Efficacy of tyrosine kinase inhibitors in EGFR-mutant lung cancer women in a real-world setting: the WORLD07 database.

BACKGROUND: The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer. METHODS: WORLD07 database sets up in 2007, and prospectively stores clinical characteristics, treatment, outcome, and follow-up of lung cancer women. All women with epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) were selected for this analysis. RESULTS: From October 2007 to December 2012, a total of 1775 NSCLC women were recruited. EGFR mutation was identified in 34.4% of patients. Upfront EGFR tyrosine kinase inhibitor (TKI) reported a response rate of 60%, a median progression-free survival of 11.7 months, and median overall survival of 23.0 months. EGFR TKI, EGFR-mutation type, and smoking status did not impact in the outcome of treated women. CONCLUSION: Prevalence of EGFR mutation in women with NSCLC is higher than overall population with NSCLC. Efficacy of EGFR TKI in this real-world setting is similar to that previously reported.

A review of the management of elderly patients with non-small-cell lung cancer.

Most patients with non-small-cell lung cancer (NSCLC) are elderly but evidence to guide appropriate treatment decisions for this age group is generally scant. Careful evaluation of the elderly should be undertaken to ensure that treatment appropriate for the stage of the tumour is guided by patient characteristics and not by age. The Comprehensive Geriatric Assessment (CGA) remains the preferred option, but briefer tools may be appropriate to select patients for further evaluation. The predicted outcome should be used to guide management decisions together with a reappraisal of polypharmacy. Patient expectations should also be taken into account. Management recommendations are generally similar to those of general guidelines for the NSCLC population, although the risks of surgery and toxicity of chemotherapy and radiotherapy are often increased in the elderly compared with younger patients; therefore, patients should be closely scrutinised and subjected to a CGA to ensure suitability of the planned treatment. If surgery is indicated, then lobectomy is generally the preferred option, although limited resection may be more feasible for some. Radiotherapy with curative intent is an alternative, with stereotactic body radiotherapy the most likely preferred modality. Adjuvant chemotherapy is also an appropriate approach, whereas adjuvant radiotherapy is generally not recommended. Concurrent chemoradiotherapy should be considered for elderly patients with inoperable locally advanced disease and chemotherapy for advanced/metastatic disease. Efforts should also be made to increase participation of elderly patients with NSCLC in clinical trials, thereby enhancing evidence-based treatment decisions for this majority group. This will require overcoming barriers relating to trial design and to physician and patient awareness and attitudes.

Single nucleotide polymorphisms in MDR1 gen correlates with outcome in advanced non-small-cell lung cancer patients treated with cisplatin plus vinorelbine.

UNLABELLED: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. In this study, we assessed whether the presence of polymorphisms in ERCC1, XPD, RRM1 and MDR1 genes can affect the efficacy and the tolerability of cisplatin and vinorelbine in NSCLC patients. MATERIAL AND METHODS: Eligible patients had histological confirmed stage IV or IIIB (with malignant pleural effusion) non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy; World Health Organization performance status (PS) 0-1. Patients received intravenous doses of vinorelbine 25 mg/m² on day 1 and 8 and cisplatin 75 mg/m² on day 1, every 21 days, for a maximum of eight cycles. RESULTS: 94 patients were included. Median age was 61 years; 84% were male; WHO performance status (PS) was 0 in 24%; and 88% of patients had stage IV disease. The median number of cycles was 6. Overall median survival was 10.92 months (95% CI 9.0-12.9). Overall median time to progression was 5.89 months (95% CI 5.2-6.6). Results of the multivariate analysis for time to progression showed that ECOG 0 (hazard ratio [HR] ECOG 1 vs. ECOG 0, 1.74; p=0.036), MDR13435CC (HR CT vs. CC, 2.01; p=0.017; HR TT vs. CC, 1.54; p=0.22), and decreasing age (HR of age, 0.97; p=0.016) were the most powerful prognostic factors significantly related to lower risk of progression. Whereas ECOG 0 was the only prognostic factor for survival (HR ECOG 1 vs. ECOG 0, 3.02; p=0.001). There was no significant association between any of the SNPs analysed and the occurrence of vinorelbine and cisplatin-related toxicity. CONCLUSION: In our results, the most important prognostic factors associated with lower risk of progression were MDR1 3435 CC genotype, PS 0 and younger age.

Assessment of functional status, symptoms and comorbidity in elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine and vinorelbine.

BACKGROUND: The incidence and prevalence of comorbid conditions in lung cancer patients increase with age. The aim of the study was to determine response and tolerability with the biweekly combination gemcitabine-vinorelbine in elderly non-small-cell lung cancer (NSCLC) patients. In order to characterise the population included in the study well and assess the results achieved properly, an evaluation of the functional status, comorbidity and survival was performed. PATIENTS AND METHOD: Between June 2001, and December 2003, 59 untreated advanced NSCLC patients over the age of 70 years entered the study. Treatment consisted of gemcitabine 1750 mg/m(2) and vinorelbine 30 mg/m(2) on day 1 every two weeks. The response was evaluated every f ive cycles (RECIST guidelines). Comorbidity was evaluated according to the Charlson and Kaplan Feinstein scales. To measure functional status, activities of daily living (ADL) and instrumental ADL (IADL) were considered. RESULTS: Median age was 74; ECOG performance status was >2 in 59.3%; no dependence in ADL or IADL was found in 24.8% and 42.4% of patients, respectively. A total of 381 courses were administered. Grade 3-4 neutropenia was present in 6.8% of these courses and correlated with IADL. Objective response was 22% (95% CI 12-32). Mean global survival and cause-specific survival were 29 weeks (95% CI 19.9-38.1) and 32 weeks (95% CI 23.4-40.8) respectively. Comorbidity displayed no close correlation with functional status, but comorbidity according to the Kaplan Feinstein index correlated with IADL. Performance status, ADL, IADL and weight loss were significantly related to survival in multivariate analysis. CONCLUSIONS: This biweekly combination is feasible in elderly lung cancer patients with a high burden of comorbidity and dependence. Toxicity is acceptable, whereas response rate and survival fall in the range of active regimens. ADL and IADL indices allow the identification of elderly patients with a worse prognosis.

