bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of CAT-3888 (BL22) in chemo-resistant hairy cell leukemia
Authors: Kreitman R. J. , Wilson W. H. , Stetler-Stevenson M. , Noel P. , FitzGerald D. J. , Pastan I. 
Published: March 2020

7095 Background: CAT-3888 (BL22) is a recombinant anti-CD22 immunotoxin which showed phase I activity in chemo-resistant hairy cell leukemia (HCL). Methods: Eligible patients had relapsed HCL < 4-years after prior cladribine (CdA) and needed additional treatment based on blood counts. Patients were stratified into 2 groups by most recent CdA response of < 1 year or 1–4 years. A 3rd group was added for patients with uncontrolled infection. The study used a 2-stage design of 10 patients each for the first two strata with expansion to 17–30 if hematological remission (HR, i.e. ANC, platelets and Hgb at least 1.5, 100, and 11, respectively) was achieved in at least 3/10. The third strata allowed up to 5 patients. Patients received 40 ug/Kg every other day (QOD) ×3 on cycle 1. Those achieving HR were observed. Patients without a HR and no neutralizing antibodies were retreated at 30 ug/Kg QOD ×3 every 4 weeks beginning at least 8 weeks after cycle 1. Results: 35 patients were enrolled including 25, 9 and 1 in groups 1–3, respectively. CR (44% vs 48%) and overall response (ORR)(64% vs 89%) were similar in strata 1 and 2 with 16 (47%) CRs and 8 (24%) partial responses (PRs) overall. Response was particularly high in 22 with baseline spleen size < 200 mm (95% ORR; 59% CR, 36% PR) compared to patients with spleen height > 200 (ORR 20%, p = 0.001) or patients post-splenectomy (ORR 25%, p = 0.0003). The only serious toxicity was completely reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis, in 1 (3%) patient on cycle 2. Neutralizing antibodies which prevented additional cycles were observed in 4 (11%) patients. Conclusions: The activity of CAT-3888 (BL22) in HCL is confirmed in this phase II trial. Toxicity may be limited by retreating only those who do not respond to 1 cycle. Optimal response to CAT-3888 (BL22) following CdA failure may be achieved before the occurrence of massive splenomegaly or splenectomy. No significant financial relationships to disclose.
Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced non- small cell lung cancer (NSCLC)
Authors: Acharya C. , Hsu D. , Balakumaran B. , Walters K. , Vlahovic V. , Riedel R. , Garst J. , Febbo P. , Nevins J. , Potti A. 
Published: March 2020

7501 Background: Standard treatment for advanced non-small lung cancer (NSCLC) includes platinum-based therapy. Response is however suboptimal and unpredictable. Newer agents, such as pemetrexed, have shown significant activity in the second-line setting, but their role in the first-line setting is unknown. Methods: Using in vitro drug sensitivity data, coupled with Affymetrix microarray data, gene expression signatures predicting sensitivity to cisplatin and pemetrexed were developed, using methods previously described (Nature Medicine, 2006). Signatures were validated with response data from 32 independent ovarian and lung cancer cell lines as well as 59 patient samples. Results: Genomic-derived signatures of cisplatin and pemetrexed sensitivity were shown to accurately predict response in vitro and, in the case of cisplatin, in 59 samples obtained from advanced disease patients previously treated with cisplatin. The accuracy of the cisplatin predictor, using clinical response as the endpoint, was 83.1% (Sensitivity: 100%, Specificity: 57%). In comparison, determination of ERCC1 status (IHC) had a predictive accuracy of 62% (Sensitivity: 82.8%, Specificity: 33.3%). Interestingly, a significant inverse correlation (p = 0.004) was found between the likelihood of cisplatin and pemetrexed sensitivity in the NSCLC cell lines. This relationhip was further validated in another indepedent cohort of 91 patients with NSCLC (p < 0.01). Finally, using novel cell proliferation experiments, we show that tumors from cisplatin refractory patients that are initially sensitive to pemetrexed, if treated with a taxane (docetaxel or paclitaxel) prior to pemetrexed therapy, develop resistance to subsequent pemetrexed therapy. Conclusions: The use of gene expression signatures that predict cisplatin and pemetrexed sensitivity can be incorporated into strategies to refine the selection of chemotherapeutic drugs chosen as first-line therapy in advanced NSCLC. It is critical for future prospective studies to validate the use of pharmacogenomic predictors of chemosensitivity in NSCLC, to optimize response rates and survival benefit. No significant financial relationships to disclose.
Surgery (S) and radiotherapy (RT) plus adjuvant chemotherapy (CT) versus surgery and radiotherapy in non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomised clinical trials (RCTs)
Authors: Le Pechoux C. , Tribodet H. , Pignon J. P. , Burdett S. 
Published: March 2020

