bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subanalyses of the outcome of two carboplatin-based regimens in the treatment of advanced NSCLC
Authors: Hansen O. , Schytte T. K. , Hansen K. H. , Sørensen P. 
Published: August 2020

e19067 Background: Recent data suggest that various chemotherapy regimen may have different efficacy in subsets of patients (pts.) with advanced NSCLC. For that reason we studied if it was also the case for two Carboplatin regimens, Carboplatin-Vinorelbine (CV) and Carboplatin-Gemcitabine (CG), which were used as standard treatments in our centre for two periods Methods: From 1998–2007, 800 consecutive pts. were treated with a 3-weekly schedule of C, AUC=5, plus either V (30 mg/m2 d.1+8), or G (1000 mg/m2 d.1+8) for 4–6 cycles. CV was used as the standard regimen 1998 - 2003, and CG, 2004 - 2007. All pts. were followed to death, and most data have been prospectively recorded, but supplemented with retrospectively collected data from pts. files. The endpoint of this study was crude survival. The data was analysed according to performance status (PS), gender, age, and histology (adenoca., squamous, other NSCLC) Results: 313 pts. were treated with CV, 487 with CG. Median, 1 yr and 2 yr survival was for CV: 8.6 m, 34% and 15%, and for CG: 8.6 m, 37% and 12%, p=0.32. Analysed by histology, adenoca.'s had better median survival, 9.7 m., than non-adenoca., 8.1 m, p= .002, females better than males 10.0 m. vs. 7.9 m., p=.008, and PS 0–1 better than PS=2, 10.0 m. vs. 4.7 m. (p=.000). Age was of no importance. Cox-analyses was performed separately in the two genders. In females, PS 0–1, adenoca. and CG regimen were statistically significant favourable prognostic factors while in males only PS 0–1 were of significance. In the 379 pts. with adenoca., PS and gender were of significance while the chemotherapy was of borderline significance (p=.06). In non- adenoca.'s, only PS was of significance Conclusions: While CV and CG were overall equal effective in the treatment of NSCLC, CG may be the superior regimen in females, and in adenoca.'s. No trends for differential efficacy was found in any other subset of patients [Table: see text]
Current trend in incidence of severe interstitial lung disease (ILD) due to gefitinib in Japan
Authors: Goto K. , Kenmotsu H. , Nishiwaki Y. , Kubota K. , Ohmatsu H. , Niho S. , Yoh K. , Nagai K. , Saijo N. 
Published: August 2020

e19075 Background: Although gefitinib is a promising agent for the treatment of advanced non-small cell lung cancer, ILD occurs in Japanese patients and sever ILD sometimes becomes fatal toxicity. ILD has been reported to be associated with preexisting ILD, smoking, and poor performance status. On the other hand, it has been reported that female gender, adenocarcinoma, non-smoker, and EGFR mutation are associated with sensitivity to gefitinib. Methods: To investigate the trend in incidence of severe ILD and patient characteristics receiving gefitinib, a total of 751 patients who were administered gefitinib in National Cancer Center Hospital East between 2002 and 2008 were retrospectively reviewed. To investigate how oncologists avoid administering gefitinib to patients with preexisting ILD, pretreatment chest CT films of all patients were also reviewed by two thoracic radiologists. Results: The patient number who received gefitinib in 2002/2003/2004/2005/2006/2007/2008 were 134/141/88/93/125/98/72, respectively. In these patients, percentages of female were 36/43/42/55/59/52/54%, adenocarcinoma 76/78/93/88/95/93/92%, non-smoker 35/30/40/53/49/48/46%, respectively. Almost all of the patient receiving gefitinib was recently restricted to adenocarcinoma. Grade 3–5 severe ILD was observed in 1.9% of all patients. However, the incidence rate of sever ILD were decreased as 3.0/2.8/2.3/1.1/0.8/1.0/1.4%, respectively. The rates of patients with preexisting ILD were also decreased as 22/14/15/5/2/3/6%, respectively. Conclusions: The correct information about efficacy and severe ILD about gefitinib influenced patient selection by oncologists, and it is reasonable to select more effective and safe patients in Japan. It is estimated that the incidence rate of severe ILD should be consequently controlled by the spread of these information. No significant financial relationships to disclose.
Functional profiling in stage IV NSCLC: A phase II trial of individualized therapy
Authors: Nagourney R. A. , Blitzer J. , Deo E. , Nandan R. , Schuman R. , Asciuto T. , Mc Connell D. , Paulsen M. , Evans S. 
Published: August 2020

