bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of salvage therapy for relapsed or refractory peripheral T-cell lymphoma (PTCL), anaplastic large cell lymphoma (ALCL), and diffuse large B-cell lymphoma (DLBCL)
Authors: Wu G. , Kuruvilla J. , Nagy T. , Keating A. , Crump M. 
Published: March 2020

6544 Background: Compared to patients with ALCL and DLBCL, PTCL patients have a lower response and higher relapse rate following anthracycline-based chemotherapy. However, in the case of relapsed or primary refractory disease, it is unclear if response to salvage treatment and survival are similarly inferior. Methods: Between 01/01/1995 and 12/30/2004, 45 patients with PTCL, 21 with ALCL, and 171 with DLBCL were referred to our institution for consideration of ASCT. The majority of patients (70%) received a platinum-based salvage regimen. Responding patients then received high-dose etoposide and melphalan followed by autologous stem cell transplant (ASCT). Results: The three groups were similar in age (median 53, range: 19–66), but PTCL patients had more advanced stage disease (III or IV) at salvage than ALCL and DLBCL (71 vs. 61 vs. 48%, p=0.03). Response rates to salvage chemotherapy were similar: 53% for PTCL, 57% for ALCL, and 53% for DLBCL (p=0.94). For T-cell (PTCL and ALCL) patients, there was a trend to better response if a platinum-based regimen was given (61 vs. 35%, p=0.06). Post-transplant, 9/21 PTCL, 3/11 ALCL, and 41/88 DLBCL patients relapsed (43 vs. 27 vs. 46%, p=0.47). Two-year event-free survival (EFS) rates were 28% (95% CI: 14–42%) for PTCL, 45% (23–67%) for ALCL, and 45% (37–53%) for DLBCL (p=0.068). Event-free and overall survival for all patients, and for those who proceeded to ASCT, are shown in the table . Conclusions: Two-year EFS is inferior for patients with relapsed/refractory PTCL treated with the intention of proceeding to ASCT, compared to ALCL and DLBCL, as is 2-year OS rate. However, PTCL patients had similar response to primarily platinum-based salvage chemotherapy, and achieved similar outcome post-ASCT. These findings suggest that strategies to improve the outcome of PTCL patients may include changes to first-line treatment and salvage regimens. [Table: see text] No significant financial relationships to disclose.
Correlation of CD3 and CD34 cell dose with incidence of acute GVHD in myeloablative stem cell transplantation
Authors: Saad A. , Visweshwar N. , Sehbai A. , Cumpston A. , Watkins K. , Buckhalter R. , Hobbs G. , Abraham J. , Ericson S. 
Published: March 2020

6553 Background: Allogeneic stem cell transplantation is used to treat different types of hematologic malignancies. The target stem cell dose typically is based on the recipient’s ideal body weight (IBW) with CD34 dose of 2.0–5.0 ×106/Kg. The dose of CD3 in the infusate is typically not taken into account in a stem cell product, except in T-depleted transplantation. The dose of T-cells in peripheral blood stem cell collections has been found to be at least 10-fold more than that in a bone marrow harvest product. Combined CD4+ and CD25+ cells infused have been directly correlated with increased incidence of GVHD. Methods: This is a retrospective study reporting the correlation of the CD34 and CD3 doses of stem cell transplant with incidence of acute GVHD in 67 consecutive patients who were treated between 2003 and 2005. All patients were followed up for at least 100 days following the stem cell transplant. Results: Among the 67 patients, 35 patients developed acute GVHD, while 32 patients had no evidence of acute GVHD. The CD3 and CD34 doses did not correlate. The correlation coefficient was 0.14 (P value: 0.27). Using t-test, there was NO statistical difference between the mean CD34 dose when comparing the group of patients who developed acute GVHD with the group that did not develop acute GVHD (P value: 0.31). Those who developed acute GVHD (n = 35) received a mean CD3 dose of 41.9 × 107/kg IBW (95% CI: 35.9–47.9). Those who did NOT develop acute GVHD (n= 32) received a mean CD3 dose of 33.5 × 107/kg IBW (95% CI: 27.3–39.8). By using the t-test, the P value for the different means was 0.0575. However, using a CD3 dose cutoff value of 30 × 107/kg IBW, the incidence of acute GVHD was statistically significantly less among those who received CD3 dose < 30 × 107/kg IBW. The Chi Square P value was 0.04. Conclusions: In our series, CD3 dose less than 30 × 107/kg IBW was associated with reduced risk of acute GVHD (P value: 0.04). There was no correlation between CD3 and CD34 counts in peripheral stem cell product. In addition, the CD34 dose did not influence the incidence of acute GVHD. These data suggest that, in addition to considering CD34 dose required for engraftment in allogeneic transplant, the CD3 dose will need to be considered to try to minimize the risk of acute GVHD. No significant financial relationships to disclose.
