Adjuvant chemotherapy in completely resected non-small-cell lung cancer.

Surgery alone has long been the standard treatment for patients with operable non-small-cell lung cancer (NSCLC). However, despite complete resection, 5-year survival rates have been disappointing, with about 50% of patients eventually suffering relapse and death from disease. Randomized trials conducted in the 1980s hinted at a survival benefit for postoperative cisplatin-based regimens, but they were underpowered. A meta-analysis published in 1995 found a nonsignificant 13% reduction in the risk of death associated with cisplatin-based chemotherapy, with an increase of survival of 5% at 5 years. This led to renewed interest in adjuvant chemotherapy in resected NSCLC. Thousands of patients have been included in a new generation of randomized trials in the last 10 years. Most of these recent studies have now been reported and several have demonstrated a clear survival advantage for patients treated with platin-based adjuvant therapy. These results also suggest a greater benefit with modern two-drug regimens. In view of the most recent data, postoperative platin-based chemotherapy can now be considered the standard of care for completely resected NSCLC patients with good performance status.     

Adjuvant chemotherapy for resected non-small-cell lung cancer

Because of the high rate of distant disease recurrence, the 5-year survival of patients who have undergone complete surgical resection of localized non-small-cell lung cancer (NSCLC) is approximately 50%. Initial results from early studies of adjuvant postoperative chemotherapy reported an adverse effect of alkylating agent and older chemotherapy regimens on survival. Cisplatin-based combinations were the first to show a survival advantage. A 1995 meta-analysis of these studies suggested a 13% reduction in the hazard ratio for death (HR = 0.87), leading to a 5% survival benefit at 5 years. Still, these trials involved limited numbers of patients (N = 1,394), and the results failed to reach statistical significance (P = .08). Of the five largest subsequent randomized trials of platinum-based adjuvant therapy, three showed a significant survival advantage. Although it is impossible to determine the reasons for the differing outcomes of these studies, several key features distinguish them, and the data suggest that medically fit patients with resected stage IB or II NSCLC should be offered chemotherapy with a platinum/new drug combination.     

Cisplatin-based combination chemotherapy for elderly patients with non-small-cell lung cancer

Purpose: To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients ( less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. Patients and methods: We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). Results: A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. Conclusion: Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmaco logic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status. Received: 30 October 1996 / Accepted: 20 March 1997     

吉西他滨治疗高龄晚期非小细胞肺癌

目的:观察吉西他滨治疗高龄晚期非小细胞肺癌的疗效,并与同期单纯支持治疗的患者比较,以探讨高龄晚期非小细胞肺癌的治疗方案。方法:吉西他滨组21例,采用吉西他滨单药化疗,剂量为1250mg/m2,静脉滴注,第1、8天用药,每21天为1周期,共4周期。对照组23例不用任何化疗,单纯支持对症治疗。结果:吉西他滨组总有效率为28.6%,其中PR6例,SD12例,PD3例。对照组无CR和PR者。吉西他滨组中位缓解期6.3个月。吉西他滨组和对照组中位肿瘤进展时间分别为5.8和2.6个月,中位生存时间分别为12.8和4.6个月(P<0.01);1年生存率分别为46.6%和9.2%(P<0.01)。吉西他滨组KPS、体重增加和临床症状改善情况均显著高于对照组(P<0.01)。毒副反应方面吉西他滨组12例(57.1%)出现Ⅰ、Ⅱ级血小板减少,7例(33.3%)出现Ⅰ、Ⅱ级白细胞下降,未见Ⅲ、Ⅳ级毒性反应。少数患者血红蛋白下降Ⅰ度,恶心呕吐Ⅰ/Ⅱ度。结论:吉西他滨单药治疗高龄晚期非小细胞肺癌是安全有效的。     

Adjuvant chemotherapy in elderly patients with pancreatic cancer

Background:

Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer.

Methods:

We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative.

Results:

The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ⩾70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8% P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27–2.78, P=0.002).

Conclusion:

Patients aged ⩾70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.     

老年晚期非小细胞肺癌化疗进展

老年肺癌的发病率逐年上升,多数医生对老年患者采用化疗并不积极,使许多身体状态尚好的老年患者丧失了延长生命的机会.现综述近年来应用于老年非小细胞肺癌患者的单药以及联合化疗方案.     

