bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A phase II study from the Hoosier Oncology Group
Authors: Agarwala A. K. , Einhorn L. , Fisher W. , Bruetman D. , McClean J. , Taber D. , Titzer M. , Juliar B. , Breen T. , Hanna N. 
Published: March 2020

7066 Background: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in NSCLC. Preclinical studies demonstrate significant interactions between the EGFR and cyclo-oxygenase 2 (COX-2) pathways and that simultaneous inhibition against NSCLC may have benefits over gefitinib alone. Methods: Eligibility required that pts were chemotherapy-naïve, had stage IIIb (with pleural effusion) or IV NSCLC and an ECOG PS 0–1. Pts received gefitinib 250mg orally daily plus celecoxib 400mg orally every 12 hours. Cycles consisted of 21 day treatment and continued until unacceptable toxicity or progression of disease. The primary objective of this single arm, two-stage, phase II study was to evaluate the overall response rate. If ≤ 10 out of 30 pts achieved a complete (CR) or partial response (PR), the study would be stopped early. If >10 out of 30 pts had a CR or PR, enrollment would continue to 50 pts. Results: From 1/04 to 11/04, 31 pts were enrolled: male/female 13/18; median age 70.8 years (range, 19–93); 67.7% had adenocarcinoma; ECOG PS 0/1 13/18; stage IIIb/IV 2/29; 5 were current smokers, 9 were remote (>30 years) or never smokers, 16 quit smoking > 3 months ago. Median number of cycles was 4 (range, 0–16). 6 pts (19.4%) discontinued therapy due to toxicity, including 3 who died due to treatment. Select grade 3/4 toxicities included: pulmonary (6.5%), hepatic (6.5%), diarrhea (6.5%), skin (3.2%). Responses included PR 5 (16.1%), stable disease 8 (25.8%), and progressive disease 18 (58.1%). Median duration of response, progression free survival, and overall survival was 5.7, 2.8, and 7.2 months, respectively. All responders were females with adenocarcinoma, 2 were remote or never smokers and 3 were former smokers. Conclusion: Gefitinib plus celecoxib in an unselected population of chemotherapy naïve patients with advanced NSCLC and a PS of 0–1 has a lower response rate and overall efficacy compared with historical controls of chemotherapy. [Table: see text]
Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by maintenance bevacizumab (B) in the treatment (tx) of limited-stage small cell lung cancer (LS-SCLC): Update of a phase II trial of the Minnie Pearl Cancer Research Network
Authors: Patton J. F. , Spigel D. R. , Greco F. A. , Liggett W. H. , Zubkus J. D. , Baskette M. , Schreeder M. , Woytowitz D. , Nelson E. , Hainsworth J. D. 
Published: March 2020

7085 Background: Targeting VEGF has proven to be an effective tx strategy in many solid tumors including non-small cell lung cancer. VEGF expression in SCLC provides rationale for studying B in addition to chemoradiotherapy. Methods: The endpoints of this multicenter community-based study were to assess the safety, response rate (RR), and progression-free survival (PFS) of I/C/RT followed by B in patients (pts) with LS-SCLC. Tx included: C AUC = 5 IV D1, I 50mg/m2 IV D1,8 Q 21D x 4 cycles, and RT 1.8 Gy daily to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. If no progressive disease (PD) pts received B 10 mg/kg IV Q 14D x 10 doses. Eligibility included: measurable disease, ECOG PS 0–1, informed consent, and no new brain metastases or bleeding. Results: Fifty-seven pts were enrolled from 8/03 to 10/04. Forty-five pts (79%) and 41 pts (72%) received planned tx with I/C/RT and B, respectively. The range of follow-up is 14–28 months. Baseline features: median age 65 years (42–80); male/female, 37%/63%; ECOG PS 0,1: 26%/74%. Grade (G) 3/4 non-hematologic toxicity: diarrhea (9%), DVT (4%), vomiting (11%), and fatigue (9%). G3/4 hematologic toxicity: neutropenia (37%), anemia (5%), and thrombocytopenia (13%). Only 9% of pts experienced G3/4 toxicity during B tx (1 pt each: DVT, hypokalemia, depression, pain, and colon perforation). There were 2 tx-related deaths (both from respiratory failure; 1 and 2 doses of B had been administered). Complete/partial responses were observed in 15 pts (26%)/31 pts (54%), respectively, for an overall RR of 80% (95% CI 70%-90%). Four pts had stable disease, and 5% had PD (4 pts were unevaluable.) 1- and 2-year PFS rates were 63% and 54%, respectively. 1- and 2- year overall survival (OS) rates were 71% and 29%, respectively. Median OS was 15 months. Conclusions: The safety, RR, and 1- and 2-year survival results of I/C/RT followed by B compare favorably with standard tx for LS-SCLC; and B may improve PFS. Assessing the role of B as maintenance tx in improving OS in this setting will require randomized trials. [Table: see text]
Randomized phase II trial of irinotecan plus cisplatin (IP) versus irinotecan, cisplatin plus etoposide (IPE) every three weeks in patients with extensive disease small cell lung cancer (ED-SCLC)
Authors: Sekine I. , Nokihara H. , Takeda K. , Nishiwaki Y. , Nakagawa K. , Isobe H. , Mori K. , Matsui K. , Saijo N. , Tamura T. 
Published: March 2020

7087 Background: A promising complete response rate and median survival time were obtained in our previous phase II study of IPE chemotherapy repeated every 4 weeks in patients with ED-SCLC, but the infusion of irinotecan on day 15 was omitted in 77% of patients. Methods: The objective was to evaluate toxicities and antitumor effects of IP and IPE regimens every 3 weeks and to select the arm for subsequent phase III trials. The primary endpoint was overall survival. Previously untreated ED-SCLC patients aged between 20 and 70 years old with a performance status (PS) of 0–2 were randomized to receive either IP (I 60 mg/m2 days 1, 8 and P 60 mg/m2 day 1) or IPE (the same dose of IP and E 50 mg/m2 days 1–3 with G-CSF support) every 3 weeks for 4 cycles. The projected sample size was 110 patients (Liu’s Selection design for pilot studies on survival). Results: From March 2003 to May 2005, 53 patients (43 males/10 females, median age 63) were randomized to IP and 57 patients (48 males/9 females, median age 62) to IPE. Body weight loss and PS were well balanced between the arms. Full cycles were administered in 75% of patients in the IP and in 67% in the IPE arm. Dose reduction was required in 17% of patients in the IP and 28% in the IPE arm. Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 53%, 34% and 4% of patients in the IP, and 93%, 45%, and 23% of patients in the IPE arm, respectively. Grade 3–4 infection, malaise, anorexia, and diarrhea were noted in 15%, 2%, 0%, and 15% of patients in the IP, and 30%, 11%, 15%, and 24% of patients in the IPE arm, respectively. No treatment related death occurred. Complete and partial responses were noted in 8% and 68% of patients in the IP, and 11% and 75% of patients in the IPE arm, respectively. Conclusion: Toxicity was more severe, but tumor responses seemed better in the IPE arm. The survival analysis will be carried out in April 2006. No significant financial relationships to disclose.
The occurrence of hyponatriemia in SCLC and the influence on prognosis. A retrospective study of 468 patients treated in single institution in a 10-year period
Authors: Hansen O. , Sorensen P. , Hansen K. H. , Holtved E. 
