bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of survival for non-small cell lung cancer (NSCLC) between premenopausal and postmenopausal women: An analysis of the National Surveillance, Epidemiology and End Results (SEER) Database
Authors: Oton A. B. , Belani C. , Cai C. , Owonikoko T. , Gooding W. , Siegfried J. , Ramalingam S. 
Published: March 2020

7038 Background: Estrogen signaling has been implicated in lung cancer formation and progression by pre-clinical studies. Estrogen receptor (ER) Beta is overexpressed in NSCLC. To understand the clinical impact of the estrogen pathway, we analyzed the national SEER database to compare the outcomes for NSCLC in premenopausal vs. postmenopausal women. Methods: Data from the national SEER registry between the years of 1988–2002 was analyzed. Women between the ages 40–44 were chosen as representative of the pre-menopausal group and 55–59 year-old women represented the post-menopausal group. To control the effect of age alone as a determinant of outcome, we compared the survival between 1,534 men with ages of 40–44 and 8,807 men with ages of 55–59. Survival rates were analyzed by Kaplan-Meier method and compared by Z-test through SEER*Stat software version 6.1.4. Results: A total of 7,150 women, premenopausal (1,171) and postmenopausal (5,979) were included. Adenocarcinoma (ADC) was more commonly seen in premenopausal than in postmenopausal women (58% vs 47%). Distribution by stage at diagnosis was similar between the two groups. Premenopausal women with squamous cell carcinoma (SCC) or bronchioalveolar carcinomas (BAC) had inferior overall survival than postmenopausal women. Differences in outcome between men in the two age groups were not significant. Conclusions: Premenopausal women with SCC or BAC, but not ADC have inferior survival compared to postmenopausal women. Smaller and non-significant differences were observed between males of the same aged-groups. The results suggest varying estrogen effects between the histological sub-types of NSCLC and support clinical strategies to block the ER pathway for the treatment of NSCLC. [Table: see text] No significant financial relationships to disclose.
Second Japan-SWOG common arm analysis of paclitaxel/carboplatin in advanced stage non-small cell lung cancer (NSCLC): A model for testing population-related pharmacogenomics
Authors: Crowley J. , Furuse K. , Kawahara M. , Fukushima M. , Kawaguchi T. , Williamson S. , Lara P. N. , Mack P. C. , Gandara D. R. 
Published: March 2020

7050 Background: Whether results of clinical trials performed outside the United States (US) can be fully extrapolated to US populations remains in question due to potential differences in trial designs, study-specific criteria, patient demographics, and population-related pharmacogenomics. The first of these comparisons, FACS-S0003 has been presented (Gandara, PASCO, 2004). Here we present the second comparative analysis. Methods: We prospectively designed & conducted 3 separate phase III trials in advanced NSCLC linked by a “common arm” with identical eligibility, staging, response & toxicity criteria, to: 1) determine similarities & differences in patient demographics & outcomes in cooperative group trials in Japan (in this analysis, the Japan Multinational Trial Organization LC03) & the US (SWOG 0003), 2) provide the basis for global standardization in clinical trials in NSCLC, and 3) facilitate regulatory changes needed for joint Japan-US studies. We performed a planned comparative analysis of the paclitaxel/carboplatin arms from LC03 & S0003, which had identical doses and schedules of paclitaxel dose (225mg/m2) and carboplatin (AUC 6). Conclusions: 1) This common arm analysis, as in our prior FACS-S003 report, shows great similarities in patient demographics between the LC03 and S0003. 2) Variable toxicities may be due to population-related pharmacogenomics (increased neutropenia & febrile neutropenia in LC03), and could be explained by polymorphisms in cytochrome P450 for paclitaxel metabolism (ongoing analysis). 3) Survival is increased in LC03. 4) Future joint Japan-US clinical trials should assess possible pharmacogenomic differences in drug disposition. [Table: see text] No significant financial relationships to disclose.
Retrospective study of clinical and radiographic risk factors associated with early onset, severe pulmonary hemorrhage in bevacizumab-treated patients with advanced non-small cell lung cancer (NSCLC)
Authors: Sandler A. B. , Johnson D. H. , Brahmer J. , Schiller J. H. , Ostland M. , Gray R. , Tran S. , Dimery I. 
Published: March 2020

