The impact of abdominal computerized tomography on the pretreatment staging and prognosis of small cell lung cancer.

One hundred six patients with small cell lung cancer (SCLC) were prospectively evaluated with regard to the prognostic impact of abdominal CT-scan in the pretreatment staging when compared to ultrasonography of the abdomen. Staging based on abdominal ultrasonography (US) plus bilateral bone marrow examinations gave as a result that 47 patients had extensive disease (ED) (44%). Seventeen patients with proven ED at time of referral were not included in this study. Abdominal CT-scan was performed in 76 of the 106 patients. Thirty patients of these 76 patients (39%) were classified as having ED after staging including US, but abdominal metastases were disclosed in another ten patients at the subsequent CT-scan. Liver metastases seen in two patients at ultrasonography were overlooked on the CT-scans. Median survival of the 36 patients classified as having limited disease (LD) after both procedures was 458 days, which was significantly better compared to 330 days for the ten patients with stage migration from LD to ED based on CT-scan, (p less than 0.05) and compared to 242 days in the 30 patients with ED demonstrated by both US and CT-scans (p less than 0.05). The prognostic impact of the CT-scan was further investigated in a multivariate analysis (Cox). Stage disease, performance status, LDH and alkaline phosphatase were significant prognostic factors in a proportional hazards model based on the original 106 patients. Patients in the best prognostic group were characterized by LD, good performance status (0-1) and normal LDH and alkaline phosphatase serum values. This group consisted of 22 patients (21%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging to detect bone marrow metastases in the initial staging of small cell lung carcinoma and breast carcinoma

BACKGROUND: Bone marrow is a common site of metastases in patients with small cell lung carcinoma (SCLC) and female breast carcinoma (FBC). Metastatic bone marrow involvement is found in approximately 50% of SCLC patients and up to 85% of FBC patients at autopsy. Initial staging procedures detect malignant bone marrow lesions in only 2-30% of patients with these tumors. This study was performed to assess whether MRI can improve the detection rate of bone marrow metastases in tumors with a high incidence of skeletal involvement. METHODS: Fifty-two patients with histologically verified SCLC (25 with limited stage disease and 27 with extensive stage disease) and 33 women with FBC were entered into a prospective study. The MRI protocol was comprised of coronal slices in the pelvic region and sagittal slices of the whole spine utilizing a T1-weighted spin echo sequence with a field of view of 50 cm. All patients underwent initial routine diagnostic staging procedures including bone scintigraphy, unilateral crest biopsy, and plain film radiography of suspicious skeletal areas. RESULTS: Only in two SCLC patients, MRI was positive in 25 cases. All SCLC patients with bone marrow lesions histologically verified, diagnosed by crest biopsy (six patients) or by bone scan (seven patients) had the correct diagnosis of metastases by MRI. In addition MRI revealed hypointense bone marrow foci in 14 cases. In contrast, 28 of 33 FBC patients examined during the initial staging procedure showed no evidence of bone marrow involvement. MRI was not superior compared with bone scintigraphy in FBC patients. CONCLUSIONS: The staging results obtained in SCLC and FBC patients are different, although both tumors have a high incidence of bone marrow metastases. It may be assumed that the biologic behavior of these tumors is reflected by the initial bone marrow involvement. Because of its superiority compared with biopsy and bone scan, the authors believe MRI should become an integral part of the initial staging procedures in patients with SCLC. When staging patients with FBC, MRI should be applied only in clinically indicated cases.     

Prognostic factors differ by tumor stage for small cell lung cancer

BACKGROUND:

An analysis of 14 small cell lung cancer (SCLC) trials was performed to improve the current understanding of potential prognostic factors for overall survival (OS) and progression‐free survival (PFS) in groups of patients with limited‐stage disease SCLC (LD‐SCLC) and extensive‐stage disease SCLC (ED‐SCLC) separately.

METHODS:

Data on 688 patients with LD‐SCLC and 910 patients with ED‐SCLC were included. Clinical and laboratory factors were tested for their prognostic significance using Cox regression models that were stratified by protocol. Recursive partitioning and amalgamation (RPA) analyses were used to identify prognostic subgroups.

