bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of irinotecan plus cisplatin with concurrent thoracic radiotherapy (TRT) in patients with previously untreated locally advanced non-small cell lung cancer (NSCLC)
Authors: Fukuda M. , Soda H. , Nakamura Y. , Fukuda M. , Kinoshita A. , Nagashima S. , Nakano H. , Yamaguchi H. , Kohno S. , Oka M. 
Published: March 2020

18071 Background: The combined modality of the third generation new agent plus cisplatin with concurrent TRT is considered ideal for locally advanced non-small cell lung cancer. However, it is difficult to conduct because of severe toxicities. Methods: Patients fulfilling the following eligibility criteria were enrolled: previously untreated, good performance status (PS 0–2), age <75, stage III, and adequate organ function. The patients received irinotecan 60 mg/m2 i.v. on days 1, 8 and 15, and cisplatin 80 mg/m2 i.v. on day 1 in the first group. The doses were reduced to 50 and 60 mg/m2 in the second group, respectively. Two cycles of chemotherapy were repeated every 4 weeks. Thoracic radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 28 and 32 Gy administered in the first and second cycles, respectively. Primary endpoint and objective sample size were response rate and 45 patients, respectively. Results: Fifty patients were eligible and 48 (16 in the 1st, 32 in the 2nd group) patients were assessable for response, toxicity and survival. The overall response (OS) was 83% (95% confidence interval (CI), 70–93%). Grade 4 leukopenia, neutropenia, grade 3 or 4 diarrhea, pneumonitis, esophagitis and fatigue occurred in 21%, 48%, 19%, 10% and 19%, respectively. The median time to progression was 8.2 months. The median overall survival time (MST), and the 2- and 5-year survival rates were 20.1 months, 47.1% and 17.1%, respectively. In subgroup analysis, the OS of 1st and 2nd groups were 75% and 88% (not significant), respectively. The MST of 1st and 2nd groups were 13.1 and 33.4 months, respectively, and significant favor with 2nd group (p=0.011). The execution rates of irinotecan on day 15 were significant higher in 2nd (22% vs. 48%) groups (p=0.032), and the survival separated by execution times on day 15 were significantly favor with higher execution time group (p=0.026). Conclusions: This therapy is active and further investigations are warranted at the 2nd group dose level. High execution of chemotherapy on day 15 may be important for the achievement of concurrent chemoradiotherapy. No significant financial relationships to disclose.
Radiation dose is significantly associated with overall survival in patients with stage III non-small cell lung cancer treated with combined radiation and chemotherapy
Authors: Wang L. , Zhao L. , Hayman J. , Kalemkerian G. , Kong F. 
Published: March 2020

18074 Background: Radiation dose is an independent prognostic factor for survival in patients with early stage non-small cell lung cancer (NSCLC). We hypothesized that radiation dose is also a significant independent factor associated with survival in patients with stage III disease treated with combined radiation and chemotherapy. Methods: This is an Institutional Review Board approved retrospective study. Eligible subjects included those with stage III NSCLC registered in the radiation oncology database at University of Michigan Hospital between January 1992 and July 2004. Radiation was given using 3-dimensional conformal technique with doses ranging from 30 to 102.9 Gy, corresponding to a bioequivalent dose (BED) of 39 to 124.5Gy. Median age was 65 years (range, 36–89). There were 80 males and 67 females. Median follow-up was 13.0 months (range, 2.7–145.9). Results: For patients treated with radiation alone (n=40), sequential chemoradiation (n=42), and concurrent chemoradiation (n=65), median survival was 8.6 (95% CI: 5.7–11.5), 12.8 (95% CI: 9.5–16.0) and 15.4 (95% CI: 12.7–18.0) months, respectively (P =0 .011). Multivariate Cox-regression analysis showed that BED (HR=0.96, 95% CI: 0.95–0.97, P<0.001) and administration of chemotherapy (HR=0.44, 95% CI: 0.28–0.70, P=0.001) were independent prognostic factors associated with the risk of death. T stage was marginally significant (P=0.065). Age, gender and N stage were not independent factors (P>0.05). To isolate the BED effect, multivariate analysis was performed separately in patients treated with and without chemotherapy: the hazard ratios of BED for the risk of death were 0.97 (95% CI: 0.95–0.99, P=0 .013) and 0.95 (95% CI: 0.93–0.98, P=0.001), respectively. BED also remained a significant independent prognostic factor in patients treated with chemotherapy and radiation in the dose range of 60–66 Gy (HR=0.91, 95% CI: 0.84–0.99, P=0.041). Conclusions: Radiation dose is significantly associated with survival in patients with stage III NSCLC treated with combined radiation and chemotherapy. No significant financial relationships to disclose.
Covariates of efficacy and safety in four trials of pemetrexed gemcitabine (PG) in advanced stage IIIB (with pleural effusion) or stage IV non-small cell lung cancer (NSCLC)
Authors: Van Doren B. A. , Ye Z. , Treat J. A. 
Published: March 2020

