tbuckley/cabot-search huggingface dataset:
Chemomobilization with (R)-ICE (rituximab, ifosfamide, carboplatin, etoposide) compared to G-CSF and plerixafor (G+P) mobilization in lymphoid malignancies.
Authors: Lauren Westfall Veltri, Binod Dhakal, Arun K. Singavi, Sijin Wen, Jin Luo, Michael D. Craig, Aaron Cumpston, Alexandra Shillingburg, Kathy Watkins, Jean Esselman, Marcelo C. Pasquini, Timothy S. Fenske, Parameswaran Hari, Mehdi Hamadani, Abraham Sebastian Kanate
Journal: Journal of Clinical Oncology (2015)

7033 Background: No studies have compared the efficacy and safety of chemomobilization with (R)-ICE against G+P mobilization in patients with lymphoid malignancies. Methods: We analyzed 126 consecutive patients with lymphoid malignancies undergoing chemomobilization with (R)-ICE (n = 63) or G + P (n = 63), in two different institutions. Results: Baseline characteristics are shown in Table 1. (R)-ICE mobilization provided a significantly higher total CD34+ cell yield (median 5.5 × 106 vs. 3.4 × 106 cells/kg, P < 0.001), day 1 CD34+ cell yield (2.4 × 106 vs. 1.7 × 106 cells/kg, P = 0.009) and CD34+ cell dose given at transplant (4.9 × 106 vs. 3.4 × 106 cells/kg, P < 0.001). The median number of apheresis sessions required was two in each group. Neutrophil engraftment was faster with (R)-ICE mobilization (median 10 days vs. 11 days, P < 0.001). Similarly platelet count recovery was faster with (R)-ICE (12 days vs. 16 days, P < 0.001). The transfusion of packed red blood cells was significantly higher in the (R)-ICE group. Plerixafor as a rescue was used in the (R)-ICE group if day 1 cell yield was <1.0 x 106 cells/kg (n = 12). There were no mobilization failures (failure to collect a minimum of 2.0 × 106cells/kg) in the (R)-ICE group, while four patients in the G + P group had unsuccessful collection. Conclusions: Our analysis demonstrates that chemomobilization with (R)-ICE, allowing for plerixafor rescue on day 1 leads to better resource utilization with only 20% needing plerixafor and resulted in a higher total CD34+ cell yield with faster engraftment and minimal toxicities. Mobilization Strategy P-value G+P (R)-ICE + G-CSF Median age, years (range) 56 (22-73) 49 (19-73) 0.02 Male gender 40 (63%) 44 (70%) 0.57 Race, Caucasian 61 (97%) 54 (85%) 0.05 Disease Hodgkin Lymphoma 15 (24%) 13 (21%) 0.83 NHL 48 (76%) 50 (79%) Prior Radiation 11 (17%) 13 (21%) 0.82 Pre-transplant BM cellularity (%), median (range) 43 (10-90) 56 (10-90) 0.80 Lines of Prior Chemotherapy 1-2 51 (81%) 54 (86%) 0.63 ≤ 3 12 (19%) 9 (14%) Pre-transplant Disease Status CR 34 (57%) 38 (60%) 0.40 PR 26 (43%) 23 (37%) SD 2 (3%) KPS, median (range) 80 (60-100) 90 (80-100) <0.001 HCT CI, mean (range) 2 (0-6) 1 (0-6) 0.005
Impact of patient characteristics on compliance to adjuvant chemotherapy in hormone receptor negative breast cancer: A single institution experience.
Authors: Alaa Abdelhalim Ahmed, Nuttapong Ngamphaiboon, Ellen Kossoff, Alison Meagher, Kristopher Attwood, Stephen B. Edge, Foluso Olabisi Ademuyiwa
Journal: Journal of Clinical Oncology (2012)