7068 Background: Bevacizumab (BV) added to chemotherapy prolongs survival in non-squamous NSCLC, but was uncommonly associated with serious pulmonary hemorrhage (PH) (Sandler A, et al, ASCO 2005). A retrospective study was conducted to potentially identify clinical or radiographic (CT) risk factors associated with early onset (<150 days from initial treatment) PH. Methods: A broad search of the E4599 database for selected bleeding terms among BV-treated patients was conducted. Cases of PH were identified and adjudicated. Associations between baseline clinical factors and incidence of PH were evaluated in the full cohort of E4599 patients. In addition, a separate case-control analysis, using controls matched on age and sex, was conducted to evaluate baseline CT variables. Chest CTs were evaluated by blinded independent assessment of lesion location, cavitation, size of largest tumor or nodal mass, vascular involvement, presence of an endobronchial tumor, and total number of intra-thoracic lesions. Additional analyses were also conducted including cases of late-onset PH, post-baseline variables such as unconfirmed tumor response at 6 weeks (RECIST) and cavitation, and combined CT data from E4599 and an earlier Ph II trial. Results: Of 425 BV-treated pts, 10 cases of PH were identified. Of these, 7 were PH without additional complicating factors, and 6 were of early-onset. The cohort analysis of these 6 early-onset cases is presented ( table ). The case-control analysis on CT risk factors is ongoing. Conclusion: PH was an uncommon event, and based on this, no evidence was observed for an association between the baseline clinical variables and the incidence of early-onset events of PH without additional complicating factors. Conclusions for the CT variables evaluated will be presented. [Table: see text] [Table: see text]
Randomized phase III trial of docetaxel and cisplatin combination chemotherapy versus mitomycin, vindesine and cisplatin combination chemotherapy with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer: Preliminary report
Authors: Kiura K. , Segawa Y. , Tabata M. , Takigawa N. , Kamei H. , Harita S. , Ueoka H. , Hiraki S. , Matsuo K. , Tanimoto M. 
Published: March 2020

7101 Background: Standard treatment of locally advanced non-small cell lung cancer (NSCLC) is cisplatin-based chemotherapy with concurrent thoracic radiation therapy (TRT). Furuse et al. demonstrated a superiority of mitomycin, vindesine and cisplatin (MVP) chemotherapy with concurrent TRT over that with sequential TRT (JCO 17, 1999). We demonstrated that docetaxel plus cisplatin (DP) chemotherapy with concurrent TRT shows better response rate and survival (Kiura K et al. BJC 89, 2003). We conducted a randomized phase III trial that compared DP with MVP in locally advanced NSCLC patients when concurrently administered with TRT. Methods: We randomly assigned patients with good performance status (PS)-stage IIIA/IIIB NSCLC to receive DP or MVP chemotherapy. Chemotherapy consisted of docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on days 1, 8, 29, & 36 in the DP arm and mitomycin 8 mg/m2 on days 1 & 29, vindesine 3 mg/m2 on days 1, 8, 29, & 36, and cisplatin 80 mg/m2 on days 1 & 29 in the MVP arm. In the both groups, TRT began on day 1 at a dose of 60 Gy (2 Gy per fraction and 5 fractions per week for a total of 30 fractions). Results: Two hundred patients entered the trial between July 2000 and July 2005. Pretreatment characteristics were well balanced between the two treatment arms as follows: male/female 92/7, 88/13; median age (range) 65 (40–75), 64 (34–75); stage IIIA/IIIB 33/66, 33/68; and PS of 0/1 46/53, 50/51, for the DP arm and for the MVP arm, respectively. The response rates for the DP arm and the MVP arm were 78.8% and 70.3%, respectively. The 1- and 2-year survival rates were 81.8% and 59.9% for the DP arm, and were 68.8% and 49.1% for the MVP arm, respectively. Median follow up time is 1.4 years in January 2006. Complete analysis will be fixed in July 2007. Conclusions: The DP arm is exactly reproducing the response rate and survival of the phase II trial we have previously reported. The MVP arm seems to reveal better results than that we expected. Radiation dose and schedule might explain the difference because Furuse et al. splitted 56 Gy of TRT in the MVP arm whereas we did not split 60 Gy of TRT. No significant financial relationships to disclose.
A randomized double-blind phase II study to evaluate same-day vs next-day administration of pegfilgrastim with carboplatin and docetaxel in patients with NSCLC
Authors: Belani C. P. , Ramalingam S. , Al-Janadi A. , Eskander E. , Ghazal H. , Schwartzberg L. , Elliott M. , Shahin S. , Dreiling L. 
Published: March 2020

