dose-intensive regimen produced a higher response rate but at the cost of increased
treatment-related mortality and did not result in improved progression-free or
overall survival.[7][Level of evidence: 1iiA]
References
-
Comis RL, Friedland DM, Good BC: Small-cell lung cancer: a perspective on the past and a preview of the future. Oncology (Huntingt) 12 (1 Suppl 2): 44-50, 1998.
[PUBMED Abstract]
-
Agra Y, Pelayo M, Sacristan M, et al.: Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev (4): CD001990, 2003.
[PUBMED Abstract]
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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 12 (10): 2022-34, 1994.
[PUBMED Abstract]
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Arriagada R, Le Chevalier T, Pignon JP, et al.: Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med 329 (25): 1848-52, 1993.
[PUBMED Abstract]
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Klasa RJ, Murray N, Coldman AJ: Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung. J Clin Oncol 9 (3): 499-508, 1991.
[PUBMED Abstract]
-
Elias AD, Ayash L, Frei E 3rd, et al.: Intensive combined modality therapy for limited-stage small-cell lung cancer. J Natl Cancer Inst 85 (7): 559-66, 1993.
[PUBMED Abstract]
-
Murray N, Livingston RB, Shepherd FA, et al.: Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol 17 (8): 2300-8, 1999.
[PUBMED Abstract]
Back to Top Limited-Stage Small Cell Lung Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
In patients with limited-stage small cell lung cancer (SCLC), combination chemotherapy produces
results that are clearly superior to single-agent treatment, and moderately
intensive doses of drugs are superior to doses that produce only minimal or
mild hematologic toxic effects. Current programs yield overall objective
response rates of 65% to 90% and complete response rates of 45% to 75%.
Because of the frequent presence of occult metastatic disease, chemotherapy is
the cornerstone of treatment for patients with limited-stage SCLC. Combinations containing two or more drugs are needed for maximal effect.
Mature results of prospective randomized trials suggest that combined modality
therapy produces a modest but significant improvement in survival compared with
chemotherapy alone. Two meta-analyses showed an improvement in 3-year survival
rates of about 5% for those receiving chemotherapy and radiation therapy
compared with those receiving chemotherapy alone.[1,2] Most of the benefit
occurred in patients younger than 65 years. Combined modality treatment is
associated with increased morbidity and, in some trials, increased
treatment-related mortality from pulmonary and hematologic toxic effects;
proper administration requires close collaboration between medical and
radiation oncologists.[3] In general, those studies including the SWOG-S0124 trial, for example showing a positive effect
for combined modality therapy employed thoracic radiation therapy early in the course
of treatment and concurrently with chemotherapy.[3-6]
Studies strongly suggest that minimal tumor doses in the range of 40 Gy to
45 Gy or more (standard fractionation) are necessary to effectively control
tumors in the thorax.
The combination of etoposide and cisplatin chemotherapy with concurrent chest
radiation therapy has now been used in multiple single institutional studies
and in cooperative group studies. These studies have consistently achieved
median survivals of 18 to 24 months and 40% to 50% 2-year survival with less than a 3% treatment-related mortality.[3-7] Once-daily and twice-daily chest
radiation schedules have been used in regimens with etoposide and cisplatin.
One randomized study showed a modest survival advantage in favor of twice-daily
radiation therapy given for 3 weeks, compared with once-daily radiation therapy
given for 5 weeks (26% vs. 16% at 5 years, P = .04). Although single daily fractions to higher doses are feasible, their clinical benefits are yet to be defined.[8][Level of evidence: 3iiiA] Esophagitis was increased with twice-daily treatment.[9][Level of evidence: 1iiA] The
current standard treatment of patients with limited-stage SCLC should be a combination containing etoposide and cisplatin plus chest
radiation therapy administered during the first or second cycle of chemotherapy
administration.
