Biweekly Carboplatin Plus Gemcitabine as First-Line Treatment of Elderly Patients With Advanced Squamous Non-Small-cell Lung Cancer: A Multicenter Phase I-II Trial by the Hellenic Oncology Research Group.

BACKGROUND: The present study was a phase I/II study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities of the biweekly carboplatin/gemcitabine combination and evaluate its safety and efficacy in patients aged ≥ 70 years with advanced squamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged ≥ 70 years with advanced or metastatic squamous NSCLC received escalated doses of carboplatin (area under the curve [AUC] 2-2.5 intravenously) and gemcitabine (800-1100 mg/m2 intravenously) every 2 weeks (phase I). In the phase II, the drugs were administered at their previously defined MTDs (carboplatin, AUC 2.5; gemcitabine, 1100 mg/m2). The primary endpoint was the overall response rate. RESULTS: A total of 69 patients were enrolled (phase I, n = 15). The median age was 76 years (range, 70-84 years); 52 patients had stage IV disease, and 61 and 8 patients had Eastern Cooperative Oncology Group performance status of 0 to 1 and 2, respectively. The MTDs could not be reached at the predefined last dose levels. The dose-limiting toxicities were grade 5 renal toxicity and grade 3 thrombocytopenia. In the phase II study, the overall response rate was 35.8% (95% confidence interval [CI], 23.0%-48.8%). In the intention-to-treat analysis, the median progression-free survival was 6.7 months (95% CI, 4.2-8.8 months), and the median overall survival was 13.3 months (95% CI, 7.1-19.6 months). Grade 3 or 4 neutropenia was observed in 7 patients (12.3%), grade 3 or 4 thrombocytopenia in 4 patients (7.1%), and grade 2 or 3 fatigue in 10 patients (17.5%). One toxic death occurred in the phase I of the study. CONCLUSION: The biweekly regimen of gemcitabine and carboplatin showed satisfactory efficacy and a favorable toxicity profile in elderly patients with advanced or metastatic squamous cell NSCLC.

Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging?

Aging of an individual entails a progressive decline of functional reserves and loss of homeostasis that eventually lead to mortality. This process is highly individualized and is influenced by multiple genetic, epigenetic and environmental factors. This individualization and the diversity of factors influencing aging result in a significant heterogeneity among people with the same chronological age, representing a major challenge in daily oncology practice. Thus, many factors other than mere chronological age will contribute to treatment tolerance and outcome in the older patients with cancer. Clinical/comprehensive geriatric assessment can provide information on the general health status of individuals, but is far from perfect as a prognostic/predictive tool for individual patients. On the other hand, aging can also be assessed in terms of biological changes in certain tissues like the blood compartment which result from adaptive alterations due to past history of exposures, as well as intrinsic aging processes. There are major signs of 'aging' in lymphocytes (e.g. lymphocyte subset distribution, telomere length, p16INK4A expression), and also in (inflammatory) cytokine expression and gene expression patterns. These result from a combination of the above two processes, overlaying genetic predispositions which contribute significantly to the aging phenotype. These potential "aging biomarkers" might provide additional prognostic/predictive information supplementing clinical evaluation. The purpose of the current paper is to describe the most relevant potential "aging biomarkers" (markers that indicate the biological functional age of patients) which focus on the biological background, the (limited) available clinical data, and technical challenges. Despite their great potential interest, there is a need for much more (validated) clinical data before these biomarkers could be used in a routine clinical setting. This manuscript tries to provide a guideline on how these markers can be integrated in future research aimed at providing such data.

Completion of radiotherapy is associated with the Vulnerable Elders Survey-13 score in elderly patients with cancer.

