bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute promielocytic leukemia: 14 years experience at the University Hospital, San Juan, Puerto Rico
Authors: Lopez-Enriquez A. T. 
Published: August 2020

e18006 Background: Acute promielocytic leukemias (APL) are a unique example in carcinogenesis, of maturation arrest at the promielocytic stage, associated with a chromosomal reciprocal translocation of a portion of chromosome 15 and 17 with the formation of fusion proteins between the PML gene and the alpha-retinoic acid receptor site. Methods: Since 1994 when transretinoic acid (ATRA) became available to us, we developed a protocol incorporating this drug to the standard regime of induction chemotherapy for acute leukemias used in our institution of 7 days of continuous infusion of cytosine arabinoside (Ara-C) and three days of daunorubicine (7+3), starting the ATRA on day 14 at 45 mg/m2 and continued daily for 120 days. Two to three more courses of consolidation with high-dose Ara-C, Ara-C with daunorubicine or daunorubicine alone where given. Results: We have treated 91 patients with APL since 1994 up to November 2008. Eighty-nine (89) patients received 7+3+ATRA. Nineteen of eighty-nine (19/89) died early in the first two weeks of treatment mainly secondary to bleeding and sepsis for a 21% early death rate. Sixty-seven of seventy (67/70) patients went into complete remission for a 98% rate. Four patients developed ATRA syndrome; three early pulmonary syndromes with one death, and the other two responded to steroids and went into remission. A fourth developed increased intracranial pressure two weeks on ATRA, resolved on steroids, Diamox, and continued on a lower ATRA dose. Fifty-three (53) has remained in complete remission with a range of 6months to 14 years, for a rate of 76%. Seventeen (17) patients or 25% (17/70) relapsed within the first 2 years of treatment. Thirteen of 17 (13/17) relapsed after receiving Dauno x3 x3 as consolidation chemotherapy for a 76% relapsed rate. Conclusions: The initial high early mortality needs to be addressed with a more aggressive support system. A 98% complete remission rate for induction chemotherapy is extraordinary, no ATRA syndrome when started on day 14 of treatment, reducing further morbidity and mortality. Daunorubicine as a single agent in consolidation is inappropriate in our population. No significant financial relationships to disclose.
MO19390 (SAiL): Incidence of thromboembolic events and congestive heart failure with first-line bevacizumab (Bv)-based therapy in advanced non-small cell lung cancer (NSCLC)
Authors: Pavlakis N. , Hirsh V. , Reck M. , Wu Y. , Dansin E. 
Published: August 2020

e19003 Background: MO19390 (SAiL) is a single-arm, multicenter, international trial evaluating the safety and efficacy of first-line Bv with standard chemotherapy in over 2,000 patients (pts). Methods: Key eligibility criteria were untreated locally advanced, metastatic or recurrent non-squamous NSCLC, ECOG PS 0–2, tumor not abutting major blood vessels, no uncontrolled HTN (systolic >150mmHg and/or diastolic >100mmHg) or active cardiovascular disease at baseline. Pts received Bv (7.5 or 15mg/kg) with standard chemotherapy for up to six cycles. Non-progressors proceeded to receive Bv until disease progression. The primary endpoint was safety, including the incidence of serious adverse events (SAEs) related to Bv, and the incidence of AEs of special interest. Results: Safety analyses (data cut-off July 2008) were based on 2,008 pts. Pts (%) were: male 60.1; stage IIIB/IV 19.5/80.5 (no data for 3 pts); adenocarcinoma/large cell/other 85.8/7.1/7.1; ECOG PS 0/1/2 38.1/56.1/5.8. 4.2% of pts were receiving anticoagulants at baseline. A total of 1,008 pts (50.2%) experienced at least one adverse event of special interest (all grades). Of these, 172 pts (8.6%) experienced an arterial or venous thromboembolism, which included pulmonary embolism (49 pts; 2.4%), deep vein thrombosis (40 pts; 2.0%), thrombophlebitis (26 pts; 1.3%), myocardial infarction (12 pts; 0.6%), cerebral hemorrhage (2 pts; 0.1%), cerebral ischemia (4 pts; 0.2%) and cerebrovascular accident (6 pts; 0.3%). 59 pts (2.9%) experienced congestive heart failure (CHF). Conclusions: The incidence of thromboembolic events and CHF was low in Bv-treated pts enrolled in the SAiL trial. These results, taken together with the overall safety analysis from the SAiL trial, confirm that Bv-based therapy has a well-established and manageable safety profile. Updated results will be presented. [Table: see text]
Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC)
Authors: Gadgeel S. M. , Wozniak A. , Edelman M. J. , Valdivieso M. , Heilbrun L. , Venkatramanamoorthy R. , Shields A. , LoRusso P. , Hackstock D. , Ruckdeschel J. 
