Treatment of lung cancer--state of the art in 2000

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.     

Recent topics in chemotherapy for elderly patients with lung cancer

With the prolongation of life expectancy in Japan, lung cancer is increasing not only in the elderly but also in poor-risk patients who can not undergo standard chemotherapy. Because survival benefits from chemotherapy are clearly expected in patients with small-cell lung cancer (SCLC), standard chemotherapy should be established for the elderly as well as for poor-risk patients with SCLC. We recently reported that the combination of AUC-based carboplatin and a standard dose of intravenous etoposide was an active and relatively nontoxic regimen for elderly patients with SCLC (J Clin Oncol 17: 3540-3545, 1999). Had chemotherapy with concurrent chest irradiation been used for patients with limited disease (LD), better survival might have been achieved in this study. However, Pignon et al. reported that combined chemoradiotherapy in elderly patients with LD-SCLC is a possible poor prognostic factor in their meta-analysis. A recent randomized controlled clinical trial has shown that vinorelbine monotherapy contributed to longer survival in elderly patients with advanced non-small-cell lung cancer (NSCLC), compared to best supportive care. Several retrospective studies have shown that cisplatin can be safely and effectively administered to elderly patients who are eligible for protocol treatment. However, there have been no randomized trials indicating that cisplatin-based combination chemotherapy improves survival in elderly patients with advanced NSCLC, compared to single-agent chemotherapy. Similarly, the role of combined chemoradiotherapy remains controversial in elderly patients with locally advanced NSCLC. Thus, standard therapies proven to be beneficial to non-elderly patients with lung cancer have not always been proven to be beneficial to elderly patients. In order to solve these difficult problems, phase III studies are warranted in elderly or poor-risk patients with lung cancer. Moreover, new agents with relatively low toxicities recently approved in Japan should be applied in clinical trials for the elderly or poor-risk patients with lung cancer.     

Time and chemotherapy treatment trends in the treatment of elderly patients (age >/=70 years) with small cell lung cancer

Platinum-based treatment for small cell lung cancer (SCLC) has been established since 1995. This study investigates treatment outcome of elderly patients (age >/=70 years) with SCLC over the past 20 years in a large UK cancer centre. Comparison of all-cause survival was assessed in patients presenting between two predefined time periods: 1982-1994 and 1995-2003. All the survival analysis were adjusted for stage and performance status and age if appropriate. Survival between different chemotherapy treatment regimens was compared. A total of 322 elderly patients (31% of all) registered between 1982-2003 received chemotherapy for SCLC. Patients presenting in 1995-2003 had an overall better median survival (43 vs 25 weeks) and a 1-year survival (37 vs 14%) than patients presenting in 1982-1994 (P<0.001). This applied to patients with both limited and extensive stage disease and all age groups. There was a trend towards the use of more platinum-based treatments in the later cohort but the use of radiotherapy remained constant. Patients who received platinum combinations (Carboplatin or Cisplatin) had significantly improved survival over those who received single agents or other combinations (P<0.001) and there was no significant difference between carboplatin and cisplatin (P=0.7). The analysis demonstrates that there has been a significant improvement in survival for elderly patients with lung cancer treated by chemotherapy in the past 20 years despite more very elderly patients being treated with a poorer performance status. This change is probably multifactorial and may be due to the increased use of platinum-based treatment and improved supportive care.     

New targeted therapies and small-cell lung cancer

Small-cell lung cancer (SCLC) accounts for almost 15% of lung carcinomas. Chemotherapy is the cornerstone of treatment of patients with SCLC. In limited disease, median survival is about 12-20 months, with no more than 6%-12% of patients surviving beyond 5 years. In extensive disease, median survival is 7-12 months, with < 5% of patients living beyond 2 years and a 5-year survival rate of just 2%. Several therapeutic approaches have been used in an attempt to improve the outcome of SCLC. Among these, a better understanding of tumor biology and the subsequent development of novel therapeutic strategies have been identified as a possible approach for increasing the survival rate of patients with SCLC. Several targeted agents have been introduced into clinical trials in SCLC, and a few phase III studies, including matrix metalloproteinase inhibitors, thalidomide, and vaccines, have already produced definitive results. Currently, negative results are more commonly reported than positive ones. However, this first generation of clinical trials represents only the beginning of clinical research in this field. To date, no targeted therapy has been approved for use in the treatment of patients with SCLC. Nevertheless, clinical research in this field is still in progress considering that several new targeted agents, such as antiangiogenic agents and mammalian target of rapamycin inhibitors, offer a promise of improved outcomes. This review will focus on the reported results and the future development of the main novel biologic agents for the treatment of patients with SCLC.     

