Chemotherapy for elderly patients with non-small cell lung cancer: a review of the evidence

Chemotherapy for elderly patients with non-small cell lung cancer (NSCLC) has been questioned due to the perceived potential for higher toxicity in this population, possibly attributable to progressive organ failure and comorbidities. This non-systematic review presents the authors' selection of key evidence for the use of chemotherapy for elderly patients with NSCLC. To date, single-agent chemotherapy with agents such as vinorelbine, gemcitabine, docetaxel, and paclitaxel has been a reasonable option. Data on non-platinum-based combinations are limited, but recent investigations of gemcitabine plus vinorelbine failed to show superiority over either agent alone. Retrospective subset analyses from large randomized trials suggest that the efficacy and tolerability of platinum-based combination chemotherapy are similar in both the elderly and their younger counterparts. Further phase III trials that specifically examine platinum-based combinations in selected elderly NSCLC patients are therefore warranted. The potential impact of new targeted therapies-alone or in combination with chemotherapy-is being investigated.     

紫杉醇联合卡铂治疗老年和中青年晚期非小细胞肺癌的研究

目的研究紫杉醇联合卡铂治疗老年和中青年晚期非小细胞肺癌患者的疗效、预后和毒副反应。方法对2002年1月~2005年12月我院收治的50例≥70岁的肺癌患者（老年组）和同一时间随机选择的50例〈70岁肺癌患者（中青年组）分别给予紫杉醇联合卡铂方案化疗。结果老年组有效率37.5%,中青年组有效率38.8%,差异无显著性（P〉0.05）。老年组中位生存时间为11.8个月,1年、2年生存率分别为31.3%、6.3%,中青年组中位生存期11.3个月,1年、2年生存率28.6%、4.1%,无显著性差异（P〉0.05）。主要毒副反应是骨髓抑制,Ⅲ及Ⅳ中性粒细胞减少老年组34.0%,中青年组30.0%,差异无显著性（P〉0.05）。结论年龄不是影响肺癌患者疗效、预后和毒副反应的主要因素。     

An analysis of the outcomes of treatment of small cell lung cancer in the elderly

Abstract Background: Many cases of small cell lung cancer will occur in the elderly population but optimal management of the disease in this age group remains uncertain.
Aims: To evaluate treatment of small cell lung cancer in the elderly in Australia and to compare treatment received and outcomes with those of younger patients. To draw insights from these observations into the optimal management of small cell lung cancer in the elderly.
Methods: A retrospective review of treatment charts and case notes for 51 elderly patients and 102 younger patients was undertaken.
Results: Elderly patients had similar baseline parameters with respect to disease stage and performance status. Elderly patients were mostly treated uniformly with combination chemotherapy, but suffered more dose reductions than younger patients. Benefits of chemotherapy were seen even in patients with poor performance status. Despite the dose reductions, response rates and survival times for elderly patients were usually similar to younger patients.
Conclusions: Combination chemotherapy is beneficial to elderly patients with small cell lung cancer. Optimal therapy for the elderly may be different from that for younger patients and should be defined through prospective randomised clinical trials.     

Chemotherapy of non-small-cell bronchial carcinoma in elderly patients

The incidence of lung cancer increases with age, and non-small-cell histotypes account for approximately 85% of lung cancers in patients aged older than 65 years. Results of large multicentric trials provide no evidence that elderly lung cancer patients who receive systemic chemotherapy have a worse outcome than younger patients. There is, however, an underrepresentation of older patients in cancer treatment trials, at least in part due to the stringent eligibility criteria of these trials. Recent studies specifically designed for elderly patients with advanced non-small-cell lung cancer have shown that chemotherapy improves survival and disease-related symptoms also in this age group. However, the degree of comorbidity was found to affect both the tolerance to treatment and the survival outcome.     