7110 Background: Combination therapy with carboplatin and docetaxel has demonstrated activity against non-small cell lung cancer (NSCLC), but is associated with at least a moderate risk of febrile neutropenia (FN). Though pegfilgrastim is given only once-per-cycle 24 hours after chemotherapy (CT), administering pegfilgrastim on the same day as CT would be convenient for patients (pts). Methods: Pts ≥18 years with previously untreated stage IIIB or IV NSCLC and ECOG ≤2 who were candidates for carboplatin AUC 6 and docetaxel 75 mg/m2 were randomized 1:1 to receive pegfilgrastim 6 mg within 4 hours or approximately 24 hours after CT. The primary endpoint was the duration of grade 4 neutropenia (DSN) in cycle 1. Same-day administration was considered noninferior to next-day if the upper 95% confidence interval (CI) limit for the difference in DSN between groups in cycle 1 was <2 days. Results: As planned, 90 pts were enrolled. 88 pts received blinded study drug. Pts in the same-day and next-day groups had comparable mean baseline ANC and similar proportions of pts completed the study (43% vs 45%). In cycle 1, only 5% of pts in both groups experienced grade 4 neutropenia; resulting in a mean DSN of 0 days. Similarly in cycle 4, 10% (lasting for 1 day only) and 0% of pts in the same-day and next-day groups experienced grade 4 neutropenia. No pts experienced FN during the study. 44% of pts in the same-day and 33% of pts in the next-day group experienced serious adverse events. Conclusions: In this study of lung cancer patients receiving carboplatin and docetaxel, use of pegfilgrastim from the first cycle was well-tolerated in both treatment groups. Although the incidence of grade 3/4 neutropenia was lower than previously reported for this regimen, DSN appeared to be similar for patients in the same-day and next-day groups. Additionally, few patients experienced reductions or delays in CT delivery. [Table: see text] [Table: see text]
Effect of paclitaxel-carboplatin (PC) consolidation chemotherapy after weekly PC concurrent chemo-radiotherapy (CCR) for patients with locally advanced non-small cell lung cancer (LA-NSCLC): 3-year definitive results of the B001-phase III GERCOR-study
Authors: Colin P. , Jovenin N. , Ganem G. , Duhamel J. , Oster J. , Guichard F. , Cretin J. , Terrioux P. , Brechot J. , Morere J. 
Published: March 2020

7112 Background: Local control rate of LA-NSCLC seems better after concurrent CCR than after sequential schedule; the role of additional chemotherapy is not clearly defined. A multi-institutional phase-III trial was conducted to evaluate the role of chemotherapy consolidation after CCR Methods: Eligibility criteria included mediastinoscopy-controlled unresectable NSCLC stage IIIA (27%) - IIIB (59%) and inoperable mediastinal recurrence after surgery (14%), PS < 3, clinical target volume compatible with a minimal 60 Gy dose radiation. After registration, patients (pts) were treated with combination of weekly P (45 mg/m2), C (AUC 2), and radiotherapy 60–66 Gy (5 × 2 Gy per week). The pts with response or stable disease were randomized either to receive 3 cycles of P (175 mg/m2) and C (AUC 5) consolidation on days 1–22–43 or observation. Primary endpoint was OS (log-rank test), planned sample was 122 pts. Results: Actually, 71 pts were enrolled. Thirty pts (42%) were not randomized because of progression (22%) and disease-related death (22%), toxicity (26%), refusal (9%), protocol violation (21%). Toxicity grade 3–4 per patient: for the PC-TRT sequence; neutropenia 5%, febrile neutropenia 5%, thrombopenia 5%, pneumonitis 5%, oesophagitis 19%. For the PC consolidation sequence; neutropenia 24%, febrile neutropenia 6%, thrombopenia 0% (no treatment-related death). After a minimal follow-up of 3 years, despite poor inclusion rate, OS and PFS were greater in the PC consolidation group with 3-year OS: 29.9% vs 10% (HR = 0.45; CI 0.95: 0.22–0.91) (p = 0.002) and 3-year PFS: 27.8% vs 10% (HR = 0.6; CI 0.95: 0.3–1.3) (p = 0.17). Nine pts developed metastasis in each treatment arm. Conclusions: The addition of PC consolidation to PC-CCR is not easily feasible for all LA-NSCLC. For selected pts (only 58% of pts in this trial), despite premature ending of the trial because of slow accrual, PC consolidation significantly improved the 3-year OS and probably PFS. Because no difference in the metastatic incidence was observed, the effect of chemotherapy dosage in the consolidation arm could be explained by delaying metastasis. No significant financial relationships to disclose.
A prospective phase II study of single-agent gemcitabine at prolonged constant infusion at 10mg/m2/min rate (PCI-G) in first-line treatment of elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): The MILES-2G study
Authors: De Maio E. , Morabito A. , Barbera S. , Robbiati S. F. , Piazza E. , Brancaccio L. , Rosetti F. , Foa P. , Verusio C. , Gridelli C. 
Published: March 2020