Population-based outcomes for small cell lung cancer: impact of standard management policies in British Columbia

Survival data for small cell lung cancer (SCLC) is typically reported from clinical trials or institutional series that include patients fit enough to meet treatment criteria. The denominator of all SCLC patients from which the treated population is derived is rarely reported and the impact of new treatment strategies on population-based outcomes is difficult to measure. The British Columbia Cancer Agency (BCCA) is a single centralized agency that coordinates cancer treatment services in the province and develops and circulates province-wide treatment guidelines. All SCLC cases diagnosed in BC in 1990 and 1995 (n=331 and 297, respectively) were identified. These 2 years were chosen specifically to examine the impact of a change in practice guidelines from consolidative to early concurrent thoracic radiation (RT) for patients with limited stage disease. Demographic, staging, treatment, and outcome details were obtained for 100% of cases. A total of 628 patients were reviewed, 207 with limited stage disease (LSCLC) and 407 with extensive stage disease (ESCLC); 14 cases diagnosed at post-mortem were excluded. Of the 207 patients with LSCLC disease, 170 (82%) received chemotherapy, and 138 (81%) of those that received chemotherapy also received thoracic radiation. A similar proportion (73 and 70%) of LSCLC patients received thoracic RT in both years but more patients in 1995 received early concurrent versus consolidative thoracic RT compared to those treated in 1990 (64% versus 17%, respectively, P=0.001). Of the 407 patients with ESCLC, 71% received chemotherapy. The median overall survival for all patients was 7 months. Patients with LSCLC who received any chemotherapy had a median survival of 14.3 months (26.9 and 9.9% for 2- and 5-year survival, respectively). Patients with LSCLC who received chemotherapy plus thoracic RT had a median survival of 15.1 months (32 and 12% for 2- and 5-year survival, respectively). Early concurrent thoracic RT in LSCLC was associated with an improved 5-year survival from 9.6 to 16.3% (P=0.91). Patients with ESCLC who received any chemotherapy had a median survival of 8.4 months (7.3 and 2.3% for 2- and 5-year survival, respectively). Standard treatment guidelines generated population-based survival outcomes that are similar to published clinical trials.     

Irinotecan: future directions in small-cell lung cancer

Small-cell lung cancer (SCLC) accounts for approximately 20%-25% of all cases of lung cancer and has an especially poor prognosis, resulting in about 25% of all lung cancer deaths. About two thirds of patients with SCLC will present with more advanced and less treatment-sensitive extensive disease (ED). Five-year survival is negligible for patients with ED. Combination chemotherapy is the most effective treatment modality for SCLC. For patients with ED SCLC, chemotherapy can increase median survival from about 1.5 months to 7-11 months, with 2-year survival uncommon. Several new agents, including carboplatin, ifosfamide, and the taxanes, have been shown to be active against SCLC but have not resulted in improvement in overall survival. Among the most active to date has been the topoisomerase I inhibitor, irinotecan. A recent phase III study of the combination of irinotecan/cisplatin indicates improved survival over cisplatin/ etoposide. Survival results indicate that overall survival with irinotecan/cisplatin was significantly better than the standard treatment arm (12.8 months vs. 9.4 months, P = 0.0021, unadjusted one-sided log-rank test). These results represent a major advance and, if confirmed, may establish this regimen as the new standard of care for ED SCLC. These future directions will include the confirmation of the Japanese phase III trial in ED SCLC, evaluating the role of irinotecan in limited-stage disease, new doublet and triplet combinations containing irinotecan, and evaluation of irinotecan combinations with the newer molecularly targeted agents (ie, SU5416).     