The relative effectiveness of two- to five-drug regimens and different schedules of
chest radiation therapy appear to be similar. A representative selection of
regimens incorporating chemotherapy plus chest radiation therapy are listed
below. The use of alternating chemotherapy regimens has not proven more
effective than the consistent administration of a single regimen.[3,6,7,10-12]
The optimal duration of chemotherapy for patients with limited-stage SCLC is not clearly defined, but no improvement exists in survival
after the duration of drug administration exceeds 3 to 6 months.[3,7,13] No evidence is available from randomized trials EORTC-LCCG and European Lung Cancer Working Party that maintenance chemotherapy prolongs
survival for patients with limited-stage SCLC.[10,14]
Patients presenting with superior vena cava syndrome are treated with
combination chemotherapy with or without radiation therapy.[15,16] (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.) A small
minority of limited-stage patients with adequate pulmonary function and with
tumor pathologically confined to the lung of origin, or the lung and
ipsilateral hilar lymph nodes, may possibly benefit from surgical resection
with or without adjuvant chemotherapy.[17-20]
Patients treated with chemotherapy with or without chest radiation therapy who have
achieved a complete remission can be considered for administration of
prophylactic cranial irradiation (PCI). Patients whose cancer can be
controlled outside the brain have a 60% actuarial risk of developing central
nervous system metastases within 2 to 3 years after starting treatment.[21,22]
The majority of these patients relapse only in their brain, and nearly all of
those who relapse in their central nervous system die of their cranial
metastases.[3,7,22] The risk of developing central nervous system metastases
can be reduced by more than 50% by the administration of PCI in doses of 24
Gy.[22] A meta-analysis of seven randomized trials evaluating the value of PCI in
patients in complete remission reported improvement in brain recurrence,
disease-free survival, and overall survival (OS) with the addition of PCI. The 3-year OS was improved from 15% to 21% with PCI.[22][Level of evidence: 1iiA]
Retrospective studies have shown that long-term survivors of SCLC (>2 years from the start of treatment) have a high incidence of central
nervous system impairment.[23-25] Prospective studies have shown that
patients treated with PCI do not have significantly worse neuropsychological
function than patients not treated.[22] In addition, the majority of patients
with small cell lung cancer have neuropsychological abnormalities present
before the start of cranial irradiation and have no detectable decline in their
neurological status for as long as 2 years after the start of their cranial
irradiation.[26] Patients treated for SCLC continue to have
declining neuropsychologic function after 2 years from the start of
treatment.[23-25] Additional neuropsychologic testing of patients
beyond 2 years from the start of treatment will be needed before concluding
that PCI does not contribute to the decline in intellectual function.
Standard treatment options:
- Combination chemotherapy with chest
irradiation (with or without PCI given to patients with complete responses):
- EC: etoposide plus cisplatin plus 45 Gy chest radiation therapy.[3,7]
- Combination chemotherapy (with or without PCI in patients with complete
responses), especially in patients with impaired pulmonary function or poor
performance status.
- Surgical resection followed by chemotherapy or chemotherapy plus chest
radiation therapy (with or without PCI in patients with complete responses) for
patients with stage I disease.[17-20]
Treatment options under clinical evaluation:
Areas of active clinical evaluation for patients with limited-stage SCLC
include new drug regimens, variation of drug doses in current regimens,
surgical resection of the primary tumor, new radiation therapy schedules and
techniques (e.g., three-dimensional treatment planning), and timing of thoracic
radiation.[27,28]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with limited stage small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Pignon JP, Arriagada R, Ihde DC, et al.: A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 327 (23): 1618-24, 1992.
[PUBMED Abstract]
-
Warde P, Payne D: Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 10 (6): 890-5, 1992.
[PUBMED Abstract]
-
Murray N, Coy P, Pater JL, et al.: Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11 (2): 336-44, 1993.
[PUBMED Abstract]
-
Turrisi AT 3rd, Glover DJ: Thoracic radiotherapy variables: influence on local control in small cell lung cancer limited disease. Int J Radiat Oncol Biol Phys 19 (6): 1473-9, 1990.
[PUBMED Abstract]
-
McCracken JD, Janaki LM, Crowley JJ, et al.: Concurrent chemotherapy/radiotherapy for limited small-cell lung carcinoma: a Southwest Oncology Group Study. J Clin Oncol 8 (5): 892-8, 1990.
[PUBMED Abstract]
-
Takada M, Fukuoka M, Kawahara M, et al.: Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 20 (14): 3054-60, 2002.
[PUBMED Abstract]
-
Johnson BE, Bridges JD, Sobczeck M, et al.: Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. J Clin Oncol 14 (3): 806-13, 1996.