A multicenter randomized study comparing vinorelbine plus gemcitabine versus capecitabine monotherapy as salvage treatment in patients with advanced breast cancer pretreated with taxane and anthracycline chemotherapy: A preliminary report
Authors: Mavroudis D. , Ardavanis A. , Boukovinas I. , Varthalitis I. , Syrigos K. , Potamianou A. , Kouroussis C. , Georgoulias V. 
Published: March 2020

658 Background: Both Vinorelbine plus Gemcitabine (VG) regimen and Capecitabine (C) monotherapy are active salvage treatments in patients (pts) with advanced breast cancer (ABC). In this multicenter study we compared the efficacy and tolerability of the two regimens as salvage treatment in pts with ABC pretreated with taxane and anthracycline chemotherapy. Methods: Pts were randomized to receive either vinorelbine 25 mg/m2 plus gemcitabine 1000 mg/m2 (VG) both on day 1 in cycles every 2 weeks or capecitabine 1250 mg/m2 (C) twice a day on days 1–14 in cycles every 3 weeks. The primary end point of the study was to compare the time to disease progression (TTP). Results: A total of 114 pts were randomized to VG (n=60) and C (n=54). All pts were evaluable for toxicity and 58 VG and 54 C pts for response. Seven (VG) vs 9 (C) pts had stage IIIB disease and 6 vs 5 pts had PS 2. We observed one complete response on each arm and 14(24%) vs 12(22%) partial responses for an overall response rate of 25.8% vs 24.1% (p=0.8) in VG vs C pts, respectively. The median duration of response was 5 vs 12 months (p=0.02) and the median TTP 3.7 vs 5.8 months (p=0.4) for VG and C pts, respectively. A total of 339 VG and 270 C cycles were administered with no toxic deaths. Both regimens were overall well tolerated; grade 3–4 neutropenia 17% vs 4% (p=0.02), anemia 4% vs 2% (p=0.6), grade 3 thrombocytopenia 2% vs 2%, neurotoxicity 3% vs 2%, grade 2–4 hand-foot syndrome 2% vs 15% (p=0.009) for VG and C pts, respectively. Conclusions: In this preliminary analysis the VG and C regimens showed similar activity but different although rarely severe toxicity. Updated results will be presented at the meeting. No significant financial relationships to disclose.
Early results of modified fludarabine, cyclophosphamide, and rituximab (mFCR) for patients with previously untreated advanced chronic lymphocytic leukemia (CLL)
Authors: Tarhini A. A. , Land S. , Lim F. , Kiefer G. J. , Pietragallo L. , Pinkerton R. A. , Sulecki M. , Meisner D. , Schaefer P. M. , Foon K. A. 