Published: March 2020

7091 Background: Hyponatriemia is very often seen in SCLC due to the paraneoplastic syndrome SIADH. Hyponatriemia has been found to be associated with poorer outcome in some but not in the majority of published studies. This study was performed to investigate the prognostic value of hyponatriemia in SCLC. Methods: Data from the patient files from 468 patients diagnosed with SCLC and treated at Odense University Hospital 1995 to 2005. In the 444 cases data on the initial S-Na was available. A Cox multivariate analysis was performed including possible prognostic factors. Results: Stage: Extensive disease (ED) 283 (64%), limited disease (LD) 161 (36%). The standard chemotherapy was 6 cycles of carboplatin-etoposide. 70% of the patients with LD received thoracic radiotherapy, usually in a dose of 45 Gy/22–30 F and 49% received PCI usually as 25 Gy/11F. Median survival in ED 7.2 months with a 1 and 2-year survival rate of 21% and 6%. In LD the figures was 15.2 months, 65%, 31% and a 5-year survival rate of 16%. S-Na was <125 mEq/L in 36 patients (8%), between 126–135 mEq/L in 158 (36%). 250 patients (56%) showed normal values of S-Na. In a Cox multivariate analysis, hyponatriemia was associated with poor prognosis. Other independent prognostic factors included LDH, gender, age, performance status and stage. Among non-significant factors were hemoglobin, WBC, and alkaline phosphatase. Conclusions: Hyponatriemia was a significant prognostic factor associated with poor prognosis with an odds ratio of 1.5 (p = 0.0013) if S-Na was 1.25–1.35 mEq/L and an odds ratio of 1.9 (p = 0.0008) if S-Na was <1.25 mEq/L. [Table: see text] No significant financial relationships to disclose.
The influence of radiotherapy technique and dose on the patterns of failure for mesothelioma patients following extrapleural pneumonectomy
Authors: Allen A. M. , Den R. , Wong J. S. , Janne P. A. , Zurakowski D. , Soto R. , Bueno R. , Sugarbaker D. J. , Baldini E. H. 
Published: March 2020

7094 Background: Extrapleural pneumonectomy (EPP) is an effective treatment of pleural mesothelioma(MPM). We present a comparison of moderate-dose hemithoracic radiation (MDRT) to high-dose hemithoracic radiation (HDRT) following EPP for MPM. Methods: From 7/94 to 4/04, 39 pts underwent EPP and adjuvant radiotherapy (RT) at DFCI/BWH. From 1994–2002, MDRT, 30Gy to the hemithorax with boosts to the mediastinum or chest wall to 40–54 Gy was given, generally with concurrent chemotherapy (CT). Beginning in 2003, HDRT to 54 Gy as published by Yajnik et al (IJROBP 03’) was given with sequential CT. Results: Thirty-nine pts received RT following EPP. Median age was 59 yrs (range 44–77). Histology was epithelial in 25 (64%) pts and mixed/sarcomatoid in 14 (46%) pts. Twenty-four pts were treated with MDRT. 19 pts received concurrent platinum-based CT with MDRT. Three received cyclophosphomide, adriamycin and cisplatin (CDDP) CT prior to radiotherapy and 2 did not receive CT. 14 pts (39%) were treated with HDRT. 10/14 received sequential CDDP/gemcitabine, 4 received CDDP/pemetrexed and 1 patient received intraoperative CDDP. The median follow-up was 20 mos (range, 6–73 mos). Overall survival (OS) was 19 mos (95% CI, 14–24 mos). The median times to distant failure (DF) and local recurrence (LR) were 20 mos (95% CI, 14–26 mos) and 26 mos (95% CI, 16–36 mos), respectively. No significant differences in outcome between the two radiotherapy regimens were seen. One patient died of radiation-induced liver disease, one of pneumonitis and one of an MI. Four pts who received HDRT are alive and NED. On univariate and multivariate analysis mixed histology was predictive of DF and OS (p < .006; p < .004). Neither RT technique nor type of CT were predictive of LF, DF, or OS. The patterns of failure are in the table below. Conclusions: HDRT appears to limit in field local failures as compared to MDRT. Distant failure remains a significant challenge, with half of the patients experiencing distant failure. [Table: see text] No significant financial relationships to disclose.
A phase II study of intravenous (IV) milataxel (M) for the treatment of non-small cell lung cancer (NSCLC) refractory to platinum-based therapy
Authors: Mekhail T. , Serwatowski P. , Dudek A. , Belani C. , Jankowska R. , Pandya K. J. , Arnold S. , Brahmer J. , Gitlitz B. , Govindan R. 
