bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim results of protracted low doses of temozolomide in high-risk acute myeloid leukemia
Authors: Medeiros B. C. , Gotlib J. R. , Coutre S. E. , Jones C. , Khan S. A. , Rajwanshi R. , Rajwanshi R. , Zehnder J. , Zehnder J. 
Published: August 2020

7052 Background: High treatment-related mortality and low response rates often discourage elderly patients with acute myeloid leukemia from receiving treatment. Previous data demonstrate that only patients lacking expression of O6-alkylguanine-DNA alkyltransferase (AGAT) in leukemic blasts are sensitive to temozolomide. Protracted exposure to low doses of temozolomide can significantly inhibit AGAT enzymatic activity. Methods: Phase II clinical trial of tailored temozolomide therapy to high-risk AML patients according to AGAT methylation promoter status. Patients demonstrating evidence of AGAT promoter methylation were stratified to conventional doses of temozolomide at 200 mg/m2 orally x 7 days. Patients demonstrating lack of AGAT promoter methylation (unmethylated) received protracted doses of temozolomide (100 mg/m2 orally x 14 days) followed by conventional doses of temozolomide. Patients who achieved CR were given up to 5 consolidation treatments. Results: Fifteen patients have completed treatment to date. The median age was 78 (68–83) and nine were male. De novo AML was diagnosed in eight patients and five patients had s-AML. Nine patients had a normal karyotype and three patients had a complex karyotype. Two patients had only a NPM1 mutation and one had NPM1mut/FLT3-ITD. In 13 patients, the AGAT promoter was found to be unmethylated. AGAT protein was present in 5/11 patients. All patients had an intact mismatch repair pathway. Thirteen patients had HCT-CI scores of 0–2. Six patients (6/13) achieved a complete remission (CR) after 1 cycle of therapy (1/2 for patients with methylated and 5/11 for patients with unmethylated AGAT promoter). Nonhematologic toxicities were minimal. Drug-related hematologic toxicities were difficult to distinguish from disease-related cytopenias. Three patients remain in CR with a median duration of 22 weeks (14–36 weeks). Seven patients have died from disease progression, while two patients died of neutropenic sepsis (early deaths). With a median follow-up of 38 weeks (10–48), the median overall survival for the entire population is 12 weeks (3.5 - 38) weeks (responders 26.5 weeks). Conclusions: These preliminary results suggest that temozolomide therapy may be individually tailored to elderly patients with AML according to AGAT promoter status. [Table: see text]
Phase I study of pemetrexed in patients with relapsed or refractory acute leukemia or lymphoid blast phase chronic myelogenous leukemia
Authors: Plunkett W. , Thomas D. A. , O'Brien S. M. , Federl S. , Giles F. J. , Nicol S. J. , Gill J. , Zhao L. , Ravandi F. , Kantarjian H. 
Published: August 2020

7068 Background: Pemetrexed is a folate antimetabolite that is clinically active in a number of different cancers. The purpose of this phase I trial was to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of pemetrexed given with vitamin supplementation to patients with relapsed or refractory leukemia. Secondary objectives were pharmacokinetic (PK) and pharmacodynamic (PD) analyses of pemetrexed. Methods: Patients ≥15 years of age were enrolled with relapsed or refractory leukemia, Eastern Cooperative Oncology Group performance status ≤2, adequate renal and hepatic function, and life expectancy of ≥6 weeks. Enrollment was planned using a 3+3 dose escalation design. Intravenous pemetrexed was given at a starting dose of 900 mg/m2 over 1 hour every 3–4 weeks. Doses were escalated to 1,200, 1,500, 2,000, 2,700, and 3,600 mg/m2. Folic acid and Vitamin B12 were given with pemetrexed. Response was assessed by standard blood and bone marrow criteria. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0. Results: Twenty-two patients entered the trial; median age was 50 years (range: 18–75); 15 patients had acute myeloid leukemia and 7 patients had acute lymphocytic leukemia (ALL). Two patients were ineligible and did not receive study drug. At the 1,200 and 1,500 mg/m2 dose levels, 1 patient per level developed grade (G) 3–4 liver enzyme and bilirubin elevations attributed to sepsis. At the 3,600 mg/m2 dose level, 1 patient had a G3 liver enzyme elevation and 2 added patients also had G3 liver toxicity. In addition, 2 patients in the 3,600 mg/m2 cohort developed G2 liver abnormalities. Based on liver toxicities, the DLT dose level was established at 3,600 mg/m2. Two patients died during the study due to disease progression and 1 patient discontinued due to a subdural hematoma of unknown cause. One patient with ALL achieved a partial response. There were no other objective responses. PK and PD data were not available for this report. Conclusions: The MTD and RP2D of pemetrexed were determined to be 2,700 mg/m2. Due to limited observed efficacy, a planned phase II trial was canceled. [Table: see text]
Phase II trial of old age acute myeloid leukemia treatment by arsenic trioxide and low-dose subcutaneous cytosin arabinoside
Authors: Ghavamzadeh A. , Hashemi S. , Alimoghaddam K. , Nasri Moghaddam Z. , Shadpour M. , Jalili M. 
Published: August 2020

