Treatment of small cell lung cancer

The incidence of small cell lung cancer (SCLC) is declining in the United States (US). SCLC is nearly universally smoking-related and is very sensitive to both chemotherapy and radiation therapy. In contrast to non-small cell lung cancer (NSCLC), SCLC is staged as either limited-stage disease (LD) or extensive-stage disease (ED). Chemotherapy remains the essential component for treatment of all patients with SCLC, regardless of stage or performance status. In LD, the addition of radiation therapy improves survival over chemotherapy alone. However, the dose, timing and schedule of radiation are not well defined. Prophylactic cranial irradiation (PCI) reduces brain relapse rates, and modestly improves survival in patients in a clinical remission. Many chemotherapy agents and combinations result in high response rates in ED SCLC; however, median survival time remains 8-10 months. Cisplatin (or carboplatin) and etoposide is the standard doublet used in the United States. One study has shown cisplatin plus irinotecan to have a survival benefit over cisplatin plus etoposide, but confirmatory studies are needed. Patients with ED frequently relapse, and relapsed/refractory SCLC has a poor prognosis. The challenge remains to identify novel therapies and molecular targets to improve survival in SCLC.     

Treatment of advanced non small cell lung cancer

Lung cancer is the major cause of cancer death in the world. Non Small Cell Lung Cancer (NSCLC) accounts approximately 80-85% of all lung cancer diagnosis; the majority of patients will be diagnosed with non operable, advanced-stage disease. Palliative chemotherapy and/or radiotherapy represent the standard of care of this disease. Platinum based doublets with third generation agents are considered the standard of first line advanced NSCLC treatment. However, data arising from the availability of pemetrexed suggest that histology could play a key role in decision making. Advances in understanding of the molecular pathogenesis of lung cancer have led to the identification of several specific targets such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) for therapeutic agents. Bevacizumab is the first recombinant humanized monoclonal antibody (mAb) binding VEGF to demonstrate clinical benefit and a rather survival prolongation in combination with chemotherapy in the treatment of non squamous chemo-naive advanced NSCLC patients. Two types of anti-EGFR targeting agents have reached advanced clinical development: mAbs and small molecule inhibitors of the EGFR tyrosine kinase enzymatic activity (TKIs). Among TKIs gefitinib has been tested in several phase II-III studies showing an improvement in survival and responses in first, second and third line treatment in selected patients with specific clinical and molecular characteristics. Furthermore, erlotinib has showed to significantly improve survival in an unselected population of patients following the failure of one or two chemotherapy regimens. This review will discuss the different therapeutic options for first and second line treatment in the clinical practice.     

Treatment of 100 patients with small cell lung cancer

100 patients with small cell lung cancer were treated in Peking Union Medical College Hospital from 1963 through 1987. The five year survival rate in patients received combined treatment (resection + chemotherapy+radiotherapy, resection+chemotherapy or resection+radiotherapy,) was 18.52% (5/27). It was better than patients received nonsurgical treatment (chemotherapy,radiotherapy or chemotherapy+radiotherapy, 58 patients). And also it was better than patients received surgical resection only (11 patients). This advantage was especially marked in patients with lesion of IIIa stage. The five year survival rate in this group was 26.31%(5/19). It was suggested that combined method (resection+chemotherapy+radiotherapy) is the first choice for the treatment of small cell lung cancer.     

复发性小细胞肺癌的治疗策略及进展

小细胞肺癌是一种对放、化疗敏感,但易复发的实体性肿瘤.对于身体状况许可的小细胞肺癌复发患者,应接受二线化疗;若一线治疗无效或无疾病进展时间小于3个月,应选择与一线化疗非交叉耐药的二线化疗;若一线治疗有效且无疾病进展时间大于3个月,拓扑替康是首选;若无疾病进展时间超过6个月,则可继续原方案治疗;若出现有症状的脑和骨转移、胸腔内复发和(或)出现大气道阻塞、上腔静脉阻塞综合征的患者,可考虑放疗或放、化疗结合.针对小细胞肺癌的生物靶向治疗有待进一步研究.     

