bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of venous thromboembolism in lung cancer and its effect on survival.
Authors: Mozayen Mohammad , Tesfaye Anteneh A. , Sarangi Manas ranjan , Talluri Jyothsna , Katato Khalil 
Published: March 2020

7102 Background: Lung cancer is a major risk factor of venous thromboembolism (VTE). The incidence of VTE in different histological patterns of lungs cancer and its impact at the disease outcome is not well studied. We aim to evaluate the incidence rate of VTE in lung cancer and its effect on survival. Methods: Patients (pts) with lung cancer diagnosis from cancer database of community hospital were reviewed. Pts’ medical records were checked for VTE over 3 years after diagnosis. Pts’ demographics, pathology, TNM stage and overall survival were studied. Development of VTE was primary outcome and 3 year overall survival was the secondary outcome. Results: A total 2,164 pts with lung cancer between 1995 and 2008 were included. Median age of the study population was 70 years. Males were 53%, African Americans were 7%. 200 pts (9%) were diagnosed with VTE. Out of 1783 pts with non-small cell lung cancer (NSCLC), 176 pts (9.9%) had VTE whereas out of 381 pts with small cell lung cancer (SCLC) 24 pts (6.3%) had VTE (p=0.015). Among NSCLC pts, 13.5% of pts with adenocarcinoma had VTE, whereas 6.6% of pts with squamous cell carcinoma had VTE (p<0.05). The incidence of VTE in stages I, II, III, IV of all pts were (8.4%, 7.3%, 13%, 7.5%) (p=0.007) respectively. In NSCLC, three years overall survival of pts with and without VTE was 22% and 24% respectively (p=0.34). In SCLC, three years overall survival of pts with and without VTE was 21% and 11% respectively (p=0.09). Conclusions: There is a higher incidence of VTE in non-small cell lung cancer than in small cell lung cancer. Among the NSCLC, VTE’s incidence was higher in adenocarcinoma than squamous carcinoma. VTE maybe higher at advanced stages (stage III) in both NSCLC and SCLC combined. There was no significant difference in the 3 years overall survival of lung cancer patients with and without VTE.
A phase (Ph) I/II study of belinostat (Bel) in combination with cisplatin, doxorubicin, and cyclophosphamide (PAC) in the first-line treatment of advanced or recurrent thymic malignancies.
Authors: Thomas Anish , Rajan Arun , Khozin Sean , Szabo Eva , Carter Corey Allan , Guha Udayan , Manu Michell , Berman Arlene W , Kunst Tricia , Piekarz Richard , Schrump David S. , Giaccone Giuseppe 
Published: March 2020

7103 Background: Belinostat is a hydroxamic acid histone deacetylase (HDAC) pan-inhibitor with single agent activity in thymic malignancies. PAC has activity against thymic cancers. Synergy between Bel and several chemotherapeutic agents, including P, A, and C, has been demonstrated in preclinical models. Methods: Patients with histologically confirmed, treatment naive advanced thymic malignancies, PS<2, measurable disease, and adequate renal, hepatic and hematopoietic functions were eligible. Ph1 evaluated safety and tolerability of the combination using increasing dose levels (DL) of Bel (1000-2000 mg/m² over 48 h CIVI) and PAC (50/50/500 mg/m² IV/cycle) (3+3 dose escalation schema), administered every 21 days for no more than 6 cycles followed by optional maintenance Bel every 4 weeks. Primary end point of Ph2 is overall response rate (ORR). Results: From March 2010 to January 2012, 13 patients were enrolled [7 thymoma (T), 6 thymic carcinoma (TC); 8 in Ph1 and 5 in Ph2; median age: 49 years (range, 23-76)]. In Ph1, 6 patients were treated at DL1 (Bel 1000 mg/m2+ PAC) and 2 patients at DL2 (Bel 2000 mg/m2+ PAC). Dose Limiting Toxicities were Grade 3 nausea and diarrhea, and Grade 4 neutropenia and thrombocytopenia. Recommended phase II dose (RP2D) was set at DL1. Most common grade 3/4 treatment-related adverse events (AE) were lymphocytopenia (100%), leucopenia (85%), neutropenia (77%) thrombocytopenia (54%), anemia (38%), hypophosphatemia (38%), hypomagnesemia, hypokalemia, elevated AST, prolonged QTc and infusion-catheter related thromboembolic complications (23% each). Outcomes included one complete response (CR; T at DL1), 6 partial responses (PR; 4 T, 2 TC; 4 in Ph1, 2 in Ph2) and 6 stable disease (SD; 2 T, 4 TC; 3 each in Ph1 and Ph2). Four patients previously deemed unresectable underwent surgical resection. Conclusions: Belinostat in combination with PAC has activity in thymic malignancies with a predicable AE profile. ORR was 54% including 33% PR in the TC subgroup. RP2D of the combination has been defined. Accrual to Ph2 part and molecular profiling of patient tumors is ongoing.
Neoadjuvant treatment of primary inoperable or local recurrent thymoma with octreotide LAR to improve tumor resectability.
Authors: Schalke Berthold , Boy Sandra , Hofmann Hans-Stefan , Stroebel Philipp , Marienhagen Joerg , May Christoph , Stuermer Andrea , Marx Alexander 
Published: March 2020