Published: March 2020

7098 Background: M (TL139, MAC-321) is a novel taxane that has shown activity when administered IV or orally in both taxane-resistant and susceptible nude mouse xenograft models. The current study is an open-label study in previously treated patients (pts) with locally advanced, metastatic, or recurrent NSCLC to determine response rate. Methods: Pts with cytologically or histologically confirmed NSCLC must have received 1 or 2 prior regimens including prior platinum, and may have received prior paclitaxel or docetaxel. Good performance status (ECOG 0 or 1), and adequate hematologic, hepatic and renal function were required. Pts with clinically active brain metastases were excluded. Pts were treated with M 35 mg/m2 as a 4 hr IV infusion every 3 weeks. The primary end point was objective response rate. Results: A total of 46 pts were treated: 21 (46%) female pts and 25 (54%) male pts. Mean age was 59 (range 41–85), ECOG was PS 0 in 13 (28%) pts, PS 1 in 31 (67%) pts and unknown in 2 (4%) pts. The number of prior chemotherapy regimens was > 1 in 21 (46%) pts. Twenty-five (54%) pts had one prior taxane and 7 (15%) pts had both paclitaxel and docetaxel previously. The median number of cycles was 3 (range 1–14). Nine (20%) pts required dose reduction. Five (11%) pts discontinued treatment due to adverse events. A total of 25 (54%) pts reported drug related grade 3 or 4 adverse events. Non-hematologic grade 3 or 4 drug-related events occurring in more than 1 pt included: neuropathy 4 (9%) pts, neutropenic fever 3 (7%) pts, arthralgia 2 (4%) pts. There was no treatment related mortality. Objective responses were confirmed in 4 (9%) pts (3 PR, 1 CR). Three pts with response (including pt with CR) had received prior docetaxel. PR duration was 175, 250, and 315 days. Pt with CR received 4 cycles of M and discontinued due to the CR. Pt remained in CR at day 504. Conclusions: Milataxel 35 mg/m2 as a 4 hr IV infusion every 3 weeks provided durable responses in heavily pretreated pts including pts who had previously received taxanes. No significant financial relationships to disclose.
Phase III study comparing cisplatin/vinorelbine plus cetuximab versus cisplatin/vinorelbine as first-line treatment for patients with epidermal growth factor (EGFR)-expressing advanced non-small cell lung cancer (NSCLC) (FLEX)
Authors: Von Pawel J. , Park K. , Pereira J. R. , Szczesna A. , Yu C. , Ganul V. L. , Krzakowski M. , Roh J. K. , Pilz K. , Pirker R. 
Published: March 2020

7109 Background: Cisplatin plus vinorelbine is a commonly used regimen for first-line therapy of advanced NSCLC, achieving response rates of 20–30% and median survival times of 6 to 11 months (mths). An earlier phase II trial investigated cetuximab in combination with cisplatin and vinorelbine in this setting and found improved response rates in the cetuximab arm, warranting this larger phase III trial. Methods: Patients (pts) with EGFR-expressing advanced NSCLC (stage IIIB with documented malignant pleural effusion and stage IV) were randomized 1:1 either to Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2 weekly, cisplatin 80 mg/m2 on day 1, vinorelbine 30 mg/m2 on day 1 and 8) or to Group B (cisplatin and vinorelbine as before) for a maximum of 6 three-weekly cycles. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, tumor response, disease control, safety, and quality of life. Enrollment of 1,100 pts was planned to show an increase of median survival time of 25% with 90% power. The Data Safety Monitoring Board (DSMB) performed an independent preplanned safety analysis from the first 370 pts. Patients were followed for a minimum of 6 weeks (2 cycles). Results: Since November 2004, 1,037 pts have been randomized, 689 are under treatment, and 348 pts have discontinued the study. Demographics of the first 370 pts reflected known advanced NSCLC characteristics: 91% stage IV, median age 60 yrs (31–79), 38% female, 80% ECOG PS 0/1, 52% adenocarcinoma, 30% squamous cell carcinoma; 29% never-smokers, 17% Asian. The ten most frequent adverse events were: nausea, neutropenia, vomiting, anorexia, fatigue, constipation, anemia, febrile neutropenia, rash, and diarrhoea. Conclusions: The trial continued after review of all relevant baseline and safety information from the first 370 pts. Recruitment is ongoing. [Table: see text]
Cisplatin plus gemcitabine with or without vinorelbine as neo-adjuvant therapy for radically treatable stage III non-small cell lung cancer. Results of a randomised study of the Grupo Oncológico del Norte de España
Authors: Esteban E. , Villanueva N. , Muñiz I. , De Sande J. , Fra J. , Fernández Y. , Vieitez J. , Luque M. , Jimenez P. , Buesa J. , Lacave A. 