Chemotherapy in advanced non-small cell lung cancer

Although patients with advanced non-small cell lung cancer (NSCLC) cannot be cured, cytotoxic chemotherapy in patients with reasonable performance status can improve overall survival and quality of life. No one regimen has demonstrated superior efficacy results, and platinum-based doublets remain the current standard of care. The toxicity profiles of acceptable regimens differ, allowing treatment to be tailored to a specific patient. The duration of first-line chemotherapy should not exceed four to six cycles. Second- and third-line treatment regimens also have established survival benefits, which has led to increasing improvements in overall survival for patients with advanced NSCLC. Treatment approaches in patients with borderline performance status remain controversial. Although the optimal treatment approach for elderly patients has not yet been established, it is clear that the elderly do benefit from chemotherapy, and fit elderly patients can be treated with the same regimens as younger patients. It is critical that all patients with advanced NSCLC be referred to medical oncologists. Patients considering chemotherapy must have a clear understanding of the expected benefits, limitations, and toxicities.     

Toxicity and efficacy of chemotherapy for non-small cell lung cancer with cavitary lesions

BackgroundConcurrent chemoradiation in stage III non-small cell lung cancer (NSCLC) patients with cavitary lesions is reported to cause serious lung complications and is a predictor of poor survival. However, the efficacy and toxicity associated with chemotherapy for advanced NSCLC patients with cavitary lesions is not clear. We investigated the toxicities, particularly hemoptysis and cavity infection, and efficacy associated with chemotherapy for NSCLC patients with cavitary lesions.MethodsWe retrospectively reviewed consecutive patients who received first-line chemotherapy, including platinum-based chemotherapy, single-agent chemotherapy, or epidermal growth factor receptor-tyrosine kinase inhibitors, at our institution between January 2008 and December 2010.ResultsWe found tumor cavitation prior to treatment in 23 of 415 NSCLC patients (5.5%). The response rate of all the patients was 30%, and the median survival time (MST) was 8.9 months. The MST of the 15 patients treated with platinum-based chemotherapy was 11 months. Grade 1 bronchopulmonary hemorrhage occurred in 2 patients. Grade 3 cavitary infection occurred in 2 patients, resulting in the discontinuation of chemotherapy.ConclusionsThis study indicates that the toxicity of chemotherapy for NSCLC patients with cavitary lesions is tolerable; however, the development of cavitary infection should be carefully considered. In addition, this study suggests that the efficacy of chemotherapy for NSCLC patients with cavitary lesions is similar to the response rates reported in the literature; however, the survival of these patients may be worse than that for general NSCLC patients.     

Comparison of the safety and efficacy of paclitaxel plus gemcitabine combination in young and elderly patients with locally advanced or metastatic non-small cell lung cancer. A retrospective analysis of the Southern Italy Cooperative Oncology Group trials

We retrospectively assessed tolerability and efficacy of paclitaxel plus gemcitabine combination in 259 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) enrolled in three randomized SICOG trials according to their age (70 years) at study entry. Apart from age, demographic and clinical characteristics were similar in the two groups. Response rate of paclitaxel plus gemcitabine was similar in younger and in elderly (36% versus 30%). Chemotherapy was well tolerated, but severe neutropenia (12% versus 7%), anaemia (6.6% versus 1.8%), and vomiting (5% versus 0) were more frequent in elderly patients. Both median progression-free survival (PFS, 5.5 months versus 4.2 months), and overall survival (OS, 11.1 months versus 9.1 months) resulted slightly prolonged for younger patients. However, only stage and performance status resulted independently affecting PFS and OS. In conclusion, paclitaxel plus gemcitabine were similarly tolerated and active in younger and elderly patients. This regimen should be considered an option for the management of fit elderly patients.     

