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Objectives: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC), The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting. Material and methods: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomizedl:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on days 1 and 8 in 4-week cycles; 2 cycles in concomitance). Both groups received concomitant radiotherapy 2 Gy/day (66 Gy). The primary endpoint was progression free survival (PFS). Results: One hundred and forty patients were enrolled. Sixty-nine patients received OVP and 71 received EP. Globally adverse events grade 3/4 per cycle were fewer in the vinorelbine arm (19.4%) than in the etoposide arm (62.6%) (p < 0.001). One patient (1.5%) in the OVP arm and 12 pts (17.6%) in the EP arm presented esophagitis grade 3/4 (p = 0.002). Median PFS was similar in both groups (10.8 [95% CI 7.7-13.8] and 9.6 months [95% CI 4.4-14.8]; p = 0.457, respectively). Preliminary median overall survival was 30 months in the OVP arm and 31.9 months in the EP arm (p = 0.688). Conclusions: Our findings show that OVP could be considered a standard combination with similar efficacy and better safety profile for the treatment of LA-NSCLC patients.

The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer. 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. 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. 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.

Background There is scarce data of the impact of inflammatory indexes in locally advanced NSCLC, which is a highly heterogeneous illness. Choice of therapy is complex and often, combined CRT, either concurrently or sequentially is used. We aim to determine the impact of NLR monitoring in patients with stage III NSCLC treated with CRT. Methods Patients with stage III NSCLC treated with CRT were identified from Jan2010 to Dec2015 in our centre. NLR (neutrophils/lymphocytes) was retrospectively collected at baseline (B) and 5-6 weeks after CRT (C). It was considered a continuous variable and categorised (low Results 92 patients were included; median age 65.5 years (39-83); 85.87% were male and 90.3% had ECOG 0-1. Predominant histologies: adenocarcinoma (41.3%) and squamous-cell carcinoma (56.5%). Concurrent treatment in 78.9% patients and sequential in 21.1%. Median PFS and OS were 16.23 and 30.36 months (mo), in the overall population. On the multivariate analysis, the good prognostic group had significant longer median PFS and OS than the poor group: 33.9 vs 11.1 mo (p Table . 1466P Multivariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value ECOG 1.65 (0.81 – 3.38) 0.169 2.55 (1.17 – 5.56) 0.018 Sequiential vs. Concurrent CRT 0.87 (0.41 – 1.81) 0.703 0.87 (0.38 – 1.97) 0.732 Baseline NLR 1.01 (0.83 – 1.23) 0.918 0.84 (0.66 – 1.07) 0.158 Post CRT NLR (low vs high) 1.08 (1.01 – 1.15) 0.018 1.11 (1.05 – 1.19) Prognostic groups (good vs poor) 3.00 (1.49 – 6.02) 0.002 2.83 (1.30 – 6.14) 0.009 Conclusions NLR could be used as a prognostic factor in stage III NSCLC especially when considering its dynamic evolution. Our results provide the opportunity to evaluate this inexpensive and reproducible index as a prognostic or predictive biomarker in prospective studies, particularly with the novel use of anti-PD-1/L1 after CRT. Legal entity responsible for the study Hospital Universitario Doctor Peset. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