Published: August 2020

e19007 Background: There are only limited data regarding the use of anti-VEGF therapy in recurrent NSCLC and no data in NSCLC pts previously treated with bevacizumab. We are currently conducting a phase II trial evaluating cediranib, an oral inhibitor of VEGFR 1,2 and 3, and pemetrexed in recurrent NSCLC pts who may or may not have previously received bevacizumab. Methods: Pts with progressive and measurable NSCLC, 1 or 2 prior regimens, PS0–2, all histologic sub-types, BP ≤ 140/90, treated brain metastases are eligible. Pts on anti-coagulants are allowed. Pts with hemorrhage within 4 weeks are excluded. Pts start on cediranib 30mg daily followed 7 days later by pemetrexed at 500 mg/m2 every 21 days and cediranib daily. The study consists of two cohorts- cohort A (no prior bevacizumab) and cohort B (prior bevacizumab). Planned accrual is 37 pts each cohort. Consenting pts will undergo FLT PET scans and blood draw for circulating tumor cells before therapy, 1 week after cediranib, and after 1 cycle of the combination. Results: 33 pts have started therapy, (Cohort A- 20, Cohort B- 13), median age- 60, males- 56%, ever smokers- 88%, adenocarcinoma- 64%, squamous- 12%, brain mets- 27%, 1 prior regimen- 52%, PS0–1- 88%. Median cycles- 4 (range- 0–15). Grade 3/4 toxicities- neutropenia- 7pts, febrile neutropenia- 1pt, fatigue-7pts, diarrhea- 3pts, hypertension- 1pt, anorexia- 2pts, cardiac ischemia- 1pt, bronchopleural fistula- 1pt, esophagitis- 1pt. No major hemorrhage. Of the 17 pts who received cediranib for ≥ 4 cycles, 71% required dose reduction and of the 18 pts who received pemetrexed for ≥ 4 cycles, 22% required dose reduction. 31 pts (Cohort A- 19, Cohort B- 12) are response evaluable. Confirmed response rate is 16%(90% CI- 0.08–0.30) (Cohort A- 10%, Cohort B- 25%) and disease control rate (response+stable disease) is 71% (90% CI-0.56–0.82) (Cohort A- 74%, Cohort B- 67%). 8 of 9 pts who had FLT PET scans had a 20% or greater decline in standard uptake value after 1 week of cediranib alone. Conclusions: Cediranib and pemetrexed combination is tolerable. Efficacy has been observed with the combination in recurrent NSCLC pts, including those previously treated with bevacizumab. Accrual to this trial is ongoing. [Table: see text]
Evidence for long-term survival in a sizeable proportion of good performance status (PS) patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Simon G. R. , Schell M. J. , Begum M. , Kim J. , Chiappori A. , Haura E. , Antonia S. 
