Phase I-II trial of gemcitabine-based first-line chemotherapies for small cell lung cancer in elderly patients with performance status 0-2: the G-STEP trial.

Introduction: Treatment of elderly patients with small cell lung cancer (SCLC) is based on scanty evidence. Methods: Patients with extensive SCLC, age >70 years, and performance status 0-2 were eligible for a study looking for optimal two-drug combination of gemcitabine (Gem) with vinorelbine (Vin), etoposide (Eto), cisplatin (Cis), or carboplatin (Car). Gemcitabine dose was the same (1000 mg/m2, days 1-8) in all combinations. A two-stage minimax flexible design for response was applied to GemVin combination (Vin 25 mg/m2, days 1-8). For GemCar, GemCis, GemEto, a phase I-II Bayesian design was applied, looking for the optimal dose of the partner drugs. Objective response rate ≥60% and un…

Lung cancer: does age affect treatment strategy?

Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients.

Bevacizumab is a humanized anti-VeGF monoclonal antibody able to produce clinical beneit in advanced non-squamous non-small cell lung cancer (nsCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identiied and validated for baseline patient selection. preclinical indings suggest an important role for myeloid-derived inlammatory cells, such as neutrophils and monocytes, in the development of VeGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inlammatory index, the neutrophil-toly…

Cetuximab and gemcitabine in elderly or adult PS2 patients with advanced non-small-cell lung cancer: The cetuximab in advanced lung cancer (CALC1-E and CALC1-PS2) randomized phase II trials

Background:Two parallel randomized phase 2 trialswere performed to choose the optimal way of combining cetuximab with gemcitabine in the first-line treatment of elderly (CALC1-E) and adult PS2 (CALC1-PS2) patients with advanced NSCLC. Methods: Stage IV or IIIB NSCLC patients, aged ≥70 years with PS 0–2 for CALC1-E or aged <70 with PS2 for CALC1-PS2, not selected for EGFR expression,were eligible. Patients were randomized to concomitant (gemcitabine, for a maximum of 6 cycles, plus cetuximab until progression) or sequential (gemcitabine, for a maximum of 6 cycles, followed by cetuximab) strategy. A selection design, with 1-year survival rate as the primary endpoint, was applied, requiring 58…

Effect on quality of life of cisplatin added to single-agent chemotherapy as first-line treatment for elderly patients with advanced non-small cell lung cancer: Joint analysis of MILES-3 and MILES-4 randomised phase 3 trials

Abstract Objectives To evaluate the effect on quality of life (QOL) of the addition of cisplatin to single-agent chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) enrolled in two parallel phase 3 trials, MILES-3 and MILES-4. Patients and methods Advanced NSCLC pts, >70 years old, performance status (PS) 0–1, were eligible. Patients were randomly assigned to chemotherapy without or with cisplatin. EORTC QLQ C30 and LC13 questionnaires were planned at baseline, end of cycle 1 and end of cycle 2 in both trials and were used for joint QOL analysis. Trial-specific data including questionnaires at non-shared time-points were used for additional ana…

Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of …

Informal caregiving burden in advanced non-small cell lung cancer: the HABIT study.

Introduction This study's aim was to assess economic data regarding the home assistance burden for advanced non-small cell lung cancer (NSCLC) patients in Italy. Patients and Methods One hundred four NSCLC patients in second-line chemotherapy (2LC) or in supportive therapy (ST) were enrolled in 18 Italian oncology departments and were observed for 3 months. The main caregiver's workload was assessed monthly by a task scale; other caregivers' activities were also registered. Eastern Cooperative Oncology Group performance status was assessed by physicians, and patients completed the Lung Cancer Symptoms (LCS) subscale. Formal caregiving time was valued according to market prices; informal car…

Phase II study of mitomycin C, etoposide and vindesine in metastatic stage IV non-small-cell lung cancer.

A total of 72 patients with metastatic stage IV non-small-cell lung cancer (NSCLC) were treated with combination chemotherapy comprising the MEV regimen (mitomycin C, 8 mg/m2 given i. v. on day 1; etoposide, 100 mg/m2 given i.v. on days 1–3; and vindesine, 3 mg/m2 given i.v. on day 1; treatment repeated every 3 weeks). In 64 evaluable patients, the objective response rate was 37% (complete responses, 4.7%; partial responses, 32.3%). The median survival was 7.6 months for all patients. The treatment was very well tolerated. MEV proved to be an active and non-toxic regimen for the treatment of metastatic NSCLC.

Weekly docetaxel vs. docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients

Abstract Background Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:. NCT00345059 ). Methods NSCLC patients, aged 2 on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m 2 on days 1, 8, 15) plus gemcitabine (800 mg/m 2 on days 1, 8 q 4 weeks) or plus vinorelbine (20 mg/m 2 on days 1, 8 q 4 weeks) depending on which of the two had been u…

Vinorelbine plus cisplatin versus cisplatin plus vindesine and mitomycin C in stage IIIB-IV non-small cell lung carcinoma: a prospective randomized study.

Abstract Purpose: To compare a regimen of vinorelbine and cisplatin (VC) to the combination of mitomycin, vindesine, and cisplatin (MVP) in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC). The main endpoits were analysis of objective response rates, toxicity, time to progression, and overall survival. Patients and methods: 247 eligible patients were randomized to receive (a) vinorelbine 25 mg/m 2 intravenous bolus on days 1and 8 plus cisplatin 100 mg/m 2 on day 1 every 4 weeks, or (b) mitomycin c 8 mg/m 2 i.v. on day 1, vindesine 3 mg/m 2 i.v. on days 1, 8, 15 and 22, plus cisplatin 100 mg/m 2 on day 1 every 4 weeks. In subsequent cycles vindesine was given every oth…

Clinical assessment of patients with advanced non-small-cell lung cancer eligible for second-line chemotherapy

Purpose: Knowledge of prognostic factors for advanced non-small-cell lung cancer (NSCLC) patients eligible for second-line treatment is scarce. The aim of this study was to assess the prognostic role of a number of routinely collected clinical variables and to provide a summary index to discriminate patients according to probability of survival.Methods: individual data from nine randomised trials of second-line treatment in advanced NSCLC were analysed. Primary end-point was overall survival (OS). Cox model, stratified by trial, was used for multivariate analyses, and a prognostic index was provided and validated according to an internal/external procedure.Results: Out of 1239 patients, 119…

Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% …

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials

Summary Background Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. Methods We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO g…