Efficacy and safety of amurubicin for the elderly patients with refractory relapsed small cell lung cancer as third-line chemotherapy

Background: While more elderly patients are being diagnosed with lung cancer every year, no anti-lung cancer therapy designed specifically for the elderly has been established yet. This is the first retrospective study to examine the efficacy and safety of amurubicin (AMR) for elderly patients with refractory relapsed small cell lung cancer (SCLC) as second or third-line chemotherapy. Materials and Methods: Thirty-six patients were eligible for analyzing the frequency of hematologic and non-hematologic toxicities and effectiveness of AMR for refractory relapsed SCLC in both elderly (≥70 years) and non-elderly (<70 years) groups. Results: Among these patients as third-line chemotherapy, the response rate and the disease control rate of refractory relapsed cases were 44.4 and 55.6%, respectively. The median of progression-free survival time was 3.0 months and the median of overall survival time was 5.1 months. There were no significant differences in the frequency of the grade 3-5 hematologic or non-hematologic toxicity between the elderly (≥70 years) and non-elderly (<70 years) patients or second and third-line chemotherapies. Conclusions: AMR could be one of the effective tools in the treatment of elderly patients with refractory relapsed SCLC as third-line chemotherapy, and the recommended dose is 30 mg/m 2 for three consecutive days.     

Small cell lung cancer treated in southeast Wales

AimsIn small cell lung cancer (SCLC), consolidation thoracic irradiation (CTI) increases 3-year absolute survival by 5.4% in patients with limited disease and a complete response to chemotherapy. Early concurrent thoracic radiotherapy has been shown to improve local control and prolong survival compared with CTI in some trials. The standard management of patients with SCLC in southeast Wales is CTI in individuals with limited disease and a complete response to chemotherapy. A review of patients with SCLC was carried out to establish whether survival locally is comparable with that reported in published studies, and if patients given CTI have survival comparable with that reported in studies where early concurrent thoracic radiotherapy was used.Materials and methodsBetween January 2000 and December 2002, 303 patients were registered with SCLC in southeast Wales. One hundred and fifteen (47%) patients had limited disease and 60/115 (52%) received CTI.ResultsPatients with limited disease receiving CTI had a median survival of 17.7 months (95% confidence interval: 15–27.9 months). The 2- and 5-year survivals were 38 and 13%, respectively.ConclusionsThese results compare favourably with previously published studies on SCLC. There are no plans to change our current treatment policy for SCLC in southeast Wales.     

FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) granted approval to atezolizumab and durvalumab in March of 2019 and 2020, respectively, for use in combination with chemotherapy for first‐line treatment of patients with extensive stage small cell lung cancer. These approvals were based on data from two randomized controlled trials, IMpower133 (atezolizumab) and CASPIAN (durvalumab). Both trials demonstrated an improvement in overall survival (OS) with anti–programmed death ligand 1 antibodies when added to platinum‐based chemotherapy as compared with chemotherapy alone. In IMpower133, patients receiving atezolizumab with etoposide and carboplatin demonstrated improved OS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.54–0.91; p = .0069), with median OS of 12.3 months compared with 10.3 months in patients receiving etoposide and carboplatin. In CASPIAN, patients receiving durvalumab with etoposide and either cisplatin or carboplatin also demonstrated improved OS (HR, 0.73; 95% CI, 0.59–0.91; p = .0047) with median OS of 13.0 months compared with 10.3 months in patients receiving etoposide and either cisplatin or carboplatin. The safety profiles of both drugs were generally consistent with known toxicities of immune‐checkpoint inhibitor therapies. This review summarizes the FDA perspective and data supporting the approval of these two agents.Implications for PracticeEffective therapeutic options for small cell lung cancer (SCLC) are limited, and there has been modest improvement in the overall survival (OS) of patients with SCLC over the past 3 decades. The approvals of atezolizumab and of durvalumab in combination with chemotherapy for first‐line treatment of patients with extensive stage SCLC represent the first approved therapies with OS benefit for this patient population since the approval of etoposide in combination with other approved chemotherapeutic agents. Additionally, the efficacy results from IMpower133 and CASPIAN lay the groundwork for possible further evaluation in other treatment settings in this disease.     