Published: August 2020

e19016 Background: Approximately 40% of NSCLC pts present with metastatic disease where treatment is considered palliative. Here we examine whether prolonged survival is possible in a sizeable proportion of NSCLC pts with good PS and stage IV disease particularly given the availability of personalized chemotherapy approaches. Methods: NSCLC pts with stage IV disease and an ECOG PS of 0/1 were prospectively accrued to four phase II clinical trials, at the H. Lee Moffitt Cancer Center and treated with the following regimens; Trial A) carboplatin/gemcitabine first-line followed by docetaxel second-line, Trial B) docetaxel and gefitinib combination therapy in patients aged 70 years or older, Trial C) combination therapy with carboplatin/paclitaxel/atrasentan, Trial D) personalized therapy (PT) based on ERCC1 and RRM1. Pts with low RRM1/low ERCC1 received gemcitabine/carboplatin; low RRM1/high ERCC1, gemcitabine/docetaxel; high RRM1/low ERCC, docetaxel/carboplatin; high RRM1/high ERCC1, vinorelbine/docetaxel. Data were updated as of 10/23/08. Overall survival was estimated using the piecewise exponential survival function which showed a dramatic shift at 29 months. Results: A total number of 181 pts were accrued. The median survival for the entire cohort was 10.5 months improving dramatically to 85.3 months, if alive at 29 months (adjusted P = 0.005). In the entire cohort, 16.7% of pts survived to 29 months compared to 25% of pts in the PT group. For pts who were alive at 29 months, the probabilities of surviving to 48, 60, 72 and 84 months were 79%, 68%, 59% and 51%, respectively. Conclusions: Long term survival is possible in a sizeable proportion of stage IV NSCLC with good PS. Our treatment paradigm should shift from palliation to achieving long term survival. Molecularly-based PT may be one way of achieving this goal. No significant financial relationships to disclose.
Predictive scoring systems for brain metastasis at diagnosis and at recurrence in non-small cell lung cancer
Authors: Maunglay S. T. , Fulp W. J. , Chiappori A. , Simon G. R. 
Published: August 2020

e19020 Background: Brain metastasis (BM) is a major cause of mortality and morbidity in Non Small Cell Lung Cancer (NSCLC) but large studies analyzing potential factors that could be predictive of BM at diagnosis or recurrence are lacking. We have developed 2 predictive scoring models to identify the patients at risk. Methods: A retrospective analysis on 4,294 NSCLC cases, seen between 1994 and 2006, at the Moffitt Cancer Center and Research Institute, Tampa, FL was performed utilizing the cancer center's registry data. 477 (11.12%) patients had BM at the time diagnosis and additional 252 (5.82%) patients developed new BM as first recurrence. Results: For patients with BM at diagnosis, age younger than 63 years, non squamous histology and current or never smoking status were all significant in both univariate and multivariate analysis (N= 4174). Based on calculated odds ratios, a scoring system of 0 to 6 points was developed for these patients. Higher scores predicted higher risk for BM (0- 2=3.38%, 3- 4=9.93%, 5=13.65% and 6=21.03%; p <.0001). For patients with new BM at first recurrence, age younger than 63 years, non squamous histology, and the stage at diagnosis (i.e., BM risk in stage III>IV>II>I), were all significant in both univariate and multivariate analysis (N=4291). Based on calculated odds ratios, a scoring system of 0 to 7 points was developed for these patients. Higher scores predicted higher risk for BM (0–1=3.38%, 2–3=4.72%, 4–5= 8.76%, and 6–7=11.83%; p<.0001). Similar risk percentage results were seen after testing the 2 scoring systems in 3 chronologically divided patient groups. Conclusions: The 2 scoring systems developed based only on clinical data were predictive of BM in NSCLC at diagnosis and recurrence. These scoring systems should be helpful for establishing initial and follow up cranial imaging schedules in NSCLC patients. [Table: see text] No significant financial relationships to disclose.