[PUBMED Abstract]
-
Bogart JA, Herndon JE 2nd, Lyss AP, et al.: 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys 59 (2): 460-8, 2004.
[PUBMED Abstract]
-
Turrisi AT 3rd, 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 340 (4): 265-71, 1999.
[PUBMED Abstract]
-
Giaccone G, Dalesio O, McVie GJ, et al.: Maintenance chemotherapy in small-cell lung cancer: long-term results of a randomized trial. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 11 (7): 1230-40, 1993.
[PUBMED Abstract]
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Goodman GE, Crowley JJ, Blasko JC, et al.: Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol 8 (1): 39-47, 1990.
[PUBMED Abstract]
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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 83 (12): 855-61, 1991.
[PUBMED Abstract]
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Bleehen NM, Girling DJ, Machin D, et al.: A randomised trial of three or six courses of etoposide cyclophosphamide methotrexate and vincristine or six courses of etoposide and ifosfamide in small cell lung cancer (SCLC). I: Survival and prognostic factors. Medical Research Council Lung Cancer Working Party. Br J Cancer 68 (6): 1150-6, 1993.
[PUBMED Abstract]
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Sculier JP, Paesmans M, Bureau G, et al.: Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party. J Clin Oncol 14 (8): 2337-44, 1996.
[PUBMED Abstract]
-
Urban T, Lebeau B, Chastang C, et al.: Superior vena cava syndrome in small-cell lung cancer. Arch Intern Med 153 (3): 384-7, 1993.
[PUBMED Abstract]
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Würschmidt F, Bünemann H, Heilmann HP: Small cell lung cancer with and without superior vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases. Int J Radiat Oncol Biol Phys 33 (1): 77-82, 1995.
[PUBMED Abstract]
-
Osterlind K, Hansen M, Hansen HH, et al.: Treatment policy of surgery in small cell carcinoma of the lung: retrospective analysis of a series of 874 consecutive patients. Thorax 40 (4): 272-7, 1985.
[PUBMED Abstract]
-
Shepherd FA, Ginsberg RJ, Patterson GA, et al.: A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. A University of Toronto Lung Oncology Group study. J Thorac Cardiovasc Surg 97 (2): 177-86, 1989.
[PUBMED Abstract]
-
Prasad US, Naylor AR, Walker WS, et al.: Long term survival after pulmonary resection for small cell carcinoma of the lung. Thorax 44 (10): 784-7, 1989.
[PUBMED Abstract]
-
Smit EF, Groen HJ, Timens W, et al.: Surgical resection for small cell carcinoma of the lung: a retrospective study. Thorax 49 (1): 20-2, 1994.
[PUBMED Abstract]
-
Nugent JL, Bunn PA Jr, Matthews MJ, et al.: CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer 44 (5): 1885-93, 1979.
[PUBMED Abstract]
-
Aupérin 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 341 (7): 476-84, 1999.
[PUBMED Abstract]
-
Johnson BE, Patronas N, Hayes W, et al.: Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol 8 (1): 48-56, 1990.
[PUBMED Abstract]
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Laukkanen E, Klonoff H, Allan B, et al.: The role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae. Int J Radiat Oncol Biol Phys 14 (6): 1109-17, 1988.
[PUBMED Abstract]
-
Cull A, Gregor A, Hopwood P, et al.: Neurological and cognitive impairment in long-term survivors of small cell lung cancer. Eur J Cancer 30A (8): 1067-74, 1994.
[PUBMED Abstract]
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Komaki R, Meyers CA, Shin DM, et al.: Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys 33 (1): 179-82, 1995.
[PUBMED Abstract]
-
Turrisi AT 3rd: Incorporation of radiotherapy fractionation in the combined-modality treatment of limited small-cell lung cancer. Chest 103 (4 Suppl): 418S-422S, 1993.
[PUBMED Abstract]
-
Ettinger DS: Concurrent paclitaxel-containing regimens and thoracic radiation therapy for limited-disease small cell lung cancer. Semin Radiat Oncol 9 (2 Suppl 1): 148-50, 1999.