Published: March 2020

6599 Background: Recent data reporting results of FCR therapy in previously untreated advanced CLL patients (F-25 mg/m2 d1–3 q 4wk; C-250 mg/m2 d 1–3 q 4wk; R-500 mg/m2 d1 q 4wk for 6 cycles) demonstrated complete remission (CR) of 70% and overall response (OR) of 95% (J Clin Oncol 2005;23:4079). The major toxicity was grade 3/4 neutropenia during 52% of courses. One approach to decrease neutropenia without compromising efficacy could be by reducing the doses of F and C and increasing the dose of R as high-dose R has been reported to be more efficacious in CLL. Methods: We conducted a phase II study for previously untreated advanced CLL patients treated with mFCR (F-20mg/m2 d1–3 q 4 wk; C-150 mg/m2 d1–3 q 4 wk; R-500mg/m2 d1 and d14 q 4wks; maintenance R-500 mg/m2 q 3 months until progression). A Simon two-stage design was used where 15 patients were accrued in the first stage and because of acceptable toxicity and response rate in stage I an additional 35 patients will be treated. The primary endpoint was response rate. Results: Twenty patients (13 male, 7 female), age 36–85 years (median 59) were treated with a total of 105 mFCR courses. All 20 patients were evaluable for toxicity. Grade 3/4 neutropenia occurred during 11(10.5%) courses. There were no episodes of neutropenic fever. Grade 3/4 thrombocytopenia occurred during 4 (3.8%) courses. Two patients are currently on study and not evaluable for response and among the 18 evaluable patients, the CR was 68%, PR was 32% with an OR of 100%. Eleven of the 12 CR patients had no evidence of CD5+/CD19+ coexpressing cells in their bone marrow after therapy and one had <1%; all 12 were NED by CT scan. Conclusions: Our preliminary results suggest mFCR is highly effective with considerably less grade 3/4 neutropenia than standard FCR. Complete responders had minimal residual disease in their bone marrow following mFCR. [Table: see text]
Pooled safety analysis of oblimersen alone or with fludarabine and cyclophosphamide in patients with advanced chronic lymphocytic leukemia
Authors: Koziner B. , O’Brien S. , Boyd T. , Larratt L. , Moore J. , Chanan-Khan A. 
Published: March 2020

6611 Background: Bcl-2 is an antiapoptotic protein linked to chemotherapy resistance and poor prognosis in chronic lymphocytic leukemia (CLL) patients (pts). Oblimersen (Obl), an anti-Bcl-2 oligonucleotide, has been shown to enhance apoptosis induced by fludarabine (Flu) + cyclophosphamide (Cy) in pts with relapsed CLL. We combined safety results from 2 CLL clinical trials to determine the relative effect of Obl on treatment-emergent adverse events (TEAEs) in Obl+Flu+Cy therapy. Methods: This analysis included 30 pts who received Obl 3mg/kg/d alone by continuous IV on days 5–7 and 230 pts who received Flu 25mg/m2/d + Cy 250mg/m2/d on days 5–7, every 28th day, either with (n=115) or without (n=115) Obl 3mg/kg/d on days 1–7. Mean number of cycles initiated were 3.3, 3.6, and 4.0 for Obl, Obl+Flu+Cy, and Flu+Cy, respectively. Results: The most frequent (>2% patients) grade 4 TEAEs were mainly hematologic: neutropenia (Obl alone, 0.0%; Flu+Cy, 11.3%; Obl+Flu+Cy 7.0%), thrombocytopenia (3.3%, 1.7%, 4.3%), anemia (0.0%, 5.2%, 3.5%), febrile neutropenia (0.0%, 0.9%, 2.6%), hypotension (0.0%, 0.0%, 2.6%), and leukopenia (0.0%, 2.6%, 0.0%). Thrombocytopenic events with Obl-Flu-Cy were reversible and were not associated with clinically significant bleeding events. The most frequent non-hematologic grade 3–4 TEAEs (>5%) were nausea (0.0%, 1.7%, 7.8%), vomiting (0.0%, 0.9%, 6.1%), fatigue (3.3%, 4.3%, 6.1%), and dyspnea (3.3%, 1.7%, 5.2%). Serious TEAEs occurred at a rate of 23.3%, 32.2%, and 57.4%, respectively. TEAEs resulting in death occurred in 2 pts (Obl alone), 5 pts (Flu+Cy), and 9 pts (Obl+Flu+Cy). One Obl+Flu+Cy death was due to cytokine release reaction and one to tumor lysis syndrome. Discontinuation due to TEAEs occurred in 20.0% of pts who received Obl alone, in 34.8% of Flu+Cy pts, and in 34.8% of Obl+Flu+Cy pts. Conclusions: The addition of Obl to Flu+Cy was well tolerated, with similar low frequencies of grade 3+4 TEAEs, primarily the same type observed with Flu+Cy alone. Despite an increased incidence of serious TEAEs observed with Obl+Flu+Cy, the percentage of patients who discontinued protocol therapy due to a TEAE was the same in each group. First cycle reactions mandate close observation when initiating combination therapy. [Table: see text]
Retrospective analysis of WSG AM01 tandem high dose chemotherapy trial in high risk primary breast cancer: A hypothesis generating study
Authors: Nitz U. A. , Gluz O. , Herr A. , Ting E. , Mohrmann S. , Frick M. , Jackisch C. , Poremba C. , Lindemann W. , Diallo-Danebrock R. 