Management of small cell lung cancer

Small cell lung carcinoma typically presents as a central endobronchial lesion in chronic cigarette smokers with hilar enlargement and disseminated disease. The diagnostic pathology should be reviewed by a pathologist accomplished in reading pulmonary pathology, and, if any doubt exists in the diagnosis, additional special stains or diagnostic material should be obtained. Patients with extensive stage disease should be managed by combination chemotherapy, whereas patients with limited stage disease should be treated with etoposide/cisplatin plus concurrent chest irradiation. The chemotherapy should be administered for 4 to 6 months and then should be discontinued. Prophylactic cranial irradiation should be given to patients who achieve a complete remission. Patients should be retreated with chemotherapy if they develop a relapse of their small cell lung cancer. The patients who are followed in complete remission should be observed carefully for second cancers, and appropriate therapy should be administered if the cancer reappears.     

Mixed small cell and non-small cell lung cancer

Seventeen (10 percent) of 176 patients with small-cell carcinoma of the lung seen at this hospital since 1976 proved to have mixed small-cell and non-small-cell tumors. The presence of a mixed lung cancer was established prior to chemotherapy or irradiation in nine patients. Eight were initially diagnosed as pure small-cell carcinoma but proved to have a mixed tumor at either surgery or autopsy. Of the 17 patients, eight received chemotherapy, and four had a partial response. Six of the 40 autopsies performed on patients with small-cell lung cancer demonstrated intrathoracic tumor which was histologically mixed. Extrathoracic metastases in these patients were heterogeneous and included pure small-cell, pure non-small-cell, and mixed histologic type. We conclude that mixed small-cell and non-small-cell lung cancers are relatively frequent and carry important prognostic and therapeutic implications. Clinical management of patients with small-cell lung cancer should therefore be flexible and tailored to the potential for histologic diversity. Mixed lung cancer in previously untreated patients suggests a common endodermal origin for small-cell and non-small-cell pulmonary tumors.     

Surgical treatment of small cell lung cancer

Thirty four small cell lung cancer (SCLC) patients underwent operation in Kyoto University from 1976. The mean age was 62 years old; 25 male cases, 9 female, respectively. All case were limited disease (LD) except 2 patients with rib metastasis. Seventeen patients had a performance status (PS) of 0 and 17 PS 1, twenty eight patients were treated with chemotherapy. Of the remaining 5 patients, 2 were treated by only oral 5-FU derivatives, one died within 30 days of operation, one could not be treated owing to old-age, and one refused chemotherapy. Except one operational death 33 cases were able to be evaluated. Out of 28 patients, 16 patients were treated by only postoperative chemotherapy. Concerning operational radicality, 21 cases out of 31 were operated radically (68%). The survival rates of these 33 patients were 78% 37% at 1, 3 and 5 years respectively. The MST was 26 months. The neoadjuvant group head better results than the non-adjuvant group.     

Current management of small cell lung cancer

Confined to one side of the chest, limited stage small cell lung cancer is treated with a combination of chemotherapy and radiotherapy, yet has a long-term survival rate of only 15%. Extensive stage disease has initial response rates to chemotherapy exceeding 70%. However, the disease almost invariably progresses and becomes fatal. Many recent clinical trials have failed to show superiority of newer chemotherapeutics or targeted therapies compared with the standard chemotherapy backbone of platinum plus etoposide. Numerous promising targeted therapies and other agents are still in development.     

Spontaneous regression of small cell lung cancer

Abstract:   Spontaneous regression of cancers is extremely rare and is associated with specific malignancies. Spontaneous regression of bronchogenic lung cancer has rarely been reported, and regression of small cell lung cancer is even less common. Such regression is generally ascribed to immunological factors but is not well understood. This case report describes a patient with spontaneous regression of small cell lung cancer that has persisted for 11 years and considers possible mechanisms.     