7521 Background: Our previous IPD meta-analysis of CT (BMJ 1995;311:899) suggested that CT may have a role in the treatment of various stages of NSCLC. However, the results in the S + RT setting were uncertain because of the small number of patients in this setting. We have updated this meta-analysis, including trials and outcomes not available in 1995. We report here on the effectiveness of S+RT+CT compared to S+RT. Methods: Systematic searches for RCTs were followed by the central collection, checking and re-analysis of updated IPD. Results from individual trials were combined using the stratified (by trial) log rank test to calculate pooled hazard ratios (HRs). Previously included old trials using long-term alkylating agents were excluded from this analysis. Results: IPD were obtained from 2,626 patients (12% with incomplete resection) from 11 RCTs. This represents 86% of all known randomised patients and adds a further 5 trials and 1,956 patients to the 1995 analyses. Median follow-up is 6.3 years. Ten trials used sequential RT-CT. 8 RCTs used cisplatin + vinca alkaloid/ etoposide, 1 used cisplatin + tegafur and 2 used other platinum regimens. There is a significant benefit of CT on survival (HR=0.88, 95% CI=[0.80–0.96], p=0.0062), with an absolute benefit of 4.7% (from 29% to 34%) at 5 years. The HRs for older (0.93 [0.79–1.10]) and more recent trials (0.89 [0.81–0.97]) were comparable (test for interaction p=0.49). Results were similar for recurrence-free survival (0.84, [0.77–0.93], p=0.0006), local (0.79 [0.67–0.94], p=0.0075) and distant recurrence-free interval (0.75 [0.66–0.87], p<0.0001) (data available for 7 trials). There was no clear evidence of a difference in effect by type of CT given. Also, there was no clear evidence that any patient subgroup defined by age, sex or stage benefited more or less from CT. Conclusion: These results demonstrate now a benefit of adjuvant chemotherapy in resected lung cancer associated with radiotherapy. These results are very similar to those of the meta-analysis without radiotherapy. They provides robust estimates for future policy and research. Unrestricted grants from PHRC, LNCC and sanofi-aventis. [Table: see text]
Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM)
Authors: Karrison T. , Kindler H. L. , Gandara D. R. , Lu C. , Guterz T. L. , Nichols K. , Chen H. , Stadler W. M. , Vokes E. E. 
Published: March 2020