RESULTS:

Poorer performance status (PS) led to worse OS and PFS in the ED‐SCLC group but not in the LD‐SCLC group. The prognostic impact of PS was strong for men but weak for women in the ED‐SCLC group (interaction P value <.012 for OS and PFS). Other negative prognostic factors included increased age and men for the LD‐SCLC group and increased age, men, increased number of metastatic sites at baseline, and increased creatinine levels for the ED‐SCLC group. In patients with the ED‐SCLC, RPA analyses identified 5 subgroups with different prognosis based on baseline PS, creatinine levels, sex, and the number of metastatic sites.

CONCLUSIONS:

The current pooled analysis identified baseline creatinine levels and the number of metastatic sites as important prognostic factors in patients with ED‐SCLC in addition to the well established factors of sex, age, and PS. There was a significant interaction between sex and PS within the ED‐SCLC group, suggesting that PS is highly prognostic in men but has no significant impact in women. Within the LD‐SCLC group, only age and sex were identified as important prognostic factors. RPA analyses confirmed many of these findings. Cancer 2009. © 2009 American Cancer Society.     

The Role of Integrated 18F-FDG PET-CT as a Staging Tool for Limited-Stage Small Cell Lung Cancer: A Retrospective Study

Background: The aim of this study was to evaluate whether positron emission tomography-computed tomography (PET-CT) could be used as part of the staging work-up in patients with limited-stage disease (LD) small cell lung cancer (SCLC). Patients and Methods: Between January 2002 and December 2007, a total of 73 patients with presumed LD on CT, who underwent a PET-CT scan, were included in this study. Results: Conventional work-up revealed distant metastases in 12 patients. Out of 61 patients diagnosed as LD SCLC, PET-CT found unexpected distant metastases in 15 (24.6%) patients (LD/extensive-stage disease (ED)) of whom 13 (21.3%) were upstaged as a consequence. In 10 (76.9%) of the 13 upstaged patients, treatment was changed. The median survival of LD/LD SCLC patients who underwent concurrent chemoradiotherapy and chemotherapy only was 21.9 and 17.5 months, respectively. The median survival of LD/ED and ED/ED SCLC patients who received chemotherapy only was 17.4 and 14.1 months, respectively. The median survival of LD/LD SCLC patients who received concurrent chemoradiotherapy was superior to that of LD/ ED and ED/ED patients who received chemotherapy only (p = 0.037 and 0.004, respectively). Conclusion: The addition of PET-CT seems to allow more accurate staging and may thus protect a percentage of SCLC patients from potentially futile and toxic radiotherapy.     

小细胞肺癌患者的临床特点及预后分析

目的 分析小细胞肺癌(SCLC)的临床特点及预后影响因素.方法 收集明确诊断的SCLC患者260例,给予综合治疗(同步放化疗或化疗±放疗±手术),对比不同治疗方法患者的生存期差异,采用Kaplan Meier法绘制生存曲线,寿命表法计算生存率,SPSS单因素、COX多因素分析预后因素.结果 260例中局限期189例,广泛期71例,全组中位生存期25个月,局限期为29个月,广泛期为13个月,两者生存期差异有统计学意义(P =0.000),全组1年、3年、5年生存率分别为82.3％、21.5％、4.6％,其中局限期患者1年、3年、5年生存率分别为87.1％、28.0％、6.5％,广泛期患者1年、3年、5年生存率分别为70.3％、5.4％、0％.单因素分析示:一线治疗效果、分期、治疗方式、预防性颅脑放疗可影响生存期,伴有少量胸腔积液、锁骨上淋巴结转移患者的预后与局限期患者更相近,伴有上腔静脉综合征的患者预后介于局限期及广泛期患者之间.多因素COX分析示:一线治疗是否有效、分期、治疗方法是影响患者预后的主要因素.结论 对于一般情况良好的小细胞肺癌患者,T1～2No手术治疗、同步放化疗、提高完全缓解率、复发及进展后进一步治疗,均可提高其生存率,有利于患者长期生存.     