OBJECTIVES: Vulnerability assessment of geriatric patients with cancer may contribute to improved anti-cancer treatment with maximal results and minimal side effects. The aim of the present study was to evaluate whether the Vulnerable Elders Survey-13 (VES-13) score is associated with completion of radiotherapy among elderly patients with cancer. MATERIALS AND METHODS: This was a prospective observational study that included patients greater than age 75 with histologically confirmed cancer disease, referred to the Department of Radiation Oncology to receive radical or palliative radiotherapy, from 2010 to 2012. VES-13 forms were filled in before the initiation of radiotherapy and scores were assigned according to a standardized scoring procedure. RESULTS: Of a total of 230 participants (median age 78.5 years), 41 (17.8%) did not complete radiotherapy. These patients had higher VES-13 scores (median with interquartile range: 5 [2-8.5]) compared to those who completed the treatment (3 [1-7]; P = 0.008). A VES-13 score >3 was associated with 2.14 times higher probability of not completing radiotherapy, whereas in patients with scores >7 this probability was 3.34 times higher. The association between higher VES-13 scores and non-completion of radiotherapy was independent of other factors, such as age, sex, comorbidities, type of radiotherapy, and presence of side effects. CONCLUSION: Patients with higher VES-13 scores had increased probability of not completing radiotherapy in our study, and this effect was independent of other factors that might affect radiotherapy completion.

Lung cancer in never smokers: disease characteristics and risk factors.

It is estimated that approximately 25% of all lung cancer cases are observed in never-smokers and its incidence is expected to increase due to smoking prevention programs. Risk factors for the development of lung cancer described include second-hand smoking, radon exposure, occupational exposure to carcinogens and to cooking oil fumes and indoor coal burning. Other factors reported are infections (HPV and Mycobacterium tuberculosis), hormonal and diatery factors and diabetes mellitus. Having an affected relative also increases the risk for lung cancer while recent studies have identified several single nucleotide polymorphisms associated with increased risk for lung cancer development in never smokers. Distinct clinical, pathology and molecular characteristics are observed in lung cancer in never smokers; more frequently is observed in females and adenocarcinoma is the predominant histology while it has a different pattern of molecular alterations. The purpose of this review is to summarize our current knowledge of this disease.

Targeting tumor neovasculature in non-small-cell lung cancer.

Recent insight into the molecular biology of cancer and mechanisms of tumorigenesis, has allowed for the identification of several potential molecular targets and the development of novel "targeted therapies". One of the most active research fields in NSCLC is the discovery of therapies that target angiogenesis. The vascular endothelial growth factor (VEGF) pathway represents a crucial component of the tumor angiogenesis process. Two different strategies have been developed in clinical practice in order to restrict tumor vasculature development; either the use of monoclonal antibodies against VEGF or small molecule tyrosine kinase inhibitors to target the tyrosine kinase domain of VEGF receptor. Among these agents that have been tested bevacizumab, a monoclonal antibody against VEGF, has been approved for the treatment of metastatic NSCLC in combination with chemotherapy, while several other agents are under phase III investigation. Moreover, several issues such as predictive biomarkers of response to antiangiogenic therapy and mechanisms of resistance to these agents remain to be elucidated. The purpose of this paper is to present the current status of antiangiogenic therapies in the treatment of NSCLC and to discuss these issues.

High prevalence of osteoblastic bone reaction in computed tomography scans of an European Organisation for Research and Treatment of Cancer prospective randomised phase II trial in extensive stage small cell lung cancer.

BACKGROUND: Osteoblastic bone reaction is an important phenomenon defined by an increase in apparent bone density of previously known bone metastasis or development of new osteoblastic lesions in the presence of response in other tumour sites. Osteoblastic bone reaction in lung cancer has only been described in a few reports and mostly in patients with pre-existing bone metastasis. METHODS: In this report we present the data of an independent, blinded and preplanned radiological review of the occurrence of osteoblastic lesions in patients with extensive stage small cell lung cancer (SCLC). The computed tomography (CT) scans of the chest and upper abdomen of 71/88 patients who had an investigator reported complete response (CR), partial response (PR) or stable disease (SD) were retrospectively analysed for the development of osteoblastic lesions. Furthermore, baseline exams were reviewed for the presence and location of bone metastasis and local radiological reports were reviewed for any knowledge of bone metastasis. RESULTS: There were 14 patients with osteoblastic bone lesions in the reviewed follow-up CT scans. Three patients had known bone metastases at baseline, and 11 patients had no history or findings of bone metastases on the baseline scan. During the course of the disease, 13 out of 14 patients developed new osteoblastic lesions, while all responded in other sites. The prevalence of osteoblastic bone reaction in our study was 19.7%. CONCLUSION: In this study osteoblastic bone reaction was observed in a larger number of patients without previously documented bone metastases, indicating a high prevalence of occult bone metastases in SCLC. If bone metastases are not documented at diagnosis, then osteoblastic bone reaction may cause confusion in a responding patient.