The aim of this study was to evaluate systemic exposure to carboplatin and its haematological toxicity in patients with advanced non-small cell lung cancer both older and younger than 70 years when the target area under the curve (AUC) in elderly patients was reduced by 20%. For this purpose, a population pharmacokinetic model was developed and the haema- tological toxicity of the drug was assessed. A total of 33 patients received carboplatin on day 1 and gemcitabine (1250 mg ⁄ m 2 ) on days 1 and 8. This schedule was repeated every 21 days. The Calvert-Crokcoft-Gault formula was employed to calculate a dose of carboplatin with a target AUC of 5 mg ⁄ min. ⁄ mL in patients under 70 years and 4m g⁄ min. ⁄ mL in patients aged 70 or older. The data of 24 patients were treated for population modelling performed with the NONMEM (University of California, San Francisco, CA, USA) approach. Haematological toxicity was evaluated for all 33 patients enrolled in the study. The carboplatin systemic exposure measured by the AUC (mg ⁄ min. ⁄ mL) was 5.98 (5.45; 6.51) and 5.36 (5.02; 5.69) for the younger patients and older groups, respectively. No significant differences were observed between the two groups with respect to rates of grade 3+ anaemia, neutropenia or thrombocytopenia. In clinical practice, a target AUC of 4 mg ⁄ min. ⁄ mL carboplatin is applied to patients aged 70 and over, but the actual systemic exposure to the drug is higher. This supports a target AUC of 4 mg ⁄ min. ⁄ mL carboplatin for patients older than 70 years when the dose is calculated by means of the Calvert-Crokcoft-Gault formula. Elderly patients with cancer, independently of the anticancer agent they receive, often present medical and physiological changes that require individualization of the treatment to optimize their response in terms of efficacy and toxicity (1,2). Non-small cell lung cancer (NSCLC) accounts for between 80% and 85% of lung cancers, and more than 50% of advanced cases are diagnosed in patients over 65 years of age, with a mean age at diagnosis of 70 years (1). Physiologi- cal changes associated with ageing, such as declining renal function and a decreasing reserve in multiple organ systems, predispose the elderly to the toxic effects of cancer drugs (3). As a consequence of toxicity, the elderly often receive signifi- cantly fewer doses of chemotherapy than younger patients or their treatment must be discontinued, and as a result, an optimal response is not achieved (4). Carboplatin is usually recommended for elderly patients owing to its low non-haematological toxicity and acceptable levels of haematological toxicity (5). Owing to the close relationship between area under the curve (AUC) and parameters of response and ⁄ or toxicity, specifically thrombo- cytopenia, the standard practice for dose individualization of carboplatin is to calculate the dose of the drug for a

Background Mean age of patients with lung cancer rises as a result of increasing life expectancy. So, the proportion of patients with serious comorbidity also increases [1] , [2] . Lung cancer treatment is characterized by a narrow therapeutic index. When life expectancy is short and therapeutic benefit is limited, it is of paramount importance to know the specific cause of death. Comorbidity is understood as a competing cause of death, and is the main exclusion criterion for lung cancer clinical trials. The aim of this study was to determine the prevalence of comorbidity in elderly lung cancer patients seen in an outpatient oncology department and to determine its correlation with survival. Patients and methods Between January 2006 and February 2008, 83 untreated lung cancer patients over the age of 70 years were enrolled in the study. Comorbidity was evaluated according to the Charlson comorbidity index (CCI) [3] and the simplified comorbidity score (SCS) [4] . Results 83 patients (97.6% men, mean age 77 years) were studied. Comorbidities: tobacco consumption (94.6%), cardiovascular diseases (65%), and chronic obstructive pulmonary disease (COPD) (59%). Mean CCI was 3 (range 0–9). Mean SCS was 9 (range 4–19), and 47% of patients had an SCS > 9. Comorbidity was fairly well correlated with age, ADL, IADL, and stage. Neither the CCI nor the SCS was related to survival (p: 0.47 and p: 0.24, log rank, respectively). Median survival was 326 days (95% CI, 259–393 days; or 10.8 months, 95% CI 8.6–13.1 months). Main cause of death was lung cancer disease progression (69.5%, 57 patients), with 20 patients (25%) dying of other non-neoplastic causes. Stage was significantly associated with survival (log rank: p Conclusions Although there was a high prevalence of comorbidity in our population, comorbidity was not related to survival. Comorbidity is one of the main reasons for undertreatment of elderly lung cancer patients, but this study indicates that this undertreatment may not be warranted given that those comorbidities may not cause a patient's death. Our data generated more of a hypothesis than a conclusion. Comorbidity should be an impetus for treatment design instead of an exclusion criterion for oncologic treatment.

e20521Background: This study aims to compare efficacy and safety of two widely used combinations of cisplatin (P) in this setting: as etoposide (E) and vinorelbine. This last, in its oral formulati...

We studied the role of TS ( 5'VNTR, 5'SNP and 3'UTR ), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimidine/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3'UTR +6bp/+6bp (hazards ratio, HR=2.62, p =0.007) and ERCC1- 118C/T or C/C (HR=1.96, p =0.050) genotypes correlated with a shorter progression free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8m, 9.6m and 25.8m for 0, 1 or 2 FG; p =0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p =0.001). In the multivariate analysis, ERCC1-118 (HR=2.12, p =0.0037) and TS-3'UTR (HR=2.68, p =0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3'UTR +6bp/+6bp and ERCC1- 118C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.