Safety of bevacizumab (B) and erlotinib (E) therapy in patients (pts) with treated brain metastases (mets) in the phase III, placebo (P)-controlled, randomized BeTa trial for pts with advanced non-small cell lung cancer (NSCLC) after failure of standard first-line chemotherapy
Authors: Otterson G. A. , O’Connor P. G. , Lin M. , Herbst R. S. ,   for the BETA Lung Investigators
Published: August 2020

e19025 Background: Bevacizumab (B) + carboplatin/paclitaxel received FDA approval in 10/06 for improving survival in first-line treatment of advanced NSCLC patients (pts). In the past, pts with brain mets had been excluded from trials of B due to concerns about the possibility of CNS hemorrhage. We report on the safety of B therapy in combination with E in a subset of pts with treated brain mets who enrolled in the BETA lung study for NSCLC. Methods: Pts in the subset had recurrent advanced stage NSCLC. Their disease at enrollment included brain mets previously treated with whole brain radiation therapy. Neurosurgery and stereotactic radiosurgery were permissible in addition to WBRT. Patients with an ongoing requirement for dexamethasone treatment and those who had previously been treated with anti-angiogenesis or epidermal growth factor receptor-targeted therapy were not eligible. Pts were treated with E+B or E+P. E dosing was at 150 mg daily; B/P dosing was 15mg/kg intravenous every (q) 3 weeks. Responses were evaluated q 6 wks until wk 24 and every 12 wks thereafter. Treatment continued until disease progression. Results: 68 pts with brain metastases were enrolled between June 2005 and April 2008. 37 pts received E+B and 31, E +P, with median treatment durations of 2.6 and 2.7 months respectively. No CNS hemorrhages or Gr 3+ bleeding events were reported among these pts. 3 Gr 3–4 nervous system adverse events (AE) were reported in each arm. One convulsion, one case of memory impairment and one case of toxic encephalopathy was reported in the E+P arm and a case of ataxia, headache, and cerebral ischemia were reported in the E+B arm. Conclusions: 37 pts with previously treated brain mets were treated with E+B in the BETA study. No CNS hemorrhages were reported in this subset and no new safety signals identified. The treatment duration for subjects with metastasis was equivalent in the E+B and E+ P arms. These data suggest an acceptable safety profile for the subset of patients with brain mets treated with B in the BETA lung study. [Table: see text]
First-line cisplatin (P) with docetaxel (TXT) or vinorelbine (VNR) in patients with advanced non-small cell lung cancer: A randomized phase II trial of the Gruppo Oncologico Italia Meridionale
Authors: Gebbia V. , Galetta D. , Lorusso V. , Caruso M. , Riccardi F. , Maiello E. , Borsellino N. , Ferraù F. , Colucci G. , Cinieri S. 
Published: August 2020

e19042 Background: P-based doublets are considered standard therapy for advanced NSCLC. The GOIM consider P/VNR as a reference treatment. P/TXT doublet has been reported to be active but it's not well known its real impact on QoL in comparison to P/VNR. Methods: Pts received either 6 courses of P/TXT or P/VNR with QoL and safety being the primary endpoints. Secondary endpoint included response rate, TTP, OS, and tolerability. Patients with stage IV/IIIB, age ≤70, and ECOG PS 0–1, were eligible. Sample size was calculated according to Fleming's single-stage procedure. QoL was analysed using the EORTC questionnaire, responses and toxicity according to the RECIST and NCI-CTC criteria. Pts were randomized to: TXT 75 mg/m2 over 60 min followed by P 75 mg/m2 on d1 every 21 d, or VNR 30 mg/m2 on d 1,8 and P 80 mg/m2 on d1 every 21 d. Results: From 12/06 to 3/08 86 pts were enrolled: P/TXT 