e19568 Background: Adherence to adjuvant chemotherapy (ACT) has been implicated in poor outcomes in early breast cancer (BC). We investigated factors that may contribute to non-compliance (NC) in hormone receptor (HR) negative BC. Methods: 310 HR- patients (pts) who received adjuvant chemotherapy (ACT) at Roswell Park Cancer Institute (RPCI) between 2002 and 2008 were eligible for this retrospective analysis. Patients were categorized as Compliant or Non Compliant (NC). Compliance was subdivided into adequate Tx (AT) and inadequate Tx due to Toxicity (ITT). NC was discontinuation or delays in ACT for reasons other than toxicities. The 3 groups were compared based on baseline characteristics, treatment-related toxicities, and survival. Fisher’s exact, logistic regression, Cox regression, and log-rank tests were used to analyze the data. A significant p value was assigned at ≤ 0.05. Results: 192 pts were included, with a median age of 55 (range 27-86), and median follow up of 4.9 yrs. NC was observed in 19 (10%) pts, ITT in 47 (24%), and AT in 126 (66%). ITT and NC pts were more likely to have a higher Charlson co-morbidity index (CCI) (p=.019), ECOG performance status (p=.048), more hospital stays (p=&lt;.001) and more heme/non-heme toxicities (p=&lt;.001). Comparing NC/ITT/AT groups; 63/94/100 % completed ≥ half of planned Tx (p=&lt;.001), 22/41/5 % had hematologic toxicity (p=&lt;.001). The groups did not differ by trastuzumab use. There were no statistically significant differences in OS and DFS among the 3 groups. Conclusions: Predictors of non-compliance among HR- breast cancer patients receiving ACT include co-morbidities, and performance status. Clinicians should be aware that this group of pts are likely to have problems completing adjuvant chemotherapy and should be proactive about managing toxicities.
Attendance to Hodgkin lymphoma survivorship care clinics in the Netherlands.
Authors: Annelies Nijdam, Roel J. de Weijer, Cecile P.M. Janus, Eefke J. Clevers-Petersen, Judith M. Roesink, Pieternella J. Lugtenburg, Mars B. van 't Veer, Berthe M.P. Aleman, John M. M. Raemaekers, Flora Van Leeuwen
Journal: Journal of Clinical Oncology (2017)

71 Background: Survivors of Hodgkin lymphoma (HL) are at risk for late adverse effects of treatment. The Dutch BETER consortium, consisting of healthcare providers, researchers and patient representatives, has set up survivorship care clinics where HL survivors are screened for late effects. Methods: In order to assess patient characteristics and clinical attendance rates, descriptive statistics were calculated for data on HL survivors who were invited to attend the BETER clinics in the University Medical Center Utrecht (UMCU) and Erasmus University Medical Center (EMC). Results: Overall 291 survivors were invited to attend one of the two BETER clinics. Median age at invitation was 46 years (interquartile range IQR: 40-55 years), median age at HL diagnosis 29 years (IQR: 22-37 years) and median time since diagnosis 16 years (IQR: 11-22 years). Survivors were referred to the BETER clinic by the general EMC/UMCU outpatient clinics where they were still under surveillance (42%) or invited by phone (37%) or letter (20%). While 79% of survivors responded to the invitation, only 53% of all patients actually visited the BETER clinic. Most common reasons to not attend were: undergoing surveillance or treatment for late effects elsewhere (91%) and unwillingness to attend (8%; e.g. due to financial or emotional burden). Ninety-eight% of survivors who were still under surveillance in EMC/UMCU hospitals attended the BETER clinic, as opposed to only 19% of survivors who were no longer under surveillance. Survivors initially invited by letter were more likely to attend (38%) than those who were first contacted by phone (11%). Age at invitation and age at HL diagnosis were similar in those who did and did not attend. Similar data for another 3 clinics are being collected and will be presented at the ASCO Survivorship Symposium. Conclusions: These preliminary data show that only half of HL survivors who were invited, attended a BETER clinic. Unfortunately, survivors who were no longer under medical surveillance were less likely to attend, especially when first contacted by phone. Future, more detailed, evaluation of (non-)attendance in more BETER clinics may reveal the need for additional implementation measures to improve the BETER survivorship care program.
Dose-specific clearance of TRC105 (anti-CD105 antibody) in advanced solid tumor patients.
Authors: Shawn D Spencer, William Douglas Figg, Lee S. Rosen, Michael S. Gordon, Herbert Hurwitz, Michael K.K. Wong, Jonathan Wade Goldman, David S. Mendelson, Bonne J. Adams, Delia Alvarez, Ben K. Seon, Charles P. Theuer, Bryan R. Leigh
Journal: Journal of Clinical Oncology (2012)

