bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of cladribine (2-CdA) and rituximab in patients with CLL and SLL: Preliminary report of a single institution
Authors: Bertazzoni P. , Laszlo D. , Gigli F. , Bassi S. , Calabrese L. , Saronni L. , Quarna J. , Alietti A. , Cocorocchio E. , Martinelli G. 
Published: March 2020

7093 Background: Byrd et al (Blood 2003) confirmed the synergistic effect of Rituximab and Fludarabine in the treatment of CLL patients (pts). The choice of purine analogue still remains controversial. We evaluated feasibility, efficacy, and toxicity of 2-CdA-Rituximab combination in the treatment of CLL and SLL pts requiring treatment. Methods: The combination therapy consisted of intravenous Rituximab at a dose of 375 mg/m2 on Day 1 and 2-CdA at a dose of 0.1 mg/kg (sc injection) per day on Days 2 through 6. The course was repeated at 4-week intervals for 4 times. 31 pts (21 CLL and 10 SLL) was enrolled in the study and the median age was 59 years (31–73); 42% of pts were pre-treated. A CT scan was abnormal in 95% of CLL pts. Immunophenotypic evaluation by ZAP-70 was positive in 70% of pts while no evaluable pts showed an adverse prognostic cytogenetic features by FISH. Minimal residual disease (MRD) assessment was performed by flow-cytometry and PCR methods. Results: 2 pts had to discontinue therapy after 2 cycle: one due to herpes zoster reactivation and the other one to the progression disease (PD). We observed grade 3 and 4 neutropenia in 4 pts (12%), major infections in 4 pts (12%) and no episodes of grade 3–4 thrombocytopenia. 24 pts were evaluable for response with an ORR of 96%. At the end of therapy 10 pts (42%), 7 CLL and 3 SLL, achieved a CR, with negative MRD (by PCR) in 4 pts (3 untreated); 13 pts (54%) obtained a PR and 1 patient had no response. With a median follow-up of 12 months (range 3–34) 7 pts (2 pts with MRD+CR and 5 pts with PR after treatment) experimented a PD; 5 of these pts were pre-treated and 2 died because of PD. Conclusions: The combination of 2- CDA and Rituximab seems to be tolerable and active principally for untreated pts and able to induce a molecular clearance also in pre-treated pts. The achieving of a CR with negative MRD seems to be the most important issue to improve the outcome. No significant financial relationships to disclose.
Assessing the impact of comorbidities on autologous hematopoietic cell transplant (AHCT) outcomes using the hematopoietic cell transplant-comorbidity index (HCT-CI) in lymphoma
Authors: Kassar M. , Gregory S. A. , Shell K. , Venugopal P. , Shammo J. , Farhat M. I. , Batus M. , Law A. , Fung H. C. 
Published: March 2020

7102 Background: Sorror et al. has identified HCT-CI as a valid scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival after allogeniec HCT. We recently reported on the validity of HCT-CI in predicting morbidity outcomes after AHCT for lymphoma (BBMT in press). High HCT-CI score predicted for prolonged hospitalization and high incidence of hospital re-admission after AHCT. The objective of this study is to evaluate the impact of HCT-CI on mortality risk after AHCT. Methods: We included pts above age of 40 with advanced HL or NHL, who underwent AHCT in our institution between 01/98 & 05/06. Median follow up was 29.4 mo. Pts were assigned scores based on the HCT-CI. Defenition of comorbidities were recently reported (Kassar et al, BBMT in press). Results: 80 pts were included (NHL: 74, HL: 6). 61 pts were male. Median age was 56 years (42–76). Comorbidities (points, prevalence%): mild hepatic (1,14), cardiac (1,15), cerebrovascular (1,4), arrhythmia (1,9), moderate pulmonary (2,11), severe pulmonary (3,8), rheumatologic (2,5), DM (1,23), inflammatory bowel disease (1,3), psychiatric (1,11), infection (1,6), obesity (1,11), and renal (2,1). Median HCT-CI was 1 (0: 37 %, 1: 26%, 2–7: 37%). 22 pts died: 15 from relapse and 7 from non relapse mortality (NRM) causes. Cumulative day-100 NRM and 1-year NRM rates are: 1.3% and 4%, respectively. Pts were categorized into 2 groups: low-risk (scores of 0–1) and high-risk (scores 2–7). Using Cox Regression model and adjusting for age and histology, low-risk group had a significantly better OS (1 wk-58.6 mo, median 34.1 mo) compared to high-risk group (5 days-23.6 mo, median 6 mo) (HR: 3.73, p = .01, 95% CI 1.32, 10.54). 1-year OS rate was 75% vs. 25%, respectively (p=.04). Conclusion: HCT-CI is a valid scoring of pre-transplant comorbidities that predicted mortality after AHCT for pts with lymphoma. The physiologic burden of comorbidities is likely to impact the tolerance to AHCT or to other therapies administered upon relapse after transplant. HCT-CI can serve as important tool for both the transplant administrator when planning for resources allocation and clinical trials, and for pts during pre-transplant evaluation and counseling. No significant financial relationships to disclose.