Prognostic factors in small cell lung cancer: A simple prognostic index is better than conventional staging

Conventional staging in small cell lung cancer (SCLC) is only of limited prognostic value and is often based on elaborate investigations. We have carried out univariate and multivariate analysis of possible prognostic factors at presentation in 333 consecutive patients with SCLC. Fifteen parameters were found to have individual prognostic significance, of which the most powerful were serum albumin, bone marrow aspirate, disease extent and performance status (all P < 0.00005). Factors which were not of prognostic significance included age, sex, SVC obstruction, and pleural involvement. Multivariate analysis excluded many factors including bone marrow aspirate as not being independently variable, and a simple combination of clinical performance status, serum albumin and alanine transaminase could be used to define 3 groups (good; medium; poor) of better prognostic significance (survival at 1 year 50% vs. 27% vs. 3%) than conventional limited/extensive disease staging (1 year survival 48% vs. 18%). Other simple combinations of biochemical parameters including plasma sodium and alkaline phosphatase achieved almost as good prognostic groupings. We suggest that consideration should be given to replacing the conventional limited/extensive disease staging system with a simpler system along the lines we have described.     

Bone marrow involvement in small cell lung cancer. Clinical significance and correlation with routine laboratory variables

Of 129 patients with small cell lung cancer (SCLC) who underwent bone marrow examination for staging, 39 (30%) had bone marrow involvement. Only three of 129 patients (2.3%) had bone marrow involvement as the only site of metastatic disease. When patients with bone marrow metastasis were compared with patients whose bone marrow was normal, there were significant differences in serum levels of lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (AP), albumin, and sodium (Na). We found no clinically significant difference in survival between patients with extensive disease with or without bone marrow involvement. Serum Na, albumin, SGOT, and uric acid were important prognostic determinants of survival. Based on the results of this study, we do not recommend routine bone marrow examinations in the staging of SCLC.     

Concomitant monitoring of serum neuron-specific enolase and creatine kinase BB in small cell lung cancer.

Serum neuron-specific enolase (NSE) and serum creatine kinase isoenzyme BB (CK-BB) were measured in 43 small cell lung cancer (SCLC) patients. The overall sensitivity of NSE (greater than 12.5 ng/ml) was 65%; in limited disease (LD) 48% and in extensive disease (ED) 100%. CK-BB was detected in 14 patients (32%); the sensitivity was 17% in LD and 64% in ED. During treatment NSE declined or stabilized to normal level in LD together with objective response in 75% (21/28), and rose again with progression in 28% (6/21). CK-BB fell to normal in all 5 patients with LD, in 3 of them with objective response. In ED elevated NSE and CK-BB declined to normal with objective response in 73% (8/11) and in 25% (2/8) of the evaluable patients respectively. We conclude that serum NSE is a potential marker for staging and response monitoring in SCLC, but that CK-BB gives additional information of limited value.     

Assessing outcomes of cancer care: Lessons to be learned from a retrospective review of the management of small cell lung cancer at the Cancer Therapy Centre,Liverpool Hospital,January 1996−July 2000

The purpose of the present paper was to review the outcomes of care of small cell lung cancer (SCLC) at one Sydney teaching hospital. A retrospective cohort study was carried out of patients with SCLC seen between January 1996 and July 2000. The main outcomes were relapse‐free and overall survival. Secondary outcomes of interest were the uniformity of staging investigations, initial treatment, use of prophylactic cranial irradiation (PCI), patterns of relapse and treatment received following relapse. One hundred and three patients with SCLC were treated at the Liverpool Hospital Cancer Therapy Centre during this period. There were 58 men (56%) and 45 women (44%). Forty‐two patients (41%) had limited stage disease (LD) and 61 (59%) had extensive stage disease (ED). There was considerable variation in staging investigations. There was little variation in systemic treatment of SCLC. Only 32 of 42 patients with limited stage SCLC were candidates for thoracic radiotherapy and only seven patients received PCI. Median relapse‐free survival was 11.2 months (95% confidence interval (CI): 7.7?14.8) for patients with LD and 6 months (95%CI: 4.4?7.5) for ED. Median overall survival was 15.1 months (95%CI: 11?19.1) for patients with LD and 8.9 months (95%CI: 7.5?10.2) for ED. Some health outcomes similar to that reported in clinical trials can be achieved in clinical practice. Measuring health outcomes is an important process of maintaining quality of care.     