Small-cell lung cancer: current therapy and novel agents

Among patients with lung cancer, approximately 15% have small-cell lung cancer (SCLC). Although, without therapy, untreated SCLC is a rapidly proliferating tumor with a poor prognosis, response rates to chemotherapy and radiotherapy are high. SCLC is usually staged as either limited disease or extensive disease. Extensive disease is treated primarily with chemotherapy. A recent Japanese randomized trial compared IP (irinotecan [Camptosar]/cisplatin [Platinol]) with EP (etoposide/cisplatin). Patients in the IP arm had significantly better outcomes than patients in the EP arm. In the IP arm, the response rate was 84%, and the median overall survival period was 12.8 months. Limited disease is usually treated with concurrent chemotherapy and accelerated radiation therapy, and approximately 20% of patients are cured. Further investigations to improve local control and inhibit distant metastasis are clearly warranted. The dose-rate escalation in radiotherapy (administered concurrently with chemotherapy) is important in improving local control, and the introduction of molecular-targeting agents is necessary to inhibit distant metastasis.     

Progress in treatment of small-cell lung cancer: role of CPT-11

Small-cell lung cancer (SCLC) accounts for approximately 15% of all cases of lung cancer and is a particularly aggressive form of lung cancer characterised by a poor prognosis, rapid tumour growth, and early metastasis. Roughly, two-thirds of patients with SCLC present with extensive disease (ED) and one-third with limited disease (LD). Combination chemotherapy is the most effective treatment modality for SCLC, and several new agents, including carboplatin, ifosfamide, taxans, and topotecan, have been demonstrated to be active; however, there are no data on the survival benefit of these drugs. A CPT-11+ cisplatin regimen has shown improvement in overall survival over the global gold standard regimen, etoposide + cisplatin (Japanese Clinical Oncology Group: JCOG 9511), and three confirmatory randomised controlled trials are in progress to determine the reproducibility of the JCOG 9511 study. JCOG is evaluating the role of CPT-11 and a new triplet regimen containing CPT-11 in limited-stage SCLC. Strategies and the current protocols of the JCOG are presented and discussed. In the future, it will be essential to evaluate molecular target-based drugs for LD and ED SCLC with new standard combination chemotherapy regimens that include CPT-11.     

Lung cancer

Aging society is coming now, the ratio of elderly patients among all lung cancer patients has currently been increasing. It is necessary for elderly patients who are under-represented in clinical trials to study their suitable regimen. Thus, phase II and III clinical trials have been performed specifically for elderly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients all over the world. As for single agent chemotherapy, there is a strong rationale for docetaxel and vinorelbine in elderly patients with advanced NSCLC. Recently, there are phase I and II clinical trial for CPT-11 monotherapy, and gefitinib and TS-1 are reasonable options for elderly patients. Alimta is tolerable for elderly, and subset analysis is performed for the elderly with recurrent NSCLC. As platinum-based chemotherapy, there are several elderly subset analyses and JCOG 0207, which is a phase III trial now in progress comparing weekly cisplatin+weekly docetaxel and weekly docetaxel. In SCLC, there is no evidence of single agent chemotherapy but combination chemotherapy such as carboplatin+etoposide is recommended. A phase III study of carboplatin+etoposide versus amrubicin under way. These studies should aim to optimize several agents for elderly patients and prolong survival, palliative care.     

Chemotherapy as treatment of primary and recurrent small cell lung cancer

Chemotherapy is the treatment of choice in metastatic stage of small-cell lung cancer (SCLC). Radiation therapy, surgery and other forms of therapy are only included in special treatment situations, particularly for different local problems. A wide range of chemotherapeutic agents have proven to be effective in SCLC, including carboplatin, cisplatin, cyclophosphamide, doxorubicin, epirubicin, etoposide, ifosfamide, teniposide and vincristine. However, treatment results could not be improved over the last 10 years and the median survival of patients with metastatic disease is limited to 7-10 months. New agents like docetaxel, gemcitabine, irinotecan, paclitaxel, topotecan and vinorelbine have shown promising results in phase-II investigations. Yet, no evidence is provided from randomized trials to employ these drugs in first line treatment. Clearly, polychemotherapy is superior to single agent treatment. Compared to the combination of cisplatin and etoposide, no other combination has clearly shown improved results in large phase-III randomised trials, yet. The combination of cisplatin and irinotecan has also shown promising results in a single randomised trial with the need to be confirmed in larger settings. Neither extending the initial treatment beyond the median number of six cycles, nor maintenance treatment have-so far-resulted in any increase in survival results for patients with metastasised SCLC. Nor has dose-intensification, which causes significantly higher toxicities in patients, shown a clear impact on the overall survival of these patients. Brain metastases represent a high frequent complication associated with SCLC. In these cases, the combination of chemotherapy and whole brain radiation therapy is advocated. Second-line treatment should always be considered in patients with relapse or failure to first-line therapy. In addition to a rechallenging with the prior drug combination or selecting a different potentially non-cross resistant one, monotherapy with topotecan proved to be effective as well. In summary, up to now, no standard chemotherapy combination exists for metastatic SCLC. The individual therapy strategy can only be selected by considering the clinically relevant conditions of the patient.     