Targeted (and chemotherapeutic) agents as maintenance treatment in patients with metastatic non-small-cell lung cancer: current status and future challenges.

Maintenance treatment has been intensively investigated in the field of advanced/metastatic non-small lung cancer in order to improve outcomes in this devastating disease. Two different approaches have been evaluated; the so-called continuation maintenance when the maintenance agent was part of initial therapy and is continued in the absence of disease progression ("maintained") or switch maintenance when a third agent is initiated after a defined number of cycles chemotherapy in the absence of disease progression. Several phase III trials with both chemotherapeutic and targeted agents have demonstrated either PFS prolongation (continuation maintenance) or both PFS and OS benefit (switch maintenance). Currently, erlotinib and pemetrexed are registered as maintenance treatment in patients with NSCLC not progressing after four cycles of standard platinum-based doublet chemotherapy. However, the development of maintenance treatment has raised a series of questions such as the role of treatment-free intervals, the timing of second-line treatment, selection of patients for maintenance treatment and selection of the most proper agent, and trial design issues such as optimal end-points. The purpose of this paper is to present and discuss the current trials investigating the main treatment paradigms and argue on the above mentioned questions.

A phase II trial of erlotinib as front-line treatment in clinically selected patients with non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of erlotinib as front-line treatment in clinically selected patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-nine previously untreated white patients who had stage IIIB/IV pulmonary adenocarcinoma or bronchoalveolar carcinoma and who were nonsmokers or former light smokers were treated with erlotinib 150 mg daily, irrespective of the EGFR mutation status. RESULTS: In an intention-to-treat analysis, the overall response rate (ORR) was 24.5%. The median progression-free survival (PFS) was 6.7 months, the median overall survival (OS) was 15.5 months, and the 1-year survival rate was 61.3%. Among the 36 patients for whom tumor material was available, 9 (25%) had activating EGFR mutations. The ORR was 66.7% in patients with activating EGFR mutations and 14.8% in patients with wild-type EGFR (2P = .006). In patients with activating EGFR mutations, the OS has not been reached, whereas it was 12.9 months in patients with EGFR wild type (2P = .045). Twenty-four patients had a PFS of > 6 months; 11 (45.8%) of them had EGFR wild type and 7 (29.1%) had EGFR mutation. CONCLUSIONS: The selection of patients for treatment with EGFR-directed tyrosine kinase inhibitors (TKIs) should be based on mutation testing. However use of clinical (smoking status) and pathologic (adenocarcinoma) criteria may identify a subgroup of patients with advanced/metastatic NSCLC who can benefit from front-line treatment with erlotinib when mutation testing is not feasible.

Is there a standard regimen for first-line treatment of advanced/metastatic Non-Small-Cell Lung Cancer? What has meta-analyses contributed to today's standard of care.

Despite the fact that Non-Small Cell Lung Cancer (NSCLC) represents the leading cause of cancer-related death in the western, after two decades of intensive clinical research, there still remains a substantial lack of consensus regarding the appropriate chemotherapeutic management of patients with advanced stage disease. For patients with metastatic disease and good performance status, what is considered "standard" treatment is a platinum-based doublet. Several meta-analyses have been performed in order to answer several questionable issues in the treatment of these patients. Their conclusions could be used as an effective instrument for resolving various clinical questions, such as advantage of chemotherapy for advanced NSCLC and identification of the most active combinations and most active agents, or treatment duration and thus providing more reliable evidence for clinical practice.

Nutritional status, acute phase response and depression in metastatic lung cancer patients: correlations and association prognosis.