Imaging studies and the prognostic value of serum calcitonin in staging small-cell lung cancer

The controversial prognostic significance of serum calcitonin in small-cell lung cancer (SCC) prompted this retrospective study relating serum levels to (1) stage of disease [limited disease (LD) vs. extensive disease (ED)], (2) imaging studies of metastases to bone, liver, and brain, and (3) survival. Of the 127 previously untreated patients with SCC presenting from 1979 to 1984, calcitonin levels could be compared to the stage of the disease in 69 patients (25 LD and 44 ED) and to various staging procedures including 99mTc methylene diphosphonate bone scans (63 patients), 99mTc sulfur colloid liver-spleen scans (64 patients), computed tomography of the head (63 patients) and serum calcium (61 patients). 71% (49/69) of patients had elevated calcitonin of whom 65% (32/49) had ED. 29% (20/69) had normal levels of whom 60% (12/20) had ED. 40% (18/45) of patients with raised calcitonin had liver metastases. 100% (19/19) with normal calcitonin had no liver involvement. Two patients with hypercalcemia and increased calcitonin had extensive bony metastases. The survival experiences of patients with normal and elevated serum calcitonin levels were analyzed. No significant differences were found within each stage or in the group overall. The positive correlation of serum calcitonin to liver metastases was statistically significant. No such relationship could be demonstrated with stage of disease, bone metastases, brain metastases, or survival.     

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.     

血清NSE、ProGRP和LDH在小细胞肺癌诊断治疗中的作用

背景与目的小细胞肺癌（small cell lung cancer, SCLC）是一种生长迅速、具有神经内分泌特性的肿瘤。血清神经元特异性烯醇化酶（neuron specific enolase, NSE）、胃泌素释放肽前体（pro-gastrin-releasing peptide, ProGRP）和乳酸脱氢酶（lactic dehydrogenase, LDH）已在SCLC的诊断和治疗中起到一定的辅助作用,本研究旨在通过治疗前后SCLC患者NSE、ProGRP和LDH的变化探讨标志物在肿瘤分期、疗效评价及预测复发方面的价值。方法纳入中国医学科学院肿瘤医院的SCLC初治病例,回顾性分析其临床数据,包括临床特征、治疗前及2周期化疗后的血清NSE、ProGRP及LDH,疗效及无进展生存期。结果治疗前,广泛期（extensive disease, ED）患者NSE、ProGRP及LDH均高于局限期（limited disease, LD）（P<0.005）;LD患者的NSE水平随淋巴结分期的升高而明显增加（P=0.010）;有体重下降的患者NSE及LDH均高于无体重下降者（P=0.032, P=0.014）。化疗2周期后,有效患者的NSE及ProGRP下降程度明显高于疗效为稳定或无效的患者（P=0.015, P=0.002）。LD组化疗周期数>4个及治疗后ProGRP下降明显的患者较化疗周期数≤4个及ProGRP下降不明显的患者复发风险低;而远处转移数目≤2个、疗前LDH正常及治疗后ProGRP的明显下降,提示ED患者的近期复发风险低。此外,肿瘤复发类型（敏感复发、耐药复发、难治复发）与化疗后ProGRP下降程度呈负相关（P=0.044）。多因素分析结果提示治疗周期数是LD组SCLC近期复发的独立影响因素,远处转移数目及治疗后ProGRP的下降程度是ED组SCLC近期复发的独立影响因素。结论血清肿瘤标志物升高的程度与肿瘤负荷相关,ProGRP在治疗后的下降程度可能预测疗效及复发风险。     

Examination of bone marrow biopsy specimens and staging of small cell lung cancer

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.     