Correlations among vitality, physical competence, lipid profile and measures of inflammation in transplant survivors with chronic graft versus host disease
Authors: Gerber L. , Mitchell S. , Li L. , Diao G. , Odom J. , Atlam N. , Cowen E. , Sportes C. , Bishop M. , Pavletic S. 
Published: March 2020

7108 Background: Chronic graft vs. host disease (cGVHD) is a multi-system disorder and a late complication of cancer therapy experienced by more than 50% of survivors after allogeneic hematopoietic stem cell transplantation. An improved understanding of the underlying biology and its relation to clinical symptoms may guide the development of better treatments for cGVHD. Methods: In a prospective, cross-sectional natural history protocol we examined the associations among organ/system dysfunction, measures of physical performance and health status with clinical measures of inflammation and fat metabolism. Variables included: 1. a composite severity score (CAS) rated by clinician-specialists (skin, eyes, mouth, gastrointestinal/liver, hematological, gynecological, pulmonary function evaluations); 2.functional measures [2 minute walk time (WT), grip strength (GS), SF-36 physical component summary score (PCS), vitality (VT) subscale, maximal activity score (MAS) of the Human Activity Profile]; 3.Laboratory tests (glucose, LDH, hemoglobin, ferritin, platelets, lymphocytes, pre-albumin, cholesterol, lipoproteins (HDL, LDL), triglycerides (TG), beta-2microglobulin (B2), and CRP. Results: 43 pts (mean age 47 yrs) with prior hematologic malignancy participated (mean 3 yrs post transplant). An average of 3.5 organ systems were affected, 77% were on systemic treatment for cGVHD, and 67% had prior acute GVHD. The mean body mass index (BMI) was 25, TG 255, cholesterol 222, LDL 132. They were moderately disabled by self-report (MAS), had slower than normal WT (540 ft/min), lower than normal GS (63 pounds), PCS (36) and VT (46) than a healthy population. Using a backward selection model with a significance of 0.1, low lung diffusing capacity (p<.001) and low PCS (p=0.01) correlated with high CAS. VT correlated negatively with LDH, platelets, B2 and LDL (all p<0.01). Low GS correlated with high LDH and B2 (p=0.01). Conclusions: Reported physical function and vitality in cGVHD patients are associated with abnormal lipid profiles and markers of inflammation. Establishment of such profiles is a critical step in the development of testable and validated outcome measures and for evaluation of new therapies in cGVHD. No significant financial relationships to disclose.
Pemetrexed + carboplatin versus gemcitabine + carboplatin in the treatment of stage IIIB/IV non-small cell lung cancer
Authors: Gronberg B. H. , Bremnes R. , Aasebø U. , Brunsvig P. , Fløtten Ø. , Hjelde H. , Wammer F. , Stornes F. , Tollåli T. , Sundstrøm S. H. 