Treatment of small cell lung cancer in the elderly based on a critical literature review of clinical trials

At diagnosis, 25-40% of patients with small cell lung cancer (SCLC) are 70 years of age or older, and many of them have been undertreated because of fear of excessive toxicity associated with chemotherapy. Papers retrieved by a Medline search using the key words "elderly or older" and "small cell lung cancer" and by a manual search were classified into the three types: (1) case-series studies, (2) subgroup analyses of phase II and phase III trials by age, and (3) prospective clinical trials in the elderly. Treatment regimens, delivery, toxicity, antitumor activity, and patient survival were reviewed in elderly patients with good and poor general condition. The standard chemotherapy regimens for the general population could be applied to elderly patients in good general condition (performance status of 0-1, normal organ function, and no comorbidity), but etoposide and carboplatin regimen with dose modification was frequently used for unselected elderly patients. A combination of full-dose thoracic radiotherapy and chemotherapy was the treatment of choice for limited SCLC in the elderly. Full cycles of chemotherapy were tolerable by 80% of the elderly patients with good general condition, but two cycles may be optimal for unselected elderly patients. Although the evidence levels based on clinical trials available today are low, these results are helpful for clinical practice and future clinical trials for elderly patients with SCLC.     

Treatment of lung cancer in elderly part II: small cell lung cancer

There is a general trend worldwide of an increasing incidence of elderly population. Age is the greatest risk factor for cancer; therefore, this demographic shift is a main reason for an increase of cancer incidence. Lung cancer is a typical disease of the elderly patients. Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancer cases. This review summarises the issues of treatment of SCLC in elderly. The number of randomised phase III trials concerning treatment of SCLC in elderly patients are very limited. Although currently most treatment decisions are based on lower grades of evidence, some conclusions can be drawn from the current studies. Age alone is a very uncertain prognostic criteria for outcome or tolerability of treatment. Much more important is the geriatric assessment of each individual patient. Current treatment standards for limited disease (LD)-SCLC (polychemotherapy plus local thoracic irradiation and additional prophylactic cranial irradiation in case of complete remission) seems to be also feasible for 'fit' elderly (>70 years) LD-SCLC patients with a good performance and full functional capacities. There are preliminary data indicating that a similar outcome in elderly patients can probably be achieved a with reduced number of treatment schedules (e.g. 2 instead of 4 cycles in combination with radiotherapy. Surgical resection is also feasible in selected elderly patients with very early stage SCLC, where this maybe an appropriate approach, although no phase III data are available, which demonstrated the benefit of additional surgery compared to chemotherapy alone in early stage SCLC. In patients with extensive disease-SCLC age alone does not necessarily restrict the use of multiagent regimen, although the risk of haematological toxicity seems to be higher than in the younger patients. When standard treatment is not feasible due to co-morbidity or loss of functional capacity, several alternative combination regimens are available, which appear to be slightly superior to single agent treatment, although randomised data for elderly on that issue are sparse. Carboplatin and etoposide seems currently the most appropriate two-drug combination in elderly patients, but there are a variety of active and low toxic third generation agents like taxanes, gemcitabine and vinorelbine which are active in both, non-small cell lung cancer and SCLC. For the comparison of trials in elderly patients it will be of key importance to include a comprehensive and standardised geriatric assessment in such studies.     

