bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II study of sequential carboplatin/paclitaxel (CP) and gefitinib (G) in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC): Preliminary results
Authors: Nokihara H. , Ohe Y. , Kawaishi M. , Kato T. , Yamamoto N. , Sekine I. , Kunitoh H. , Saijo N. , Tamura T. 
Published: March 2020

7096 Background: G has been shown to exhibit antitumor activity against NSCLC, however, the optimal timing of its administration remains unclear. We conducted a randomized phase II study of CP followed by G or G followed by CP in chemotherapy-naïve advanced NSCLC patients in order to select the candidate arm for a subsequent phase III study. Methods: Chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged between 20 to74 years, performance status 0–1, were randomized to either Arm A (carboplatin (AUC 6, day 1) plus paclitaxel (200 mg/m2, day 1) every 3 weeks for 4 courses followed by daily G (250 mg/day)) or Arm B (daily G until disease progression followed by CP every 3 weeks for 4 courses). The primary endpoint was overall survival, and the planned sample size for this randomized phase II study was 96 patients (Liu’s selection design for pilot studies on survival). Results: From June 2003 to October 2005, 97 patients were enrolled, and 96 of these patients were treated in this study. Forty-nine patients (males/females: 28/21, median age: 63 years, adeno/non-adeno: 43/6, stageIII/IV: 11/38, smoker/non-smoker: 27/22) were randomized to Arm A and 48 patients (males/females: 28/20, median age: 61 years, adeno/non-adeno: 42/6, stageIII/IV: 11/37, smoker/non-smoker: 28/20) to Arm B. The response rate to CP in Arm A was 32.7% (16/49), and that to G in Arm B was 29.8% (14/47). The median survival was not yet reached, and the 1-year survival rates were 64.5% and 70.5% in Arm A and arm B, respectively. As of January 2006, one patient had died of treatment-related perforative peritonitis and two patients had developed interstitial lung disease. Conclusions: G exhibits similar antitumor activity to CP in chemotherapy-naïve patients with advanced NSCLC. The preliminary survival analysis is proposed to be conducted in April 2006. No significant financial relationships to disclose.
Phase I/II study of ABI-007 as first line chemotherapy in advanced non-small cell lung cancer (NSCLC)
Authors: Rizvi N. A. , Azzoli C. , Miller V. , Ng K. , Fiore J. , Chia G. , Brower M. , Heelan R. , Hawkins M. , Kris M. 
Published: March 2020

7105 Background: ABI-007 is a 130-nm albumin-bound form of paclitaxel. This study was designed to determine (1) the MTD and DLTs of ABI-007 in patients with stage IV chemotherapy-naive NSCLC and (2) the efficacy and safety of ABI-007 at the MTD. Methods: Eligibility requirement included ECOG PS 0–1, adequate organ function and sensory neuropathy ≤ grade 1. No prior chemotherapy for metastatic disease was allowed. Prior EGFR TKI therapy was allowed. ABI-007 was administered on days 1, 8, and 15 every 28 days (IV over 30 min. without premedication). In the phase I portion, 3 dose levels were studied (100, 125 and 150 mg/m2) and in the phase 2 portion, 40 patients were treated at the MTD. Results: 50 patients received ABI-007; the median age was 70 yo and 76% of patients were ≥ 65 yo. No DLTs were observed at the 100 and 125 mg/m2 dose level. However at the 150 mg/m2 dose level 2/6 patients had a DLT (febrile neutropenia and sensory neuropathy, respectively) during cycle 1 such that the MTD was exceeded. The 125 mg/m2 dose level was identified as the MTD and expanded to 40 patients in the phase 2 portion of this study. Toxicity and efficacy data is presented for the phase 2 portion. Ten patients (25%) had received prior neoadjuvant or adjuvant chemotherapy and 5 (13%) had received prior gefitinib or erlotinib. Sensory neuropathy was the most frequent toxicity with grade 2 and 3 toxicity occurring in 8% and 15% of patients. Grade 2 and 3 fatigue was observed in 8% and 13% of patients. Grade 3 and 4 neutropenia occurred in 10% and 3% of patients with no febrile neutropenia observed. Response was assessed by RECIST. One CR and 14 PRs were observed for an overall response rate of 15/40 (38%). The median survival was 10.3 months. Conclusions: The MTD for ABI-007 administered over 30 min. on days 1, 8, and 15 every 28 days was 125 mg/m2. No hypersensitivity reactions were observed and no premedication was given. In the phase 2 portion, a 38% response rate and 10.3 month survival was observed. Non-hematologic toxicities were primarily sensory neuropathy and fatigue. Myelosuppression was minimal and no febrile neutropenia was observed. Further development of ABI-007 in NSCLC is warranted based on the encouraging single agent activity observed in this study. [Table: see text]
Evolution of statistical methodology and design of phase II/III clinical trials in non-small cell lung cancer (NSCLC)
Authors: Bagai R. K. , Dowlati A. 
Published: March 2020