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial.

BACKGROUND: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. PATIENTS AND METHODS: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. RESULTS: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010]. CONCLUSIONS: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.

Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Fifty percent of lung cancers arise in patients over 65 years old and 30% in those over 70. The aim of this study was to evaluate response, survival and tolerability of the combination carboplatin-gemcitabine in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between May 1998 and December 2000, 88 patients were included. Median age was 74 (range 65-83). Treatment consisted of gemcitabine 1250 mg/m(2) (1000 mg/m(2) in the first six patients) on days 1 and 8, and carboplatin AUC=4 on day 1, every 21 days. Prognostic factors for survival were analysed. Performance status (PS) and symptoms were evaluated before and after three and six courses. RESULTS: A total of 400 cycles were administered (median of four per patient). WHO grades 3-4 toxicities were: neutropenia in 13% of the cycles, thrombocytopenia and anaemia in 4.5 and 14.7% of patients in any cycle. There was one treatment-related death. According to the intent-to-treat analysis, 33 patients achieved objective response, 33 had stable disease, and 22 had treatment failure (progression in 18 patients). Median and 1 year survival were 9 months and 34%, respectively. Median time to progression was 8 months. Only disease stage and PS showed independent prognostic value. Comorbidity and PS displayed no close correlation. Symptom improvement was seen as follows: pain (61.7%), dyspnea (50%), haemoptysis (80%), anorexia (62.5%) and asthenia (61.5%). CONCLUSIONS: The combination carboplatin-gemcitabine at these doses is feasible in elderly patients with advanced non-small cell lung cancer. Tolerability and toxicity are acceptable. Response rate and survival stand in the range of the most active regimens. Comorbidity and PS showed prognostic independence.

Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. Phase I studies have shown that single-agent full doses of both drugs can be safely combined. The aim of this multicenter study was to assess the efficacy and toxicity of the combination in patients with 5-fluorouracil (5-FU)-refractory ACC. PATIENTS AND METHODS: Between October 1999 and December 2000, 52 patients (31 males, 21 females) with a median age of 62 years (range 39-75) were included and received CPT-11 (350 mg/m(2) as a 60-min infusion) plus raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after CPT-11), with courses repeated every 21 days. Objective response was assessed after every three courses, and treatment maintained until tumor progression or unacceptable toxicity. RESULTS: A total of 313 cycles were administered, with a median of six cycles per patient (range 1-14). Seven patients (13.5%) achieved a partial response and one a complete response (1.9%), for an overall intention-to-treat response rate of 15.4% (95% confidence interval 6.1% to 27.2%). The incidence of grade 3/4 toxicity was 23.1% for diarrhea, 21.2% for asthenia, 17.3% for neutropenia, 13.4% for emesis and 7.7% for infection. There were no treatment-related deaths. With a median follow-up of 20 months, median survival was 11.9 months and median time to progression was 4.6 months. CONCLUSIONS: CPT-11 plus raltitrexed is active in patients with 5-FU-refractory ACC, at the expense of moderate toxicity.

Vinorelbine, ifosfamide and cisplatin as first-line treatment in patients with inoperable non-small cell lung cancer.

To assess, in a multicenter setting, the effectiveness of a combination of vinorelbine, ifosfamide and cisplatin in the treatment of non-small cell lung cancer, 123 patients (males=116) with a mean age of 60 years (range 27-75) with stage IIIb/IV non-small cell lung cancer (NSCLC) and performance status

Pretreatment prognostic factors for survival in small-cell lung cancer: a new prognostic index and validation of three known prognostic indices on 341 patients.

AIMS: a) To identify which pretreatment clinical or blood parameters were predictive of patients survival in small-cell lung cancer (SCLC) in a retrospective analysis. b) To validate three known prognostic indices: Royal Marsden Model (index 1), London Group (index 2) and Manchester Score (index 3). PATIENTS AND METHODS: From 1981 to 1993, 341 SCLC patients were treated with chemotherapy with or without surgery or radiotherapy. Univariate and multiple regression analyses of survival were performed and the feasibility of these models was explored, index 1: Karnofsky index, albumin, sodium and alkaline phosphatase; index 2: ECOG performance status (PS), albumin and alanine transaminase; and index 3; lactate dehydrogenase (LDH), disease extent, sodium, Karnofsky index, alkaline phosphatase and bicarbonate. RESULTS: Significant prognostic factors for survival after univariate and multiple regression analysis were: disease extent, PS, creatine kinase, neutrophilia, LDH, hypoalbuminemia, hyperglycemia and bicarbonate. A new prognostic index was performed that included LDH, hypoalbuminemia, neutrophilia, disease extent and PS. It defined three prognostic groups (PG). Median survival and two-year survival for these PG were 12.3, 8 and 3.4 months and 16.5%, 2.3% and 0%, respectively. The following PG were identified after application of the three models proposed: Index 1 identified two PG with 0% and 16.6% two-year survival (P < 0.001); index 2 detected three PG with 0%, 5% and 15.7% two-year survival (P < 0.001) and index 3 detected three PG with 0%, 2.5% and 16.2% two-year survivals, respectively (P < 0.001). CONCLUSION: A new prognostic index is proposed allowing identification of three different PG. The feasibility of three known prognostic models was validated and demonstrated. Variables other than disease extent or PS (albumin or LDH) should be taken into account in designing future clinical trials.