7075 Background: AML is a disease of old age, but unfortunately due to several factors standard treatment can not be delivered to these patients. Here we tried to achieve to bet possible response to these patients. Methods: Eleven old age patients selected for this trial. Patients couldn't tolerate standard treatment of AML due to old age or comorbid disorders. Treatment consist of best supportive care plus administration of low dose ARA-C (20mg/day as SQ) for 10 days each months and arsenic trioxide 10 mg/day as 2 hour iv infusion each month. Patients followed by CBC and BMA/B when peripheral blood normalized or every other month. Results: This cohort consist of 8 men and 3 women. Median age was 75 y/o (55–80). Median WBC count Hb level and platelet count at presentation were 42,860μl, 8.3g/dl and 30,500/μl, respectively. Complete remission observed in 6 and partial remission in one patient (RR = 63.6%), but remission was short live, after 6 months one patient was in CR and one in PR. After 12 months, only one patient was in PR. Median survival was 6 months and 6 patients survive more than 6 months. Two patients are alive after 12 months. Conclusions: Although prognosis of old age AML remain poor, but with this type of treatment RR is acceptable. In this very high-risk group of very old AML, combination of ATO and ARA-C possibly could improve survival. No significant financial relationships to disclose.
Role of serum erythropoietin, erythropoietin-independent erythroid colony formation, and bone marrow assessment in the diagnosis of polycythemia vera in patients with JAK2 V617F mutation
Authors: MacKenzie-Feder J. M. , Eaves C. , Lambie K. , Abdi-Ali A. , Ramadan K. M. , Young S. , Horsman D. , Galbraith P. , Eaves A. , Foltz L. 
Published: August 2020

7085 Background: The discovery of the JAK2 V617F mutation in over 95% of polycythemia vera (PV) patients has led to the development of the new 2008 World Health Organization diagnostic criteria for PV. These specify a requirement for an elevated hemoglobin (Hb, males: >185 g/L, females: >165 g/L) and either evidence of JAK2-mutant cells plus any one of the following minor criteria: a below normal level of serum erythropoietin (Epo), detectable Epo-independent erythroid colony (EEC) formation in vitro, or panmyelosis in the bone marrow, or two of the latter in the absence of detectable JAK2-mutant cells. However, in patients with an elevated Hb and JAK2V617F positivity, there are few data to determine whether any of the 3 minor criteria actually add an independent contribution to the diagnosis of PV. Methods: We performed a retrospective chart review of 77 patients who had an elevated Hb and were positive for the JAK2 V617F mutation and who also had a test for at least one of the 3 minor criteria (serum Epo level: n = 53; EEC formation: n = 66; bone marrow examination: n = 16) to determine the frequency of cases who might lack one or more of these. Results: Although the number of patients with a complete set of data was limited, the results, nevertheless, were sufficient to show that all 3 minor criteria were highly represented and all 77 of the patients analyzed (100%) were positive for at least one of them; i.e., 47 of 53 tested (89%) had a reduced serum Epo level; 65 of 66 tested (98%) had EECs and 15 of 16 tested (94%) had evidence of bone marrow panmyelosis. Conclusions: Neither the Epo level, nor the presence of EECs nor evidence of bone marrow panmyelosis provided additional diagnostic specificity in a population of 77 patients with both JAK2 V617F-positive cells and an elevated Hb. Consideration should be given to limiting serum Epo, EEC, and bone marrow assessments to JAK2 mutant-negative patients. No significant financial relationships to disclose.
Comparative efficacy of reduced or standard doses of lenograstim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantation
Authors: Ozturk M. , Arpaci F. , Ataergin S. , Ozet A. , Cetin T. , Kuzhan O. , Ozturk B. , Kilic S. , Komurcu S. , Guler T. , Budakoglu B. 
Published: August 2020