[PUBMED Abstract]
Back to Top Extensive-Stage Small Cell Lung Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
As in limited-stage small cell cancer (SCLC), chemotherapy should be given as
multiple agents in doses associated with at least moderate toxic effects to produce the best results in patients with extensive-stage disease. Doses and
schedules used in current programs yield overall response rates of 70% to 85%
and complete response rates of 20% to 30% in patients with extensive-stage disease. Since
overt disseminated disease is present, combination chemotherapy is the
cornerstone of treatment of this stage of SCLC. Combinations
containing two or more drugs are needed for maximal benefit.
The relative effectiveness of most two- to four-drug combination programs appears
similar, and a large number of potential combinations are available. Some studies
such as the ECOG-7593 trial, for example, have administered two of these or other regimens in alternating sequences, but
no proof exists that this strategy yields substantial survival
improvement.[1-4] A phase III study conducted in Japan compared a standard two-drug regimen of cisplatin and etoposide with a combination of cisplatin and
irinotecan.[5][Level of evidence: 1iiA] The planned enrollment was 230
patients younger than 70 years, however, the trial was stopped early with a
total of 154 patients when an interim analysis found a significant difference
favoring the irinotecan arm. The median survival in the cisplatin and
irinotecan group was 12.8 months (95% confidence interval [CI], 11.7–15.2
months), while it was 9.4 months in the cisplatin and etoposide arm (95% CI, 8.1–10.8 months). The 2-year survival was 19.5% versus 5.2%. Hematologic toxic
effects were more severe in the etoposide and cisplatin treated patients, while
gastrointestinal toxic effects were worse in the irinotecan-treated and cisplatin-treated patients. However, no difference in response rate, median time-to-progression, or overall survival (OS) was reported from a second study that involved 331 patients with extensive disease and compared cisplatin and etoposide with a modified weekly regimen of cisplatin and irinotecan.[6][Level of evidence: 1iiA] The modified weekly irinotecan/cisplatin regimen resulted in less myelosuppression but more diarrhea and vomiting.[6][Level of evidence: 1iiA] A third study (SWOG-S0124) comparing irinotecan versus etoposide with cisplatin using doses and schedules similar to the original Japanese study is under way. In a randomized trial of 784 patients, the combination of oral topotecan given with cisplatin for 5 days was not found to be superior to etoposide and cisplatin.[7] The 1-year survival rate was 31% (95% CI, 27%–36%) and was deemed to be noninferior as the difference of -0.03 met the predefined criteria of no more than 10% absolute difference in 1-year survival.
The optimal duration of chemotherapy is not clearly defined, but no
obvious improvement in survival occurs when the duration of drug administration
exceeds 6 months.[8,9] No clear evidence is available from reported data that
maintenance chemotherapy will improve survival duration.[10-13]
Combination chemotherapy plus chest radiation therapy does not appear to improve
survival compared with chemotherapy alone in patients with extensive-stage SCLC. Radiation therapy, however, plays an extremely important role in
palliation of symptoms of the primary tumor and of metastatic disease,
particularly brain, epidural, and bone metastases.
Chest radiation therapy is sometimes given for superior vena cava syndrome, but
chemotherapy alone, with irradiation reserved for nonresponding patients, is
appropriate initial treatment. (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.) Brain metastases are appropriately treated with
whole-brain radiation therapy. Intracranial metastases from small
cell carcinoma, however, may respond to chemotherapy as readily as metastases in other
organs.[13,14]
Patients with small cell lung cancer treated with chemotherapy with or without
chest irradiation, who have achieved a complete remission, can be considered for
administration of prophylactic cranial irradiation (PCI). Patients whose
cancer can be controlled outside the brain have a 60% actuarial risk of
developing central nervous system metastases within 2 to 3 years after starting
treatment.[15,16] The majority of these patients relapse only in their brain,
and nearly all of those who relapse in their central nervous system die of
their cranial metastases.[16-18] The risk of developing central nervous system
metastases can be reduced by more than 50% by the administration of PCI in
doses of 24 Gy.[16] A meta-analysis of seven randomized trials evaluating the value of PCI in
patients in complete remission reported improvement in brain recurrence,
disease-free survival, and OS with the addition of PCI. The 3-year OS was improved from 15% to 21% with PCI.[16][Level of evidence: 1iiA]
Retrospective studies have shown that long-term
survivors of SCLC (>2 years from the start of treatment) have
a high incidence of central nervous system impairment.[19-21] Prospective studies, however, have shown that patients treated with PCI do not have
detectably different neuropsychological function than patients not treated.[16]
In addition, the majority of patients with SCLC have
neuropsychological abnormalities present before the start of cranial
irradiation and have no detectable decline in their neurological status for as long as 2
years after the start of their cranial irradiation.[22] Patients treated for
SCLC continue to have declining neuropsychologic function
after 2 years from the start of treatment.[19-21] Additional
neuropsychologic testing of patients beyond 2 years from the start of treatment
will be needed before concluding that PCI does not contribute to the decline in
intellectual function.