18076 Background: P and G have demonstrated antitumor activity as a first-line treatment in pts with locally advanced or metastatic NSCLC. The impact of covariates such as age and gender on the activity and toxicity of this doublet has not been elucidated. Methods: A total of 220 pts with Stage IIIB (with pleural effusion) or IV NSCLC were treated with PG in four Phase 2 clinical trials. Three trials used G 1250 mg/m2 D 1,8 and P 500 mg/m2 on D 1 or D 8, and one used a 14-d regimen of G 1500 mg/m2 D 1 and P 500 mg/m2 D 1. Two types of analyses were performed to determine covariates’ relationship to variables of response (CR+PR), disease control (CR+PR+SD), and toxicity. Using logistic regression, odds ratios (ORs) were calculated by comparing pt covariates to outcomes. In a separate analysis, pt populations were stratified by baseline covariates, which were treated as categorical variables. Results: Conclusions: Neither age nor gender were statistically significant prognostic factors for activity or toxicity using either analysis, although older pts may have had a slightly better response rate and disease control rate when compared with younger pts. Complete analyses will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
Long-term effect of COPD on patients with lung cancer
Authors: Panwalkar A. , Kessinger A. , Loberiza F. , Ganti A. 
Published: March 2020

18077 Background: Despite the association between chronic obstructive pulmonary disease (COPD) and lung cancer, their inter-relationship has not been studied. Their pathogenesis suggests that they may be a continuum of a single disease. The effect of COPD on outcomes in lung cancer has been primarily studied in surgical candidates in the peri-operative period, however long-term effects are unclear. We proposed to study the influence of COPD on overall survival in this patient population. Methods: After IRB approval a retrospective chart review was performed on patients with stage I and II, non-small cell lung carcinoma (NSCLC) diagnosed from 1994 through 2005. Data including demographics, smoking, treatment given, pulmonary function tests (PFTs) and survival were collected. Patients were classified as having COPD based on FEV1/FVC ratio of < 70%, and further graded by the percentage of predicted FEV1 value. Overall survival was computed by multiple linear regression and the p-value was calculated using the chi-square test. Results: Of the 399 patients with early stage NSCLC, 107 had PFTs evaluated before treatment of the cancer. Of these 42 (39%) did not have COPD, while 65 (61%) had COPD. Patients with COPD presented with a later stage (IB or II) as compared to those without COPD. After adjusting for age, stage, histology, treatment or smoking history, there was no difference in the overall survival among the two groups. The probability of 2-year overall survival for patients with mild, moderate, severe and very severe COPD was 100%, 79%, 77% and 62% respectively, compared with 72% for those without COPD. (p = 0.64). Conclusions: Patients with COPD presented with a later stage (IB or II) as compared to those without COPD. Despite this there was a trend toward an improvement in overall survival in patients with mild to moderate COPD that underwent surgical resection. This may be related, in part, to the beneficial effects of volume reduction of the diseased lung. The data are limited by low power that may have led to insignificant results. Further larger studies are required to better assess the relationship between COPD and lung cancer and its long term effects. No significant financial relationships to disclose.
A prospective phase II study of gefitinib in non-small cell cancer patients with epidermal growth factor receptor gene (EGFR) mutations
Authors: Sugio K. , Uramoto H. , Oyama T. , Onizuka T. , Ichiki Y. , Yasuda M. , Sugaya M. , Nozoe T. , Takenoyama M. , Hanagiri T. , Yasumoto K. 
Published: March 2020