7105 Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma is poor. Most important factor for long-term survival in thymoma patients is complete resection (R0) of the tumor. The study was performed to evaluate the efficacy of octreotide LAR plus prednisone in patients with primary inoperable or local recurrent thymoma to reduce tumor size. Methods: This was an open label, single-arm study in patients with inoperable or local recurrent thymoma. Patients were considered unlikely to achieve R0 resection at enrollment. Octreotide LAR was administered once every 2 weeks in combination with prednisone. Two stages were planned according to Fleming’s one sample multiple testing procedure for phase II clinical trials. The objective of the study was to show that octreotide LAR is effective in this patient population with respect to tumor shrinkage. Response was defined as decrease in tumor volume of at least 20% at month 3 as compared to baseline. Results: 17 thymoma patients at Masaoka stage III were recruited. Octreotide LAR showed a response in 15 of 17 patients (88.24%) at week 12. Two patients had discontinued the study before week 12 due to unsatisfactory therapeutic effect or adverse events. At Week 12, 5 patients (29.41%) operable for radical resection. 10 patients (58.82%) were not operable for radical resection. 16 of 17 patients (94.12%) experienced adverse events (AEs). The most frequent AEs were gastrointestinal disorders (70.59%), infections and infestations (64.71%), and blood/lymphatic system disorders (41.18%). Conclusions: Octreotide LAR was shown to be effective in patients with inoperable thymoma with respect to tumor shrinkage.Octreotide LAR was generally well tolerated. The reported AEs are in accordance with the known safety profile.
Three-arm randomized phase II study of carboplatin (C) and paclitaxel (P) in combination with cetuximab (CET), IMC-A12, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology Group (ECOG) study (E4508).
Authors: Hanna Nasser H. , Dahlberg Suzanne Eleanor , Kolesar Jill , Hirsch Fred R. , Ramalingam Suresh S. , Schiller Joan H. 
Published: March 2020

7516 Background: Pre-clinical evidence supports the clinical investigation of inhibitors to the insulin-like growth factor receptor (IGFR) and the epidermal growth factor receptor (EGFR) alone and in combination with one another in patients (pts) with NSCLC. Methods: Pts w/ chemotherapy-naïve, advanced NSCLC, not eligible for bevacizumab-based therapy, ECOG PS 0/1 were eligible. Pts with uncontrolled or untreated brain mets and/or severe hyperglycemia were ineligible. Pts were randomized to receive: C AUC 6 iv + P 200 mg/m2 iv on day 1 every 3 wks combined with either CET iv weekly (arm A), IMC-A12 iv every 2 wks (arm B), or both (arm C). Patients with non-progressive disease (PD) after 12 weeks of therapy were permitted to continue on maintenance antibody therapy until PD. The primary objective was PFS. Secondary objectives included OS and toxicity. The design required 180 eligible patients and had an 88% power to detect a 60% increase in median PFS for either comparison (arm A vs C or arm B vs C) (1-sided 0.10 level test). Results: Characteristics for arms A (n=39)/B (n=42)/C (n=48): males were 51%/57%/54%; median age was 60, 62, 60; PS 0 49%/52%/60%; stage IV 87%/83%/94%; adenocarcinoma 44%/26%/42%. The study was closed prematurely due to safety concerns after 129 eligible pts were treated. 13 patients died during treatment (A=6; B=2; C=5), including 9 w/in ~1 mo of starting therapy. G3-5 toxicities, all attributions, A/B/C: anemia 16%/7%/13%; neutropenia 27%/29%/42%; febrile neutropenia 7%/5%/4%; thrombocytopenia 7%/10%/13%; pneumonia 9%/2%/6%; hyperglycemia 2%/10%/15%; rash 5%/2%/8%; hyponatremia 2%/5%/17%; thromboembolic events 2%/10%/0%; fatigue 16%;22%/13%. The estimated median PFS and OS for arms A/B/C were 3.4, 4.3, and 4.1 mos and 11.7, 8.6, and 8.4 mos, respectively. Conclusions: Based upon apparent lack of efficacy and excessive premature deaths, this study does not support the continued investigation of C + T + IMC-A12 alone or in combination with CET in pts with advanced NSCLC not eligible for bevacizumab.
Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR).
Authors: Mitsudomi Tetsuya , Morita Satoshi , Yatabe Yasushi , Negoro Shunichi , Okamoto Isamu , Seto Takashi , Satouchi Miyako , Tada Hirohito , Hirashima Tomonori , Asami Kazuhiro , Katakami Nobuyuki , Takada Minoru , Yoshioka Hiroshige , Shibata Kazuhiko , Kudoh Shinzoh , Shimizu Eiji , Saito Hiroshi , Toyooka Shinichi , Nakagawa Kazuhiko , Fukuoka Masahiro ,   West Japan Oncology Group
Published: March 2020