Treatment of advanced non-small cell lung cancer in the elderly

Non-small cell lung cancer (NSCLC) is primarily a disease of the elderly. Although NSCLC is the leading cause of cancer death in the United States and the overall prognosis of this disease is poor, treatment improves survival compared with best supportive care, independent of the stage of disease. Elderly patients have a particularly poor prognosis with NSCLC compared with younger patients, likely due to age-related biases in referral and treatment patterns. There is an emerging literature regarding the tolerability of NSCLC treatments in elderly patients. In advanced disease, subgroup analyses of the elderly population participating in randomized clinical trials as well as elder-specific prospective randomized trials have demonstrated that elderly NSCLC patients derive equivalent survival benefit from the treatment of NSCLC as younger patients. This treatment is tolerable for "fit" elderly patients, and modified regimens are available for the more frail elderly patients. Evaluating the relative fitness of an elderly patient may be achieved through an assessment of functional ability. As the U.S. population ages and the incidence of NSCLC rises, an understanding of treatment options for elderly patients with NSCLC is vital for all clinicians involved in their clinical care.     

Chemotherapy for colorectal carcinoma in the elderly

With nearly 50 % of all colorectal cancers being diagnosed in patients at the age of 70 or above colorectal cancer is a disease of the elderly. In an adjuvant setting, fit elderly patients can receive the same benefit from cytotoxic therapy as younger patients with an only slightly increased toxicity. In a palliative setting, the treatment of elderly patients with respect to clinical endpoints such as response, time to progression or overall survival is as effective as in their younger counterparts. In clinical studies, older patients are generally underrepresented and among the elderly patients involved in clinical studies there is a bias towards particularly fit patients. Therefore it is not possible to extrapolate the results of many randomized trials to all elderly patients. A Comprehensive Geriatric Assessment (CGA) should be applied to detect the diversities in the geriatric population. Based on this assessment elderly patients classified as suitable for chemotherapy should be enrolled into clinical trials for colorectal cancer.     

Who gets chemotherapy for metastatic lung cancer?

STUDY OBJECTIVES: To determine the prevalence and factors associated with chemotherapy use in elderly patients presenting with advanced lung cancer. DESIGN: A retrospective cohort study using administrative data. SETTING AND PATIENTS: We analyzed the medical bills for the 6,308 Medicare patients > 65 years old with diagnosed stage IV non-small cell lung cancer (NSCLC) in the 11 SEER (survival, epidemiology, and end results) regions between 1991 and 1993. The main outcome measure, chemotherapy administration, was identified by the relevant medical billing codes. Patient sociodemographic and disease characteristics were obtained from the SEER database and census data. RESULTS: Almost 22% of patients received chemotherapy at some time for their metastatic NSCLC. As expected, younger patients and those with fewer comorbid conditions were more likely to receive chemotherapy. However, several nonmedical factors, such as nonblack race, higher socioeconomic status, treatment in a teaching hospital, and living in the Seattle/Puget Sound or Los Angeles SEER regions, also significantly increased a patient's likelihood of receiving chemotherapy. CONCLUSION: Compared to previous reports, the prevalence of chemotherapy use for advanced NSCLC appears to be increasing. However, despite uniform health insurance coverage, there is wide variation in the utilization of palliative chemotherapy among Medicare patients, and nonmedical factors are strong predictors of whether a patient receives chemotherapy. While it is impossible to know the appropriate rate of usage, nonmedical factors should only influence a patient's likelihood of receiving treatment if they reflect patient treatment preference. Research to further clarify the costs, benefits, and patient preferences for chemotherapy in this patient population is warranted in order to minimize the effect of nonmedical biases on management decisions.     

Treatment Outcomes in Elderly with Advanced-Stage Non-small Cell Lung Cancer

Purpose

Lung cancer remains the top cause of cancer morbidity and mortality in the world. Although the identification of epidermal growth factor receptor (EGFR) gene mutations could predict efficacy of tyrosine kinase inhibitor (TKI), testing for predictive biomarkers are not always possible due to tissue availability. The overall therapeutic decision remains a clinical one for a significant proportion of elderly patients with advanced stage lung cancer but no known EGFR mutation status. The purpose of this study was to compare the outcome of drug treatment modalities in progression-free survival (PFS) and overall survival (OS) for elderly with advanced-stage non-small cell lung cancer (NSCLC) and to identify clinical parameters that could predict treatment outcome.