Published: March 2020

665 Background: The WSG AM 01 trial is the first one to report superiority of HDC in terms of DFS and OS in patients with >9 positive axillary lymph nodes. Retrospectively we tried to identify patient subgroups with maximum benefit from HDC. Methods: 403 patients were randomized to tandem HDC or to dose-dense conventional chemotherapy (DD). 236 tumors were available for central pathologic review (117/119). A panel of 34 markers were determined by IHC in TMA. Kaplan-Meier, Log rank and Cox proportional hazard models were used for uni- and multivariate analysis. We choose K-means clustering with K=5 and using Manhattan distance as similarity measure. Results: Pts: n=236 (HDC/DD): mean age 47.3/47.4 yrs, mean tumor sizes 3.5/3.4cm, mean positive lymph nodes 17.2/17.0, HR+ 55%/53%, G3 44%/35%. HDC was superior to DD (p=0.02). Multivariate analysis demonstrated a significant correlation for grading, tumor size, PR+. HR > 2 were reported for the following markers: Her2neu+, p53+, bcl2−, Ck 5/6 and 17+, Ck8−, c-kit+, vimentin+, ETR 1/2, BCRP+. Triple negative tumors (TN) (31%) had a large benefit from HDC (HR DD vs. HD: 3.06, 95%CI:1.41–6.06). Groups identified by K-means clustering could be attributed to luminal-A-(31%), luminal-B-(27%), her2-(11%), basal like-(11%) type and a so far undefined proliferative group (20%) characterized mainly by the absence of specifying markers. Interestingly, the proportion of the above mentioned molecular subtypes within of high risk populations very similar to those reported for less selected populations. Her2, basal-like and the undefined proliferative group had significantly worse outcome when compared to luminal tumors (p<0.01). Very poor prognosis if treated by conventional CT was observed in basal like (HR DD vs HD=2.66 95%CI: 0.9–7.9) und the undefined group (HR=1,72, 95%CI:0.92–3.21), where most of the TN tumors were found. Conclusions: Tandem HDC is superior to DD conventional CT for treatment of HRBC. The largest benefit from high dose chemotherapy was reported for younger patients with TN poor differentiated tumors, >2cm. Negative hormone receptor status, p53+, bcl2−, MIB/p16+ and BCRP+ predicted benefit from dose intensification. Subgroups are small and may help to generate further hypothesises. No significant financial relationships to disclose.
Impact of chemotherapy dose-related factors on survival in breast cancer patients treated with adjuvant anthracycline-based chemotherapy
Authors: Chirivella I. , Bermejo B. , Insa A. , Perez-Fidalgo A. , Magro A. , Rosello S. , Garcia-Garre E. , Martin P. , Bosch A. , Lluch A. 