18081 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer are associated with a significant clinical response to gefitinib, a tyrosine kinase inhibitor that targets EGFR, especially in patients with adenocarcinoma, females, and/or never/light smokers. In our retrospective study, cases with EGFR mutations (exon19del or L858R) showed a high sensitivity to gefitinib, and the patients with sensitive EGFR mutations also tended to have a more favorable prognosis than those with wild-type after gefitinib treatment (Uramoto, et al. Lung Cancer 2006;51:71). In the present study, we prospectively assessed the efficacy of gefitinib and the survival benefit for patients with EGFR mutations. Methods: Patients with either recurrent disease after undergoing surgery or advanced disease (IIIB or IV) of NSCLC which demonstrated EGFR mutations were eligible for this study. EGFR mutations in exons 19–21 were examined by our previously described screening method (Sugio, et al. Br J Cancer 2006;94:896) and confirmed by direct sequencing after informed consent was obtained from all patients. The patients with EGFR mutations were enrolled in this study after obtaining informed consent a second time, and they were thereafter treated with gefitinib. Results: Between 2005 and 2006, 16 patients (10 males/6 females, all adenocarcinoma) who had EGFR mutations were enrolled onto this study. Six pts had a deletion in exon 19, 8 pts had a missense mutation in exon 21 (L858R), 1 pt had both an exon 19 del and L858R, and 1 pts had an exon19 del and missense mutation in exon 20 (G796A). The overall response rate was 50%, and the disease control rate was 88%. In patients with exon19 del and L858R, the response rates were 83% and 25%, respectively. A case with a deletion in exon19 and a missense mutation in exon20 (G796A) showed resistance to gefitinib. The median progression-free survival time was 8.8 months, and the median survival time was 15.4 months. No life-threatening toxicity was observed. Conclusions: EGFR mutations in exons 19 or 21 are therefore considered to a good predictor of the efficacy of gefitinib, and the treatment with gefitinib was also found to achieve a prolonged survival. No significant financial relationships to disclose.
A phase II study to determine if sensory neuropathy of nab-paclitaxel can be reduced by prolonging infusion in patients with non-small cell lung cancer (NSCLC)
Authors: James L. P. , Kris M. G. , Heelan R. T. , Ng K. K. , Chia G. H. , Gomez J. E. , Krug L. M. , Moore E. , Hawkins M. J. , Rizvi N. A. 
Published: March 2020

18087 Background: We have previously reported that nab-paclitaxel (ABI-007; Abraxane) administered at 125 mg/m2 over 30 minutes on days 1, 8, and 15 every 28 days has a response rate (RR) of 30% and median survival of 11 months [Rizvi, Proc. ASCO 2006]. We also observed 15/40 (38%) patients developed grade 2/3 sensory neuropathy with a 30 minute infusion. We hypothesize that a longer infusion with nab-paclitaxel may reduce peak plasma levels and accordingly reduce sensory neuropathy. Methods: After enrollment of 40 patients at 125 mg/m2 over 30 minutes on days 1, 8, and 15 every 28 days, we amended the protocol to study an additional 25 patients with chemotherapy naïve stage IV NSCLC with a 2 hour infusion. The enrollment criteria and treatment schedule otherwise remained the same. Our goal was to detect 1 to 2 grade improvement of peripheral neuropathy with 80% power at the two sided p=0.10 significance level compared to the 40 patients treated with this dose given over 30 minutes. Results: To date, 22 of 25 planned patients have been treated with a 2 hour infusion. The mean number of doses administered was 11 for the initial 40 patients treated with a 30 minute infusion and 10 for the 22 patients treated with the 2 hour infusion. We observed 9/40 grade 2 and 6/40 grade 3 sensory neuropathy with the 30 minute infusion and 2/22 grade 2 and 1/22 grade 3 sensory neuropathy with the 2 hour infusion. The combined grade 2 and 3 toxicities were less with the 2 hour infusion (3/22, 14%) compared with the 30 minute infusion (15/40, 38%; p=0.078, Fisher’s exact test). Conclusions: Prolonging the infusion rate of nab-paclitaxel from 30 minutes to 2 hours is associated with a significant decrease in grade 2 and 3 sensory neuropathy. Efficacy data is presently being evaluated. [Table: see text]
Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC)
Authors: William W. N. , Kies M. S. , Fossella F. V. , Gladish G. , Heymach J. V. , Glisson B. S. , Tse W. H. , Liu D. , Herbst R. S. , Lippman S. M. 
Published: March 2020