BACKGROUND AND AIM: Cancer cachexia is a metabolic syndrome related with poor outcome. Cytokines play a key role in the pathophysiology of that syndrome. The aim of this study was to investigate the potential correlations between nutritional status, systemic inflammation, and psychological distress in cancer patients. The prognostic significance of the recorded parameters was also assessed. PATIENTS AND METHODS: Patients with metastatic lung cancer were eligible. Mini Nutritional Assessment (MNA) was used for the evaluation of nutritional status, Glasgow Prognostic Score (GPS) for the estimation of systemic inflammation, and Hospital Anxiety and Depression Scale (HADS) for psychological assessment. RESULTS: Totally, 122 patients were enrolled (71.3% with NSCLC and 28.7% with SCLC). The following correlations were observed: MNA and GPS (r = 0.289, p = 0.001), MNA and HADS (depression scale) (r = 0.275, p = 0.002), GPS and HADS (depression scale) (r = 0.256, p = 0.004), and GPS and HADS (anxiety scale) (r =0.194, p =0.033). In univariate analysis, GPS (p = 0.002) and MNA (p = 0.010) emerged as significant predictors of survival. In multivariate analysis, both MNA (p = 0.032) and GPS (p = 0.020) retained their importance. CONCLUSIONS: This study highlights the associations between nutritional status, systemic inflammation, and psychological distress, supporting their common underlying pathophysiological mechanisms and further suggesting the necessity of a holistic anti-cachectic approach.

Docetaxel vs. vinorelbine in elderly patients with advanced non--small-cell lung cancer: a hellenic oncology research group randomized phase III study.

BACKGROUND/PURPOSE: This study compared front-line treatment with docetaxel or vinorelbine in elderly patients with advanced/metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with inoperable stage IIIB and stage IV NSCLC who were > 65 years of age with performance status (PS) of 0-2 were enrolled. Patients were assigned to receive either docetaxel 38 mg/m(2) or vinorelbine 25 mg/m(2) by intravenous (I.V.) infusion on days 1 and 8 every 3 weeks. RESULTS: One hundred thirty elderly patients were enrolled in the study (docetaxel n = 66 and vinorelbine n = 64 patients). The objective response rate was 12.1% and 14.1% in patients treated with docetaxel and vinorelbine, respectively (2P = .799). The median time to tumor progression (TTP) was 2.33 and 1.9 months (2P = .298) and the median overall survival (OS) was 6.07 and 3.87 months (2P = .090) in the docetaxel and vinorelbine arms, respectively. Grade 3/4 neutropenia occurred in 4.5% and 29.7% of patients in the docetaxel arm and vinorelbine arm, respectively (2P < .001). Febrile neutropenia occurred in 1.5% and 1.6% of patients in the docetaxel arm and the vinorelbine arm, respectively (2P = .950) and the use of granulocyte colony-stimulating factor (G-CSF) was more frequent in patients treated with vinorelbine (37.1% vs. 22.5%; 2P < .001). There were no deaths from toxicity. Nonhematologic toxicity was mild. CONCLUSIONS: Docetaxel has an efficacy comparable to that of vinorelbine as first-line treatment in elderly patients with NSCLC and has an acceptable toxicity profile. The trial was closed prematurely because of low accrual, thus limiting the strength of the conclusions derived.

Second-line paclitaxel/carboplatin versus vinorelbine/carboplatin in patients who have advanced non-small-cell lung cancer pretreated with non-platinum-based chemotherapy: a multicenter randomized phase II study.

PURPOSE: This study evaluates the activity and toxicity of the paclitaxel/carboplatin (PC) doublet versus vinorelbine/carboplatin (VC) doublet as second-line treatment in patients who have advanced non-small-cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Patients pretreated with front-line docetaxel and gemcitabine were randomized to receive either PC (n = 75), which consisted of paclitaxel at a dose of 140 mg/m(2) and carboplatin area under the curve (AUC3), or VC (n = 78), which consisted of vinorelbine at a dose of 45 mg/m(2) orally and carboplatin AUC3; both drugs were administered on days 1 and 15. RESULTS: The overall response rate was 18.6% (95% confidence interval, 9.85%-27.49%; one complete and 13 partial responses) in the PC arm and 7.7% (95% confidence interval, 1.78%-13.61%; one complete and five partial responses) in the VC arm (P = .056). Median time to tumor progression was 3.5 months (range, 0.3 - 23.73 months) and 3.07 months (range, 0.37-18.5) in the PC and VC arm, respectively (P = .287). Median overall survival was 7.83 months (range, 0.3-45.03 months) and 7.60 months (range, 0.5-30.27 months) for PC and VC arms, respectively (P value = .633). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed. CONCLUSIONS: Platinum-based doublets with either paclitaxel or vinorelbine in patients with advanced/metastatic NSCLC pretreated with front-line docetaxel/gemcitabine show comparable efficacy when used in the second-line setting.