Published: March 2020

668 Background: The relationship between chemotherapy (CT) dose intensity and patient (pt) outcome in the management of early stage breast cancer (EBC) is still controversial. Although randomised clinical trials have provided evidence that supports the delivery of full standard doses of CT on schedule, precise thresholds for CT dose-related factors and their impact on survival-related endpoints have not yet been fully defined. The objective of this project is to assess the impact of CT dose-related factors on event-free and overall survival in a large group of EBC pts treated with anthracycline-based chemotherapy. Methods: A total of 1056 EBC (stage I-II-IIIA) cases diagnosed and treated from January 1980 to December 2000 were retrospectively studied. All of them received adjuvant anthracycline non-taxanes-based CT. Consecutive charts from 793 pts that were fully completed were included in the analysis. Survival-related endpoints were analysed through Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards models. Results: With a median follow-up of 10.0 years, pts exposed to either > 2 cycle-delay (delay at any cycle defined as ≥ 3 days vs. plan), or ≥ 15 day-delay across the whole CT regimen, or < 95% relative dose intensity (RDI) showed significantly worse 10-year Event-Free Survival (EFS) and Overall Survival (OS) as compared to pts with no dose delay/reduction (data shown below). Controlling for age at diagnosis, disease stage, histological grade, menopausal status and year of treatment did not modify these results. Conclusions: Based on this preliminary analysis, CT dose delays and reductions in EBC pts treated with adjuvant anthracycline-based regimens have a significantly negative impact on EFS and OS. [Table: see text] No significant financial relationships to disclose.
Urinary n-telopeptide (NTX) predicts palliative pain response in metastatic breast cancer patients receiving second-line zoledronic acid
Authors: Dranitsaris G. , Clemons M. , Ooi W. , Cole D. 
Published: March 2020

679 Background: A substantial number of breast cancer patients will have bony progression or develop skeletal related events (SRE) despite treatment with a bisphosphonate (BP) such as clodronate or pamidronate. What could be of use to the practicing oncologist is a marker for predicting which patients will derive palliative benefit with the second-line use of a more potent BP such as zoledronic acid. In this study, we assessed the clinical utility of using early changes in urinary NTX as a predictor of palliative response to second-line zoledronic acid. Methods: 30 patients with either a documented SRE or bony progression while on either clodronate or pamidronate were switched to infusions of zoledronic acid (4 mg) every 4 weeks for 12 weeks. Urinary NTX and worst pain score using the Brief Pain Inventory were evaluated weekly for the first 4 weeks & again at week 8. No change in systemic anti-cancer treatment was allowed in the month before or after commencing study treatment. A palliative response was defined as a reduction of at least two units in the worst pain score. Logistic regression analysis was used to determine if a decrease in urinary NTX at week 1 relative to baseline was a significant predictor of palliative response to zoledronic acid when measured at week 8. Results: At week 1, 23 of 30 (76.7%) had a drop in their urinary NTX excretion relative to baseline. At week 8, these 23 patients experienced a 2.4 unit decline in their worst pain score, compared to only a 0.28 unit reduction in the 7 patients whose week 1 urinary NTX increased relative to baseline (P=0.11). A week 1 drop in urinary NTX was identified as an important predictor for palliative response to zoledronic acid when measured at week 8 (OR=9.4; 95%CI: 2.28 to 79.8, P=0.014). Conclusions: Our findings imply that a decline in urinary NTX at week 1 is a useful marker for identifying which patients will derive palliative benefits from second-line zoledronic acid. Additional data on a larger sample of patients is needed to validate the clinical utility of using early changes in urinary NTX as a rapid predictor of patient benefit. [Table: see text]
An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer
Authors: Tsao M. , Zhu C. , Sakurada A. , Zhang T. , Whitehead M. , Kamel-Reid S. , Ding K. , Seymour L. , Shepherd F. 