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/m2 administered every 3 weeks (3W arm) or docetaxel 36 mg/m2 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.

Background 5-fluorouracil (5-FU), irinotecan, and oxaliplatin are the most active drugs in advanced colorectal cancer (CRC), and survival is improved with patient exposure to all of them. The efficacy and safety of an alternating schedule of continuous-infusion 5-FU with leucovorin (LV) plus oxaliplatin (ie, FOLFOX regimen) or irinotecan (ie, FOLFIRI regimen) was assessed in the first-line setting. Patients and Methods Seventy-nine patients with previously untreated, unresectable CRC were included. Treatment consisted of 5-FU/LV (de Gramont schedule) plus oxaliplatin (85 mg/m2) alternated biweekly with the same 5-FU/LV regimen plus irinotecan (180 mg/m2). Treatment was maintained until tumor progression or unacceptable toxicity was noted. Results Median age was 62 years. Performance status was 0/1 in 91% of patients, 63% had 1 organ involved, and 80% had liver metastases. A median of 6 courses per patient (range, 1–9) and a total of 952 infusions were given. The most frequent grade 3/4 toxic events were neutropenia (32%), diarrhea (26%), and asthenia (7%). Grade ½ neurotoxicity was seen in 59% of cases, but no grade 3/4 neurotoxicity was observed. There were no toxic deaths. An objective response rate of 54% (4 complete responses plus 39 partial responses) was attained. Median time to progression and overall survival were 13 months and 18 months, respectively. Conclusion This alternating schedule is active, with efficacy results similar to those seen with sequential protocols, the advantages of less toxicity, and 100% patient exposure to irinotecan and oxaliplatin.

Purpose Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. Patients and Methods Patients ≥ 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. Results By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. Conclusion Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.

Objectives: The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment. Methods: Between May 2000 and March 2001, 62 previously untreated patients received irinotecan (350 mg/m2) plus raltitrexed (3 mg/m2), with courses repeated every 21 days. Objective response was assessed every three courses, and treatment maintained until tumor progression or unacceptable toxicity. Results: A total of 331 cycles were administered, with a median of five cycles per patient (range, 1–16). Seventeen patients achieved a partial response and 2 a complete response, for an overall intention-to-treat response rate of 30% (95% confidence interval, 18–44%). The incidence of grade 3–4 toxicity per patient was diarrhea (27%), emesis (13%), anemia (12%), neutropenia (9%), and asthenia (7%). Three patients (5%) died from treatment-related adverse events (diarrhea plus neutropenia). The median potential follow-up is now 37 months. Median survival was 12.2 months, and median time to progression was 6.3 months. Conclusions: The combination of irinotecan plus raltitrexed is an easy comfortable schedule for patients with metastatic CRC, but both efficacy and toxicity results seem suboptimal for first-line treatment.

Irinotecan and raltitrexed are active against advanced colorectal cancer, act through different mechanisms, and have non-overlapping toxicity profiles. In vitro studies have shown a schedule-dependent synergism between both drugs. The aim of this multicenter study was to determine the maximum tolerated dose (MTD) of this combination. Patients with 5-fluorouracil-refractory, advanced colorectal cancer were eligible. Dose escalation consisted of irinotecan (250–350 mg/m2 as a 60-min infusion) in combination with a fixed dose of raltitrexed (3 mg/m2 as a 15-min infusion, 1 h after irinotecan). Courses were repeated every 21 days. Three to 6 patients were to be included at each dose level. Dose limiting (NCI-CTC grade 3–4) toxicities (DLT) were assessed during the first 2 cycles. Thirteen patients were recruited (4, 3 and 6 in levels I, II and III, respectively). Main toxicity was diarrhea and asthenia, whereas myelotoxicity was mild. At level III, 2/6 patients experienced DLT (grade 4 diarrhea and neutropenia). The MTD was not reached, but further dose escalation was not attempted. Among 12 patients with measurable disease, 2 partial responses were observed for an overall response rate of 17%. The combination of single-agent full doses of irinotecan (350 mg/m2) and raltitrexed (3 mg/m2) in a 3-weekly schedule is feasible, with mild toxicity and a promising clinical activity. Diarrhea is the DLT, but it is not more common or severe than that described with irinotecan alone.