3042^ Background: CD105 is an endothelial cell membrane receptor highly expressed on angiogenic tumor vessels. TRC105 is an anti-CD105 monoclonal antibody that inhibits angiogenesis and tumor growth by endothelial cell growth inhibition, ADCC and apoptosis. Methods: Patients with advanced solid tumors and normal organ function were treated with escalating doses of intravenously administered TRC105 and assessed for safety and pharmacokinetics (PK). PK parameters for determining dose-linearity were estimated following single doses on in 16 patients at 3, 10 and 15 mg/kg and correlated with safety. Results: TRC105 was tolerated at 10 mg/kg weekly and 15 mg/kg every 2 weeks, but hyproliferative anemia was dose-limiting at 15 mg/kg weekly and was associated with TRC105 accumulation in serum from target saturation. Preliminary evidence of activity was observed with 21 of 45 evaluable patients progression-free at 2 months, including two ongoing responders. The AUC-single dose relationship of TRC105 revealed supra-proportionality in serum exposure at 15 mg/kg compared to 3 and 10 mg/kg. Dose proportionality using a power model revealed a nonlinear pharmacokinetic process (log[AUC] = 0.125*Dose+2.67, r 2 = 0.92, ANOVA p&lt;0.0035). The steady state volume of distribution was low (≈ 5.40 L/70kg) indicating TRC105 was confined to the vasculature with a low capacity target (i.e., low relative abundance) making it susceptible to saturation. The post-infusion Cmax however was linearly related to dose (r = 0.85) which suggested the nonlinearity in clearance was attributed to target-mediated disposition. The nonlinear disposition in the presence of low distribution indicated TRC105 bound avidly to endothelial cells. Concentrations expected to saturate CD105 binding were achieved continuously at 15 mg/kg dosed every 2 weeks and 10 mg/kg/wk. TRC105 accumulated at 15 mg/kg/wk as the accumulation factor at 56 days was 1.77-fold over single doses on C1D1. Conclusions: TRC105 clearance decreased above the MTD resulting in drug accumulation and hypoproliferative anemia with weekly dosing. The nonlinearity in clearance was attributed to saturating target-mediated disposition, consistent with binding to proliferating endothelial cells.
Evaluation of lymphocyte infiltrate composition in triple-negative mammary carcinomas and its association with clinical-pathologic and demographic data.
Authors: Geraldine Eltz Lima, Felipe D'Almeida Costa, Alexandre Andre Balieiro Anastacio da Costa, José A. Rinck, Andrea Paiva G. Guimaraes, Vladmir C. Lima
Journal: Journal of Clinical Oncology (2014)

1131 Background: Triple-negative breast cancer corresponds to 15-20% of cases. Despite the advances in development of therapies for breast cancer treatment, this subtype still have a dismal prognosis. Chronic inflammation is involved in cancer development. However, the regulatory mechanisms underlying the recruitment and functioning of inflammatory cells in tumors are not completely clarified. The role of tumor lymphocytic inflammatory infiltrate in predicting survival of breast cancer patients is controversial. Our objective was to evaluate the lymphocyte inflammatory infiltrate and its association with clinical, pathological and demographic characteristics in triple-negative mammary carcinomas patients Methods: We studied a retrospective cohort of51 stage I to III, operated triple-negative breast cancer patients. Clinical data was recovered from electronic medical charts. Pathological samples were arranged in duplicate in a TMA, with tissue blocks from core biopsies or surgical specimens. Slides were stained with antibodies against CD4 and CD8, FOXP3. The number of positive staining cells for each antibody in each core was counted. The mean value of duplicates was used in all calculations. Fisher's exact and Mann-Whitney tests were used to verify the association between clinical-pathological and demographic data and the number lymphocytes. Overall (OS) and disease free survival (DFS) curves were calculated using Kaplan-Meier method and comparisons between curves was done by log-rank test. Results: Median age was 43 years-old. Mean OS was 101 months (87-115) and mean DFS was 87,35 months (71,84-102). There was no association between CD4+ cell counts and any other variable. CD8+ cell counts were associated with tumor size, and larger tumors presented with more intense CD8+ infiltrate. Higher FOXP3+ cell counts were associated with high histological and nuclear grade. There was no statistically significant association between any lymphocyte subset and OS or DFS. Conclusions: CD8+ and FOXP3+ lymphocyte infiltration are associated with pathological tumor characteristics and may play a role in tumor development, progression and prognosis.
A multicenter, open-label, phase 3 trial to compare the efficacy and safety of lenvatinib (E7080) versus sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma.
Authors: Richard S. Finn, Ann-Lii Cheng, Kenji Ikeda, Masatoshi Kudo, Toshiyuki Tamai, Corina E. Dutcus, Steven Younger, Kwang-Hyub Han, Shukui Qin, Eric Raymond
Journal: Journal of Clinical Oncology (2014)