Undertreatment of elderly patients with non-small-cell lung cancer

The absolute number of patients with lung cancer is rising as a result of our aging population. Until recently, clinicians have been reluctant to aggressively treat elderly patients with non-small-cell lung cancer (NSCLC) because of a lack of supportive data and concern for potential toxicity. Recently, evidence has emerged that suggests that, similar to younger patients, healthy elderly patients can benefit from therapy in all stages of NSCLC. This review will discuss the findings that indicate that chronologic age alone should not be a barrier to appropriate treatment for NSCLC, but consideration should be given to more important prognostic factors such as comorbidities and performance status.     

Adjuvant chemotherapy for early-stage non-small-cell lung cancer. Single-centre experience and literature review

Background In recent years platinum-based chemotherapy has become the standard of care for patients with good performance status after complete resection in stages IB-IIIA non-small-cell lung cancer (NSCLC), although the benefit is mainly in stages II and IIIA. Patients and methods In a retrospective trial we evaluate the clinical efficacy and toxicity profile of a platinum- and taxanes-based adjuvant chemotherapy in completely resected IB-IIIA NSCLC. The primary end point was relapse- free survival (RFS); principal secondary end points were overall survival (OS) and safety of the regimen. Potential predictive factors of efficacy and clinical patterns of relapse were also analysed. Results From January 2003 to December 2006, 41 patients met the inclusion criteria and were evaluable. Median age at diagnosis was 68.1 years (CI 95% 54-72; range 45-78). Most patients were males (87.7%) and had an Eastern Cooperative Oncology Group performance status score (PS) of 0-1 (87.8%), and 53.6% had adenocarcinomas. Pathological stages were as follow: 48.7% stage IB, 24.3% stage II and 26.8% stage IIIA. 75.6% of patients underwent a lobectomy and mediastinal lymphadenectomy and were treated with a combination of carboplatin AUC6 and paclitaxel 200 mg/m(2) (85.36%) for 3 or 4 cycles. With a median follow-up of 18.2 months (range 5.1-46.5), 26 patients (63%) were free of disease and 32 of them were alive (78%). Median RFS was 12.1 months (CI 95% 9.8-14.9) and median OS had not been reached at the time of analysis. Patients with PS相似文献   

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER–Medicare analysis

We have used population-based data from the SEER–Medicare registry to show that adjuvant chemotherapy is associated with improved survival among elderly patients with early-stage non-small-cell lung cancer ≥4 cm. These findings extend the results of a prior RCT to the growing population of older patients with cancer.BackgroundThe role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly.Patients and methodsWe identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score.ResultsOverall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68–0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64–2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8–76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction.ConclusionsPlatinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.     

Second-line chemotherapy with a modified schedule of docetaxel in elderly patients with advanced-stage non-small-cell lung cancer

PURPOSE: In patients with advanced-stage non-small-cell lung cancer (NSCLC) pretreated with chemotherapy, docetaxel 75 mg/m2 every 3 weeks prolongs survival compared with best supportive care alone or chemotherapy with ifosfamide or vinorelbine. Neutropenia is the dose-limiting toxicity of this schedule, and thus limits its use in elderly patients. Therefore, we studied a modified schedule of docetaxel in order to reduce the toxicity of this regimen and to improve the compliance to treatment in an elderly population, while maintaining the same dose intensity of the original regimen. PATIENTS AND METHODS: Thirty-three elderly patients (aged > or = 70 years) with advanced-stage NSCLC, Eastern Cooperative Oncology Group performance status 0-2, and a median age of 74 years (range, 70-83 years) who had progressed after 1 line of chemotherapy were treated with docetaxel 37.5 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 courses. RESULTS: Seven of 33 patients (21.2%; 95% confidence interval, 8.98%-38.91%) exhibited a partial response (according to the intent-to-treat analysis), 12 patients (36.3%) exhibited stable disease, and 14 patients (42.4%) exhibited progression. Grade 3 (National Cancer Institute Common Toxicity Criteria) neutropenia and anemia were observed in 9% and 3% of patients, respectively. The main nonhematologic toxicity consisted of grade 3 nausea/vomiting, diarrhea, and asthenia in 6% of patients each, and grade 3 nail toxicity in 3% of patients. CONCLUSION: Our modified schedule of docetaxel is an active and well-tolerated second-line treatment in elderly patients with advanced-stage NSCLC and has a favorable toxicity profile.     