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.

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 ≤2 were treated with vinorelbine (VNR; 25 mg/m 2 ) on days 1 and 8; ifosfamide (IFO; 3 g/m 2 ) on day 1; and cisplatin (CDDP; 80 mg/m 2 ) on day 1, in repeated cycles of 21 days. Response rates, overall patient survival and toxicity profiles of the three-drug combination were assessed. The number of evaluable patients was 112, with a total of 441 cycles administered (mean=3.6 cycles/patient). Dose intensities (mg/m 2 /week; calculated in patients who concluded the proposed treatment and expressed as mean, median, and standard deviation) were: VNR 13.65, 13.32, 4.7; IFO 918.88, 868.97, 258.1; CDDP 23, 24.68, 6.98. Response rates were: complete response=3 (2.4%); partial response=58 (47.2%%); stable disease=20 (16.3%). The most frequent toxic events were nausea and vomiting (G1=33%, G2=31%, G3=8%). Neutropenia was the dose limiting toxicity (G1=6%, G2=11%, G3=10%, G4=7%). Alopecia G3 was a common undesirable effect in all the patients. Time to progression was 296 days (95% confidence interval 261–332) and the mean survival time was 338 days (95% CI 301–374). We conclude that the described therapeutic schedule is effective with good survival rates and response ratios together with a good tolerance and an acceptable toxicity level.

Lung cancer chemotherapy decisions in patients ≥ 70 years old are complex because of toxicity, comorbidity and the limited data on patient preferences. We examined the relationships between preferences and chemotherapy use in this group of patients.We used a questionnaire describing four hypothetical lung cancer treatment options. Eighty-three elderly (≥ 70 years old) lung cancer patients were informed about their diagnosis and therapeutic choices and then asked to choose one of the four options. Patients had previously been included in a prospective study to explore geriatric evaluation in an oncology unit and all had given written informed consent.Older patients (n=83) diagnosed with lung cancer (non-small- and small-cell lung cancer) from January 2006 to February 2008 were recruited from a single centre. The mean patient age was 77 years (range: 70-91). Eighty-one patients (97.6%) were men. Non-small-cell lung cancer (NSCLC) was the diagnosis in 63 patients (76%). Most patients selected active treatment (38.6% most survival benefit, 18% less survival benefit) and 31.3% selected no active treatment. Elderly lung cancer patients were significantly more likely to accept aggressive treatments despite high reported toxicities. Although most of the patients were symptomatic at diagnosis, the "symptom relief" option was chosen less frequently than the options that could prolong survival. Factors significantly related to patients' attitude toward chemotherapy were age (p0.001), frailty (p=0.0039), depression and poor performance status (PS).Elderly lung cancer patients want to be involved in the decision-making process. Survival was the main treatment objective for more than half of the patients in this study. We have not found other published studies about elderly lung cancer patients' decisions about chemotherapy.

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/m 2 on day 1 and 8 and cisplatin 75 mg/m 2 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.

Purpose Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients. Patients and methods 348 patients were randomized to capecitabine 1000mg/(m 2 12h), days 1–14 plus oxaliplatin 130mg/m 2 day 1, every 3 weeks or weekly infusional 5-FU 2250mg/m 2 over 48h plus bimonthly oxaliplatin 85mg/m 2 . We evaluated response rate, time to progression, overall survival and toxicity according to age. Results ORR for elderly and young patients were 34.9% and 44.7%, respectively ( p =0.081). Median TTP did not differ between the two groups: 8.3 months for patients ≥70 years and 9.6 months for those p =0.114). Median OS was 16.8 months and 20.5 months for the ≥70 and p =0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those ≥70 years (25% vs. 8%, p =0.005). For FUOX, only paresthesia was significantly lower in patients ≥70 years (53% vs. 71%, p =0.032). Conclusion Elderly patients with MCRC benefit from first-line oxaliplatin–fluoropyrimidine combinations as much as younger patients, without increased toxicity.

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. 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/m2 and vinorelbine 30 mg/m2 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. Median age was 74; ECOG performance status was

Purpose To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. Patients and Methods Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. Results All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. Conclusion UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.

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.