Methods

Clinical records of patients aged 70 years or older with advanced-stage NSCLC who have received treatment were reviewed. A group of gender- and histology-matched subjects younger than age 70 years were identified as controls.

Results

Fifty-six elderly patients were included. The median age at diagnosis was 73 years; 60.7 % received only one line of treatment. Baseline performance status (PS) was the only predictor of improved PFS (p = 0.042) and OS (p = 0.002). There was no difference in survival between the upfront chemotherapy and the TKI groups

Conclusions

In elderly with advanced-stage NSCLC without known EGFR mutation status, use of EGFR–TKI and chemotherapy resulted in comparable survival benefits. Age was not predictive of worse treatment outcome. The baseline PS should be taken into consideration in the therapeutic decision in elderly with NSCLC where the EGFR mutation status is not known.     

Comparison of efficacy of automatic implantable cardioverter defibrillator in patients older and younger than 65 years of age

PURPOSE: The efficacy of the automatic implantable cardioverter defibrillator (AICD) was compared in elderly patients and younger patients with life-threatening ventricular tachyarrhythmias. Clinical characteristics, surgical complications, and long-term survival rates were compared between the two age groups. PATIENTS AND METHODS: A retrospective study was conducted of 54 elderly patients (greater than 65 years) and 79 younger patients (less than 65 years) who had had AICDs implanted for recurrent symptomatic ventricular tachycardia and/or ventricular fibrillation. RESULTS: In 85% of elderly patients and 78% of younger patients, coronary artery disease was the underlying disease (NS). The mean left ventricular ejection fraction was 31.4 +/- 14.3% in the elderly patients and 35.7 +/- 17.6% in the younger patients (NS). Concomitant myocardial revascularization was performed in 37% of elderly patients and 29% of younger patients (NS); however, only 4% of elderly patients had concomitant left ventricular resection or cryoablation, compared with 15% of younger patients (p less than 0.001). Two patients in each age group died perioperatively (4% versus 3%, NS), and no significant difference in surgical morbidity or length of hospital stay following AICD implantation was noted between the age groups. In conjunction with AICD, elderly patients more commonly received antiarrhythmic drugs, with 54% of elderly patients taking amiodarone at the time of hospital discharge compared with 29% of the younger patients (p less than 0.008). In contrast, beta-blockers were more commonly used in younger patients (16% versus 2%, p less than 0.03). At a mean follow-up of 25 months, 11 (20%) elderly patients and 16 (20%) younger patients had died. Six deaths in elderly patients and five deaths in younger patients were classified as arrhythmic deaths (NS); however, only one younger patient and three elderly patients died suddenly (NS). Calculated survival curves demonstrated similar survival rates in the two age groups with approximately 90%, 87%, and 80% of the patients alive at 1, 2, and 3 years, respectively. Theoretic survival curves calculated from appropriate AICD shocks demonstrated significantly lower survival compared with actual survival. CONCLUSION: It is concluded that AICD is a very effective treatment for life-threatening ventricular tachyarrhythmias, and this benefit applies to elderly patients as well as younger patients.     

Cisplatin-based chemotherapy in elderly patients with advanced stage (IIIB and IV) non-small cell lung cancer patients