7521 Background: WJTOG3405 met its primary endpoint of progression free survival (PFS) (9.2 months (mo.) for G vs. 6.3 mo. for CD, hazard ratio (HR) 0.489, 95% confidence interval (CI): 0.336-0.710). (Mitsudomi et al., Lancet Oncol., 2010). However, the impact on overall survival (OS) was not clear then because of relatively short follow-up period. Methods: Overall survival (OS) was re-evaluated using updated data (data cutoff, 31 July, 2011, median follow-up, 34 months) for 172 patients. Results: Eighty-two events had occurred (48%). Median survival time (MST) for G arm was 36 mo. (95% CI: 26.3 -) which was not significantly different from 39 mo. (95% CI: 31.2 -) for CD arm (HR 1.185, 95% CI 0.767-1.829). Multivariate analysis using Cox proportional hazards model revealed that none of covariates (treatment arm, smoking status, sex, age, postoperative recurrence or IIIB/IV, and mutation type) significantly affected OS. In the G arm, MST of patients with exon 19 deletion (36 mo.) was comparable to that of patients with L858R (35 mo.). In the CD arm, 78 patients (91%) received EGFR-TKI as the 2nd or later line treatment, whereas in the G arm, 52 patients (61%) received platinum doublet. Accordingly, 130 patients received both platinum doublet and EGFR-tyrosine kinase inhibitor (TKI) and 34 patients received EGFR-TKI without platinum doublet in their whole courses of therapy. MST for the former and the latter group were 36 months (95% CI: 31.2-45.7) and 45 months (95% CI: 25.6-), without significant difference. Conclusions: This update OS analysis revealed that G for advanced NSCLC with EGFR mutation offers distinct survival benefit of 3 years. There was no difference in OS whether the first-line treatment was G or CD, in accordance with the precedent studies. The reason why PFS difference was not translated into OS difference is probably due to high cross over rate to EGFR-TKI. However, it was noteworthy that 40% of patients in the G arm could be managed without platinum doublet and yet had similar outcome.
Differential progression-free survival (PFS) to erlotinib according to EGFR exon 19 deletion type in non-small cell lung cancer (NSCLC) patients (p) in the EURTAC study.
Authors: Carcereny Costa Enric , Taron Miquel , Queralt Cristina , de Aguirre Itziar , Capdevila Laia , Cros Sara , Vergnenegre Alain , De Marinis Filippo , Massuti Bartomeu , Reguart Noemi , Ono Mayumi , Buges Cristina , Provencio Mariano , Garrido López Pilar , Viteri Ramirez Santiago , Gasco Amaya , Sanchez Jose Miguel , Cobo Manuel , Drozdowskyj Ana , Rosell Rafael 
Published: March 2020