42pts, M/F 32/10, IIIB/IV 8/34, squamous/not-squamous:13/29, median age 61 (r 41–70); P/VNR 44 pts, M/F 35/9, IIIB/IV 10/33, squamous/not-squamous 14/30, median age 62 (r 44/70). No statistically significant differences were observed in QoL among the two arms. Detailed analysis of side-effects showed no difference among the two regimens with the exception of G3–4 neutropenia and leukopenia with were slightly higher in the P/VNR arm (p=0.02 and p=0.0005 respectively). The use of G- CSF/darbopoietin was more frequent in pts treated with P/VNR than in the P/TXT arm (p=0019). Conclusions: Final data show an equivalence among the two arms regarding QoL and activity but with a slightly more hematological toxicity in the P/VNR arm. Both regimens are to be considered as standards in the treated of advanced NSCLC. [Table: see text]
Development of cavitation while on bevacizumab (BV) therapy in patients (pts) with non-small cell lung cancer (NSCLC): Results from ARIES—A bevacizumab (BV) treatment observational cohort study (OCS)
Authors: Kosty M. P. , Kumar P. , Wozniak A. , Jahanzeb M. , Chung C. , Wang L. , Sing A. , Lynch T. ,   for the ARIES Investigators
Published: August 2020

e19045 Background: BV (Avastin), an anti-VEGF monoclonal antibody, prolongs progression-free and overall survival in advanced NSCLC pts. Severe (≥grade 3) pulmonary hemorrhage (sPH) is a rare but serious event that has been associated with BV-based therapy in phase 3 trials (rate of 2–4%). Potential risk factors include squamous histology, prior history of hemoptysis, and presence of tumor cavitation. Rates of baseline (BL) cavitation in NSCLC pts and development of cavitation on BV therapy are unknown. Pts in ARIES, an OCS of approximately 2,000 pts with NSCLC, had BL scans assessed for tumor cavitation. A substudy of approximately 250 pts also had follow-up scans to analyze the likelihood of developing cavitation on BV therapy. For the entire ARIES population, any pt developing sPH is assessed for tumor cavitation. Methods: Pts at specified ARIES sites submitted on-treatment CT scans to an independent review facility (IRF), in addition to BL scans. Evaluable pts had measurable disease at BL and at least one-post-BL scan. Correlations between cavitation (pre-existing or developing on-study) and clinical, tumor and treatment characteristics are evaluated using a chi-squared test or t-test. Incidence of sPH based on cavitation status will be assessed using Fisher's exact test. Results: As of 9/15/08, 210 pts had a post-BL CT scan reviewed by the IRF. Of these pts, 171 had measurable tumors at BL. For the 171 pt cohort: median F/U is 9.2 m; 99% have ≥1 quarterly update. Key BL characteristics for the substudy and overall cohorts, respectively, include: 44% vs 51% ≥65 yrs; 67% vs 67% adenocarcinoma; 6% vs 5% therapeutic AC. BL radiographic features: 41% vs 39% presence of central tumor; 13% vs 15% presence of cavitation. In substudy pts, there is 1 sPH to date in a pt without baseline cavitation. Conclusions: sPH is a rare, potentially serious event in pts with NSCLC receiving BV. Whether cavitation (BL or developing on-treatment) is associated with an increased risk of sPH has not been defined. The final analysis of an ARIES Lung substudy assessing on-study development of cavitation and association with sPH will be presented at the meeting. [Table: see text]
A prospective evaluation of quality of life (QOL) in a phase II trial of pemetrexed (P) plus carboplatin (Cb) ± enzastaurin (E) versus docetaxel (D) plus Cb as first-line treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Raju R. N. , Socinski M. , Stinchcombe T. , Couch L. S. , Kocs D. M. , Jotte R. , Wang Y. , Bromund J. , Marciniak M. , Obasaju C. 