7108 Background: A significant heterogeneity exists in the design and reporting of phase II and III therapeutic clinical trials in NSCLC. This has led to difficulty in interpretation of these trials leading to over- or underestimation of therapeutic efficacy. We set out to investigate the statistical methodology and design reporting of chemotherapeutic trials in NSCLC published in the Journal of Clinical Oncology (JCO) over 20 years. Methods: We identified all phase II and III NSCLC chemotherapy trials published in the JCO from January 1983 to August 2005. All manuscripts were reviewed to evaluate components of statistical design that were reported, including: sample size calculation, power, type I error, single or multiple drug trials, relative response sought in phase II trials and improvement in survival time or response rate sought in phase III trials. Results: One hundred forty eight trials were identified. 52% of studies were phase III and 48% were phase II. The majority (78%) were conducted in advanced stage NSCLC. Sample size calculations were reported for only 58% of phase III studies and 31% of phase II studies. Power was reported in 66% of phase III studies and 13% of phase II trials. Type I error was reported in 47% of phase III studies and 17% in phase II studies. 60% of phase III trials defined endpoints (percentage improvement in survival time, improvement in survival time in months or increase in response rate). 41% of phase II trails defined the target response rate, ranging from response rates of 15% to 70%. The frequency of adequate reporting of statistical design was shown to increase from 31% in 1990–1995 to 64% in 2000–2005 ( table ). Conclusions: Significant heterogeneity exists in trial design and reporting of phase II and III trials in NSCLC. This impacts the ability to adequately interpret these studies. More widespread application of statistical methods in planning and reporting of lung cancer clinical trials are necessary to increase reliability of data. [Table: see text] No significant financial relationships to disclose.
Efficacy and pharmacogenomic correlation of the combination of oxaliplatin and paclitaxel in first line advanced non-small cell lung cancer (NSCLC). Preliminary results of the Spanish Lung Cancer Group (SLCG) 0103 phase II trial
Authors: Garrido Lopez P. , Isla D. , Gil B. , López-Brea M. , Lianes P. , González Larriba J. , Medina B. , Sánchez Ronco M. , Taron M. , Rosell R. 
Published: March 2020

7122 Background: Ox is an attractive platinum analogue that has not been fully explored in NSCLC. We tested the combination of ox/pac as first-line therapy in NSCLC. We also assessed single nucleotide polymorphisms (SNPs) in several DNA repair genes (XRCC1 Arg399Gln, XRCC3 Met241Thr, XPD Lys751Gln and XPD Asp312Asn) and correlated the results with outcome in these patients (p). Methods: 68 stage IIIB (pleural effusion) and IV NSCLC p received up to 6 cycles of p 200 mg/m2 on day 1 plus ox 130 mg/m2 on day 2 every 21 days. Response was assessed after the third and sixth cycles. SNPs were determined by TaqMan assay in peripheral blood extracted at baseline Results: p characteristics: median age 62; 82% male; performance status 0, 54.5%; adenocarcinoma 48%; CNS metastases (mets), 15%, liver mets, 17%. 259 cycles delivered. Grade (G) 3–4 toxicity profile: neutropenia 11%; febrile neutropenia 8%; neurosensory (G3) 5%; asthenia (G3) 8%; diarrhea (G3) 5%. Laryngodysesthesia was observed in 1 p. There were 2 deaths due to neutropenic fever. In 52 evaluable p, overall response rate was 48% (PR 46%, CR 2%, SD 6%, PD 21%). Median time to progression was 4.4 months (m) (95% CI, 2.9–5.9 m). Median survival was 7.9 m (95% CI, 5.5–10.3 m). Conclusions: The combination of ox/pac offers similar results to other platinum-based regimens with an acceptable different toxicity profile and without a significant increase in neurotoxicity. Final data on response, time to progression and survival according to SNPs will be presented. No significant financial relationships to disclose.
Initial results of a phase II study of biweekly pemetrexed and gemcitabine in patients with advanced NSCLC
Authors: Dudek A. , Larson T. , McCleod M. , Schneider D. J. , Dowell J. E. , Ye Z. , Cunneen J. , Monberg M. , Tai F. , Obasaju C. K. 
Published: March 2020