7540 Background: Different exon 19 deletion types have shown different in vitro sensitivity to erlotinib, with the lower IC50 for deletion E746_A750 (ELREA) (Yuza et al. Cancer Biol Ther 2007). This information prompted us to examine outcome according to type of exon 19 deletion in the EURTAC study. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Progression-free survival (PFS) was 9.7 months (m) vs 5.2 m, respectively (P<0.0001). Exon 19 deletions were divided into two groups: ELREA vs non-ELREA deletions. Results: Exon 19 deletions were present in 57 p in the erlotinib arm and in 58 p in the chemotherapy arm. ELREA deletions were found in 41 p (71.9%) in the erlotinib arm and in 38 p (65.5%) in the chemotherapy arm. Non-ELREA deletions were found in 16 p in the erlotinib arm and in 20 p in the chemotherapy arm. There were no differences in p characteristics between treatment arms according to type of deletion. PFS for p with ELREA deletions was 9.4 m in the erlotinib arm and 4.6 in the chemotherapy arm (HR, 0.36; P=0.0004). PFS for p with non-ELREA deletions was not reached in p in the erlotinib arm and was 5.3 m for p in the chemotherapy arm (HR, 0.17; P=0.001). The multivariate analysis identified erlotinib arm (P<0.001) and non-ELREA deletions (P=0.001) as independent markers of longer PFS. Overall survival (OS) for p with ELREA deletions was 17 m in the erlotinib arm and 18.4 in the chemotherapy arm (P=0.575). OS for p with non-ELREA deletions was not reached in the erlotinib arm and 19.5 m in the chemotherapy arm (P=0.216). Response rate (RR) for p with ELREA deletions was 53.6% in the erlotinib arm vs 15.7% in the chemotherapy arm (P=0.004). RR for p with non-ELREA deletions was 68.7% in the erlotinib arm vs 10% in the chemotherapy arm (P=0.001). Conclusions: To date, no biological reason has been identified that can explain the greater sensitivity to erlotinib in p with non-ELREA exon 19 deletions. Our findings indicate the need to define the type of deletion prior to treatment since this information can be helpful in predicting the duration of response.
A randomized, double-blind, placebo-controlled multicenter phase II study of the COX-2 inhibitor apricoxib (A) in combination with either docetaxel (doc) or pemetrexed (pem) in advanced non-small cell lung cancer (NSCLC) patients (pts) selected by urinary PGE-m suppression.
Authors: Edelman Martin J. , Tan Ming Tony , Fidler Mary J. , Sanborn Rachel E. , Otterson Gregory Alan , Sequist Lecia V. , Evans Tracey L. , Schneider Bryan J. , Keresztes Roger , Rogers John S. , Antunez de Mayolo Jorge , Medeiros Michelle , Zaknoen Sara L. 
Published: March 2020

7546 Background: Overexpression of COX-2 has been associated with advanced stage and worse outcomes in NSCLC, possibly due to elevated levels of the COX-2 dependent prostaglandin, PGE-2. COX-2 inhibitors in addition to standard therapy has been associated with superior outcome in pts in whom the urinary metabolite of PGE-2, PGE-M is suppressed by the inhibitor. We hypothesized that pts defined by PGE-M suppression would benefit from the addition of apr to doc or pem. Methods: Pts with NSCLC, progressive after one platinum based therapy, PS 0-1, normal organ function, alb ≥2.5, CCr ≥ 45 were eligible for screening. A 5 day run in period with apr 400mg qd was performed. Only pts with a ≥ 50% decrease in urinary PGE-M could actually enroll. Chemotherapy was doc 75 mg/m2 or pem 500 mg/m2 q21 d per the investigator plus apr/placebo (P) 400 mg qd. The primary endpoint was progression free survival (PFS). Results: A total of 109 pts were screened of whom 72 demonstrated ≥50% suppression and enrolled (table). Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib vs. placebo. By chemotherapy assignment: pem/apr vs. pem/P : 103 days vs. 98 (p =.49); doc/apr vs. doc/P: 75 vs. 97 (p=.18). An adverse interaction between baseline PGE-M and doc was seen in survival (p=.026); each unit increase in urinary PGE-M increased the HR by 1.014 (p < 0.038 ) vs. pem (HR =.990, p=n.s.). There was no correlation between baseline PGE-M or magnitude of PGE-M suppression and benefit from apr. Conclusions: 1. Apr did not improve outcome despite patient selection. 2. There was a trend towards an adverse outcome when apr was combined with docetaxel, that was not evident with pemetrexed. 3. Baseline urinary PGE-M may be an adverse prognostic factor for treatment with doc. [Table: see text]
Final results of a randomized, double-blind, phase II study of gemcitabine plus vandetanib or plus placebo in the treatment of advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) elderly patients (ZELIG study NCT00753714).
Authors: Gridelli Cesare , Novello Silvia , Zilembo Nicoletta , Foa Paolo , Favaretto Adolfo G. , De Marinis Filippo , Genestreti Giovenzio , Crinò Lucio , Grossi Francesco , Caffo Orazio , Ferraù Francesco , Cruciani Giorgio , Brandes Alba Ariela , Galetta Domenico , Barni Sandro , Fasola Gianpiero , Siena Salvatore , Mari Ettore , Iannacone Claudio , Ciardiello Fortunato 
Published: March 2020