TPS4153 Background: Lenvatinib (L, E7080) is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET and KIT. Given the role of angiogenesis in hepatocellular carcinoma (HCC), a phase 1/2 open-label study evaluated the safety and efficacy of L in 46 patients with advanced disease and Childs-Pugh (CP) A liver function status (Kudo ILCA 2013). Patients were treated with a starting dose of L 12 mg qd (28-d cycles) until disease progression or development of unmanageable toxicities. Median time to progression (TTP) was 12.8 months (mo; 95% confidence interval [CI] 7.23–14.7) and median overall survival (OS) was 18.7 mo (95% CI 12.8–25.1). The most common adverse events were hypertension 76% (Gr3 54%), palmar-plantar erythrodysesthesia syndrome 61% (Gr3 7%), proteinuria 59% (Gr3 20%), anorexia 57% (Gr3 2%), thrombocytopenia 50% (Gr3 33%), and fatigue 48% (Gr3 0%). Overall response rate (ORR) was 37%; 45.7% had stable disease. Methods: Based on these phase 2 data, a global, randomized, open-label phase 3 trial was designed to determine if L is non-inferior or superior compared to sorafenib (S) in advanced HCC. Eligible patients (N=940) with Barcelona Clinic Liver Cancer Stage B or C HCC, CP A status, and ECOG 0-1 will be randomized 1:1 to either L 12 mg or 8 mg orally qd (based on body weight [BW]) or S 400 mg orally bid. Patients will be stratified by region; macroscopic portal vein invasion, extrahepatic spread, or both; ECOG-PS; and BW (<60 vs ≥60 kg). The primary endpoint is OS. Secondary endpoints include progression-free survival, TTP, ORR (modified RECIST criteria), safety and PK/PD. Given an estimated median OS for S of approximately 10 mo, a 2.5 mo improvement was derived to achieve a hazard ratio (HR) of 0.8. Statistical study power (using a non-inferiority test by the 95% CI lower-limit method on log HR for OS) was determined based on this HR and a non-inferiority margin of 1.08, corresponding to 60% retention of S effect vs placebo. Based on these assumptions, the study power to declare non-inferiority or superiority is approximately 97% and 82%, respectively. The overall false positive rate is 0.05 (2-sided). Clinical trial information: NCT01761266.
Assessment of safety with abbreviated, weight-based bevacizumab infusions in a variety of solid tumors
Authors: J. W. Hart, J. R. Murillo, M. S. Oholendt, H. A. Preti
Journal: Journal of Clinical Oncology (2007)

19674 Background: Bevacizumab (BEV), a humanized monoclonal antibody that neutralizes vascular endothelial growth factor, has shown improved responses in patients with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) while displaying activity in a variety of other solid tumors. Phase I clinical trials with BEV utilized standard 90- 60-, and 30-minute infusions for 1 st , 2 nd , and subsequent infusions, as tolerated; initial doses reported less than 3% incidence of infusion-related adverse events (AEs), with 0.2% grade III/IV reactions. Recommended infusion rates for BEV remain unchanged despite the minimal risk of infusion-related AEs. Saltz and colleagues recently reported novel data supporting the safety and tolerability of abbreviated BEV infusions in CRC patients within a single institution. Our objective was to replicate previously reported safety profiles while utilizing abbreviated infusions of BEV in multiple tumor types. Methods: An internal retrospective analysis revealing minimal infusion AEs with standard infusions facilitated this current study. BEV- naïve and previously-treated patients were consented for the study utilizing the following weight-based infusion times: 5, 10, and 15 mg/kg doses over 10, 20, or 30 minutes, respectively, for all doses. Patients were assessed throughout and immediately following the infusion for any infusion-related AE. Results: A variety of tumor types are represented in 26 enrolled patients including CRC, NSCLC, breast, ovarian, pancreatic, and brain. Central nervous system involvement accounted for 35% of patients [primary brain (23%) and metastatic disease (12%)]. A considerable number of patients (19%) were treated with single-agent BEV. Nine BEV-naïve patients were initiated on abbreviated infusions, while 16 were converted from the standard infusion schedule. Seventy-seven total doses utilizing the abbreviated infusions failed to produce infusion-related AEs. Conclusion: These results support previous data affirming the safety and tolerability of abbreviated BEV infusions in CRC patients, while also reporting promising safety of abbreviated infusions in a variety of additionally unreported solid tumors types. No significant financial relationships to disclose.
A pilot study to evaluate the levels of inter-alpha inhibitor proteins (IAIPs) in metastatic cancer patients.
Authors: Peter C. Kurniali, John A Gerlach, Yow-Pin Lim, Joseph Qiu, Sarah Siemiontkowski, Susan C Forney, Anas Al-Janadi
Journal: Journal of Clinical Oncology (2015)