7099 Background: 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. However,in our previous randomized study we demonstrated that a 7.5 microg/kg/day dose of lenograstim has been as efficacious as 10 microg/kg/day of filgrastim. In this study, we investigated whether a reduced dose of lenograstim is equavalent to standard dose for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. Methods: A total of 49 consecutive patients were randomized to either low dose (7.5 microg/kg/day, n = 24) or standard dose (10 microg/kg/day, n = 25) of lenograstim. These two groups were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each dose of lenograstim was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, lenograstim was given at 5 microg/kg/day until leukocyte engraftment. Results: Successful mobilization with the first apheresis, was achieved in 10/24 (42%) patients in low dose group versus 14/25 (56%) patients in standard dose group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Conclusions: Lenograstim 7.5 microg/kg/day is as efficious as Lenograstim 10 microg/kg/day for autologous PBSC mobilization and transplantation. No significant financial relationships to disclose.
Impact of number of resected and involved lymph nodes (LN) at the time of surgical resection on the survival of non-small cell lung cancer (NSCLC)
Authors: Saji H. , Tsuboi M. , Miyajima K. , Shimada Y. , Ohira T. , Ikeda N. 
Published: August 2020

7514 Background: Total number of lymph-nodes has recently proven prognostic in early breast and colorectal cancer. In this study we retrospectively evaluated the prognostic impact of the number of resected and involved lymph-nodes on the survival of stage I-III NSCLC. Methods: A series of 928 consecutive NSCLC pts who underwent complete lobectomy, bilobectomy or pneumonectomy with lymph-nodes dissection from 1/2000 to 11/2007 at Tokyo Medical University was eligible. Log rank and Cox proportional hazard model was used to estimate survival rates and relative risks. Results: Demographics are as follows: median age: 65.0 (22–87yrs), sex: 547 males and 381 females, median follow-up time: 2.5 yrs, clinical stage: 765 stage I, 84 stage II and 76 stage III, histology: 684 adenocarcinoma, 182 squamous cell carcinoma, and 62 others, operation: 870 lobectomy, 42 bilobectomy and 16 pneumonectomy, mean number of resected LN: 15 (1–49), mean number of involved LN: 0.9 (0–22). We observed a statistically significant increasing trend in overall survival (OS) between 0–3 and 4 and more of number of involved LN (P<0.001). Although a significant increasing in OS of 0–9 of number of resected LN cases compared with 10 and more was observed in all stages (P=0.024), no significant differentiation was observed in clinical stage I cases. Conclusions: This data suggests that there is a significant decrease in OS with 10 and more number of resected LN examined at surgery in NSCLC pts. However, there is no significant different in stage I pts, which implies that selected LN sampling is enough in clinical stage I cases. Further study such as LN dissection vs LN sampling in clinical stage I will be needed. No significant financial relationships to disclose.
CALGB 140803—Association between cardiorespiratory fitness and overall survival in operable lung cancer patients: Ancillary analysis of protocol 9238
Authors: Kohman L. , Watson D. , Herndon J. , Eves N. , Haithcock B. , Loewen G. , Jones L. 
Published: August 2020