艾迪联合化疗治疗老年晚期NSCLC的临床观察

目的 观察艾迪注射液联合以铂类为基础的联合方案化疗治疗老年性晚期非小细胞肺癌(NSCLC)的近期疗效、生活质量和毒副反应.方法 将96例60岁以上经细胞学或病理学证实的晚期NSCLC患者随机分为两组,治疗组用艾迪联合化疗,对照组单用化疗.每例患者至少治疗2个周期以上进行疗效评价.结果 两组近期疗效差异无统计学意义(P＞0.05).治疗组生活质量Kamofsky评分提高率60.0%,对照组提高率35.0%,两组差异有统计学意义(P＜0.05).治疗组白细胞减少和肝肾毒性的发生率显著少于对照组(P＜0.05).结论 艾迪注射液联合化疗具有改善生活质量和减毒作用,增加患者化疗耐受性.     

Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study.

PURPOSE: The aims of this study were to assess the effect of adjuvant chemotherapy on overall survival, disease-free survival, and relapse pattern, as well as its toxicity in patients who underwent radical surgery for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred ten patients with T1-3N0 (World Health Organization [WHO] 1981) NSCLC underwent radical surgery during the period of 1982 through 1987. After surgery, the patients were randomized to receive adjuvant chemotherapy (n = 54) (cyclophosphamide 400 mg/m2, doxorubicin 40 mg/m2, and cisplatin 40 mg/m2 [CAP] for six cycles) or no active treatment (n = 56). RESULTS: After 10 years from the start of the study, 61% of patients were alive in the chemotherapy group and 48% were alive in the control group (P = .050). Seventeen patients (31%) in the CAP group and 27 patients (48%) in the control group had a recurrence during the follow-up period (P = .01). The 5-year survival rate was 67% in the chemotherapy group and was 56% in the control group (P = .050). The patients in the chemotherapy group who completed the planned treatment had a slightly better 5-year survival than those whose chemotherapy was discontinued (72.5% v 50.3%; P = .15). Chemotherapy-related gastrointestinal toxicity grade 3 to 4 (WHO) occurred in 63% and was the main reason why patients refused further planned therapy. CONCLUSION: Our results suggest that patients with NSCLC at pathologic stage I who have undergone radical surgery benefit from adjuvant chemotherapy.     

Adjuvant chemotherapy in elderly patients with breast cancer: key challenges

Elderly women with early breast cancer (BC) form a heterogeneous and large subgroup (41.8% of women with BC are over 65). Decision making in this subgroup is made more difficult by lack of familiarity with their physical, cognitive and social issues. Adequate management depends on biological factors and accurate clinical evaluation through comprehensive geriatric assessment (CGA). CGA can help to better select and determine potential risks factors for patients who are candidates for adjuvant chemotherapy. It is still recently introduced in geriatric oncology and there is a lack of awareness of its importance. Available data on adjuvant chemotherapy for BC is limited but suggests it can be of benefit for well selected patients, though the risk of short and long-term toxicity is significant. Here we provide a discussion of the key practical issues in decision making in the setting of adjuvant chemotherapy for elderly BC patients.     

Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy

Objectives

Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy.

Methods

Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT₃ receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy.

Results

A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2–88.1%) and 67.2% (95% CI, 55.3–77.2%; odds ratio (OR), 0.50; 95% CI, 0.22–1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08–0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07–0.65; p < 0.01).

Conclusion

Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT₃ receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.     

Treatment of elderly patients with stage IV non-small-cell lung cancer

Every thoracic oncologist could be considered a geriatric oncologist as the median age of presentation with metastatic non-small-cell lung cancer is 71 years. Subgroup analyses and population-based studies suggest similar benefits to treatment of the fit elderly compared with younger patients. In 2011, a Phase III trial demonstrated the superiority of doublet chemotherapy over single-agent therapy for the elderly. For elderly patients there has been sufficient time to fully express any genetic predispositions, and the cumulative wear and tear, including the effects of cigarette smoke, can degrade performance status and impair organ function, leading some older patients to be less fit. Comprehensive geriatric assessment can augment the standard examination in defining the strengths and weakness of the elderly patient who is considering chemotherapy. In the future, biochemical assessment of physiologic age may further aid this assessment.