Published: March 2020

7517 Background: A prospective, randomized, multicentre study was conducted to compare pemetrexed + carboplatin (PC) with a standard regimen, gemcitabine + carboplatin (GC). Methods: Chemonaive patients with verified non-small cell lung cancer, stage IIIB (ineligible for curative radiotherapy) or stage IV, WHO performance status (PS) 0–2, adequate hematology and creatinine-clearance > 45 ml/min were eligible. All patients were supplemented with folic acid 0.4 mg OD and vitamin B12 1 mg IM every 9 weeks, from >= 5 days before and through the treatment period. Patients were randomized to receive either pemetrexed 500 mg/m2 + carboplatin AUC=5 (Calvert) day 1 or gemcitabine 1,000 mg/m2 day 1 & 8 + carboplatin AUC=5 (Calvert) day 1. Maximum 4 courses every 3 weeks were given. Primary endpoints: QoL defined as global health status, nausea/vomiting, dyspnea and fatigue - measured by the EORTC QLQ-C30 and LC13 before every cycle and 3 & 11 weeks after the last cycle. Secondary endpoints: Overall survival (OS) and toxicity measured by the CTCAE v3.0. Stratification was done for age (−75 vs +75 years), stage (IIIB vs IV) and PS (0–1 vs 2). 190 evaluable patients in each arm were required to detect a 15% improvement on predefined QoL parameters with an a of 0.05 and β of 0.80. A 15% loss to follow up was expected. Results: 446 patients were included from Apr 05 - Jul 06. The two arms were well balanced with respect to age, sex, stage, PS and histological classification. 436 patients were eligible for the primary QoL-analyses. No statistical significant differences in mean score of the QoL-scales were observed between the arms. So far, 384 patients have been analysed for toxicity. Significantly more patients in the GC arm experienced grade 3–4 thrombocytopenia (48 vs 107, p<0.001), leucopenia (44 vs 89, p<0.001) and granulocytopenia (78 vs 98, p=0.02). No difference in the frequency of neutropenic fever was recorded. More patients in the GC arm received transfusion of platelets (5 vs 19, p=0.02). At present, 291 patients are deceased. We expect to present complete OS analyses for a minimum of 380 patients at the annual meeting. Conclusions: No differences were detected between the two arms with respect to the primary QoL outcome. Patients in the PC arm experienced less toxicity. No significant financial relationships to disclose.
IFCT0002 phase III study comparing a preoperative (PRE) and a perioperative (PERI) chemotherapy with two different CT regimens in resectable non-small cell lung cancer (NSCLC): Early results
Authors: Milleron B. , Quoix E. , Westeel V. , Puyraveau M. , Braun D. , Breton J. L. , Bigay Game L. , Pujol J. L. , Morin F. , Depierre A. 
Published: March 2020

7519 Background: Recent trials have shown a survival benefit of CT in resectable NSCLC. The primary objective was to define the best timing of CT (all before surgery versus perioperative). Another objective was to compare two regimens, gemcitabine-cisplatin (GP) and paclitaxel-carboplatin (TC). Methods: Between May 2001 and Dec 2005, 528 patients (pts) with a stage IA-II resectable NSCLC were randomized to 4 parallel arms: A: 2 GP + 2 GP in responders, then surgery, B: 2 GP - surgery + 2 GP in responders, C: 2 TC + 2 TC in responders then surgery, D: 2 TC - surgery + 2 TC in responders (GP: Gemcitabine 1250 mg/m2/d1, 8 and cisplatin 75 mg/m2/d1 q3 wk; TC: Paclitaxel 200 mg/m2/d1 and carboplatin AUC 6, q3 wk). Results: Pathological tumor volume and pathological complete response rate did not differ with the number of preoperative cycles. Proportions of pts receiving cycles 3 and 4 were higher when all CT was given before surgery. There were several significant differences in the main toxicities between GP and TC. Conclusions: 1- GP and TC were effective and safe. 2- Results of pathological response suggested that 2 cycles might be as effective as 4 cycles. 3- Dose intensity was higher when all chemotherapy was given before surgery compared to both before and after surgery. No significant financial relationships to disclose. [Table: see text]
Outcomes for elderly advanced stage non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P): Analysis of Eastern Cooperative Oncology Group (ECOG) 4599 study
Authors: Ramalingam S. S. , Dahlberg S. E. , Langer C. J. , Gray R. , Belani C. P. , Brahmer J. R. , Sandler A. , Schiller J. H. , Johnson D. H. 