7125 Background: Single-agent chemotherapy is the standard treatment for elderly pts with advanced NSCLC, following the results of the ELVIS and MILES-1 trials. Some hints that infusing gemcitabine at a fixed dose rate of 10 mg/m2/minute can optimize its pharmacokinetics have been reported. A prospective phase 2 study was conducted to describe activity and toxicity of PCI-G. Methods: Advanced (stage IV or IIIb with supraclavear nodes or pleural effusion) NSCLC pts, aged >70, PS 0–1, were eligible. 51 patients were required according to a single-stage phase 2 design to have 90% confidence in estimating a 25% ±10% response rate. Response was assessed with RECIST; toxicity was coded with NCI-CTC. Results: From October 2002 to June 2003, 51 pts were enrolled. 26 pts (51%) were older than 75 years. Two complete and seven partial responses were observed, for an overall response rate of 17.6% (95% exact CI: 8–31). The median progression-free survival was 16 wks (95% CI: 11–21) and the median overall survival was 41 wks (95% CI: 28–51). Two toxic deaths were recorded (1 bronchial bleeding and 1 hepatic toxicity). Other relevant toxicities were (% of pts): grade 3–4 neutropenia (11.8%), grade 3 thrombocytopenia (5.9%), grade 3 pulmonary toxicity (3.9%) and grade 3 liver toxicity (3.9%); platelet transfusion, grade 3 anemia, RBC transfusion, non-neutropenic infection, and grade 4 neurotoxicity were all reported in one pt each. Conclusions: In this phase 2 prospective study dedicated to elderly pts with advanced NSCLC, PCI-G was not sufficiently active to warrant further investigation. No significant financial relationships to disclose.
Dose-dense pemetrexed (P) and gemcitabine (G) as neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC)
Authors: Bepler G. , Robinson L. , Sommers E. , Sharma A. , Williams C. , Chiappori A. , Haura E. , Simon G. , Antonia S. , Tanvetyanon T. 
Published: March 2020

7129 Background: Adjuvant chemotherapy is standard of care for NSCLC stage IB-III after complete resection. Neoadjuvant therapy has potential advantages. P and G are efficacious in NSCLC with low toxicity. In combination, they can be given dose-dense, which may result in better efficacy, lower toxicity, and higher patient acceptability than traditional platinum-based therapy. Methods: Patients with resectable IB-IIIA and selected IIIB, PS 0–1, w/o prior therapy were eligible. CT, PET, brain MRI, and mediastinoscopy were used for staging. P (500 mg/m2) and G (1,500 mg/m2) were given on d1, 15, 29, and 43. Imaging studies were repeated 7–14 days after treatment and response determined by RECIST. Patients had surgery 3–4 weeks after the last treatment. F/U was every 3 months for 2 years with imaging studies. The primary clinical endpoint is radiographic disease response rate. The secondary endpoints are overall and disease-free survival, pathologic response rate, treatment-related toxicity, and surgical respectability and outcome Results: From 4/04 to 12/05, 45 eligible patients were enrolled. The disease stages were IB in 17, IIA in 3, IIB in 10, IIIA in 12, and IIIB in 3 patient. 8 had adeno, 15 squamous, and 22 large cell or unspecified NSCLC on initial diagnosis. 27 had a PS of 0 and 18 PS 1. 3/45 had weight loss. 22 were women. The median age was 67 (range 42–83 years). 2 were never-smokers, 24 had quit, and 19 were active smokers. Disease response rates to PG were 3% CR, 34% PR, 55% SD, and 8% PD. An R0 resection was performed in 75% of patients, 15% had an incomplete resection, and 10% did not have a thoracotomy. There have been no deaths or unexpected morbidities related to surgery or chemotherapy. Conclusions: Dose-dense PG is well tolerated with acceptable side effects. It appears to be equally as efficacious as platinum-containing chemotherapy doublets in terms of radiographic response rates. Survival rates and the median survival time are forthcoming to allow for a better comparison of this regimen with platinum-containing doublets. No significant financial relationships to disclose.
Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung
Authors: Wittgen B. P. , Kunst P. W. , van der Born K. , Peters G. J. , Perez-Soler R. , Metzheiser B. , Nicholson S. , Perkins W. , Pilkiewicz F. , Postmus P. E. 
Published: March 2020