Published: March 2020

7121 The combinations of cisplatin (C) with gemcitabine (G) and/or vinorelbine (V) have shown to be effective and safe regimens in the first line treatment of NSCLC. This study has been designed to detect a 25% increase in objective response measured by CT scan with the triplet combination (CGV) with respect to cisplatin/gemcitabine combination (CG) administered as neo-adjuvant therapy in patients with radically-treatable stage III NSCLC. With 80% of power and one-sided 5% significant level, the simple size required to confirm this hypothesis is 75 evaluable patients in each arm of treatment. Patients (pts) ≤ 75 years old, Karnofsky index ≥ 70% and adequate haematological, renal and hepatic function are stratified by stage (IIIA versus IIIB) and randomly assigned to: C 50 mg/m2 i.v. and G 1250 mg/m2 i.v. d1 and d8 alone (CG) or in combination with V 25 mg/m 2 i.v. d1 and d8 (CGV) both regimens every 3 weeks for 3 consecutive cycles followed by definitive local treatment (LT). From December 1999 to December 2005, a hundred and forty-nine pts have been randomised (CG/CGV); median age 58/58; median Karnofsky index 80/80; stage IIIA 24/26; stage IIIB 51/48; squamous 37/39; adenocarcinoma 31/32; anaplastic 7/3. Major haematological toxicities grade 3–4 were (CG/CGV; %); Anaemia (5/5) neutropenia (31/34); thrombocytopenia (4/5). Two pts in CG (2.7%) and 4 in CGV arm (5.5%) developed neutropenic fever. Major non-haematological toxicities grade 2–3 were: N/Vomiting (31/32) and fatigue (12/20). Global recurrences have been registered in 57% and 54% of pts treated with CG and CGV arm respectively. Exclusive local/ distant failure (%) has been 16/23 in CG and 23/18 in CGV arm. Preliminary results show similar high efficacy associated with moderate toxicity in both groups of treatment. The study is continuing. [Table: see text] No significant financial relationships to disclose.
Interim results of two prospective trials measuring plasma total DNA and methylated genes before and after surgery, or chemotherapy, in patients with non-small cell lung cancer (NSCLC)
Authors: Azzoli C. G. , Park S. , Ginex P. , Vincent A. , Jones J. , Venkatraman E. , Danenberg K. , Danenberg P. , Rusch V. R. , Kris M. G. 