Published: March 2020

7535 Background: PC administered in combination with bevacizumab extends survival for advanced non-squamous NSCLC pts. Based on SEER data, elderly pts (age ≥70 years) represent >50% of all new cases of lung cancer and present unique therapeutic challenges. The ECOG 4599 database was analyzed to compare the outcomes in elderly pts treated with PCB vs. PC alone. Methods: Pts ≥ 70 years at study entry constituted the elderly cohort. Each arm (PCB vs. PC) and age group (≥70 vs. <70) was compared with respect to baseline pt characteristics, response rate (RR), progression-free survival (PFS), survival and toxicity. Results: Out of 850 eligible pts, 26% (N=224) were ≥ 70 years of age (1.6% ≥ 80 years). Median age for the elderly was 74 yrs; 44% were ≥ 75 yrs. Baseline characteristics of the elderly cohort were similar to the younger group except for a higher proportion of males (62% vs. 52%, P = 0.005). For the elderly pts, there was a trend towards superior response rate (29% vs. 17%, P = 0.067) and median PFS (5.9 mos vs. 4.9 mos, P = 0.063) with PCB when compared to PC, though there was no difference in overall survival (PCB = 11.3 mos; PC = 12.1 mos; P = 0.4). Grades 3–5 toxicities (CTC version 2.0) were noted in 87% of elderly pts treated with PCB compared to 61% with PC (P < 0.001). Treatment-related death rates with PCB vs. PC were 6.3% vs. 1.8% (NS) for the elderly. Febrile neutropenia (6% vs. 0.9%), proteinuria (8% vs. 0) and hypertension (6% vs. 0.9%) were more common with PCB than PC among the elderly. When compared to younger pts, the elderly experienced more neutropenia (34% vs. 22%), bleeding (7.9% vs. 3.2%), proteinuria (7.9% vs. 1.3%), muscle weakness (7.9% vs. 2.2%) and motor neuropathy (3.5% vs. 0.6%) with PCB. Conclusions: The proportion of elderly patients in ECOG 4599 is the highest recorded among ECOG phase III studies for advanced NSCLC. Increased toxicity with the addition of bevacizumab in those ≥ 70 yrs may have contributed to the absence of survival benefit for PCB vs PC, but this observation is limited by its post-hoc, retrospective nature. No significant financial relationships to disclose.
Can baseline complete geriatric assessment (CGA) predict toxicity in elderly non-small cell lung cancer (NSCLC) patients (pts) receiving combination chemotherapy? Results from the first 100 pts in the prospective multicenter NVALT-3 study
Authors: Wymenga M. , Biesma B. , Vincent A. , Dalesio O. , Stigt J. , Smit H. , Groen H. 
Published: March 2020

7537 Background: Nearly 50% of NSCLC pts are aged over 70 years, but only few receive combination chemotherapy. Undertreatment results from a fear of associated toxicities. CGA may predict which patients are prone to toxicities, and thus allow patient selection for such treatment. Methods: A total of 182 NSCLC pts = 70 years with stage IIIb/IV disease were randomized to 4 cycles carboplatin/gemcitabine (group 1) or carboplatin/paclitaxel (group 2). Before treatment, CGA was performed using the following instruments: WHO Performance Scale (PS), Charlson comorbidity index (CCI), Cumulative Illness Rating Scale-Geriatrics (CIRS-G), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Timed “Up&Go” (TUG), Mini-Mental State Examination (MMSE), Geriatric Depression Score (GDS-15), Groningen Frailty Indicator (GFI). Toxicity was scored using NCI-CTC v2. Toxicity related outcomes were defined as all grade III/IV toxicities, toxicity related SAEs, = grade II neurological toxicity and the ability to finish all cycles. Results: In the first 100 pts mean age was 75 yrs (range 70–85). PS was 0 in 30%, 1 in 56% and 2 in 14%. 57% completed all 4 cycles. 11% stopped treatment prematurely due to toxicity and 12% due to PD. Overall, grade III/IV toxicity occurred in 66% of pts, toxicity related SAEs in 12%, and 35% experienced = grade 2 neurological toxicity (n=13 group 1, n=22 group 2). Median (range) baseline CGA scores were as follows: CCI 1.0 (0–7), CIRS-G 3.0 (0–14), ADL independent 72%, IADL independent 50%, TUG 12.0 sec.(5–40), MMSE 29 (19–30), GDS-15 normal (score 0–4) 71%, GFI 3.0 (0–10). Multivariate logistic regression indicated that, for experiencing toxicity related SAEs CIRS-G provided extra information, for experiencing neurological toxicities MMSE was predictive and for finishing all cycles, IADL provided extra information in addition to PS and stage. Conclusions: CGA can predict toxicity in elderly NSCLC pts receiving combination chemotherapy. Data on all 182 patients will be presented. No significant financial relationships to disclose.