Published: August 2020

e19050 Background: E is a selective, oral serine/threonine kinase inhibitor. PCb has shown promising clinical activity in two phase 2 trials of advanced NSCLC. This open-label, three-arm trial was designed to assess PCb ± E versus a control arm of DCb. QOL may be an important consideration with the introduction of targeted agents such as E that have a different toxicity profile than traditional chemotherapeutic agents. Methods: Pts with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, and no prior systemic therapy were enrolled. Pts were equally randomized to one of three arms: (A) P 500 mg/m2 and Cb AUC 6 every 3 wks X 6 cycles with E given orally as a loading dose of 1200 mg or 1125 mg followed by 500 mg daily until disease progression; (B) The same regimen of PCb without E; or (C) D 75 mg/m2 and Cb AUC 6 every 3 wks X 6 cycles. Pts receiving P were also administered folic acid, vitamin B12 and steroid prophylaxis. Pts on D also received steroid prophylaxis. The Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire and FACT-Taxane toxicity subscale were used to evaluate QOL at baseline and every 3 weeks up to 18 weeks during treatment. A best overall response of improved or worsened was defined as an increase or decrease from baseline to last patient visit of ≥ 0.5 standard deviations of baseline scores. Results: The intent-to-treat population of this study consisted of 218 randomized pts (PCE: 72, PC: 74, DC: 72). Baseline and ≥ 1 post-baseline score was obtained from 54 pts receiving PCE (75%), 62 pts receiving PC (84%), and 54 pts receiving DC (75%). QOL data are summarized in the table below. Conclusions: Across treatment groups, differences in mean scores were not statistically significant. In addition, differences in classification of improved, stable, or worsened were not statistically significant across treatment groups. [Table: see text] [Table: see text]
Wood-smoke exposure (WSE) as a predictor of response and survival in erlotinib-treated advanced lung adenocarcinoma (ALA) patients (pts) (ONCOLGroup study)
Authors: Castro C. , Cardona A. F. , Reguart N. , Carrasco-Chaumel E. , Otero J. M. , Carranza H. , Vargas C. , Reveiz L. , Torres D. , Blumenschein G. 
Published: August 2020

e19052 Background: There is consistent information suggesting that long-term WSE constitutes a risk factor for lung cancer. More than 50 years of WSE was associated with non-small cell lung cancer (NSCLC). In Colombia the prevalence of WSE in areas having less economic development is approximately 24%. The aim of the study was to evaluate WSE as a predictor of response and survival in ALA pts. Methods: This study included 168 pts with ALA treated between 2002 and 2007 in four referring hospitals of Bogotá. Retrospectively, we estimated overall response rates (ORR), time to progression (TTP) and overall survival (OS) in a subgroup of pts with significant WSE (exposure >5 years for at least 4 hours/day) treated with erlotinib, and compared them with the non-WSE population treated with the same compound. Results: Median age was 66 years (range, 29–96), 53% were female, 39% had never been smokers, 24% of all cohort pts had been considerably exposed to WS and 45 pts had received erlotinib during disease treatment (as 2nd or 3rd line). Sixteen of these pts (F11/M5, PS ≥70% 9 pts) had been exposed to WS and 29 not so (F17/M12, PS ≥70% 22 pts); 10 pts having WSE had been smoking for a mean of 14pk/yr history. ORR to erlotinib was 7% and 32% in pts with and without WSE respectively (p = 0.02). TTP was significantly higher in pts treated with erlotinib with no history of WSE (4.9 mo. vs 1.7 mo., p = 0.034). and in those who had received this compound as second-line (vs erlotinib used as third line, p = 0.044). Among pts with WSE history, OS was 6.6 mo. (range, 5.8–7.3) for those treated with Erlotinib and 12.7 mo. (range, 10.2–17) for those not treated with this compound (p = 0.04). Multivariate analysis was carried out for determining the factors influencing mortality between pts with WSE; only PS (HR: 4.6, 95%CI: 1.2–29, p = 0.050) and gender (HR: 3.6, 95%CI: 2.7–18, p = 0.036) were significant. Conclusions: WSE was associated with a poorer response and survival in ALA pts treated with erlotinib in Colombia. No significant financial relationships to disclose.