Published: March 2020

7005 Background: BR.21 demonstrated a significant survival benefit for patients with advanced non-small cell lung cancer (NSCLC) who received erlotinib vs. placebo (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58–0.85, p<0.001). Tyrosine kinase (TK) domain mutations and high EGFR gene copy number by fluorescent in situ hybridization (FISH) have been associated with significantly higher response rates to erlotinib, while high gene copy number is a better predictor of survival benefit than mutations. K-ras mutation has been associated with non-responsiveness to EGFR TK inhibitors and poorer outcome for patients treated with erlotinib and chemotherapy. The survival impact of K-ras mutation on single agent erlotinib therapy in NSCLC patients remains unknown. Methods: 731 patients were randomized to BR.21 (488 erlotinib, 243 placebo). K-ras mutation analysis was conducted by sequencing in 246 patient samples. Results: K-ras analysis was successful in 206 patients; 30 (14.6%) demonstrated oncogenic mis-sense mutations on codon 12 or 13 (22 on the erlotinib arm and 8 on the placebo arm). For all 206 patients with known K-ras genotype, the HR for erlotinib was 0.77 (95% CI 0.57–1.06, p=0.06). For the 176 K-ras wild type patients, the univariate HR for erlotinib was 0.69 (95% CI 0.49–0.97, p=0.03). In contrast, the HR for the thirty K-ras mutant patients was 1.67 (95% CI 0.62–4.5, p=0.31), with an interaction p value of 0.09. Overall response rates were 5% (1/20) in K-ras mutant patients, and 10.2% (10/98) in K-ras wild type patients. In patients with K-ras genotype known, the multivariate Cox regression model showed that K-ras mutation was significantly associated with shorter survival (HR 1.63, 95% CI 1.06–2.51, p=0.03). Conclusion: In BR.21, patients with K-ras mutation do not appear to derive any survival benefit from erlotinib therapy. However, the numbers of patients are small and results need to be confirmed in other studies. (Supported by the Canadian Cancer Society, Ontario Cancer Research Network, the Jacqueline Seroussi Memorial Foundation for Cancer Research and OSI Pharmaceuticals). [Table: see text]
CISCA (cisplatin vs. carboplatin) meta-analysis: An individual patient data meta-analysis comparing cisplatin versus carboplatin-based chemotherapy in first-line treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Ardizzoni A. , Tiseo M. , Boni L. , Rosell R. , Fossella F. V. , Schiller J. H. , Paesmans M. , Radosavljevic D. , Paccagnella A. , Mazzanti P. , Bisset D. 
Published: March 2020

7011 Background: The issue of the equivalence between carboplatin and cisplatin in the treatment of advanced NSCLC is still controversial. To answer this question, we conducted an individual patient (pt) data meta-analysis of randomized trials comparing cisplatin- and carboplatin-based chemotherapy (CT) in first-line treatment of advanced NSCLC. Methods: A literature search was performed to identify randomized trials investigating the substitution of carboplatin for cisplatin, combined with the same agent/s, in the first-line CT of advanced NSCLC. The primary end-point was overall survival (OS) and the secondary end-points were response rate (RR) and toxicity. For each end-point the analysis was based on a fixed-effects model. For the study of the effect on OS, Cox proportional hazards model was used. The probability to have an objective response or an adverse event was studied using a logistic regression model. Results: Nine trials were identified and the relative databases obtained. In total, 2,968 pts were randomized to receive CT with cisplatin (1,489) or with carboplatin (1,479), respectively. The RR was 30% and 24% for cisplatin- and carboplatin-based CT, respectively, with an OR of 1.37 (95% C.I.: 1.16–1.62; p < 0.001). Concerning the OS, carboplatin was associated with a relative risk of death 7% higher compared with cisplatin, even if this difference was not statistically significant (HR = 1.07; 95% C.I.: 0.99–1.15; p = 0.101). Patients on cisplatin-based CT had more nausea-vomiting and nephro-toxicity while thrombocytopenia was more frequent during carboplatin-based CT. Subgroup analyses revealed that cisplatin-based CT led to statistically significant advantage in survival in the subgroups of pts with non-squamous tumours and in those treated with third generation CT. Conclusions: CISCA is the first individual pt data meta-analysis on this subject. We found that cisplatin-based is superior to carboplatin-based CT in terms of RR; however, the increased RR does not translate into an OS benefit. Nevertheless, selected pts with advanced NSCLC may obtain slightly more benefit from cisplatin-based third generation CT. No significant financial relationships to disclose.