The Value of Bone Marrow Examination in Small Cell Carcinoma of the Lung

Of 668 consecutive patients with SCLC, 472 underwent bone marrow examination for staging. In 330 patients a triple examination (sternal aspiration, iliac crest aspiration and biopsy) was performed, otherwise a single procedure. Bone marrow infiltration (MI) was found in 37% of the patients with extensive disease, and the frequencies of a positive finding in single and triple examinaton were not statistically different. In the group having triple examination performed iliac crest aspiration alone disclosed MI in 32%. When all three procedures were included still more patients with MI were found (42%) but the two values were not significantly different. In 6.6% of patients who would have been classified as 'limited' did bone marrow examination change the stage to extensive disease. Based on these results we recommend iliac crest aspiration, but not triple examination with iliac crest biopsy, in the staging of SCLC.     

Flow cytometric analysis of tumor DNA profile related to response to treatment and survival in small-cell lung cancer

Flow cytometric (FCM) analysis of tumor DNA ploidy and S-phase fraction (SPF) has been widely used to predict prognosis and treatment response in many malignant tumors, but rarely in small-cell lung cancer (SCLC). In the present study, tumor DNA ploidy and SPF were measured from paraffin-embedded tumor biopsy samples of 36 small-cell lung cancer patients treated with combination chemotherapy and radiotherapy. Aneuploidy was detected in 69% of the tumors. There was a statistically non-significant trend towards more aneuploidy among extensive disease (ED) patients as compared to patients with limited disease (LD): 80% versus 65%, respectively (p = 0.69). The mean SPF was 213% (± 7.6) in patients with LD and 29.0% (± 5.3) in patients with ED, the difference (7.6%) being statistically significant(p = 0.008, 95% CI for the difference 2.2-13.1). No significant differences was detected in the survival of aneuploid and diploid patients or patients with low (⩽24.9%) and high (>24.9%) SPF. Similarly, no significant difference was observed between aneuploid and diploid cases in relation to response to treatment or response duration. It is concluded that the difference detected in the SPF with LD and ED of SCLC may indicate the biological aggressiveness of extensive SCLC.     

Detection of bone marrow metastases of small cell lung cancer with magnetic resonance imaging: early diagnosis before destruction of osseous structure and implications for staging

Small cell lung cancer (SCLC) frequently metastasizes to bone and bone marrow. Skeletal scintigraphy and bone marrow cytology or biopsy, are incorporated into the staging procedures to examine these organs. However, skeletal scintigraphy is not highly specific to metastases, and only one or two bone marrow sites can be examined by cytology or biopsy. We have already reported that magnetic resonance imaging (MRI) could improve the sensitivity in detecting bone marrow metastases. The result of the bone marrow MRI was an independent prognostic factor of SCLC patients [9]. In the present study, we analyzed the results of skeletal scintigraphy and bone marrow aspiration with special reference to the results of MRI examination. We also analyzed the relationship between bone marrow lesions and bone lesions. For this purpose, we visualized bone marrow metastases with MRI and determined their anatomical locations and sizes. Approximately half of bone marrow lesions stayed in bone marrow during follow-up period ranging from 57 to 154 days, whereas about half of them were accompanied by hot spots in follow-up skeletal scintigraphy, which indicates the destruction of osseous structure. Additionally, 87.5% of osteolytic changes that newly appeared in skeletal scintigraphy were preceded by adjacent bone marrow lesions. All new lesions that appeared in follow-up skeletal scintigraphy within 3 months after the initial presentation had the preceding bone marrow lesions. These results mean that almost all lesions in skeletal scintigraphy derived from bone marrow metastases. Furthermore, appreciable volume of cancer cells is present in bone marrow before osteolytic changes appear in skeletal scintigraphy.     