Many more patients with extensive-stage SCLC have greatly
impaired performance status at the time of diagnosis when compared with patients
with limited-stage disease. Such patients have a poor prognosis and tolerate
aggressive chemotherapy or combined modality therapy poorly. Single-agent
intravenous, oral, and low-dose biweekly regimens have been developed for these
patients.[23-26] Prospective randomized studies, however, have shown that
patients with a poor prognosis who are treated with conventional regimens live
longer than those treated with the single-agent or low-dose regimens.[25-27]
Standard treatment options:
- Combination chemotherapy with one of the following regimens with or without
PCI given to patients with complete responses:
The following regimens produce similar survival outcomes:
- CAV: cyclophosphamide plus doxorubicin plus vincristine.[28,29]
- CAE: cyclophosphamide plus doxorubicin plus etoposide.[30]
- EP or EC: etoposide plus cisplatin or carboplatin.[31,32]
- ICE: ifosfamide plus carboplatin plus etoposide.[33]
- Cisplatin plus irinotecan.[5]
Other regimens that appear to produce similar survival outcomes but have been
studied less extensively or are in less common use include:
- Cyclophosphamide plus doxorubicin plus etoposide plus vincristine.[34]
- CEV: cyclophosphamide plus etoposide plus vincristine.[35]
- Single-agent etoposide.[23]
- PET: cisplatin plus etoposide plus paclitaxel.[36]
- Radiation therapy to sites of metastatic disease unlikely to be immediately
palliated by chemotherapy, especially brain, epidural, and bone metastases.
- Identification of effective new agents is difficult in patients who have
previously been treated with standard chemotherapy because response rates to
agents, even of known efficacy, are known to be lower than in previously
untreated patients. This situation led to the suggestion that patients with
extensive disease who are medically stable be treated with new agents under
evaluation, with provisions for early change to standard combination therapy if
there is no response.[37] Such a strategy has been shown to be feasible, with
survival comparable to survival with initial standard therapy, as long as the
patients with extensive disease are carefully chosen.[38-40] A variety of
other strategies have been proposed, depending on the activity of the new agent
in other tumors, in preclinical SCLC models, or the activity
of drug analogs.[41] Active single agents undergoing further evaluation
include paclitaxel and topotecan.[42,43]
Treatment options under clinical evaluation:
Areas of active clinical evaluation in extensive-stage SCLC
include evaluation of new drug regimens, dose intensity, alternative drug
schedules, and high-dose chemotherapy. A meta-analysis of long-term outcomes
in extensive-stage disease did not show consistent evidence for improved
response rates or survival for more intense chemotherapy regimens.[44][Level of evidence: 1iiA]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with extensive stage small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
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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 107 (4): 451-8, 1987.
[PUBMED Abstract]
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Wolf M, Pritsch M, Drings P, et al.: Cyclic-alternating versus response-oriented chemotherapy in small-cell lung cancer: a German multicenter randomized trial of 321 patients. J Clin Oncol 9 (4): 614-24, 1991.
[PUBMED Abstract]
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Roth BJ, Johnson DH, Einhorn LH, et al.: Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 10 (2): 282-91, 1992.
[PUBMED Abstract]
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Schiller JH, Adak S, Cella D, et al.: Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 19 (8): 2114-22, 2001.
[PUBMED Abstract]
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Noda K, Nishiwaki Y, Kawahara M, et al.: Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346 (2): 85-91, 2002.