7526 Background: In phase II trials in MM, GC on a 21-day (D) schedule has response rates of 16%–26% and median overall survival (OS) of 9.6–13 months (mo). Since VEGF has a key role in MM biology, we added anti-VEGF antibody B to GC in a multi-center, double- blind, placebo-controlled randomized phase II trial. Methods: Eligible pts had unresectable MM; no prior chemotherapy; PS 0–1; no thrombosis, bleeding, or major vessel invasion. Primary endpoint: progression-free survival (PFS). Statistics: 90% power to detect HR 0.57. Stratification: PS (0/1), histology (epithelial/other). G 1,250 mg/m2 D 1, 8 Q21D, C 75 mg/m2 D1 Q21D, and B 15 mg/kg or P D1 Q21D was given × 6 cycles, then B or P Q21D until progression. Baseline plasma VEGF was measured. 115 pts enrolled 12/01- 07/05 at 11 sites, 108 (GCB/GCP) 53/55 were evaluable. Male 74%/84%; median age 62/65 (range 44–78/20–84); PS 1 55%/47%; epithelial 74%/67%; pleural 93%/91%; thrombocytosis 40%/40%. Results: Cycles: total 458/424, median 7/6, range 1–42/2–39. Statistically significantly different (SSD) toxicity (p <0.05), any grade: alopecia 60%/38%; epistaxis 62%/24%; hypertension 45%/22%; non-neutropenic infection 15%/4%; proteinuria 62%/47%; stomatitis 23%/7%. There were no SSD toxicities = grade 3. Median PFS 6.9/6.0 mo (HR 0.93, p=0.88). Median OS 15.6/14.7 mo (p=0.91). 1-year survival 59%/57%. Partial response 25%/22%; stable disease 51%/60%. Median VEGF (N=56) 131/154 pg/ml (range 31–1760/5–1786). Higher VEGF was associated with shorter PFS (p=0.02) and OS (p=0.0066). In pts with VEGF = the median, PFS (p=0.043) and OS (p=0.028) were significantly greater for GCB than GCP; in high VEGF strata this was not SSD. Conclusion: Adding B to GC in MM pts does not yield statistically significant differences in PFS, OS, response, or grade ¾ toxicity. GCB-treated pts with low VEGF levels had longer PFS and OS. Supported by NCI grant N01-CM-17102. No significant financial relationships to disclose.
A randomized phase 3 trial of gemcitabine with or without carboplatin in performance status 2 (PS2) patients (pts) with advanced (stage IIIB with pleural effusion or stage IV) non-small cell lung cancer (NSCLC)
Authors: Obasaju C. K. , Conkling P. , Richards D. , Fitzgibbons J. , Arceneau J. , Boehm K. A. , Asmar L. , Cunneen J. , Peng G. , Reynolds C. 
Published: March 2020

7533 Background: The optimal treatment of patients with advanced NSCLC and PS2 has not been resolved. A retrospective analysis of 99 pts with PS2 in CALGB 9730 (Lilenbaum, JCO 2005) demonstrated improved survival associated with combination carboplatin- paclitaxel versus paclitaxel alone (median overall survival=4.7 vs. 2.4 mos., p=.019). Gemcitabine-carboplatin (GC) is an active doublet in advanced NSCLC and is at least as active as paclitaxel-carboplatin (PC) in PS2 pts (ECOG 1599, Tester ASCO 2004). A prospective validation of the activity of GC is needed, which is addressed by comparing GC versus gemcitabine (G) alone in this setting. Methods: 161 chemonaïve pts with advanced NSCLC and PS2 were randomly assigned to G 1250 mg/m2 alone on Days 1,8 or GC (G 1000mg/m2 Days 1,8 followed by C AUC 5 on Day 1). Cycles were repeated every 21 days for 6 cycles or until disease progression or intolerable toxicity. Primary endpoint was median survival. Conclusions: GC resulted in an improved response rate among NSCLC pts with PS2 over G alone. As expected, G3–4 toxicities were greater with GC. Overall survival data will be reported at the time of the meeting. [Table: see text] [Table: see text]
Phase III randomized study of oral vinorelbine (oV) and gemcitabine (G) (oVG) versus docetaxel (D) and gemcitabine (DG) as first-line treatment of patients with advanced non-small cell lung cancer (NSCLC): A preliminary report
Authors: Agelaki S. , Androulakis N. , Agelidou A. , Agelidou M. , Kotsakis A. , Kakolyris S. , Polyzos A. , Kentepozidis N. , Ziras N. , Mavroudis D. 
Published: March 2020