Longevity in small cell lung cancer. A report to the Lung Cancer Subcommittee of the United Kingdom Coordinating Committee for Cancer Research

An analysis of the long-term results of treatment of 3,681 patients with small cell lung cancer (SCLC) is presented. The data were obtained from major centres in the UK who were conducting treatment trials during the period 1978-1986 and for whom complete computer records and follow-up were available. A total of 217 (5.9%) survived 2 years or more. Two year survival for patients presenting with limited disease (LD) was 8.5% and for extensive disease (ED) 2.2%. Death from SCLC continued until 7 years after diagnosis but not thereafter. At this point overall survival was 3% (3.6% LD, 1.1% ED). Survival after 2 years was not affected by initial disease extent, sex, thoracic radiotherapy or prophylactic cranial irradiation. Death from causes other than SCLC continued throughout the period of observation. Vascular disease, respiratory failure and second tumours were the main other causes of death. The better survival in younger patients was mainly attributable to few deaths from these other causes. These results indicate that only a small proportion of patients with SCLC are cured by current treatment. Although shorter term improvement in survival has been obtained with current treatment, the poor overall long-term results support studies exploring new approaches to cure and to palliation.     

Small-cell carcinoma of the lung: derivation of a prognostic staging system.

Retrospective data on 22 pretreatment attributes were evaluated in 614 patients with small-cell carcinoma of the lung (SCCL). The series included 284 patients with limited disease (LD) and 328 patients with extensive disease (ED) managed between 1974 and 1986. Prognostic factors were evaluated by univariate analysis and by the Cox multivariate regression model. Recursive partition and amalgamation algorithm (RECPAM), two clustering methods well suited for obtaining strata and adapted for censoring survival data, were developed and used in the formulation of a new prognostic staging system. In univariate analysis, prognosis was significantly influenced by extent of disease (DE), the number of metastatic sites, and the detection of mediastinal spread in LD. Poor performance status (PS), male sex, and advanced age were negatively correlated with survival, as were increased serum levels of alkaline phosphates (AP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), total WBC count (WBCC), and low platelet count and low serum sodium. The Cox model identified plasma LDH and mediastinal spread as the only significant factors in LD; the influence of PS, number of metastatic sites, bone metastasis, brain metastasis, and platelet count were identified as significant in ED. The RECPAM model identified four distinct risk groups defined in a classification tree by the following eight attributes: DE, PS, serum AP, serum LDH, mediastinal spread, sex, WBCC, and liver metastasis. The four groups were distinguished by median survival times of 59, 49, 35, and 24 weeks, respectively (P = .0001). Interactions among prognostic factors are emphasized in the RECPAM classification model as evidenced by reassignment of patients across conventional staging barriers into alternate prognostic groups. The advantages of using RECPAM over the more conventional Cox regression techniques for a new staging system are discussed.     

法国波尔多大学医院应用阿霉素、足叶乙甙、异环磷酰胺联合治疗69例小细胞肺癌病例的回顾分析

背景与目的:小细胞肺癌(smallcelllungcancer,SCLC)主要治疗原则为多药联合化疗,法国波尔多大学医院呼吸科应用阿霉素、足叶乙甙、异环磷酰胺联合(AVI方案)治疗SCLC10余年,本研究回顾性分析该院应用AVI方案治疗SCLC的疗效及不良反应,以探讨AVI方案在SCLC治疗中的应用价值。方法:收集法国波尔多大学医院呼吸科自1994年1月至2003年12月收治的69例接受AVI化疗的SCLC患者完整的病例资料,分析AVI化疗的有效率、不良反应和患者的生存期。结果:69例患者中,局限期(limiteddisease,LD)23例,扩散期(extendeddisease,ED)46例,化疗总有效率(OR)为60.9%,对LD和ED,OR分别为78.3%和52.2%(P=0.04),中位无进展生存期分别为11.2个月和6.7个月,中位生存期分别为11.3个月和7.2个月,1年生存率分别为47.8%和30.4%,3～4度粒细胞减少,贫血,恶心呕吐发生率分别为34.8%、15.9%、18.8%。结论:AVI治疗SCLC疗效好,主要不良反应为粒细胞减少、贫血和恶心呕吐,可作为临床实际工作中SCLC化疗方案的选择。     

Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.