[PUBMED Abstract]
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Hanna N, Bunn PA Jr, Langer C, et al.: Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 24 (13): 2038-43, 2006.
[PUBMED Abstract]
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Eckardt JR, von Pawel J, Papai Z, et al.: Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol 24 (13): 2044-51, 2006.
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Spiro SG, Souhami RL, Geddes DM, et al.: Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer 59 (4): 578-83, 1989.
[PUBMED Abstract]
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Bleehen NM, Girling DJ, Machin D, et al.: A randomised trial of three or six courses of etoposide cyclophosphamide methotrexate and vincristine or six courses of etoposide and ifosfamide in small cell lung cancer (SCLC). I: Survival and prognostic factors. Medical Research Council Lung Cancer Working Party. Br J Cancer 68 (6): 1150-6, 1993.
[PUBMED Abstract]
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Giaccone G, Dalesio O, McVie GJ, et al.: Maintenance chemotherapy in small-cell lung cancer: long-term results of a randomized trial. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 11 (7): 1230-40, 1993.
[PUBMED Abstract]
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Controlled trial of twelve versus six courses of chemotherapy in the treatment of small-cell lung cancer. Report to the Medical Research Council by its Lung Cancer Working Party. Br J Cancer 59 (4): 584-90, 1989.
[PUBMED Abstract]
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Sculier JP, Paesmans M, Bureau G, et al.: Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party. J Clin Oncol 14 (8): 2337-44, 1996.
[PUBMED Abstract]
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Twelves CJ, Souhami RL, Harper PG, et al.: The response of cerebral metastases in small cell lung cancer to systemic chemotherapy. Br J Cancer 61 (1): 147-50, 1990.
[PUBMED Abstract]
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Lee JS, Murphy WK, Glisson BS, et al.: Primary chemotherapy of brain metastasis in small-cell lung cancer. J Clin Oncol 7 (7): 916-22, 1989.
[PUBMED Abstract]
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Nugent JL, Bunn PA Jr, Matthews MJ, et al.: CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer 44 (5): 1885-93, 1979.
[PUBMED Abstract]
-
Aupérin 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 341 (7): 476-84, 1999.
[PUBMED Abstract]
-
Murray N, Coy P, Pater JL, et al.: Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11 (2): 336-44, 1993.
[PUBMED Abstract]
-
Johnson BE, Bridges JD, Sobczeck M, et al.: Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. J Clin Oncol 14 (3): 806-13, 1996.
[PUBMED Abstract]
-
Johnson BE, Patronas N, Hayes W, et al.: Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol 8 (1): 48-56, 1990.
[PUBMED Abstract]
-
Laukkanen E, Klonoff H, Allan B, et al.: The role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae. Int J Radiat Oncol Biol Phys 14 (6): 1109-17, 1988.
[PUBMED Abstract]
-
Cull A, Gregor A, Hopwood P, et al.: Neurological and cognitive impairment in long-term survivors of small cell lung cancer. Eur J Cancer 30A (8): 1067-74, 1994.
[PUBMED Abstract]
-
Komaki R, Meyers CA, Shin DM, et al.: Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys 33 (1): 179-82, 1995.
[PUBMED Abstract]
-
Carney DN, Grogan L, Smit EF, et al.: Single-agent oral etoposide for elderly small cell lung cancer patients. Semin Oncol 17 (1 Suppl 2): 49-53, 1990.
[PUBMED Abstract]
-
Evans WK, Radwi A, Tomiak E, et al.: Oral etoposide and carboplatin. Effective therapy for elderly patients with small cell lung cancer. Am J Clin Oncol 18 (2): 149-55, 1995.
[PUBMED Abstract]
-
Girling DJ: Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Medical Research Council Lung Cancer Working Party. Lancet 348 (9027): 563-6, 1996.
[PUBMED Abstract]
-
James LE, Gower NH, Rudd RM, et al.: A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial. Br J Cancer 73 (12): 1563-8, 1996.
[PUBMED Abstract]
-
Souhami RL, Spiro SG, Rudd RM, et al.: Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy. J Natl Cancer Inst 89 (8): 577-80, 1997.