7128 Background: Pemetrexed (P), a multi-targeted antifolate, is synergisitic with gemcitabine (G) in preclinical models. A phase I study examining a biweekly schedule established a recommended phase 2 dose of G 1500 mg/m2 followed by P 500mg/m2. Methods: Patients with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, no prior systemic chemotherapy, immunotherapy, or biological therapy were enrolled. G was infused over 30 minutes, followed immediately by P given intravenously over 10 minutes once on day 1 every 14 days. Cycles were repeated until 12 treatments or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Results: Data on 53 patients (29 male, 24 female) are currently available. Median age: 64 (range: 35, 80), ECOG performance status 0:1 = 38%:60%, Stage IIIB:IV = 19%:81%. Three hundred twelve cycles of treatment were administered with 14 dose reductions (26.4%); median number of doses was 5 for both G and P, and median dose intensity was 98.05% for both G and P. Response data included 1 complete response (1.9%), 14 partial responses (26.4%), 24 stable diseases (45.3%), and 10 progressive diseases (18.9%), with a response rate of 28.3% (95% CI: 16.8–42.3%). Patient-based Grade 3/4 hematologic events included febrile neutropenia (9.4%), neutropenia (28.3%), and thrombocytopenia (1.9%). Grade 3/4 non-hematologic events included fatigue (22.6%), dyspnea (7.5%), dehydration (7.5%), diarrhea (5.7%), constipation (3.8%), and pneumonia (1.9%). Preliminary median survival was 7.8 months (95% CI: 6.0–10.8) with 43.4% patients censored and median TTPD was 4.6 months (95% CI: 2.8–6.1). Conclusion: Biweekly G and P appear to be well tolerated in advanced NSCLC. A clinical benefit rate (ORR + SD) of 73.6% indicates activity in patients with advanced NSCLC. The dose intensity for biweekly G and P is higher than a previously reported 6-cycle, 21-day regimen with median dose intensity of 83.2% for P and 82.2% for G (West, et al. Proc ASCO 2005; 7117). [Table: see text]
Impact of gemcitabine (G) on the activity of first-line chemotherapy in non-small cell lung cancer (NSCLC): A meta-analysis
Authors: Pappagallo G. L. , Belvedere O. , Vinante O. , Grossi F. 
Published: March 2020

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.
A phase I study of talotrexin (PT-523) in patients with relapsed or refractory non-small cell lung cancer (NSCLC)
Authors: Rocha Lima C. S. , Orlov S. V. , Garst J. , Manikhas G. M. , Dowlati A. , Quesada J. A. , Andrews C. , Ramirez M. L. , Choy G. S. , Berk G. 
Published: March 2020