Lung cancer continues to be the leading cause of cancer-related mortality and approximately 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. More than 50% of lung cancer cases are diagnosed in patients over the age of 65 years. The doublet chemotherapies consisting of platinum plus one of the third-generation agents become currently the standard regimen, the first line chemotherapy The most of the available data regarding the optimal treatment of lung cancer comes from clinical trials in which the vast majority of patients are significantly younger than 65 years of age. We aimed to investigate whether there is any difference in tolerability and efficacy in between adult(<65 years old) and elderly(≥65 years old) patients who received cisplatin based chemoteherapy or chemoradiotherapy for stage IIIB and IV non-small cell lun cancer. We retrospectively evaluated the total 134 patients with advanced stage (stage IIIB or IV) NSCLC, in Ondokuzmay?s University, Faculty of Medicine, Department of Pulmonary Medicine between 2001 and 2004. The response rates were 30.3% in adults and 28.8% in elderly patients. The median survival was 13.6±1.4 months and 11.8±2.0 months for adults and elderly patients, respectively. The one-year, two year and five year survival rates were 37%, 9% , 4% for adult patients and 29%, 7%, 4% for elderly patients, respectively. There was no statistical difference between the groups. Percentages of grade 3-4 anemia (0% vs 6.6%) and grade 3-4 neutropenia (0% vs 4.4%) were higher in elderly patients than adult patients. Other toxic effects were similar among both of groups. In conclussion; standart cisplatin containing chemotherapy regimens (cisplatin plus gemcitabine or vinorelbine) can be used in elderly patients with advanced non-small cell lung cancer.     

Combination chemotherapy with carboplatin and docetaxel for elderly patients with non-small-cell lung cancer

The efficacy and toxicity of treatment with carboplatin (AUC= 5)+ docetaxel (70mg/m2) were analyzed retrospectively in 27 elderly patients with advanced non-small-cell lung cancer (NSCLC) aged 70 years or more. The median age of the patients was 74 years (range, 70-83 years). The performance status (ECOG), clinical stage, and tumor histology in the patients were as follows: PS: PS 0, 12 patients; PS 1, 11 patients; PS 2, 4 patients; disease stage: stage IIIA, 5 patients; stage IIIB, 11 patients; stage IV, 11 patients; tumor histology: adenocarcinoma, 18 patients; squamous cell carcinoma, 9 patients. The median number of treatment cycles administered was 4. The median survival time was 11.1 months and the 1-year survival rate was 40.7%. The response rate was 33.3%. The major toxicities were leukopenia and neutropenia; grade 3/4 neutropenia occurred in 22 patients (81.5%). Nonhematologic toxicities were generally mild, including grade 3 anorexia in 13 patients (48.1%) and grade 3 febrile neutropenia in 9 patients (33.3%). No treatment-related deaths were observed. Thus, it was concluded that the combination of carboplatin + docetaxel is a feasible, well-tolerated, and effective regimen for fit elderly patients with NSCLC. Prospective studies comparing carboplatin + docetaxel with third-generation single-agent chemotherapy or non-platinum-based combination chemotherapy are needed to confirm the efficacy and safety of this drug combination.     

Outcome of treated advanced non-small cell lung cancer with and without central airway obstruction

OBJECTIVE: In patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy, we compared survival in patients with treated central airway obstruction to those who did not have central airway obstruction. METHODS: One hundred forty-four patients with advanced and inoperable NSCLC were included. These consisted of 52 consecutive patients treated with therapeutic bronchoscopy plus chemotherapy with or without radiotherapy (group A) and 92 consecutive patients who did not have central airway obstruction treated with chemotherapy alone (group B). Chemotherapy consisted of cisplatin or carboplatin, and one third-generation chemotherapy agent. RESULTS: There was no significant difference in the survival of patients with and without central airway obstruction (p = 0.395). There was no influence of the histologic subtype on survival in both groups combined and also in each group separately. Median survival in patients belonging to group A was 8.4 months and those in group B was 8.2 months; 3-, 6-, and 12-month survival rates in patients in group A were 90%, 71%, and 40%, respectively, and those in group B were 82%, 63%, and 34%. CONCLUSION: Patients having advanced NSCLC with locally treated malignant central airway obstruction in combination with chemotherapy do not have a worse survival compared to those with advanced NSCLC without central airway obstruction. Therapeutic bronchoscopy should be offered to patients with NSCLC and central airway obstruction.     