Gemcitabine/platinum alone or in combination with cetuximab as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: Butts C. A. , Bodkin D. , Middleman E. L. , Englund C. W. , Ellison D. , Alam Y. Z. , Pautret V. , Weber M. , Kreisman H. , Shepherd F. A. 
Published: March 2020

7539 Background: This randomized phase II study was conducted to evaluate the benefit of adding cetuximab, an IgG1 monoclonal antibody targeting the EGF receptor, to gemcitabine/platinum chemotherapy in patients with recurrent or metastatic NSCLC. Methods: Patients with previously untreated stage IIIB (malignant pleural effusion) or stage IV NSCLC irrespective of their EGF receptor status were eligible for this study. Patients on arm A received cetuximab (400 mg/m2 IV on day 1 followed by 250 mg/m2 weekly) combined with either cisplatin (75 mg/m2 IV q3 weeks) and gemcitabine (1,250 mg/m2 IV days 1 and 8) or carboplatin (AUC 5 IV q3 weeks) and gemcitabine (1,000 mg/m2 IV days 1 and 8). Patients on Arm B received the same chemotherapy regimen without cetuximab. The primary endpoint was tumor response rate with progression-free (PFS) and overall survival (OS) as secondary endpoints. Results: 73 women and 58 men, median age 66 years (35–88) were randomized to arm A (n=65) or arm B (n=66). Partial responses occurred in 18 (27.7%, 95% CI: 17.3–40.2) patients in arm A and 12 (18.2%, 95% CI 9.8–29.6) in arm B. Median PFS was 5.09 months for arm A (95% CI: 4.17–5.98) and 4.21 months (95% CI: 3.81–5.49) in arm B; median OS was 11.99 (95% CI: 8.80–15.20) and 9.26 months (95% CI: 7.43–11.79) respectively. The incidence of drug related infusion reactions (any grade) in arm A was 15.6% and 1.5% in arm B. Three patients in arm A had grade 3–4 cetuximab related infusion reactions. Severe acneform rash was observed in 14.1% of patients in arm A and none in arm B. Other toxicities were similar and only 18.5% of patients in arm A and 10.6% patients in arm B discontinued treatment for toxicity. Conclusions: These data confirm the previously observed benefit for the combination of cetuximab with a platinum based doublet chemotherapy regimen patients with metastatic NSCLC. The difference of 2.7 months in median OS between treatment arms seems to suggest a more substantial clinical benefit. Fully powered phase III studies addressing this question are on- going and results will become available in 2007. [Table: see text]
Accelerated conformal radiotherapy for stage I non-small cell lung cancer (NSCLC) in patients with pulmonary dysfunction: A CALGB phase I study
Authors: Bogart J. , Watson D. , Seagren S. , Blackstock A. W. , Wang X. , Lenox R. , Vokes E. , Turrisi A. T. , Green M. R. 