7538 Background: Non-platinum based doublets are effective treatments for advanced NSCLC. We performed a multicenter phase III trial to compare the efficacy and tolerance of oVG and DG in NSCLC patients (pts). Methods: Chemotherapy-naive pts with stage IIIB/IV NSCLC and PS (WHO) 0–2 and adequate organ function were eligible. Pts received oV 70 mg/m2 combined with G 900 mg/m2 on days 1, 15 of a 4-week cycle or D 75 mg/m2 on day 1 combined with G 1,000 mg/m2 on days 1, 8 of a 3-week cycle. Primary endpoint was OS and secondary endpoints were response rate (RR), time to progression (TTP) and toxicity. Stratification was done for age, stage and PS. Results: 254 pts received oVG (n=121) or DG (n=133). Median age was 64 and 63 years, and PS was 0–1 in 94.2% and 94%, for oVG and DG, respectively. Most patients had disease stage IV and were =70 years (80.9% vs 74.4% and 74% vs 77%, in oVG and DG, respectively). After a median follow-up time of 6.1 months, median OS was 9.0 vs 10.7 months and 1-yr survival was 38% vs 46% for oVG and DG, respectively (p=0.486). Significantly more responders were observed in the DG arm (11% vs 23%, p=0.018). Median TTP was 3.1 vs 3.9 for oVG and DG, respectively (p=0.335). A similar toxicity profile was observed except for a trend for higher neutropenia grade 3–4 in DG compared to oVG (p= 0.066). There was no difference with respect to neutropenic infections (p= 0.124). An analysis of the influence of age (=70 and = 70) on OS and toxicity revealed that OS was similar for both arms in the two age groups but grade 3–4 neutropenia was lower in the oVG arm for pts =70 years. Conclusions: A higher RR that was not translated to a survival benefit was recorded for the DG arm. Both regimens were well tolerated without significant differences in toxicity. No significant financial relationships to disclose.
Increased BRCA1 mRNA: An independent prognostic variable in completely resected chemo-naive non-small cell lung cancer (NSCLC) patients (p)
Authors: Rosell R. , Jassem E. , Skrzypski M. , Taron M. , Mendez P. , Perez L. , Szymanowska A. , Rzyman W. , Gulida G. , Jassem J. 
Published: March 2020

7551 Background: Following surgical resection in operable NSCLC, 5-year survival is 60% in stage I, 39% in stage IIB and 23% in stage IIIA, with relapse commonly as distant metastases. The average benefit of adjuvant chemotherapy is 5%, ranging from nil in stage I to 15% in stage II-IIIA. Caretaker genes involved in keeping genetic alterations to a minimum include the nucleotide excision repair genes ERCC1 and myeloid zinc finger 1 (MZF1), which mediates ERCC1 expression, and other stability genes, such as BRCA1, which control processes involving large portions of chromosomes. Thioredoxin-1 (TRX1) is a redox protein overexpressed in NSCLC that is correlated with poor prognosis, and TWIST contributes to metastasis by promoting epithelial-mesenchymal transition. Methods: In order to identify p with a high risk of relapse, we investigated the expression of these 5 transcripts in frozen resected tumors from 126 resected NSCLC p by real-time quantitative PCR. Gene expression was normalized using β-actin and 18SrRNA expression as internal references. Results: Adenocarcinoma (adeno), 33 p; squamous cell carcinoma (SCC), 93 p. Stage: IA, 18 p; IB, 53 p; IIB, 33 p; IIIA, 22 p. Tumoral transcript expression with β-actin: ERCC1, 1.23; MZF1, 0.53; BRCA1, 3.65; TRX1, 1.82; TWIST, 7.75. A strong correlation was observed between the expression of ERCC1, MZF1 and BRCA1 (P<0.001). Expression of each of the 5 transcripts was higher in SCC than in adeno (P<0.001). Median survival (MS): low ERCC1 (<1.5) = not reached (NR), high ERCC1 = 33 months (m) (P=0.21); low MZF1 (<0.5) = NR, high MZF1 = 33 m (P=0.04); low BRCA1 (<5) = NR, high BRCA1 = 22 months (m) (P=0.01); low TRX1 (<0.8) = NR, high TRX1 = 39.5 m (P=0.02); no differences in MS according to levels of TWIST. In a multivariate Cox model for survival, BRCA1 and stage emerged as independent prognostic variables ( Table ). Conclusion: Increased BRCA1 is associated with shorter survival, and BRCA1 assessment could be useful for customizing adjuvant chemotherapy. No significant financial relationships to disclose. [Table: see text]
Mortality risk for stage I NSCLC with poor histologic grade, tumor size ≥4 cm, and non-upper lobe tumor location: An epidemiologic study of 19,702 patients in the California Cancer Registry from 1989 to 2003
Authors: Ou S. I. , Zell J. A. , Ziogas A. , Anton-Culver H. 
Published: March 2020