7142 Background: Talotrexin is a nonpolyglutamatable antifolate which has demonstrated improved antitumor activity in a broad spectrum of cancer models by targeting DHFR to inhibit tumor growth. Talotrexin binds more tightly (15-fold, Ki 0.35 pM) to DHFR than methotrexate (MTX). In lung cancer cell lines, talotrexin inhibits tumor cell proliferation at sub- to low nanomolar concentrations and is more potent than MTX in all cell lines tested. We conducted a dose escalation study of talotrexin administered as a 5-minute infusion on Days 1, 8, on a 21-day cycle. The primary objectives of this study are to determine the maximum tolerated dose (MTD), pharmacokinetic (PK) profile, as well as the safety and efficacy. Methods: Patients with confirmed NSCLC stage III/IV or recurrent/refractory disease, failed two-lines of therapy ± an EGFR TK inhibitor, ECOG PS 0–2, were enrolled. The starting dose was based on a Phase I solid tumor trial. Three patients were treated at each dose level in the absence of a dose limiting toxicity (DLT). Intrapatient dose escalation was allowed. All patients received folic acid and vitamin B12. Safety assessments were performed by standard laboratory and clinical DLT definitions. Responses were assessed based on RECIST criteria. Plasma talotrexin concentrations were analyzed by a LC/MS/MS method. Concentration-time profiles of talotrexin were analyzed by noncompartmental methods using WinNonlin. Results: Eighteen heavily pre-treated patients were enrolled and received a total of 61 cycles (median 3.4, range 1–7) of talotrexin at 5 dose levels (27–270 mg/m2/cycle), Male/Female: 14/4. The tentative MTD is 90 mg/m2/dose, with mucositis being the predominate DLT. Two partial responses and 9 stable diseases were observed. Talotrexin exhibits linear PK profile across the 5 dose levels evaluated. PK data (16 patients), Cmax and AUC0-∞ exhibited linear PK. Overall mean values (± SD) were CL, 1.31 ± 0.31 L/hr/m2, T1/2z, 6.5 ± 1.4 h, Vss 8.9 ± 2.5 L/m2. Conclusions: Talotrexin demonstrated acceptable tolerability with encouraging activity in relapsed or refractory NSCLC patients over multiple cycles of therapy. Phase II studies in NSCLC are planned. [Table: see text]
A prospective phase II study of induction carboplatin and vinorelbine followed by concomitant topotecan and accelerated radiotherapy (RT) in locally advanced non-small cell lung cancer (NSCLC)
Authors: Patel S. H. , Ajlouni M. , Chapman R. , Lu M. , Kim J. , Movsas B. 
Published: March 2020

7146 Background: The key limiting factor in combining chemotherapy with accelerated RT is excessive esophagitis. We investigated the toxicity, response rate, and overall survival (OS) with induction carboplatin and vinorelbine followed by concomitant topotecan and accelerated RT in patients (pts) with locally advanced/unresectable NSCLC. Methods: This was a phase II trial using a two stage study design with a planned sample size of forty pts. Stage IIIA or IIIB NSCLC pts with a KPS > 50 were eligible. Initially, pts received induction carboplatin (AUC 5.5) on days 1, 22 and vinorelbine 25 mg/m2 on days 1, 8, 22, and 29. During the concurrent chemoRT, pts received IV topotecan 0.5 mg/m2 on days 43–47, days 57–61, and days 71–75 prior to the morning RT fraction (fx). RT was given in an accelerated fashion at 2 Gy per fx, bid for 5 consecutive days, every other week to a cumulative dose of 60 Gy over a five week period. Results: Thirty-seven pts were accrued of which thirty-five were evaluable. Overall response rate was 71% (14% CR, 57% PR). Six of 35 (17%) pts had stable disease. Four (11%) pts progressed during treatment. At a median f/u of 17.4 months (3–74 mo), the median survival based on Kaplan-Meier estimates, was 18 months. OS at 1, 2, and 3 yrs was 62%, 41%, and 33%, respectively. Actuarial 5-yr OS was 21%. The median time to relapse was 12.2 months (9.1–24.7 mo). Acute RTOG grade 3 or 4 neutropenia, anemia, and thrombocytopenia were 77%, 49%, and 6%, respectively. There were no cases of grade 3 or 4 esophagitis; RTOG grade 3 or 4 pneumonitis occurred in two pts (6%). Conclusions: This combined modality regimen yielded encouraging OS rates with no grade 3/4 esophagitis. Using 4D RT treatment planning, we plan to further evaluate altered fractionation RT and chemotherapy for this group of pts. [Table: see text]
Female gender is an independent predictor of superior perioperative survival following non-small cell lung cancer (NSCLC) resection
Authors: Park B. J. , Rizk N. , Flores R. M. , Downey R. , Bains M. S. , Rusch V. W. 
Published: March 2020