7518 Background: Cardiorespiratory fitness is a well-established independent predictor of all-cause mortality in a broad range of adult populations. The association between cardiorespiratory fitness and mortality has not been investigated among individuals diagnosed with cancer. We examined the association between cardiorespiratory fitness and all-cause mortality in 398 patients with non-small cell lung cancer (NSCLC). Methods: Using a prospective, observational design, patients with known or suspected NSCLC enrolled in CALGB 9238 were studied. Prior to pulmonary resection, all participants performed an incremental exercise test with expired gas analysis to assess cardiorespiratory fitness (i.e., peak oxygen consumption; VO2peak) and were observed for death or until June 2008. Cox proportional hazards models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO2peak (<0.96 / 0.96–1.29 / >1.29 L.min-1) with adjustment for age, gender, and performance status. Results: Of the 398 patients, 335 underwent surgical resection and 63 were deemed not eligible for resection. Median follow-up was 30.8 months, 294 deaths were reported during this period. For the entire sample, mortality rates declined across increasing VO2peak categories (adjusted Ptrend= 0.012). Compared with patients achieving a VO2peak <0.96 L.min-1, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% CI, 0.46 to 0.88) for a VO2peak of 0.96–1.29 L.min-1, and 0.56 (95% CI, 0.39 to 0.80) for a VO2peak of >1.29 L.min-1. The corresponding HRs for surgical patients were 0.65 (95% CI, 0.44 to 0.96) and 0.62 (95% CI, 0.42 to 0.90) relative to the lowest VO2peak category (ptrend=0.03), respectively. For non-surgical patients, the HRs were 0.74 (95% CI, 0.32 to 1.75) and 0.43 (95% CI, 0.18 to 1.00) relative to the lowest category (ptrend<0.04). Conclusions: Low VO2peak is associated with poorer survival among surgical candidates with NSCLC. Further work is required to investigate the prognostic value of objective measures of functional capacity in NSCLC and other cancer populations. No significant financial relationships to disclose.
Biomarker analysis from completely resected NSCLC patients enrolled in an adjuvant erlotinib clinical trial (RADIANT)
Authors: Richardson F. , Richardson K. , Sennello G. , Young D. , Orlov S. , Pápai-Székely Z. , Keshavjee S. , Kim J. , Cerfolio R. , Shepherd F. A. 
Published: August 2020

7520 Background: RADIANT is a phase III trial comparing erlotinib 150 mg daily vs. placebo (2:1) in stage IB-IIIA NSCLC patients with EGFR-positive tumors (IHC and/or FISH), following complete surgical resection. Planned accrual is 945 patients. Correlative biomarker studies on primary tumor tissue, whole blood, and serum are key components of the study. Methods: Tumor tissue was evaluated by IHC for protein expression of EGFR (PharmDx Kit, Dako with + ≥ 1% positive tumor cells), by FISH for gene expression of EGFR (Vysis, Abbott), and by Wave HS for EGFR and Kras mutations. Results: Among 655 tissue samples analyzed, 96% were EGFR IHC+ and 74% EGFR FISH+. Of the 476 tissue samples analyzed to date for mutations (mut), 12% had activating EGFR and 19% had Kras mut. Preliminary comparisons suggest that EGFR mut rate increased while Kras mut rate decreased with tumor stage. EGFR mut occurred in 29/178 (16%) females (F) vs. 23/271 (8%) males (M), 19/57 (33%) Asians (A) vs. 33/392 (8%) non-Asians (NA), and 29/66 (44%) never smokers (NS) vs. 23/383 (6%) current or former smokers (S). The differences between A vs. NA and NS vs. S were significantly different (P <0.0001) for all comparisons made. Kras mut occurred in 40/180 (22%) F vs. 48/280 (17%) M, 4/57 (7%) A vs. 84/403 (21%) NA, and 3/68 (4%) NS vs. 85/392 (22%) S. The difference between A vs. NA and NS vs. S were significantly different (P ≤0.0389) for all comparisons made. In adenoca, 51/254 (20%) had EGFR and 79/261 (30%) had Kras mut, and in SCC, 0/157 (0%) had EGFR and 3/162 (2%) had Kras mut. One tumor sample demonstrated both an activating EGFR and Kras mut. Conclusions: Ongoing comprehensive biomarker assessment in the RADIANT population indicates successful sample collection and analysis. FISH positivity rates are greater than observed in late-stage tumors. Remaining results in this early-stage population are consistent with those observed in advanced-stage disease. Once complete, this study will provide a robust biomarker dataset on which to evaluate predictive and prognostic response markers, which may help determine who may benefit from treatment with erlotinib in the adjuvant setting. [Table: see text]
Randomized trial of adjuvant chemotherapy (Cx) with cisplatin plus gemcitabine (CG) versus cisplatin plus docetaxel (CD) in patients (pts) with completely resected non-small cell lung cancer (NSCLC) with quality of life (QoL) as the primary objective
Authors: Barlesi F. , Chouaid C. , Crequit J. , Lecaer H. , Pujol J. , Bérard H. , Vergnenegre A. , Letreut J. , Fabre-Guillevin E. , Loundou A. 
Published: August 2020