e19079 Background: The introduction of new classes of agents has improved survival in NSCLC yet the accurate selection of candidates for these often costly & toxic drugs remains a challenge. Genomic platforms have identified several prognostic & predictive factors e.g. ERCC1, RRM1/2, EGFr mutations but the comparatively small number of known cellular analytes has limited their broad application. Methods: To address the complexity and redundancy of cell-death signaling pathways, we applied Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) (Nagourney, R. Curr Treat Options in Oncol. 2006) to select therapies for chemo- naïve pts with metastatic NSCLC. This functional platform uses morphologic and metabolic endpoints to gauge cellular response to drugs & signal transduction inhibitors in human tumor microspheroids isolated from surgical biopsies. Modified Z-scores & synergy analyses (median-effect) were used to identify the ex vivo best regimen (EVBR) for each pt. from FDA-approved NSCLC drugs. All pts signed informed consent. Results: 22/25 (88%) pts are evaluable with 3/25 (12%) excluded, 1 for CVA & 2 inadequate PFS at time of treatment. There were CR = 2/22 (9%); PR = 10/22 (45%); SD = 9/22 (41%) & PD = 1/22 (5%) for an ORR = 12/22 (54%) & CBR = 21/22 (95%). 1st line EVBR were CDDP/Gemcitabine 10/25 (40%); CDDP/Taxane 7/25(28%); Erlotinib 5/25(20%); CDDP/Vinorelbine 1/25 (4%); CDDP/Irinotecan1/25(4%) & Ifex/Gemcitabine1/25(4%). Six of 22 (27%) stage IV pts were converted to surgical and/or radiation candidates by therapy. Accrual continues with current TTP ranges from 1.2–35+ months and OS from 1.7 to 46+ months. Conclusions: EVA/PCD ORR in Stage IV NSCLC of 54%, many durable, compares very favorably with reports in this population. By examining drug-induced cell death events in native-state microspheroids, this platform has the unique capacity to capture stromal, vascular and inflammatory cell interactions with tumor cells, now known to be crucial for clinical response prediction. EVA/PCD analysis in NSCLC warrants further evaluation. Supported by the Memorial Medical Center Foundation of Long Beach. [Table: see text]
Trends in chemotherapy for elderly patients with non-small cell lung cancer: The experience of one institution
Authors: Kim Y. , Nishiwaki Y. , Yoh K. , Niho S. , Goto K. , Ohmatsu H. , Kubota K. , Saijo N. 
Published: August 2020

e19081 Background: In approximately the year 2000, the results of a number of important studies of non-small-cell lung cancer (NSCLC) were published. These included the first elderly-specific phase III trial and phase III trials showing a survival benefit for docetaxel when used as second-line chemotherapy. These results had a significant impact on clinical practice relating to advanced NSCLC in elderly patients. Methods: Between July 1992 and December 2003, 223 patients with NSCLC aged ≥70 years received chemotherapy alone as their initial treatment at the National Cancer Center Hospital East. These patients were divided into 2 groups: those that began treatment between 1992 and 1999 (group A) and between 2000 and 2003 (group B). The details of chemotherapy regimens and outcomes were compared. Results: In group A, 83% of patients received platinum-based chemotherapy, two-thirds of these regimens comprised platinum[[Unsupported Character -  ]]plus second-generation combination chemotherapy. In contrast, although 55% of patients received platinum-based chemotherapy in group B, 41% of patients received non-platinum-based chemotherapy. Among patients in group B, performance status was significantly associated with the selection of platinum-based or non- platinum-based chemotherapy; age was marginally associated with this selection. In group A, second-line chemotherapy was administered to only 4 patients (5%) and no patients received third-line chemotherapy. In group B, second-line and third-line chemotherapy was administered to 62 (42%) and 22 (15%) patients, respectively. Median survival time (MST), 1-year survival rate, and 2 year-survival rate were 6.7 months, 14%, and 7%, respectively, in group A, and 8.1 months, 35%, and 20% in group B (p = 0.0109). However, these differences disappeared when patients treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) were removed from the analysis (6.7 months in group A vs. 6.9 months in group B, p = 0.3684). Conclusions: In and after the year 2000, chemotherapy regimens changed greatly and survival of elderly patients significantly improved. However, the improvement in survival seems to be due mostly to the use of EGFR-TKI treatment. No significant financial relationships to disclose.
Erlotinib and bevacizumab in chemotherapy-naive performance status 2 patients with advanced non-small cell lung cancer
Authors: Al Baghdadi T. , Hanna N. , Bhatia S. , McClean J. , Johnson C. , Yu M. , Taber D. , Harb W. 
Published: August 2020

