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7535 Background: PC administered in combination with bevacizumab extends survival for advanced non-squamous NSCLC pts. Based on SEER data, elderly pts (age ≥70 years) represent >50% of all new cases of lung cancer and present unique therapeutic challenges. The ECOG 4599 database was analyzed to compare the outcomes in elderly pts treated with PCB vs. PC alone. Methods: Pts ≥ 70 years at study entry constituted the elderly cohort. Each arm (PCB vs. PC) and age group (≥70 vs. No significant financial relationships to disclose.

Hypothesis To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimus (CCI-779) after induction chemotherapy in patients with extensive small-cell lung cancer. Methods Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan were randomized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression. Results Eighty-seven patients entered between January 2002 and December 2003, of whom 85 were eligible: 44 received 25 mg (arm A), and 41 received 250 mg (arm B). The overall median follow-up time for all eligible patients was 34.6 months. Median age was 59 years (range, 39–80); 42 (49.4%) were male and 43 (50.6%) female; 12.9% had brain metastases. The overall median and 1-year PFS were 2.2 months (95% confidence interval [CI]: 1.8, 2.9) and 4.7% (95% CI: 0.2%, 9.2%), respectively. The median PFS (95% CI) for arm A was 1.9 months (1.6, 2.3); for arm B, it was 2.5 months (1.9, 3.4; p = 0.24). The median overall survival from randomization was 8 months (95% CI: 6.5, 9.5). Among the 86 patients with reported toxicities, 36 (42%) had grade 3 toxicities, the most common of which were thrombocytopenia, hypophosphatemia, and fatigue, and an additional 12 (14%) had grade 4 toxicities, the most common of which was neutropenia. No patients experienced lethal toxicities. Conclusion Temsirolimus (CCI 779), given at 25 or 250 mg weekly, seemed not to increase the PFS in this patient population.

Background: To determine prognostic factors and build a model to predict 1-year overall survival (OS) and 6-month progression-free survival (PFS) in advanced non–small-cell lung cancer (NSCLC) patients treated with first-line paclitaxel and carboplatin with or without bevacizumab. Materials and Methods: We analyzed 26 pretreatment clinical variables in 850 NSCLC patients treated in the randomized Eastern Cooperative Oncology Group 4599 study. Univariate and multivariate analyses were performed to identify prognostic factors. Cox regression with 50% randomly sampled data was used to build nomograms with a prognostic score assigned to each factor. The model was validated with the remaining 50% of data. Results: Eleven poor factors for OS (hazard ratio) were as follows: skin metastasis (4.49), body mass index less than 18.5 (2.09), increased serum lactate dehydrogenase (1.74), adrenal metastasis (1.52), performance status greater than 0 (1.45), low serum albumin (1.45), men (1.39), bone metastasis (1.39), large cell/not otherwise specified histology (1.29), mediastinal nodal metastasis (1.23), and treatment without bevacizumab (1.18). Seven poor factors for PFS were as follows: skin metastasis (3.13), treatment without bevacizumab (1.52), bone metastasis (1.41), liver metastasis (1.40), low serum albumin (1.39), performance status greater than 0 (1.21), and mediastinal nodal metastasis (1.14). Based on these factors, we built and validated two nomograms predicting 1-year OS and 6-month PFS. Conclusion: Using our proposed models, the probability of survival with first-line paclitaxel and carboplatin with or without bevacizumab in nonsquamous NSCLC patients can be estimated. These prognostic models provide a tool for research design and clinical decision making, such as patient stratification and therapy selection.

ObjectivePercutaneous transluminal angioplasty (PTA) has had an expanding role as primary therapy for vein graft stenosis with variable results. The aim of this study is to identify patient and graft characteristics predictive of failure after PTA of infrainguinal vein grafts.MethodsRetrospective review from Jan 2004 to Mar 2007 of patients undergoing angioplasty for failing grafts. Demographics, comorbidities, procedural data, and follow-up information were recorded. PTA failure was defined as first significant event including restenosis by duplex scan (>3.5 × velocity ratio), occlusion, redo-PTA, surgical revision, or amputation. Descriptive, logistic regression and life-table analyses were performed.ResultsEighty-seven grafts in 79 patients underwent PTA. Mean age was 70 years (median 70; range, 39-89 years), 71% were male and 52% were symptomatic (40% with limb-threat). Mean follow-up was 17 months (median 17.4; range, 0.03-39.8 months). Freedom from PTA failure was 58% (standard error [SE] 0.0574) at 12 months. Predictors of PTA failure by multivariate analysis were: time from bypass 2 cm (HR 2.7; 95% CI 1.33-5.83; P = .007) and multiple stenoses (HR 2.5; 95% CI 1.29-5.1; P = .007). PTA patency for grafts with favorable lesions (single, less than 2 cm lesions in grafts older than 3 months) was 71% vs 35% for unfavorable lesions at 12 months. Limb-salvage was 95% and 90% and overall survival was 92% and 81% at 12 and 24 months, respectively.ConclusionPTA of failing infrainguinal vein grafts is a reasonable primary therapy for favorable lesions. Early graft stenosis, long, and multiple stenoses are markers for procedural failure and are better served with surgical revision.

Introduction E4599 compared carboplatin and paclitaxel with (PCB) or without (PC) bevacizumab in patients with advanced-stage non-small cell lung cancer. Bevacizumab improved overall survival. However, an unplanned subset analysis did not show a survival benefit for females treated with bevacizumab. Methods Known prognostic factors and toxicities were compared by sex. Proportional hazards models of survival with multiple factor combinations were used to adjust for treatment effect. Results The analysis includes 850 patients. The median survival was 8.7 months (PC) versus 11.7 months (PCB) for males (p = 0.001) and 13.1 months (PC) versus 13.3 months (PCB) for females (p = 0.87). Progression-free survival and response rate on the PCB arm were 6.3 months and 29% for males and 6.2 months and 41% for females (p > 0.05). Progression-free survival and response rate on the PC arm were 4.3 months and 16% for males and 5.3 months and 14% for females (p > 0.05). No significant demographic differences were seen between the two arms for males, whereas fewer females on the PCB arm had liver metastasis (PCB 11.7% versus PC 23.2%, p = 0.003). Adverse events with a sex difference on the PCB arm included severe hypertension (males: 4.2%, females: 9.9%, p = 0.02), constipation (males: 1.4%, females: 4.7%, p = 0.05), and abdominal pain (males: 0.9%, females: 5.2%, p = 0.01). In the proportional hazards model adjusting for the other factors, the test for a sex by treatment interaction was not significant (p = 0.09). Conclusions Multiple factors may contribute to the apparent sex-specific differences in efficacy of bevacizumab noted in this study.

4035 Background: T138067 binds irreversibly and specifically to isotypes of β-tubulin, eventually inducing apoptosis. Its cytotoxicity and anti-tumor activity have been shown preclinically. Our pri...