A multicenter phase I trial of metronomic oral vinorelbine plus cisplatin in patients with NSCLC.

The purpose of the present study was to determine the maximum-tolerated doses (MTDs) and the dose-limiting toxicities of a metronomic administration of oral vinorelbine and cisplatin in patients with advanced/metastatic NSCLC. Twenty-six patients with advanced/metastatic NSCLC were enrolled. Escalating doses of vinorelbine (40-70 mg p.o./trice per week) and cisplatin (70-85 mg/m(2) intravenous infusion) were administered on day 1 every 3 weeks. ΜΤDs were reached at 60 mg thrice/week p.o. for vinorelbine and 85 mg/m(2) for cisplatin. Grade 4 neutropenia, febrile neutropenia and grade 4 diarrhea were the dose-limiting events during the first cycle of chemotherapy. The most common grade III-IV hematologic toxicity was neutropenia occurring in seven (27%) patients, while non-hematological toxicities were relatively infrequent and mostly of grade I or II. Objective responses were observed in 20.8% of patients with measurable disease. The regimen of metronomic administration and cisplatin is feasible and active in patients with NSCLC.

A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic non-small cell lung cancer.

BACKGROUND: To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m2; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m2 on days 1 and 15). RESULTS: Response rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed. CONCLUSIONS: This study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.

DNA repair pathways and their implication in cancer treatment.

Many cytotoxic agents used in cancer treatment exert their effects through their ability to directly or indirectly damage DNA and thus resulting in cell death. Major types of DNA damage induced by anticancer treatment include strand breaks (double or single strand), crosslinks (inter-strand, intra-strand, DNA-protein crosslinks), and interference with nucleotide metabolism and DNA synthesis. On the other hand, cancer cells activate various DNA repair pathways and repair DNA damages induced by cytotoxic drugs. The purpose of the current review is to present the major types of DNA damage induced by cytotoxic agents, DNA repair pathways, and their role as predictive agents, as well as evaluate the future perspectives of the novel DNA repair pathways inhibitors in cancer therapeutics.

Molecular networks in respiratory epithelium carcinomas.

Current anti-cancer research is focused on cell surface receptors targeting, mainly epidermal growth factor receptor and vascular endothelial growth factor receptor, against which a few targeted agents are now available in clinical practice. Recent improvements of our understanding on the intracellular networks that participate in respiratory epithelium carcinogenesis have further elucidated the role of a variety of molecules that represent attractive targets for novel therapeutic strategies. The aim of this review is to explore the potential therapeutic opportunities of the manipulation of these pathways.

Treatment of small-cell lung cancer in elderly patients.

Small-cell lung cancer (SCLC) represents 15% to 20% of all lung carcinomas. Approximately 30% to 40% of these cases are diagnosed in patients older than 70 years of age. Staging of SCLC classifies patients as having either limited or extensive-stage disease. The standard treatment for limited-stage disease is platinum-based chemotherapy, combined with external-beam thoracic radiotherapy, whereas platinum-based regimens alone represent the standard of care for extensive-stage disease. In the elderly population, treatment of SCLC is more challenging given the decline in physiological organ reserve and the presence of comorbidities. The majority of data are drawn from retrospective studies, which are likely to suffer from selection bias. However, limited prospective data are available to guide treatment decisions in that special population. Nonetheless, these data demonstrate that standard approaches are feasible in carefully selected elderly patients. The purpose of this article is to review the currently available evidence on treatment of SCLC in patients older than 65-70 years of age.

A multicenter randomized phase II study of the irinotecan/gemcitabine doublet versus irinotecan monotherapy in previously treated patients with extensive stage small-cell lung cancer.