7532 Background: Adjuvant Cx with vinorelbine plus cisplatin (VC) improves survival of resected NSCLC but has an immediate negative impact on QoL (Bezjak, JCO 2008). In advanced stages NSCLC, GC and DC have comparable efficacy and might be superior to VC in QoL outcomes. This trial was designed to provide with data on other adjuvant Cx regimens for pts with resected NSCLC. Methods: Pts with stage IB to III resected (R0) NSCLC, without major postoperative complication, were eligible. Surgery has to be standardized. Cx consisted of cisplatin (75 mg/m2, D1) plus gemcitabine 1,250 mg/m2 (D1,8) or docetaxel (75 mg/m2 D1) for 3 cycles. The primary endpoint was QoL (EORTC QLQC30) and the trial was designed to detect a 10 points difference in QoL scores (α=0.05; power 80%). Relapse-free survival, overall survival (OS), safety profile and costs were the secondary endpoints. Results: 136 pts (median age: 57 yrs, 74% males, pTNM: 32% IB, 34% II, 34% III; histology: 55% ADC, 23% SCC) were included. 67 and 69 pts were randomized in the GC and DC arms, respectively. Surgery was a (bi)lobectomy in 85% of cases. No imbalance was found between arms regarding major pts characteristics. Overall, a Gr3/4 hematological toxicity occurs for 33.8% and 21.7% of pts (p=0.11) and a Gr3/4 non-hematological toxicity occurs for 33.8% and 26.1% of pts (p=0.33), in the GC and DC arms. Compliance to QoL assessment was good (93%). At inclusion, global health status (GHS) scores (/100) were comparable between arms (mean score, 63.5 and 62.7, in the GC and DC arms, p=0.8). At the end of treatment (3rd month), GHS scores have slightly improve (mean score, 64.5 and 65.4, in the GC and DC arms, p=0.8). At the time of analysis, 15 pts (7 GC, 8 DC) have died. At 1 year, 100 and 96.8% of the pts were alive in the GC and DC arms; At 2 years, 92.9 and 89.8% of the pts were alive in the GC and DC arms (log-rank, p=0.88). Conclusions: Adjuvant GC and DC have comparable effect on post-operative QoL and equivalent efficacy among pts with resected NSCLC. The GC and DC efficacy, safety profiles and QoL outcomes favorably compare with the results reported for the VC regimen. Detailed analyses will be presented at the meeting. [Table: see text]
A phase I study of pemetrexed plus carboplatin or cisplatin with concurrent chest radiation therapy (CRT) for patients with locally advanced non-small cell lung cancer (LANSCLC)
Authors: Heinzerling J. H. , Hughes R. S. , Govindan R. , Bradley J. D. , Schiller J. , Peng G. , Treat J. , Obasaju C. , Tran T. , Choy H. 
Published: August 2020

7545 Background: Pemetrexed is a multi-targeted antifolate that inhibits the synthesis of both pyrimidines and purines. Pemetrexed is an effective new chemotherapeutic agent in advanced non-small cell lung cancer. Pemetrexed has also shown preclinical activity as a radiosensitizer in lung cancer. A phase I study was performed to establish the maximum tolerated dose (MTD) and phase 2 dose of carboplatin or cisplatin given with pemetrexed and CRT in LANSCLC. Methods: Patients (pts) with LANSCLC were enrolled. Initial intent was to establish the MTD of both weekly cisplatin and weekly carboplatin in combination with pemetrexed and CRT as an alternating two-arm phase I trial. Subsequently and based on early results from the CALGB 30407 trial (also evaluating the MTD of carboplatin), the protocol was amended to establish the safety of the planned phase II doses of cisplatin and carboplatin combined with pemetrexed 500 mg/m2 and given every 3 weeks with concurrent CRT. Dose limiting toxicity (DLT) was defined as ≥ Grade 3 hematologic or nonhematologic toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD was determined by occurrence of 2 DLTs among 6 pts in each cohort. Results: 22 pts were enrolled on 3 cohorts. All pts received pemetrexed, 9 with carboplatin AUC=2, 9 with cisplatin 30 mg/m2, and 4 with cisplatin 75 mg/m2. One DLT occurred in each of the carboplatin and cisplatin 30 mg/m2 cohorts, prompting enrollment of 3 additional patients. No DLTs were seen in the cisplatin 75 mg/m2 cohort. Conclusions: The MTD of cisplatin in combination with pemetrexed and CRT was not reached. Based on these results and those from CALGB 30407, either carboplatin AUC=5 or cisplatin 75 mg/m2 in combination with pemetrexed 500 mg/m2 given every 3 weeks with CRT appears to be well tolerated, and are currently being studied in a randomized phase II trial in pts with LANSCLC. [Table: see text]