[PUBMED Abstract]
-
Feld R, Evans WK, DeBoer G, et al.: Combined modality induction therapy without maintenance chemotherapy for small cell carcinoma of the lung. J Clin Oncol 2 (4): 294-304, 1984.
[PUBMED Abstract]
-
Greco FA, Richardson RL, Snell JD, et al.: Small cell lung cancer. Complete remission and improved survival. Am J Med 66 (4): 625-30, 1979.
[PUBMED Abstract]
-
Aisner J, Whitacre M, Van Echo DA, et al.: Combination chemotherapy for small cell carcinoma of the lung: continuous versus alternating non-cross-resistant combinations. Cancer Treat Rep 66 (2): 221-30, 1982.
[PUBMED Abstract]
-
Evans WK, Shepherd FA, Feld R, et al.: VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol 3 (11): 1471-7, 1985.
[PUBMED Abstract]
-
Skarlos DV, Samantas E, Kosmidis P, et al.: Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. A Hellenic Co-operative Oncology Group study. Ann Oncol 5 (7): 601-7, 1994.
[PUBMED Abstract]
-
Thatcher N: Ifosfamide/carboplatin/etoposide (ICE) regimen in small cell lung cancer. Lung Cancer 9(Suppl 1): s51-s67, 1993.
-
Jackson DV Jr, Case LD, Zekan PJ, et al.: Improvement of long-term survival in extensive small-cell lung cancer. J Clin Oncol 6 (7): 1161-9, 1988.
[PUBMED Abstract]
-
Hong WK, Nicaise C, Lawson R, et al.: Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group. J Clin Oncol 7 (4): 450-6, 1989.
[PUBMED Abstract]
-
Glisson BS, Kurie JM, Perez-Soler R, et al.: Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma. J Clin Oncol 17 (8): 2309-15, 1999.
[PUBMED Abstract]
-
Ettinger DS: Evaluation of new drugs in untreated patients with small-cell lung cancer: its time has come. J Clin Oncol 8 (3): 374-7, 1990.
[PUBMED Abstract]
-
Blackstein M, Eisenhauer EA, Wierzbicki R, et al.: Epirubicin in extensive small-cell lung cancer: a phase II study in previously untreated patients: a National Cancer Institute of Canada Clinical Trials Group Study. J Clin Oncol 8 (3): 385-9, 1990.
[PUBMED Abstract]
-
Evans WK, Eisenhauer EA, Cormier Y, et al.: Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer. J Clin Oncol 8 (3): 390-5, 1990.
[PUBMED Abstract]
-
Ettinger DS, Finkelstein DM, Abeloff MD, et al.: Justification for evaluating new anticancer drugs in selected untreated patients with extensive-stage small-cell lung cancer: an Eastern Cooperative Oncology Group randomized study. J Natl Cancer Inst 84 (14): 1077-84, 1992.
[PUBMED Abstract]
-
Moore TD, Korn EL: Phase II trial design considerations for small-cell lung cancer. J Natl Cancer Inst 84 (3): 150-4, 1992.
[PUBMED Abstract]
-
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 13 (6): 1430-5, 1995.
[PUBMED Abstract]
-
Schiller JH, Kim K, 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 14 (8): 2345-52, 1996.
[PUBMED Abstract]
-
Klasa RJ, Murray N, Coldman AJ: Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung. J Clin Oncol 9 (3): 499-508, 1991.