7550 Background: Vandetanib (V) is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Single-agent gemcitabine (G) is a standard of care option for unselected patients (pts) unfit for doublet platinum based chemotherapy. This study assessed the progression-free survival (PFS) benefit of G+V compared to G plus placebo (P) in pts with advanced NSCLC aged ≥ 70 years. Methods: Eligible pts (stage IIIB/IV NSCLC; WHO PS 0-2; all histologies; chemonaïve, aged ≥70) were randomized 1:1 to receive G 1200 mg/m2 i.v. day 1 and 8 of each 21-day cycle, up to 6 cycles plus V 100 mg/day or plus P until progression/toxicity. The primary objective was PFS (80% power to detect a hazard ratio [HR] ≤ 0.667). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between Oct 2008-May 2010, 124 pts (median age 75 yrs (70-84); 72.6% male; 57.2% WHO PS 0-1; 74.2% past/never-smoker; 58.1% adenocarcinoma; 89.5% stage IV) were randomized to G+V (n = 61) or G+P (n = 63). Baseline characteristics were similar in both arms. At data cut-off (Apr11), 87.9% pts progressed and 73.4% pts had died. PFS was significantly prolonged for G+V (HR=0.729; 95% CI 0.484-1.096; p=0.0417), median PFS G+V=6.0 months, G+P=5.5 months. No differences were seen in ORR (14.8% and 12.7%; p = 0.74), DCR (72.1% and 66.7%; p =0.51), OS (HR=1.024 [95% CI 0.667-1.571] p=0.8960), proportion of pts alive at 1-year G+V=31.1% and G+P=30.2% (p=0.90). Adverse events (AEs) observed for V 100 mg were generally consistent with previous NSCLC studies of V 100 mg. Common AEs (any grade) occurring with a greater frequency in the G+V arm included skin toxicity (34.4% vs 15.9%) and hypertension (9.8% vs 3.2%). Diarrhea and neutropenia were similar in both arms (14.8% and 14.3%; 19.7% and 19.0%). Conclusions: Despite a marginally statistically significant improvement in PFS the study did not met the primary and secondary end points. The combination G+V was well tolerated in this clinical setting.
Randomized phase II trial of carboplatin combined with weekly paclitaxel (CP) and docetaxel alone (D) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): NJLCG 0801.
Authors: Sugawara Shunichi , Maemondo Makoto , Harada Toshiyuki , Inoue Akira , Matsubara Nobumichi , Watanabe Kana , Ishimoto Osamu , Sakakibara Tomohiro , Minegishi Yuji , Usui Kazuhiro , Ando Masahiro , Morikawa Naoto , Mori Yoshiaki , Gemma Akihiko , Nukiwa Toshihiro 
Published: March 2020

7565 Background: Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine globally. However, we have demonstrated the high efficacy of CP for elderly pts in our previous trial (Ann Oncol 2010). Meanwhile, D has been considered as an alternative option for this population in Japan according to the result of WJTOG9904 (JCO 2006). Thus we compared the two regimens to select the proper candidate for future phase III trial. Methods: Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m2 on day 1, 8, and 15) every 4 weeks or D (60mg/m2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results: Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 51% (95%CI: 36-66%) and 26% (95%CI: 12-39%) in the CP and D arm, respectively. With a median follow-up of 18.4 months, median PFS were 6.5 and 3.9 months in the CP and D arm, respectively (Logrank, P=0.0027). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm but none in CP arm. Conclusions: The platinum doublet CP achieved higher activity with an acceptable toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011).