Published: March 2020

7556 Background: The optimal treatment for medically inoperable stage I NSCLC has not been defined. Methods: CALGB 39904 is a prospective phase I study assessing accelerated once-daily radiotherapy for early stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy; and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 and T2N0 NSCLC (< 4 cm) with pulmonary dysfunction (FEV1 <40% predicted, DLCO 45mmHg, V02 max <15m1/kg/min, O2 requirement). The nominal total radiotherapy dose was held constant at 70 Gy, while the number of daily fractions in each successive cohort was reduced (table). Results: The study was activated on 12/15/2000, and closed on 7/29/2005. Forty patients were accrued with 8 on each cohort. One patient on cohort 5 declined protocol treatment leaving 39 eligible patients. Patients were generally female (53%), white (83%), and ECOG performance status = 1 (67%). The median age was 74 (range 48 to 87), and the majority of the patients (73%) had T1N0M0 disease. Treatment was well tolerated without grade 4+ toxicity. There was one hematologic toxicity (lymphopenia) in cohort 2, and one non-hematologic toxicity each in cohort 3 (dyspnea) and cohort 4 (pain).The major repsonse rate was 74% (31% complete response, 43 % partial response), and 26% of patients had stable disease. After a median follow-up of 38.1 months, 21 patients remain alive. The actuarial median survival of all eligible patients is 38.5 months (95% confidence interval= 19.45 to NE). Conclusion: Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiosurgery and limited resection,with less apparent severe toxicity. Further investigation of this approach is warranted. No significant financial relationships to disclose. [Table: see text]
IFCT0401 trial: Phase II study of gefitinib administered as first-line treatment in non-resectable adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC): Final results on efficacy and survival
Authors: Cadranel J. , Quoix E. , Debove P. , Moro-Sibilot D. , Brechot J. M. , Souquet P. J. , Soria J. C. , Morin F. , Milleron B. 
Published: March 2020

7560 Background: ADC-BACs are distinguished from other ADCs by epidemiological, clinical and CT scan presentations as well as molecular biology, leading to some responses to EGF receptor tyrosine kinase inhibitors. We therefore conducted a prospective, multicentric, phase II trial to evaluate gefitinib (250 mg/d) as first-line treatment in non-resectable ADC-BAC. Methods: Inclusion criteria were previously untreated, non-resectable cyto/pathologically proven ADC-BAC. Primary objective was disease control rate (DCR) at 3 months. Secondary objectives were progression free survival (PFS), survival, and identification of markers associated with efficacy and survival using multivariate logistic regression and cox model analyses. Results: From 04/04 to 06/05, 88/90 enrolled patients were eligible. All had stage IV disease, with pulmonary (n=86) and/or extra-thoracic metastasis (n=10). All were caucasians, median age 64 yrs (27–84), PS less than 2 in 80.7%, 48 females and 38 never-smokers. Tissue biopsies were centrally reviewed and 85/88 patients evaluable for response by a clinical trial panel. DC was achieved in 25/85 patients (DCR=29.4%, CI=[20–39]). Median PFS was 2.9 months (CI=[2.4–3.2]) and median survival 13.3 months (CI=[13.3–21.8]) with a 1-year survival of 55.7% (CI=[44.4–65.5]). DC was independently associated with age >70 yrs (OR=4.9, p=0.047); never-smoking (OR=8.1, p=0.015); teeter score (clinical pulmonary symptoms score) <9 (OR=18.7, p=0.002); non-mucinous BAC (OR=15.1, p=0.006) and rash (OR=2.1, p=0.02). Shorter PFS and survival were independently associated with teeter clinical score <9 (HR=1.9, p=0.03 and HR=3.3, p=0.006); mucinous BAC (HR=2.7, p=0.008 and HR=2.8, p=0.04), and absence of rash (HR=2.3, p=.004 and HR=2.4, p=0.02). Conclusions: Gefitinib seems active as first-line treatment of non-resectable ADC-BAC. Non-smoking patients, fewer pulmonary symptoms, non-mucinous histological subtype are predicting factors of efficacy and increased survival. Cutaneous rash is associated with efficacy and better survival. In other patients, especially with mucinous BAC, alternative therapies should be offered. No significant financial relationships to disclose.