7131 Background: Investigate the safety and pharmacokinetics of aerosolized SLIT (Sustained release Lipid Inhalation Targeting) cisplatin in patients with carcinoma of the lung. Methods: In this single-center, dose-escalating study patients received SLIT cisplatin for a maximum of 6 cycles. The dose level defines the cycle duration and number of inhalations per day. Safety data, including laboratory parameters, adverse events, pulmonary function tests, bronchial responsiveness, and radiographic imaging were collected and analyzed for all patients in order to determine toxicity. Pharmacokinetic data was collected during the first treatment course. Results: 17 patients and 1 patient on compassionate use received treatment. SLIT cisplatin was well tolerated. No dose limiting toxicity was observed. The maximum delivered dose was 60 mg/m2 in a 2 week schedule and 40 mg/m2 on a weekly schedule. Safety data showed no hematological toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Common side effects were nausea (66.7%), vomiting (44.4%), dyspnea (66.7%), hoarseness (27.8%), and fatigue (66.7%). Pharmacokinetic data showed very low systemic concentrations only at the higher doses. CTC grade-2 decrease in FEV1 and DLCO occurred both in 2 patients after 1 course, and grade-1 decrease in FEV1 and DLCO in 6 and 4 patients respectively. Best overall response was stable disease in 13 patients, while 4 had progressive disease (1 patient received only one course). These results indicate that high doses of aerosolized SLIT cisplatin can be inhaled safely. The therapeutic effect of the formulation will be tested in a phase II study. Conclusions: Inhaled SLIT cisplatin was found to be feasible and safe in patients with lung cancer. [Table: see text]
Delay in time to worsening of symptoms (TWS) of advanced non-small cell lung cancer (NSCLC) using gemcitabine (gem) maintenance therapy
Authors: Peterson P. , Zwitter M. , Krzakowski M. , Wenczl M. , Tzekova V. , Ramlau R. , Ciuleanu T. , Liepa A. , Zielinski C. , Brodowicz T. 
Published: March 2020

7140 Background: Palliation of disease-related symptoms is an important clinical benefit. For advanced disease, this may be relief or delay of worsening of symptoms. Since benefit evaluation in clinical trials is usually focused on radiological assessments, development is needed to establish symptom improvement as an efficacy endpoint. Methods: To determine if gem maintenance therapy delayed the worsening of symptoms, retrospective analyses were performed using symptom data reported by patients (pts) with advanced NSCLC from a randomized trial of gem plus cisplatin followed by gem maintenance therapy plus best supportive care (GBSC) or best supportive care (BSC) (Krzakowski, ASCO 2004). Pts rated 6 symptoms using the Lung Cancer Symptom Scale (LCSS) at baseline and every cycle. Symptom worsening was retrospectively defined as a 15-mm increase in the severity score for any symptom (based on 100-mm scales) from randomization (start of maintenance therapy). Analyses were repeated for 10- and 20-mm increases. Data were analyzed using Kaplan-Meier (KM) plots and Cox regression, with censoring at the last LCSS for pts with no worsening. Results: At randomization, 73% were stage IV and 48% had Karnofsky performance status >80. Of the 206 pts randomized, 171 were included in the symptom analyses. Although not significant, the KM plot for TWS based on the 15-mm definition (defn) showed a separation between arms in favor of GBSC beginning ∼2.5 months after randomization (p = 0.24, HR = 0.79). TWS results for the 20-mm defn were significant in favor of GBSC (p = 0.013, HR = 0.59). When the same analysis was applied to individual symptoms, all symptoms showed the same numerical trend (HR<0.77) in favor of GBSC, with significant TWS advantage for GBSC (HR<0.56) for appetite loss and fatigue (15- and 20-mm defn) and for pain (20-mm defn). Additional analyses suggested a strong correlation between TWS and time to progressive disease. Conclusions: In addition to prolonging time to disease progression, gem maintenance therapy delays pt-reported worsening of symptoms. Correlation of TWS with time to progression suggests that delayed TWS may be a clinical benefit of delayed onset of progressive disease. [Table: see text]