e22249 Background: Inter-alpha Inhibitor protein family (IAIP) is a group of structurally related serine protease inhibitors produced in the liver and found at relatively high concentrations in human plasma. IAIPs have a significant role in systemic inflammation and function as an endogenous immunomodulator. Significant reduction of IAIP level is found in dysregulated septic patients due to rapid excretion through kidney. The role of IAIPs in cancer patients is not yet defined. Methods: Serial blood samples from cancer patient (n = 10) were collected for a three-month period (before and after chemotherapy). Blood from healthy individuals (n = 10) were collected at one time point and used as a control. Patients who did not continue their treatment during the collection period were excluded. Plasma was used for the quantitative analysis of IAIPs, albumin, pre-albumin, CRP, and cytokines. Cancer patients were categorized into stable and progressive disease based on radiographic imaging done within 3 months of last specimen collection. Results: Cancer patients had a higher level of IAIPs at baseline compared to healthy controls (385 vs. 284 mg/L, p = 0.02). IAIPs level increased after first cycle of chemotherapy. When categorized based on disease status, IAIPs level increased by 24% in patients who had stable disease and decreased by 17% in patients who had disease progression from baseline. The difference was statistically significant (p = 0.03). Furthermore, we found that IAIPs level in cancer patients positively correlated with pre-albumin (r2= 0.28, p = 0.003), CRP (r2= 0.18, p = 0.02), IL-6 (r2= 0.09, p = 0.04). Conclusions: Increased IAIPs level found in metastatic cancer patients might be due to, in part, the systemic inflammatory condition. Positive correlation of IAIPs with pro-inflammatory cytokines such as IL-6 as well as albumin, pre-albumin, and CRP was consistent with the inflammatory state in these patients. IAIPs level might be useful as biomarker to predict disease severity and host response following chemotherapy. To further evaluate the relationship between IAIPs and malignancy, a longer longitudinal study is required.
A randomized placebo-controlled trial of saracatinib (AZD0530) plus weekly paclitaxel in platinum-resistant ovarian, fallopian-tube, or primary peritoneal cancer (SaPPrOC).
Authors: Iain A. McNeish, Jonathan A. Ledermann, Lee C. Webber, Lindsay E. James, Stanley B. Kaye, Gordon J. S. Rustin, Geoff Hall, Andrew Clamp, Helena Margaret Earl, Susana N. Banerjee, Rebecca Sophie Kristeleit, Fharat Raja, Amanda Feeney, Cheryl Lawrence, Linda Dawson-Athey, Mojca Persic, Iftekhar Khan
Journal: Journal of Clinical Oncology (2013)

5514 Background: Weekly paclitaxel (wPxl) has activity in platinum-resistant ovarian cancer (PROC). Upregulated Src kinase activity is seen in Pxl-resistant ovarian cancer models. This trial investigated the combination of wPxl and the oral Src inhibitor saracatinib (AZD0530) in PROC. Methods: Patients with PROC (defined as relapse within 6 months of prior platinum chemotherapy, confirmed either by CT scan or symptomatic CA125 rise) were randomised 2:1 to receive four 8 week cycles of wPxl (80mg/m 2 /week x6 with 2 week break) plus saracatinib (S; 175mg od) or placebo (P) continuously, starting 1 week prior to wPxl, until disease progression. Patients were stratified as &lt;6 months or ≥6 months taxane interval/no prior taxane. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate (RR), duration of response (DoR), time to progression (TTP) and toxicity. Results: 107 patients were randomised during 2011-12, 71 (66.4%) to wPxL+S and 36 (33.6%) to wPxL+P. Taxane interval was &lt;6 months in 23 (22.1%), ≥6 months in 76 (72.4%). 43 (41.0%) had received &gt;2 lines of prior chemotherapy; 78% (wPxL+S) vs 72% (wPxL+P) of patients received ≥1 cycle of wPxl; relative dose intensity was 96% vs 98% for wPxL+S and wPxL+P respectively. The 6-month PFS rate was 29% (wPxL+S) vs 35% (wPxL+P). Median PFS was 3.9 vs 5.3 months (HR 1.04; 95% CI 0.68, 1.59; p=0.86); median OS was 12.7 vs 12.8 months (HR 1.50, 95% CI 0.63, 3.56; p=0.36); RR were 0.0% vs 2.9% (CR) and 29% vs 38.9% (PR) for wPxL+S vs wPxL+P respectively. Median DoR was 5.6 vs 3.6 months; TTP was 3.9 vs 5.5 months (HR 1.10; 95% CI 0.71, 1.72;p=0.67). Grade 3+ Serious Adverse Events were 36.2% vs 30.6%; the most frequent toxicities (any grade) were abdominal pain (4.3%) and febrile neutropenia (4.3%) for wPxL+S, and vomiting (5.6%) for wPxL+P. Conclusions: In this randomised phase II trial, the addition of saracatinib to wPxl did not improve 6-month PFS in patients with PROC. Clinical trial information: NCT01196741.