Published: March 2020

7123 Background: Measuring DNA in plasma using quantitative RT-PCR is a promising method for surveillance of NSCLC. This strategy has the potential to assess response more accurately or quickly than radiologic tests, or to confirm the success of surgical resection and select patients for adjuvant therapy. Methylated genes may be more specific than total DNA for the presence of cancer. Methods: We are conducting two prospective trials measuring total DNA, and 10 commonly hypermethylated genes in the plasma of NSCLC patients before and after therapy. For patients undergoing surgery, plasma samples are collected before, and at three timepoints after surgery (3–8 d, 2–5 w, 2–4 m). For patients on chemotherapy, collections are before, and coincident with up to 3 radiologic response assessments. DNA is extracted from a fixed volume of plasma, and measured using quantitative PCR of the β-Actin gene. After treating DNA with sodium metabisulfite, methylation-specific RT-PCR is performed to amplify the promoter region of APC, p16, MGMT, GSTP1, DAPK, CDH1, RASSF1A, WIF-1, SOCS-3, METH-2, assuming the promoter is fully methylated. Gene levels are normalized to β-Actin in modified DNA. Results: To date, plasma analysis has been completed on 50 patients with advanced NSCLC undergoing chemotherapy (320 planned), and 60 patients with early-stage NSCLC undergoing surgery (400 planned). Pretreatment levels of total DNA are higher in metastatic NSCLC (median 9.2, range 2.2–1020 ng/ml) compared to early-stage (median 3.6, range 0–1280 ng/ml), p < 0.001 by Wilcoxon rank sum test. At least one methylated gene is detectable in pretreatment plasma in 36% of patients with metastatic NSCLC, and 20% of patients with early-stage NSCLC. Conclusions: Methylated genes are rarely found in the pre-treatment plasma of NSCLC patients in this experiment, despite testing a panel of 10 genes. Plasma total DNA levels correlate with NSCLC stage. Correlation of baseline levels of total DNA, and temporal trends during treatment, to overall survival and radiologic response are planned. Supported by R01-CA092315. [Table: see text]
Randomized phase II cross-over sequential chemotherapy trial of irinotecan/cisplatin (IP) vs. gemcitabine/vinorelbine (GV) in chemo-naïve patients with stage IIIb/IV non-small cell lung cancer (NSCLC)
Authors: Lee J. S. , Lee D. H. , Lee J. J. , Han J. Y. , Park S. H. , Song J. E. , Kim H. Y. , Kim H. T. 
Published: March 2020

7134 Background: To compare the efficacy and toxicity of IP vs. non-platinum-based GV in the treatment of advanced NSCLC, we conducted a randomized phase II trial with planned cross-over to the other regimen upon disease progression (PD) after the first-line therapy. Methods: Eligibility required stage IIIb/IV NSCLC, no prior chemotherapy, measurable disease, ECOG PS 0–2, adequate organ functions, and informed consent. After stratification by gender, stage (IIIB or IV) and performance status (PS: 0–1 or 2), eligible pts were randomized to receive either IP (I 65 mg/m2 & P30 mg/m2 on D1 & 8 q 3 weeks) first then GV (G 900 mg/m2 &V25 mg/m2 on D1 & 8 q 3 weeks) upon PD (Arm A) or GV first then IP upon PD (Arm B). Results: Between 12/2003 and 06/2005, 146 pts were enrolled in either Arm A (n = 75) or Arm B (n = 71). There was no difference in gender (male: 77.3% vs. 81.7%), age (median: 58 vs. 60 yrs), PS (PS 2: 10.7% vs. 8.5%), histology (adenocarcinoma: 72.0% vs. 76.6%) and stage (IV: 88.0% vs. 87.3%). IP tended to generate more responses than GN (42.0% vs. 29.0% as first-line, 30.2% vs. 14.3% as second-line), but there was no difference in total response rate by the treatment arm (Arm A: 45.6%, B: 43.5%). During the first-line therapy, IP caused more G3+ anemia (20.0% vs. 7.1%, p = 0.048), G2/3 nausea/vomiting (41.4% vs. 12.9%, p < 0.001), G2 alopecia (35.7% vs. 10.0%, p = 0.001) than GN while pneumonitis was noted only with GN (11.4%). Toxicity profile was similar after the second-line therapy. Both arms resulted in excellent survival outcome with no significant difference between the Arm A and B (median: 16.5 mo vs. 15.1 mo, p = 0.595). Conclusions: Platinum-based IP regimen seemed to be more effective in terms of response rate. Given the overall survival data and the mild toxicity profile of GV regimen, however, either treatment sequence seems to be acceptable for the treatment of advanced metastatic NSCLC. (Supported in part by NCC grants 0210140 and 0510140). No significant financial relationships to disclose.