Prognostic factors in small cell lung cancer

In order to find out prognostic factors and treatment results in small cell lung cancer (SCLC), 40 patients diagnosed in one year period were prospectively analysed. Following history and physical examination, patients were grouped according to ECOG performance scale and underwent Chest X-ray and thoracic computerized tomography (CT). Complete blood count, biochemical analyses, tumor markers were taken. Abdominal USG or CT, bone scintigraphy, cranial CT or MRI and bone marrow biopsy were made for detection of metastases. Limited stage patients received chemotherapy and thoracic RT, whereas cases with extensive disease received chemotherapy. Nineteen cases had limited and 21 had extensive disease. When laboratory findings between 2 stages were compared, LDH, SGOT and GGT were significantly higher in extensive stage (p= 0.005, 0.015, 0.001, respectively). Overall median survival was 6 +/- 1 months, cumulative survival in 6 and 12 months were 39% and 20.72%, respectively. Median survival was 10 +/- 2 months in limited stage and 3 +/- 1 months in extensive stage, with a statististically significant difference. Univariate analyses showed that incresed LDH, CA15-3, GGT and SGOT levels, hipoproteinemia and poor performance scale were poor prognostic signs (p= 0.024, 0.032, 0.047, 0.013, 0.021 ve 0.013, respectively), however multivariate analyses revealed no significant difference. Other blood tests, pleural effusion, age, mediastinal lymph node metastases and weight loss had no prognostic effect. Stage was found to be progniostic factor with both univariate and multivariate analyses (p= 0.045).     

Chemotherapy in small cell lung cancer.

Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC) and radiotherapy is an important adjunct in limited stage disease. The role of chest irradiation is now documented in three meta-analysis, based on the same body of data. Trials on timing, scheduling and fractionation could have followed a more stringent development line but altogether, the highest efficacy seems to be obtained with early, concurrent twice-daily chest irradiation. Patients in complete remission should have prophylactic cranial irradiation, which reduces the risk of brain metastases and of death from SCLC. Four series of chemotherapy seem to be sufficient in limited-stage disease while six is recommended in extensive disease. The combination of etoposide plus cis- or carboplatin is appropriate in both stages and addition of other agents has no clinically important impact on the survival. Use of haematological growth factors such as granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) may enable higher doses or more frequent dosage. Three randomized trials on GM-CSF showed a negative outcome while G-CSF support may result in better survival rates, but a more cost-efficient policy must be found. High-dose chemotherapy plus haematological stem-cell support is still under investigation but disappointing long-term survival rates means there is not much optimism for this strategy. New strategies in general are requested in the treatment of extensive-stage disease and of elderly patients. Phase II trials suggest that good-risk patients with extensive disease should be treated aggressively, intermediate-risk patients more gently, and palliation must be the primary aim in the treatment of poor-risk patients. In elderly patients impressive survival rates are obtained with 3-4 series of chemotherapy and radiation delivered in 5-10 fractions. A number of new agents are active but more trials are required before each has found a place, if any, in the treatment of small cell lung cancer. To conclude, the randomized trial is still an important instrument in clinical oncology, and trials in small cell lung cancer must be large, which is why the cooperation of organizations and multicentres is urgent.     

Pancoast's syndrome and small cell lung cancer

Four patients with small cell lung cancer (SCC) presenting with Pancoast's syndrome are described. Superior sulcus tumors are usually caused by epidermoid carcinoma or adenocarcinoma of the lung, and are routinely treated with radiotherapy followed by radical surgery. SCC, on the other hand, is widely disseminated at diagnosis and is best treated with chemotherapy. Although not previously reported as a cause of Pancoast's tumor, these four cases of SCC presenting as such clearly indicate the need for pretreatment histologic diagnosis to avoid unnecessary surgical intervention. Transcutaneous needle aspiration biopsy is a means by which the diagnosis can be safely made in patients presenting with apical lung tumors.     

Management of small cell cancer of the lung

Small cell lung cancer (SCLC) accounts for 20% to 25% of bronchogenic carcinoma cases. Combination chemotherapy offers the best chance for improved survival. Cisplatin plus etoposide appears to be the most reasonable choice for first line therapy. Increasing dose intensity, although sometimes associated with higher response rates, does not appear to significantly improve survival. Concurrent thoracic radiotherapy administered early in the course of chemotherapy confers a survival advantage over chemotherapy alone in limited-stage SCLC. Prophylactic cranial irradiation reduces central nervous system recurrences with minimal long-term sequelae and appears to improve survival. Several new cytotoxic agents are active in SCLC. These include gemcitabine, paclitaxel, docetaxel, topotecan, irinotecan, and JM216. Novel approaches being investigated include antibodies to factors expressed by SCLC cells and agents targeting angiogenesis, cell cycle regulation, and cell-signaling pathways.