e19082 Background: Poor performance status is a negative prognostic variable for survival and a risk for increased toxicities with standard chemotherapy. A phase 2 study combining erlotinib (E) and bevacizumab (B) demonstrated encouraging efficacy in the treatment of recurrent NSCLC with acceptable toxicity. We, therefore, tested this regimen in untreated PS 2 patients with advanced NSCLC. Methods: Single-arm phase 2 trial in treatment-naïve patients with advanced non-squamous NSCLC and either a PS of 2 or age >75. Only patients eligible for bevacizumab per label were allowed onto study. Patients received E 150 mg orally daily and B 15 mg/kg IV on day 1 every 21 days for up to 6 cycles. The primary end-point was the rate of non progressive disease at 4 months (alternative hypothesis P>60%). Other end-points included overall survival, progression free survival (PFS), toxicity evaluations and patient-reported PS (PRPS) measures. Results: 25 patients were enrolled. Patient characteristics: 56% female, median age 77 years (range: 52–90); 88% stage IV; 92% were PS 2; 20% were never or remote smokers (> 30 years) The PRPS was 1, 2, 3 in 32%, 52%, 8% respectively with data on 2 patients missing. The rate of non-progression at 4 months was 40%; overall best response: 5% PR, 40% SD, 50% PD and 5% unevaluable; median PFS 2.6 months, 95% CI (1.3–5.1); MST 5.8 months, 95% CI (3.8- 8.7). 2 patients had G3 rash. G3 diarrhea, G3 hemorrhage, G3 proteinuria, G3 duodenal ulcer and G3 pneumonitis each developed in one patient. Conclusions: E + B is an active regimen with an acceptable toxicity profile; however, this study did not meet its’ primary endpoint. Further study of this combination will not be pursued in the Hoosier Oncology Group for this patient population. [Table: see text]
Carboplatin dosing by predictive formulae and factors related to its myelosuppressive toxicity
Authors: Ayirookuzhi S. J. , McLarty J. , Mansour R. , Mills G. M. 
Published: August 2020

e19101 Background: Carboplatin is a commonly used drug in stage III/IV non-small cell lung cancer (NSCLC). Its dose in typically calculated with the Calvert equation that uses the glomerular filtration rate (GFR) from various predictive formulae such as MDRD, Cockroft-Gault, Jeliffe and Wright as well as the targeted area under the curve (AUC) for carboplatin. Myelosuppression is a common toxicity of carboplatin and this study aimed to assess the relationship between dosing and toxicity as well as if there would be any significant difference in dosing based on calculation of GFR from the above formulae in our patient population. Methods: Data from patients with Stage III and IV NSCLC seen between 1/1/99 to 12/31/2007 were analyzed. Patients who received concurrent radiation, who died before the first cycle was completed, as well as patients with missing lab values were excluded. Only the first cycle of the carboplatin based regime was used for analysis with nadir platelets, hemoglobin and wbc's used as endpoints. SPSS software was used for statistical analysis including Pearson correlation, ANCOVA, independent t-tests as well as multivariate linear regression models. Results: Of the 216 patients initially abstracted for analysis only 132 patients were analyzable. Demographically 71 were Caucasian and rest were African-American while 92 were male. The carboplatin dose calculated from all four formulae were highly correlated (p < 0.0001). The drop in the three cell counts were correlated to each other (p< 0.05), particularly the drop in platelet count with other two cell counts. The correlation between the drop in wbc and drop in hemoglobin approached significance (p=0.075). The nadir wbc was significantly associated with BSA (p=0.004), wbc level at baseline (p< 0.000) and approached significance for carboplatin dose (p=0.059) by ANCOVA analysis, while significance was not reached for nadir platelets or nadir hemoglobin. Conclusions: The different predictive equations resulted in similar doses of carboplatin that were statistically significant. BSA correlated significantly with myelosuppression while carboplatin dose only approached significance. No significant financial relationships to disclose.
Phase II study of cladribine with rituximab (R-2-CdA) therapy in patients with relapsed indolent B-cell non-Hodgkin's lymphoma
Authors: Nagai H. , Kusumoto S. , Sawada K. , Yamaguchi M. , Takayama N. , Kinoshita T. , Motoji T. , Omachi K. , Ogura M. , Hotta T. 
Published: August 2020