18098 Background: The combination of bevacizumab, paclitaxel and carboplatin has been recently shown to increase response rates and survival in patients (pts) with untreated, metastatic, non-squamous, NSCLC and is currently FDA-approved for this indication. However, there are limited data on the safety and efficacy of bevacizumab in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open-labeled, phase II trial of bevacizumab, docetaxel and carboplatin for pts with NSCLC. Methods: Eligibility criteria included chemotherapy-naïve stage IIIB or IV incurable NSCLC of non-squamous cell histology, PS 0–1, no brain metastases, no history of hemoptysis, no cavitation, stable cardiac condition and no full dose anticoagulation. Treatment consisted of docetaxel 75 mg/m2, carboplatin AUC 6, and bevacizumab 15 mg/kg IV on day 1 every 3 weeks for up to 6 cycles followed by bevacizumab 15 mg/kg alone every 3 weeks until progression. The primary endpoint was progression-free survival. Results: 20 pts (12 females) have been enrolled with a planned sample size of 50 pts. Baseline characteristics were: median age 66 years old (37–77), PS 0 (6 pts) or 1 (14 pts), stage IIIB (1 pt) or IV (19 pts). 19 pts are evaluable for response and toxicity at this time. Severe adverse events (SAEs) included: 4 pts with neutropenia (2 febrile neutropenias), mild hemoptysis in 2 pts (treated with radiotherapy), 1 pt with peritoneal perforation (who had a history of diverticula), 1 pt with pulmonary embolism, and 1 pt with grade 3 hypertension. Partial responses by RECIST have been observed in 14 pts (74%, 13 confirmed), and stable disease in 5 pts (26%, 4 confirmed). Disease control rate (PR+SD) was 100% after 4 cycles of therapy. 9/20 pts are off treatment (3 progressions, 5 SAEs, 1 maximal benefit). Progression-free survival will be reported at the completion of the trial. Conclusions: The combination of bevacizumab, docetaxel and carboplatin appears to be efficacious and tolerable for the first-line treatment of metastatic NSCLC. No significant financial relationships to disclose.
Symptom assessment in small cell lung cancer (SCLC) in a randomized trial: A psychometric analysis of Patient Symptom Assessment in Lung Cancer (PSALC)
Authors: Chen L. , Antras L. , Duh M. , Neary M. , Dharan B. , O’Brien M. E. 
Published: March 2020

18101 Background: Lung symptoms may be very burdensome for patients (pts) with SCLC. PSALC is a symptom scale that was developed for use in pts with SCLC for assessment of 9 symptoms (shortness of breath, cough, chest pain, hemoptysis, appetite loss, sleep interference, hoarseness, fatigue, interference with daily activities) scored from 1 (not at all) to 4 (very much), but has not been formally validated. The objective of this study is to evaluate the validity of the PSALC through a psychometric analysis of trial data. Methods: Data were analyzed from a randomized, open-label, multicenter trial with 141 pts with SCLC receiving either oral topotecan with best supportive care (BSC) or BSC alone. PSALC and EQ-5D were administered to pts at baseline and at 3-week intervals at subsequent visits. Endpoints for psychometric analysis included statistics for internal consistency, construct validity, reliability, and responsiveness to change in clinical status. Results: Factor analysis (n=131) indicated that there was only one factor, therefore PSALC total score (PSALC-TS) could be used for psychometric analysis. Weighted Cronbach’s alpha from all visits was 0.78. Construct validity was supported by association with established measures: higher baseline PSALC-TS (worse symptoms) was associated with worse ECOG (12.31, 16.37, 17.49 for ECOG score=0, 1, 2, respectively, p=0.0002); baseline PSALC-TS was significantly correlated with EQ-5D utility index (Pearson correlation coefficient [CC] =-0.493, p<0.0001, n=125) and EQ-5D VAS score (Pearson CC=-0.495, p<0.0001, n=122). Reliability was supported by intraclass CC of 0.68 for PSALC-TS evaluated before any change in clinical status, and concordance CC of 0.65, calculated using PSALC-TS at baseline and before first visit. PSALC-TS was responsive to change in clinical status from baseline to tumor response (responsiveness statistic (RS) =-0.99) and to tumor progression (RS=0.94). Conclusions: Retrospective analysis of trial data suggests that PSALC is a reliable, valid, and responsive scale for measuring SCLC symptoms. If feasible in SCLC population, a prospective validation study could be used to further evaluate the validity of this symptom scale. No significant financial relationships to disclose.
Phase II trial of irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) given weekly on alternating weeks with granulocyte colony-stimulating factor support in the treatment of extensive-stage small cell lung cancer
Authors: Uyeki J. , Johnson F. M. , Feng L. , Peeples B. O. , Blumenschein G. J. , Fossella F. V. , Karp D. D. , Pisters K. M. , Stewart D. J. , Glisson B. S. 
Published: March 2020