7150 Background: Selecting patients who will benefit from surgical resection of NSCLC, especially following induction therapy, can be challenging. We analyzed our modern experience to determine factors associated with superior operative outcomes. Methods: A retrospective review of a prospectively maintained database of consecutive NSCLC patients who underwent surgical exploration for resection from January 1999 through June 2005 was performed. Factors evaluated included age, sex, co-morbidities, use of induction therapy, previous thoracic operations, extent of lung resection, and in-hospital mortality. Associations between categorical variables were evaluated with a chi-squared test and for continuous variables with an analysis of variance. Multivariate analysis was done with a logistic regression model. Results: A total of 2,524 patients underwent attempt at surgical resection, 1,398 of whom were female (55.4%). One hundred and four (4.1%) patients had exploration only. The majority of patients underwent lobectomy (1,692/2,524, 67.1%), and 6.1% (154/2,524) had a pneumonectomy. Induction therapy was given in 492 patients (19.5%). Univariate analysis showed that male gender (2.4% vs 0.93%, respectively, p = 0.003), presence of cardiac co-morbidity (p = 0.05), poor diffusion capacity (p = 0.003), and greater extent of resection (p = 0.01) were associated with increased in-hospital mortality. Multivariate analysis controlling for gender, age, diffusion capacity, cardiac, and diabetic co-morbidity, as well as prior lung cancer operation, extent of resection and use of induction therapy demonstrated that increased age, decreased diffusion capacity and greater anatomic lung resection were risk factors for higher in-hospital mortality. However, female sex was an independent predictor of lower in-hospital mortality (OR 0.41, p = 0.01). Conclusions: In addition to other previously described predictors of poor surgical outcome, such as advanced age, poor lung function and greater extent of lung removal, we observed that female gender appears to be associated with better in-hospital survival following surgical resection of NSCLC. No significant financial relationships to disclose.
Lung cancer in patients ≥ 80 years of age: Analysis of the national surveillance, epidemiology and end results (SEER) database
Authors: Owonikoko T. K. , Belani C. , Cai C. , Oton A. , Potter D. , Ramalingam S. 
Published: March 2020

7156 Background: Lung cancer is a disease of the elderly with median age at diagnosis of 70 years. In spite of this, the very elderly (patients ≥ 80 years) group has not been well studied. We analyzed the national SEER database to evaluate outcome of the disease in this subgroup. Methods: All patients with primary lung cancer in the national SEER database from 1988–1997 were included, and grouped into those <80 yrs vs. those ≥80 yrs at the time of diagnosis. We compared the 2 groups for stage distribution, 3-yr & 5-yr survival, survival based on histology, sex, race, stage and treatment. The 5-yr relative survival rate, adjusted for the normal life expectancy, was utilized except for the 3-yr survival comparison. The SEER program, Stat 6.1.4, was used for analysis and all p-values were 2-sided. Results: Of the 129,003 cases of lung cancer registered over 10 years, 14,614 (11%) occurred in patients ≥80 yrs. Overall survival at 3 and 5yrs was inferior in the octogenarian group, {11.8% vs. 20% and 8.3% vs. 16.2%, respectively (p < 0.0001)}. The inferior survival was observed in both males and females {7.1% vs. 14.3% and 9.6% vs. 18.9%, respectively (p < 0.0001)} and with non-small cell histology {9.1% vs. 18.3% (p < 0.0001)}. Stage-specific analysis revealed the same trend {24.9% vs. 46.9% - stage I, 19.1% vs. 30.4% - stage II, 3.1% vs. 9.0% - stage III and 1.1% vs. 1.8% - stage IV (p < 0.0001 for all comparisons)}. Irrespective of race, elderly patients fared worse: 6.9% vs. 12.8% in blacks, 8.4% vs. 16.7% in white and 8.4% vs. 16.3% in other racial groups (p < 0.0001 for all comparisons). Although, therapy (surgery or radiation) benefited both groups, treated elderly group performed worse than younger group {4.9% vs. 8.1% (p < 0.0001) and 45% vs. 45.7% (p < 0.02) with radiation and surgery respectively}. However, only 58% of elderly patients received surgery or radiation therapy compared to 80% of patients <80 yrs. Conclusion: In general, very elderly patients with lung cancer have a worse clinical outcome than younger patients. This is irrespective of histology, stage of disease, sex, gender or race. The worse outcome in the elderly may be due to a larger proportion of them not receiving treatment. No significant financial relationships to disclose.