e19501 Background: Although cladribine has been reported to be one of active purine analogs against indolent B-cell non-Hodgkin's lymphoma (B-NHL), there are few reports of combination usage of cladribine and rituximab. We conducted a multicenter phase II study to investigate efficacy and toxicity of cladribine with rituximab (R-2-CdA) therapy for relapsed indolent B-NHL. Methods: Eligibility criteria were as follows: relapsed pts with indolent B-NHL from systemic chemotherapy, ages less than 75 years; PS 0–2 by ECOG's scale. Patients received 0.09mg/kg of cladribine intravenously (2 hrs infusion) on days 1 to 5 and 375mg/m2 of rituximab intravenously on days 1 and 15, every 4 weeks, for a total of 4 cycles. Primary endpoint was overall response rate (ORR). Secondary endpoints were % complete response (%CR), 2 years progression free survival (2-y PFS), and 2 years overall survival (2-y OS). Results: A total of 20 out of 45 planned patients were enrolled and received R-2-CdA therapy from Apr 2005 to Jul 2007. Their median age was 58.5 (42–72), and the median number of prior regimens was 2 (1–3). Histologies included 16 follicular lymphomas, 2 MALT lymphomas, 1 nodal marginal B cell lymphoma, and 1 lymphoplasmacytic lymphoma. Fifteen pts (75%) were previously treated with rituximab. The ORR was 90% with 70% of % CR. Median PFS was 20.1 months (5.6–32.9 months) at a median follow-up time of 27 months. 2-y PFS and 2-y OS were 63.2% (95%CI, 28.1–67.8%), and 89.5% (95%CI, 69.8–97.2%), respectively. Severe neutropenia and thrombocytopenia of grade 3 or 4 were observed in 15% and 10% respectively. Conclusions: R-2CdA therapy was demonstrated to have high activity with durable PFS and acceptable toxicity in relapsed indolent B-NHL, even if patients were previously treated with rituximab. Although a large-scaled further trial remains to be needed, R-2-CdA therapy could be a good option of salvage therapy in relapsed indolent B-NHL. No significant financial relationships to disclose.
A phase II study of a 1-hour infusion of romidepsin combined with bortezomib for multiple myeloma (MM) patients with relapsed or refractory disease
Authors: Berenson J. R. , Yellin O. , Mapes R. , Eades B. , Abaya C. D. , Strayer A. , Nix D. , Swift R. A. 
Published: August 2020

e19508 Background: Nonclinical studies have demonstrated that histone deacetylase inhibitors (HDACi) significantly reduce the growth of MM cells and enhance cytotoxicity of the proteasome inhibitor bortezomib (Velcade). Romidepsin, a pan-HDACi, has previously shown activity for patients (pts) with relapsed or refractory MM when administered as a 4-hr infusion in combination with dexamethasone and bortezomib. Methods: This open-label, multi-center, phase II study (GPI-08–0006) was initiated to evaluate the activity and safety of a 1-hr infusion of romidepsin in combination with bortezomib for MM pts with relapsed or refractory disease and to evaluate the safety and single dose pharmacokinetics (PK)/pharmacodynamics of romidepsin in the first 5 pts. Pts received 10 mg/m2 romidepsin on days 1, 8 and 15 and 1.0 mg/m2 bortezomib on days 1, 4, 8 and 11 of a 28-day cycle. PK sampling and triplicate ECGs were performed at 0, 0.25, 0.5, 1, 2, 3, 4, 6 and 24 hrs after initiation of the first 1-hr infusion of romidepsin. Results: To date, 5 pts have been enrolled (median age 68 [range, 65–72]) 2 pts who relapsed from recent bortezomib-containing regimens experienced minimal responses after 2 cycles. 2 pts have experienced grade 3 thrombocytopenia. No pt had a QTcF value of >480 ms the mean change in QTcF from baseline to Cmax was 4.2 ms (-10 to 13). Values for PK parameters are included in the table . When compared with data from pts who were treated with a 4-hr infusion of 14 mg/m2, the Cmax of the 1-hr infusion of romidepsin 10 mg/m2 was ∼ 20% higher and exposure (AUC0–24hr) was reduced by 70%. Conclusions: Preliminary data suggest that the 1-hr infusion of romidepsin combined with bortezomib is active for pts with MM relapsed or refractory to bortezomib. Based on the initial incidence of grade 3 thrombocytopenia and PK data, additional pts are being treated on the same schedule but with a reduced dose of romidepsin (8 mg/m2). This study continues to enroll pts. [Table: see text] [Table: see text]
CD3 immunotoxin therapy of cutaneous T cell lymphoma
Authors: Frankel A. E. , Woo J. , Zuckero S. L. , Mankin A. A. , Grable M. , Mitchell K. , Lee Y. , Neville D. M. 
Published: August 2020