Older patients more likely to die from cancer-related diseases than younger with stage IA non-small cell lung cancer: a SEER database analysis

BackgroundVarious reports showed some conflicting data on survival at different ages. This study aimed to investigate the main cause of death in older patients with lung cancer and to perform a comparison with younger patients in order to observe the differences between these two cohorts.MethodsOutcomes of patients with stage IA non-small cell lung cancer (NSCLC) ≤3 cm who underwent lobectomy without induction therapy in the Surveillance, Epidemiology, and End Results-18 (SEER-18; January 2004 to December 2016) database were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.ResultsA total of 16,672 eligible NSCLC cases were found in the SEER database. The number of patients aged ≤60, 61–70, and ≥71 years was 3,930, 6,391, and 6,351, respectively. Among these patient groups, 527 (13.4%), 1,018 (15.9%), and 1,235 (19.4%) died of lung cancer during follow-up, while 357 (9.1%), 964 (15.1%) and 1,579 (25.2%) died of non-lung cancer diseases, respectively. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of younger patients showed a significant survival advantage over older patients. After propensity-score matching (PSM) of patients aged ≤60 and ≥71 years using a ratio of 1:1, we found that 403 (12.9%) and 584 (18.7%) patients in the ≤60 and ≥71 years age groups died of lung cancer, respectively. The OS and LCSS rates of younger patients still exhibited a significant survival advantage over older patients.ConclusionsOlder patients with stage IA NSCLC have a worse prognosis compared with younger patients. Also, cancer-related causes were more frequent in older patients than non-cancer-related causes.     

Irinotecan in the treatment of elderly patients with advanced colorectal cancer

Irinotecan is an active drug in the first and subsequent lines of chemotherapy for patients with advanced colorectal cancer. Frequently, the elderly patients are excluded from receiving irinotecan alone or in combination, and on many occasions these patients receive an initial reduced dose of this drug. This revision has been focused in the role of irinotecan in elderly patients.Material and methodsData from pharmacokinetic studies, comparative analysis of prospective trials according to age and prospective studies with irinotecan alone or irinotecan-combinations in the elderly have been revised and put into context.ResultsEither pharmacokinetic and clinical data suggest that fit elderly patients may tolerate irinotecan as well as the younger population. Response rate and survival achieved in elderly patients with irinotecan combinations seem to be equivalent to that obtained in younger patients.ConclusionElderly patients with advanced colorectal cancer should be carefully evaluated in order to be classified as fit or not fit through a comprehensive geriatric assessment. For the group of fit elderly patients, irinotecan may be used as in the younger population.     

Advanced age is not correlated with either short-term or long-term postoperative results in lung cancer patients in good clinical condition

OBJECTIVES: Several investigators have reported that operative mortality in the elderly is acceptable. However, their patients are potentially biased with regard to some factors such as performance status (PS) and comorbidity. In this study, we discuss surgical indications for the elderly and effects on perioperative mortality and prognosis. STUDY DESIGN: A retrospective study was carried out by reviewing the records of 1,114 patients who were referred for treatment of non-small cell lung cancer between January 1993 and December 2002. The patients were classified into younger (< or = 75 years of age) and elderly (> or = 76 years of age) groups. The histologic subtype, TNM stage, Eastern Cooperative Oncology Group PS, and treatment were reviewed for members of each group, and the proportion of patients who underwent surgery was compared between the two groups. The surgical procedures, perioperative mortality, and prognosis of the two groups were also compared. RESULTS: There was a significant difference in the histologic distribution with no difference in TNM staging between the two groups. Regarding treatment, 51.0% of those in the younger group and 36.1% of those in the elderly group underwent surgery. The proportion of elderly patients who underwent surgery was significantly lower than that of the younger patients, mainly due to worse PS and comorbidity in the elderly patients. The perioperative mortality rates for the younger and elderly groups were 0.9% and 4.1%, respectively, with no significant difference, and the overall survival was similar between the two groups. CONCLUSIONS: When compared to younger patients, fewer elderly patients underwent surgery because of worse PS and comorbidity. However, in elderly patients with good PS and no comorbidity, the rate of perioperative mortality and the prognosis were similar to those in the younger patients. Therefore, advanced age only is not a negative factor for surgery in elderly patients.