Current perspectives in the management of small cell lung cancer

Considerable progress has been made within the last decade in the management of small cell lung cancer (SCLC) resulting in prolongation of median survival by 4 to 5 times (about 14 and 9 months in limited and extensive disease, respectively), improved quality of life, and an increase of cure rates in 15 approximately 20% of the patients with limited disease. In this review, we are focusing on the details in update treatment schedules of combination chemotherapy against SCLC, prognostic features and staging of SCLC, the role of non-cross resistant alternating chemotherapy, radiotherapy to the primary site including hilar and mediastinal lymph nodes, prophylactic cranial irradiation and surgery in the treatment of SCLC, as well as the complications of treatment.     

Food groups and risk of lung cancer in Uruguay

BACKGROUND: No standard treatment is defined for elderly patients with small cell lung cancer (SCLC). Carboplatin and etoposide are highly active agents against SCLC. In this study, we evaluated the activity and toxicity of a combination of these two agents. PATIENTS AND METHODS: Thirty-four untreated patients with limited or extensive SCLC and median age of 73.9 years entered the study. Chemotherapy consisted of carboplatin i.v. on day 1 (AUC 5 using Calvert's formula) and etoposide 100 mg/m(2) given orally on days 1-5, every 4 weeks, and thoracic irradiation was given to limited disease patients after chemotherapy. RESULTS: The overall response rates was 59% (95% CI: 43-76). The median survival for all patients was 37 weeks (range 3-76 weeks). The toxicity was mainly haematological with grade 3-4 neutropenia in 59% of courses, febrile neutropenia in 15% of courses, and toxic death in 9% of patients. CONCLUSION: The results of this regimen are disappointing with worse response and survival, and more haematological toxicity than expected and previously reported, despite the use of Calvert's formula. Possible explanations are the use of etoposide per os rather than i.v., the frequent comorbidities of older patients and the inclusion of patients with poor prognosis factors.     

小细胞肺癌免疫治疗的临床研究进展

小细胞肺癌（smallcell lung cancer ,SCLC）是一种恶性程度较高的肿瘤,约占全部肺癌的15% ,其具有侵袭性高、增殖快、早期广泛转移的生物学特点。虽然对化疗和放疗高度敏感、初治缓解率高,但极易耐药和复发,迫切需要新的治疗策略以提高疗效、延长生存期。SCLC发生发展和化疗耐药涉及众多细胞学和分子生物学异常改变,随着对SCLC生物学行为理解的加深以及分析检测技术的不断发展,免疫治疗可能突破治疗瓶颈、为SCLC治疗开辟新的途径。本文将对小细胞肺癌的免疫治疗临床研究做一综述。      

Recent advances in management of small-cell lung cancer

Small-cell lung cancer (SCLC) is a smoking-related disease with a poor prognosis. While SCLC is usually initially sensitive to chemotherapy and radiotherapy, responses are rarely long lasting. Frustratingly, most patients ultimately relapse, often with increasingly treatment resistant disease. Many strategies have been developed in an attempt to improve treatment outcomes, which have plateaued since the introduction of combination chemotherapy in the 1980s. These include trials of maintenance therapy, and dose intensification, the latter by means of increasing dose density, growth factor support and high dose chemotherapy with autologous stem cell rescue. None have been shown to improve patient survival. On the other hand, the integration of concurrent thoracic radiation and prophylactic cranial irradiation has improved the survival outcomes in patients with limited disease. In extensive disease, irinotecan combined with cisplatin has shown promise in improving survival over conventional platinum/etoposide chemotherapy schedules and a confirmatory study is awaited. The future of SCLC treatment may however lie with molecularly targeted therapies, such as antiangiogenesis agents and signal transduction inhibitors, which are being studied at present.     

Targeted therapies in small cell lung cancer: a review

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is characterized by a rapid doubling time, early onset of dissemination and high sensitivity to chemotherapy. Despite the potential for cure in patients with limited disease with concurrent chemoradiation and an initial good response to chemotherapy in extensive disease, there is a high chance of disease relapse with an overall poor median survival for both stages. With increasing translational research and a better understanding of the molecular basis of cancer, a number of molecular targets have been identified in various preclinical studies. This review summarizes potentially viable targets and new agents that have been developed and employed in recent, ongoing and future clinical trials to attempt to improve clinical outcomes in this disease.