e19511 Background: T cell lymphomas represent 12% of lymphoma cases in the U.S. Cytotoxic chemotherapies, radiation therapies, monoclonal antibodies, transcription modulators and topical therapies yield remissions, but over half of patients relapse and die with progressive disease. Patients ineligible for allogeneic transplant need additional therapeutic options. One class of T cell directed agents are immunotoxins composed of protein synthesis inactivating peptide toxins covalently linked to antibodies or hormone ligands. We prepared a new immunotoxin, A-dmDT390-bisFv(UCHT1) composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with an acidic loop on the extracellular domain of CD3epsilon. We prepared a clinical batch of drug and obtained FDA approval for a phase I trial (IND#100712). Methods: Cohort of three-six CTCL patients were treated with immunotoxin via 15min IV infusion twice daily for four days at 2.5–5ug/kg. CTCAEv3.0 toxicity grading, blood samples counts, chemistries, CMV/EBV PCR, PK, immune response and flow cytometry, and disease assessments by CT scans, skin mapping and bone marrow biopsies were done. Results: Six patients received all eight 2.5ug/kg doses. Toxicities were mild- moderate with fever, chills, nausea, transaminasemia, hypoalbuminemia, lymphopenia and reactivation of EBV and CMV. Side effects responded to antipyretics, anti-emetics, albumin infusions, rituximab and valgancyclovir. Lymphopenia was marked at the end of treatment (99.9% reduction) and was followed by partial recovery at two weeks. Circulating T regulatory cells doubled. Cmax occured 5 min post-infusion and was 18ng/mL. Half-life was 49 min. All patient had anti-immunotoxin antibodies at a median of 1.3ug/mL which increased after 30 days to 9–1700ug/mL. Two of five evaluable patients had PRs lasting one and 6+ months. Conclusions: This novel immunotoxin has dramatic clinical activity even at the lowest dose in CTCL patients and merits applications at higher doses in CTCL and other CD3+ T cell leukemia/lymphoma patients. The lymphodepletion with recovery of T regulatory cells suggests the drug may be beneficial for immunosuppression of T cell autoimmune disorders. No significant financial relationships to disclose.
Prognostic value of quantitative image analysis (QIA) for determination of proliferative index in mantle cell lymphoma (MCL) treated with sequential chemotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR)
Authors: Schaffel R. , Hedvat C. , Teruya-Feldstein J. , Portlock C. S. , Moskowitz C. H. , Zelenetz A. D. 
Published: August 2020

e19522 Background: Gene expression studies have demonstrated that the proliferation signature is the most important factor in determination of outcome in MCL. However, visual assessment of immunohistochemical staining is not standardized. QIA of MIB-1/Ki67 staining may have a greater reliability for determination of the PI. We tested the agreement between manual counting (MC) and QIA and its prognostic value in patients with MCL. Methods: 105 patients with MCL underwent therapy for de novo MCL, of these, 66 had slides stained with MIB-1 for the analysis. The PI was determined in three ways: 1) estimation by a hematopathologist using a microscope (manual count, MC); 2) visual estimation by an independent hematopathologist after whole slide digitization; and 3) QIA software (color deconvolution algorithm). The survival analysis was restricted to 47 patients that were treated with sequential therapy followed by upfront consolidation with HDT/ASCR. Results: A median of 612,394 cells per slide were analyzed by QIA. There was a good correlation between the QIA and both the MC under the microscope and digital image (0.9061, P<0.001 and 0.9336, P<0.001; Spearman test) as well as between the pathologists (0.897, P<0.001). Based on a 30% cutoff, the agreements (kappa test) were: interobserver, 0.6 (80% of slides); between QIA and MC of visual image, 0.86 (94% of slides); and between the QIA and MC using standard microscopy, 0.72 (86% of slides). In the survival analysis, the median PI was 25% (0.7% to 74%). By QIA, 27 patients had a low PI (<30%) and 20 patients had a high PI. At a median follow-up of 4.4 years, the 5 year overall survival (OS) and event free survival (EFS) were inferior in the high PI cohort (66% v 93%, P=0.003 and 0 v 71%, P<0.001, respectively). In a Cox regression analysis, both OS and EFS were significantly associated with PI and not associated with either MIPI or inclusion of rituximab during therapy. No event was reported after 4.7 years of follow-up in the low-PI group. Conclusions: Digital image analysis of MIB-1/Ki67 staining is highly reproducible and further validates the prognostic significance of a high PI in MCL using a threshold of 30%. No significant financial relationships to disclose.