18119 Background: Irinotecan has significant activity in small-cell lung cancer. Randomized trials comparing IP to EP have yielded conflicting results. Our phase I study of alternating weekly therapy with IP and EP with granulocyte colony-stimulating factor (G-CSF) support found this regimen to be tolerated and active in untreated small cell lung cancer.(Johnson et al Clin Lung Cancer 2003) Methods: Based on these findings we conducted a phase II study to estimate the efficacy of weekly combination therapy in previously untreated patients with extensive disease small-cell lung cancer (ED-SCLC). Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on day 1 and irinotecan (100 mg/m2) on day 1 and G-CSF days 2–5 (IP) alternating with cisplatin (20 mg/m2) on day 1 and etoposide 60 mg/m2 on days 1–3 with G-CSF on days 4–7 (EP). Patients with asymptomatic brain metastases were included. The primary end point was overall survival. Results: 38 patients were enrolled from 7/2001 to 7/2006. The median age was 60 years (range 37–73) and 55% were female. ECOG performance was 0 in 11 patients, 1 in 25 patients and 2 in 2 patients. 87% of patients completed 12 weekly cycles of chemotherapy (range 1–12) with 90% of the planned dose intensity of irinotecan delivered. The objective response rate in 33 evaluable patients was 87% (0 CR, 30 PR). Median follow-up time was 43.7 months. Median progression free survival was 6.4 months (95% CI 5.16–7.59 months). The median survival was 10.9 months (95% CI 8.61–13.5 months). The 2 year survival rate was 19% (95% CI 5–31%). Grade 3–4 non-hematologic toxicities included diarrhea (8%), hyponatremia (5%), dehydration (3%), and neutropenic fever (5%).Grade 3–4 hematologic toxicities included anemia (13%), neutropenia (5%), and thrombocytopenia (3%). There was 1 therapy related death due to sepsis. Conclusions: Weekly therapy with IP alternating with EP with growth factor support was well tolerated in patients with untreated ED- SCLC, but did not show improved progression-free or overall survival when compared with historical controls at our institution. No significant financial relationships to disclose.
Phase II study of docetaxel and S-1 combination therapy in patients with previously treated non-small cell lung cancer
Authors: Atagi S. , Kawahara M. , Kubo A. , Kawaguchi T. , Yumine K. , Okishio K. , Tomizawa Y. , Komatsu H. , Fukai S. 
Published: March 2020

18122 Background: Docetaxel is active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). S-1 is a novel oral fluoropyrimidine, composed of tegafur, 5-chloro-2,4-dihydroxypyridine (dihydropyrimidinedehydrogenase inhibitor), and potassium oxonate (orotate phosphoribosyl transferase inhibitor). It has been commercially available and used for NSCLC in Japan. We conducted this study to evaluate the efficacy and safety of docetaxel combined with S-1 in NSCLC patients (pts) who were previously treated with one or more regimens. Methods: Eligible pts were required to have histologically or cytologically confirmed measurable or evaluable stage IIIB or IV NSCLC, age= 20 years, one or more previous chemotherapy, a performance status (PS) 0–1, and adequate organ function and bone marrow reserve. In this study, pts received S-1 (80 mg/m2 orally on days 1–14) and docetaxel (40mg/m2 IV on days 1). Treatment was repeated every 3 weeks. Results: Between January 2005 and May 2006, 30 pts were enrolled on this study. 29 pts were eligible and evaluable. Median age was 67 (48–79), male/female (23/6), PS 0/1 (9/20), stage IIIB/IV (7/22), and prior chemotherapy regimen 1/2/3 (23/4/2). 28 pts received a platinum-based chemotherapy. Response: PR=7(24%), SD=13, PD=7, NE=2. Median survival time was 10.2 months. Grade 3/4 toxicities (% of pts) were as follows: leukocytes 6/0 (20.6%), neutrophils 7/3 (34.4%), platelets 0/0, infection 0/1 (3.4%), fever 2/0 (6.9%), diarrhea 1/0 (3.4%), neurology 0/1 (3.4%), and mucositis 1/0 (3.4%). There were no treatment-related deaths. Conclusions: The combination of docetaxel and S-1 was effective with acceptable toxicity in pts with previously treated NSCLC. These results warrant further investigations of this regimen a randomized controlled trial as a second-line treatment for NSCLC. No significant financial relationships to disclose.