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/m2 as a 60-min infusion) plus raltitrexed (3 mg/m2 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.

e19014 Background: In NS-NSCLC CPB achieved median OS > 1 y and supported use of B. A broad range of predictive/prognostic markers explored for B use. In VEGF pathway ligands and receptors play an ...

needs for information of cancer patients older than 65 and the awareness of caregivers in this regard. Summarized description of the project: Between June 2004 and February 2005, 112 elderly cancer patients (age 65 years) admitted for staging procedure at the National Cancer Institute – Aviano, Italy, with a first diagnosis of tumour and naivety for treatments, and their caregivers (n = 112), were enrolled in our study. Prior to treatments, both groups were asked to fill in a self-administered questionnaire we appropriately developed to explore the patient’s information needs and his/her information-seeking behaviours. Patients had also to complete the Psychological Distress Inventory. Results and Conclusions: Caregivers, mostly females (71.4%), offspring (44.6%) and/or partners (41.1%), believed elderly patients preferred to receive partial information by the oncologists and have poor information-seeking behaviours. Apparently, elderly patients (mean age 72 years, and mean PDI 26.1) answered similarly, but when matched with their own caregivers, the u statistic analysis showed unsatisfactory agreement for the information needs (u < 0.20) and very poor agreement for the information-seeking behaviours. Our results showed that in our Institute elderly cancer patients preferred partial information regarding their illness. They showed the desire to limit the amount of negative information they might receive and they limited their information-seeking behaviours. Caregivers do not properly recognize the real needs for information of their own patients. This misunderstanding was probably due to the caregivers protective behaviours that make the patient-to-caregiver relationship difficult. Interventions, to help both elderly patients express their unmet needs and to improve the patient-to-doctor-to-caregiver communication about cancer diseases, are necessary.

Aims: a) To identify which pretreatment clinical or blood parameters were predictive of patient survival in small-cell lung cancer (SCLC) in a retrospective analysis. b) To validate three known prognostic indices: Royal Marsden Model (index I), 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 I: 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 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). Conclusions: 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.

1531 Background: Gender differences in lung cancer (LC) have been reported, but with many unresolved issues yet. Tobacco causes the majority of women lung cancer (WLC), although the rate of never-smoking WLC is higher than in men. Several factors may play etiologic roles, and an in-depth understanding is needed. Methods: WORLD07 is a Spanish prospective, multicenter, epidemiologic female-specific LC database sponsored by ICAPEM, a professional association committed with WLC research. In order to improve the knowledge on never-smoking WLC, information has been extracted from WORLD07 database. Results: From October/2007 to October/2011, 1371 newly diagnosed WLC were included in an e-database from 32 centers, 539 (39.3%) never-smoking. Patient (p) characteristics: median age 71.1 years(y); median age of menarche 13y.; motherhood 91.2% (median 2.3 children, median age at first child 26.4y); oral contraceptive use 11.9%; postmenopausal 88.9% (median age of menopause 49y); HRT 5.2%; second-hand smokers 40% (work-exposure 17.1%, home-exposure 88.8%); obesity 16.3%; familiar history of cancer 39.9% (LC 29.8%); previous history of cancer 13% (breast/lung/cervix: 41.4/5.7/2.9%); current LC histology(%): adenocarcinoma/SqCC/LCC/SCLC: 83.4/6.2/5.5/3.9; EGFR mut+ (268 p analyzed): 55.5% (exon 19/20/21(%): 61.1/7.4/36.9); TNM NSCLC I/II/III/IV(%): 14/3.3/19.8/60.3. Treatment: EGFR-TKI in p EGFR mut+, stage IV(1st-/2nd-line)(%): 51.7/15.4; stage IV NSCLC (1st-line/2nd-line): platinum-based CT 42.5%, EGFR-TKI 33.5%, combinations with bevacizumab 2.9% / EGFR-TKI 15.8%. Overall survival: median 27 months(m), 1/2-y(%) 74.8/55.2; stage IV NSCLC: median 20.5m, 1/2-y(%) 67/46; EGFR-mut+ p: median 27.3m, 1/2-y(%) 75/54.3. Conclusions: According to our e-database, WLC showed high rates of never-smokers (39.3%), and of relatives diagnosed with malignant tumours (39.9%, ≅1/3 LC). Adenocarcinoma was the most frequent histology (76.1%), and more than half of the cases analyzed harboured EGFR mutations. Although 40% were second-hand smokers, further investigations are warranted. Survival outcomes remain satisfactory, as expected from this selected subgroup of p. Additional epidemiologic and treatment data will be presented.