[PUBMED Abstract]
Back to Top Recurrent Small Cell Lung Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
The prognosis for patients with small cell lung cancer (SCLC) that has progressed
despite chemotherapy is exceedingly poor regardless of stage. Expected median
survival is 2 to 3 months. These patients should be considered for palliative
therapy or clinical trials. Patients who are primarily resistant to
chemotherapy, and those who have received multiple chemotherapy regimens, rarely
respond to additional treatment. Patients who have initially
responded and relapsed more than 6 months following initial treatment, however, are more
likely to respond to additional chemotherapy. While no single chemotherapy
regimen should be considered standard, those that have shown activity as second
line treatment include oral etoposide, etoposide/cisplatin,
cyclophosphamide/doxorubicin/vincristine (CAV), lomustine/methotrexate,
paclitaxel, and topotecan.[1-9][Level of evidence: 3iiiDiv] A randomized
comparison of second-line treatment with either CAV or topotecan reported no
significant difference in response rates or survival, but palliation of common
lung cancer symptoms was better with topotecan.[8][Level of evidence: 1iiC]
Some patients with intrinsic endobronchial obstructing lesions or extrinsic
compression caused by tumor have achieved successful palliation with endobronchial
laser therapy (for endobronchial lesions only) and/or brachytherapy.[10]
Expandable metal stents can be safely inserted under local anesthesia via the
bronchoscope, which results in improved symptoms and pulmonary function in patients
with malignant airways obstruction.[11] Patients with progressive
intrathoracic tumor after failing initial chemotherapy can achieve significant
tumor responses, palliation of symptoms, and short-term local control with
external-beam radiation therapy. Only the rare patient, however, will
experience long-term survival following salvage radiation therapy.[12]
Patients with central nervous system recurrences can often obtain palliation of
symptoms with radiation therapy and/or additional chemotherapy. The majority
of patients treated with radiation therapy obtain objective responses and
improvement following radiation therapy.[13] A retrospective review showed
that 43% of patients treated with additional chemotherapy at the time of central nervous system relapse respond to second-line chemotherapy.[14]
Standard treatment options:
- Palliative radiation therapy.[12]
- Salvage chemotherapy can provide some palliative benefit for patients
previously sensitive to standard chemotherapy.[2,4-9]
- Local palliation with endobronchial laser therapy, endobronchial stents,
and/or brachytherapy.[10,11]
- Clinical trials of phase I or phase II drugs.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Greco FA: Treatment options for patients with relapsed small cell lung cancer. Lung Cancer 9(Suppl 1): s85-s89, 1993.
-
Johnson DH, Greco FA, Strupp J, et al.: Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol 8 (10): 1613-7, 1990.
[PUBMED Abstract]
-
Spiro SG, Souhami RL, Geddes DM, et al.: Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer 59 (4): 578-83, 1989.
[PUBMED Abstract]
-
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 3 (1): 65-71, 1985.
[PUBMED Abstract]
-
Sekine I, Nishiwaki Y, Kakinuma R, et al.: Late recurrence of small-cell lung cancer: treatment and outcome. Oncology 53 (4): 318-21, 1996 Jul-Aug.
[PUBMED Abstract]
-
Chute JP, Kelley MJ, Venzon D, et al.: Retreatment of patients surviving cancer-free 2 or more years after initial treatment of small cell lung cancer. Chest 110 (1): 165-71, 1996.
[PUBMED Abstract]
-
Ardizzoni A, Hansen H, Dombernowsky P, 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. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 15 (5): 2090-6, 1997.
[PUBMED Abstract]
-
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 17 (2): 658-67, 1999.
[PUBMED Abstract]
-
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 77 (2): 347-51, 1998.
[PUBMED Abstract]
-
Miller JI Jr, Phillips TW: Neodymium:YAG laser and brachytherapy in the management of inoperable bronchogenic carcinoma. Ann Thorac Surg 50 (2): 190-5; discussion 195-6, 1990.
[PUBMED Abstract]
-
Wilson GE, Walshaw MJ, Hind CR: Treatment of large airway obstruction in lung cancer using expandable metal stents inserted under direct vision via the fibreoptic bronchoscope. Thorax 51 (3): 248-52, 1996.
[PUBMED Abstract]
-
Ochs JJ, Tester WJ, Cohen MH, et al.: "Salvage" radiation therapy for intrathoracic small cell carcinoma of the lung progressing on combination chemotherapy. Cancer Treat Rep 67 (12): 1123-6, 1983.
[PUBMED Abstract]
-
Carmichael J, Crane JM, Bunn PA, et al.: Results of therapeutic cranial irradiation in small cell lung cancer. Int J Radiat Oncol Biol Phys 14 (3): 455-9, 1988.
[PUBMED Abstract]
-
Kristensen CA, Kristjansen PE, Hansen HH: Systemic chemotherapy of brain metastases from small-cell lung cancer: a review. J Clin Oncol 10 (9): 1498-502, 1992.
[PUBMED Abstract]
Back to Top Get More Information From NCI
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Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.
Back to Top Changes to This Summary (05/22/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
Back to Top More Information
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Additional PDQ Summaries
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