OBJECTIVES: To compare the efficacy and safety profile of irinotecan (I) versus the combination of irinotecan/gemcitabine (IG) as second-line treatment of patients with extensive stage small-cell lung cancer (SCLC). TREATMENT: Patients with SCLC who have received at least one chemotherapy regimen were randomized to receive either the IG regimen (gemcitabine 1000mg/m(2) intravenous (i.v.) on days 1 and 8 and irinotecan 300mg/m(2) i.v. on day 8) or I monotherapy (300mg/m(2) i.v. on day 1) both every 3 weeks. RESULTS: Thirty-eight patients were enrolled in the IG and 31 in the I arm. Due to slow accrual an early closure of the study was decided. Response rate was significantly higher in the IG than in I arm (23.7% vs. 0%; p=0.004). The median time to progression (TTP) was 3.9 months (range: 0.5-14.5 months; 95% CI: 1.4-6.6) and 1.7 months (range: 0.5-9.9 months; 95% CI: 1.2-2.3) (p=0.010) for the IG and I arms, respectively. There was no difference in terms of median overall survival between the two arms (6.8 months and 4.6 months for the IG and I arm, respectively). The most frequent toxicities were grade III/IV neutropenia and grade III/IV diarrhea. CONCLUSIONS: Although the IG regimen seems to be more active than the I monotherapy, the premature closure of the study prevents the drawing of definitive conclusions.

Patients' perceptions as an indicator of quality of care, in Greek patients with inflammatory bowel disease.

AIM AND METHOD: The chronic nature of inflammatory bowel disease (IBD) and its frequent relapses result to a considerable utilization of healthcare resources. Current approaches for the assessment of quality of care are based on the perception of the healthcare provider, which may be different from that of the healthcare user. The purpose of this study was to assess IBD patients' satisfaction, as an indicator of healthcare quality, with the use of a validated instrument (QUOTE-IBD). Ninety-five patients with IBD completed the GR-QUOTE-IBD questionnaire, for the assessment of patient's perception, regarding the quality of the perceived care. RESULTS: According to this evaluation suboptimal care was observed in the dimensions of accommodation, accessibility and information (mean values: 8.92, 8.94 and 8.95, respectively). In the subgroup analysis significant differences were observed in relation to patient's age groups and educational level. Differences were also noted in relation to the disease duration (longer and shorter than 5 years). CONCLUSIONS: The assessment of the quality of health care, based on patients' perception, revealed quality problems in the dimensions of accommodation, accessibility and information. According to subgroup analysis, disease type, educational status, age and disease duration play an important role in the formation of patients' expectations from the healthcare system.

Pooled analysis of elderly patients with non-small cell lung cancer treated with front line docetaxel/gemcitabine regimen: the Hellenic Oncology Research Group experience.

INTRODUCTION: Thirty to 40% of patients with non-small cell lung cancer (NSCLC) are older than 70 years and rarely are enrolled in clinical trials. Moreover, in clinical practice, > 75% of patients older than 65 years with metastatic NSCLC never receive any kind of chemotherapy. PURPOSE: To retrospectively evaluate the impact of age on efficacy and toxicity of chemotherapy regimens in patients with advanced NSCLC treated with the docetaxel-gemcitabine combination. PATIENTS AND METHODS: Pooled data from six clinical trials of the Hellenic Oncology Research Group were analyzed. According to their age, patients were divided into two groups: those with age < 70 years and those with > or = 70 years. RESULTS: A total of 858 patients were included in this analysis. Six hundred sixty-six (77.6%) patients were younger than 70 years, whereas 192 (22.4%) patients where > or = 70-year-old. Overall response rate was 30.3% and 30.2% for patients < 70 years and > or = 70 years, respectively (p = 0.974). The median time to tumor progression was 4.1 and 4.5 months for patients < 70 years and > or = 70 years, respectively (p = 0.948). Median overall survival was 9.9 and 9.2 months for patients < 70 and > or = 70, respectively (p = 0.117). The multivariate analysis revealed performance status (PS) (p = 0.0001) and stage (p = 0.0001) as independent factors with significant impact on the hazard of death. Chemotherapy was well tolerated, but the incidence of grade III/IV mucositis was significantly higher in elderly patients (0.2% versus 1.5% for patients < 70 versus > or = 70 years, respectively; p = 0.011). CONCLUSION: The docetaxel/gemcitabine regimen has a comparable efficacy and tolerance in young (< 70 years) and elderly (> or = 70 years) patients.