Meningeal myelomatosis is an extremely rare clinical presentation generally associated to terminal states of the disease and is more frequent in the presence of peripheric plasmocytosis or leukemia of the plasmatic cells. Diagnosis requires its demonstration in the cephalorhachidian liquid and its monoclonal secretion. A case of relapse of meningeal myelomatosis in a patient with multiple IgA-lambda myeloma is presented in which the systemic disease fulfilled the criteria for complete remission.

4132 Background: The possible replacement of continuous infusion 5FU by the oral pro-drug capecitabine is controversial. The aim of this work was to study genetic polymorphisms and their role in ta...

8095 Background: Pemetrexed is approved as second-line therapy in advanced NSCLC. In this study, we evaluate the efficacy and safety of pemetrexed in patients with Advanced NSCLC previously treated and we also perform a pharmacogenomic analysis to determine if biologic characteristics could be related to any clinical benefit. Methods: 195 patients with NSCLC stage IIIB (malignant pleural effusion) or IV were selected to receive pemetrexed (500 mg/m2, IV infusion) supplemented with vitamin B12, folic acid and dexamethasone prophylaxis. DNA was extracted from peripheral lymphocytes and Taqman assays for allelic discrimination were used for the following single- nucleotide polymorphism (SNP) typing: Methylene-Tetra-Hydro-Folate-Reductase (MTHFR), methionine synthase (MTR), thymidylate synthase (TS) and reduced folate carrier 1 (RFC1). Results: Median age 63 years (37–82); males: 88%; never-smokers: 9%; performance status (PS) 0: 23%; adenocarcinoma: 34%, squamous: 45%; stage IIIB: 20%, IV: 80%. The responses...

18040 Background: The clinical benefit of non-cisplatin doublets vs a single agent in elderly or unfit p is still controversial. The present study focuses on clinical outcome with VRB/GEM in elderly p and the role of functional status and comorbidities. Genetic predictive markers of response to VRB/GEM will also be examined in genomic and cDNA from tumor and circulating tumor DNA. Methods: 145 chemonaive p with stage IIIB (pleural effusion or supraclavicular lymph nodes)-IV or recurrent NSCLC and age > 70 years were accrued at 32 sites between April 2004 and January 2006. Treatment consisted of VRB 25 mg/m2 IV or 60–80 mg/m2 oral plus GEM 1200 mg/m2, days 1, 8 every 21 days. Activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities were evaluated. DNA samples were collected from primary tumors for the assessment of microtubule associated protein 4 (MAP4) and from serum for the checkpoint with forkhead-associated and ring finger (CHFR) methylation. Results: Data on 130 p is available. Median age 76 years (69–83); males: 86.8%; smokers: 70.5%; PS 0–1: 83.9%; adenocarcinoma: 34.4% / squamous: 48%; stage IIIB: 22.7%, IV: 77.3%. Self-sufficiency in ADL and IADL was 77.4% and 45.2% of the p analyzed. 68% of the p had comorbidities. Median cycles: 3 (1–8). Hematological toxicities (%p): grade 3/4 neutropenia, 7.8%/4.7%; grade 3/4 thrombocytopenia, 2.3%/0.8%; grade 3 anemia, 3.1%. Efficacy in evaluable population: PR, 23.2% (95% CI, 15.1% to 32.9%); SD, 41.1%. 24 p died during the treatment period (non toxicity related) and 21 p were not evaluable. With a median follow up of 5.8 months, median survival for the whole population was 4.97 months (m), progression free survival 4.53 m, event free survival 3.43 m, 1-year survival 26.6%. Statistically significant differences in median survival were observed among subgroups: PS 0–1/2, 6.5/2.3 m (p No significant financial relationships to disclose.

7620 Background: Neither the optimal sequence of treatment nor the best combination CT is yet well-defined in p receiving concomitant therapy Methods: P with unresectable stage III NSCLC with IK ≥ 70 and weight loss < 5% were initially randomized to sequential treatment (arm A), concurrent CT/TRT followed by consolidation CT (arm B) or induction CT followed by CT/TRT (arm C). Based on RTOG 9410 results, arm A was closed and the study continues with two concomitant arms (B, C). All p receive 2 cycles of D 40 mg/m2 d1, 8 plus G 1,200 mg/m2 d1, 8 as I or C therapy. Concomitant treatment includes D 20 mg/m2 and carboplatin (Cb) AUC 2 weekly plus 60 Gy TRT. Results: From May 01 to Jun 06, 151 p were included (A: 19, B: 66, C: 66). Due to the early closing of arm A, only data of evaluable arms B and C p are shown: toxicity 127 p (B: 63, C: 64) and response 110 p (B: 53, C: 57). All groups are well-matched for baseline disease characteristics. Toxicity grade 3–4 by CTC and RTOG criteria was: esophagitis 19.5% (arm B) and 14.2% (arm C); pneumonitis 8.8 % (arm B) and 10% (arm C). Neutropenia during I or C therapy: 22% (B) and 6.2% (C). Thrombocytopenia 8% (B) and 3% (C). Neutropenia during concomitant therapy: 6.3% (B) and 6% (C). No thrombocytopenia or severe anemia was found during CT/TRT. The reduction CT rate was superior in consolidation (35%) than in induction (15%) and in arm C during concomitant therapy (22.4% C, 6.5% B). Delay of CT dose was similar in B and C arms during I or C (22% B, 20% C) but superior in arm C during concurrent treatment (19.6% B, 30.6% C). The final response rates were 57% (B) and 56.9% (C). A trend for longer time to progression (TTP) was found (B: 7.6 months (m) and C: 9.2 m; p= 0.12) but with similar overall survival (B: 14.3 m and C: 14.7 m; p=0.38). Conclusions: Non- platinum CT plus concomitant chemoradiation offer similar response rate and a favorable hematological toxicity profile in unresectable stage III NSCLC p. No differences in OS but a trend for longer TTP in the arm C (I followed by concurrent approach) has been found. Final data are pending in order to select the best sequence for further studies. No significant financial relationships to disclose.

19641 Background: Advancing age is a major risk factor for breast cancer. Long-term follow up is recommended after diagnosis and treatment of early breast cancer. With older age, the risk of comorbid conditions and functional impairment is increased. A useful tool in the management and follow-up of these elderly patients could be a CGA Methods: Purpose of the study: Descriptive, transversal study of the prevalence of other comorbidities and of the functional impairment in elderly patients on follow-up after curative treatment of early breast cancer. Patients: Women aged ≥ 70 years at time of diagnosis, with removed early breast cancer. Attended in a outpatient unit from January 2005 to June 2006. No disease recurrences were allowed. Methods: CGA was conducted in an oncology unit. The assessment used usual screening instruments (ADL, IADL, POMA, GDS, MMSE, MNA) as well as the performance status (PS). Co-morbidity was classified using the Charlson score. Results: 91 pts underwent CGA. Mean age at surgery of primary tumour: 76 (70–92). Mean age at time of CGA: 80 (71–95). > 75% of patients had more than 84 years at time of GCA: Median follow up: 5 years (1–12). 47% PS 0. 9% PS 2. 83% were fully independent for ADL and 71% for IADL. IADL most affected was the ability to drive/use public transport. Median Charlson Score was 2 (1–6). ≥ 75% of patients had score ≥4. Most frequent comorbidity: cardiovascular disease (hypertension). Cognitive deterioration: 15%, depression: 16%. Only 28% were thin (BMI< 22). 75% were polymedicated (> 6 drugs). 28% had geriatric syndromes. 23% were “frail” (at least one of the following items): ADL < 80; ≥ 3 comorbidities, performance status < 60, ≥ 1 geriatric syndrome. Conclusions: Our results are better than reports from other geriatric teams using CGA, in terms on functional status and frailty. A high prevalence of comorbidity in our study, similar to other reports. A selection bias cannot be excluded, as the fitter patients are those that usually keep on with the follow-up. While those frail patients that do not due to their functional impairment are usually lost. Older patients with early breast cancer on follow-up have a high prevalence of comorbidity. However, in our serie, function and independence is maintained. No significant financial relationships to disclose.