7558 Background: Platinum-based adjuvant chemotherapy in randomized trials has failed to provide a survival benefit in stage I non-small-cell lung cancer (NSCLC). Using data from California Cancer Registry (CCR), we explored factors that have detrimental effect on survival in stage I NSCLC to identify a subset of patients at high risk for relapse and subsequent mortality. Methods: 19,702 stage I NSCLC cases in the CCR from 1989 to 2003 were identified and subgrouped into stage IA & IB disease. Patient demographic factors, tumor characteristics and treatment delivered were examined. Kaplan-Meier survival curves were calculated to estimate survival rates. Cox proportional hazards ratios were used to identify independent prognostic factors for survival. Results: Advanced age at diagnosis, male sex, low socioeconomic status (SES), non-surgical treatment & poorly-differentiated histologic grade (stage IA: hazard ratio [HR] = 1.14; 95% confidence interval [CI]: 1.08–1.19 & stage IB: HR = 1.11; 95% CI: 1.07–1.16) were factors identified with increased mortality risk on multivariate analysis. Non-upper lobe tumor location (RML/RLL/LLL) and tumor size ≥ 4 cm (vs < 4 cm; HR = 1.22; 95% CI: 1.15–1.30) were additional factors with increased mortality risk among stage IB patients. Conversely, bronchioloalveolar carcinoma (BAC)(vs adenocarcinoma: stage IA: HR = 0.81; 95% CI: 0.72–0.91 & stage IB: HR = 0.87, 95% CI: 0.77–0.98) & Asian ethnicity (vs Caucasian: stage IA: HR = 0.81, 95% CI: 0.70–0.94 & stage IB: HR = 0.80, 95% CI: 0.72–0.90) were associated with decreased mortality risk in stage I NSCLC. Lobectomy had the lowest HRs for death among all surgical techniques for both stage IA & IB NSCLC in the Cox proportional hazards model. Conclusions: Poorly-differentiated stage IA & IB NSCLC and stage IB NSCLC located in non-upper lobes or tumor size ≥ 4 cm carried an increased mortality risk on adjusted analysis. No significant financial relationships to disclose. [Table: see text]
A multicenter U.S. trial of neoadjuvant pemetrexed plus cisplatin (PC) followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation (RT) for stage I-III malignant pleural mesothelioma (MPM)
Authors: Krug L. M. , Pass H. , Rusch V. W. , Kindler H. L. , Sugarbaker D. , Rosenzweig K. , Friedberg J. S. , Pisters K. , Obasaju C. K. , Vogelzang N. J. 
Published: March 2020

7561 Background: The optimal management for fit patients with early stage MPM remains controversial. One approach involves neoadjuvant chemotherapy followed by EPP and hemithoracic RT and prior trials using gemcitabine and cisplatin have been reported (Weder JCO 2004, Flores JTO 2006). We administered PC, followed by EPP and RT to further assess feasibility and survival of trimodality therapy in a larger, multicenter study. Methods: Eligibility criteria: Stage T1–3 N0–2, no prior surgical resection, adequate organ function (including predicted post-op FEV1 >35%) and PS 0–1. Pts received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 with vitamin supplementation for 4 cycles. Pts without disease progression underwent EPP followed by RT (54 Gy). The primary endpoint was pathologic complete response (pCR) rate. Enrollment was completed in March, 2006. Results: 77 patients were enrolled and 72 are evaluable. Median age 63.5 (range 34–78), M:F = 51:21, Clinical stage I:II:III:IV = 5:31:33:1, epithelial:nonepithelial = 58:15, ECOG PS 0:1:2 = 28:42:2. 83% of patients completed all four cycles of PC. Grade 3/4 events related to chemotherapy included: neutropenia (4%), febrile neutropenia (3%), nausea (1%), vomiting (3%), pneumonia (6%), pulmonary embolism (1%), and chest pain (3%). Of 73 pts assessed for radiologic response, 3 CRs, 21 PRs, 36 SDs, 3 PDs, and 10 were unevaluable; (RR= 33% [95% CI, 0.22, 0.45]). Of 54 pts who underwent surgery, EPP completion rate was 87% (47/54); that is 47/77 (61%) by ITT. Pathologic stage I:II:III:IV:NE = 4:12:24:3:11. One pCR was confirmed. 35/39 completed RT. Preliminary TTP =13.1 mo (95% CI=9.6, 15.9; 48% censored) and median survival=16.6 mo (95% CI=13.9, 19.3; 55% censored;1-yr survival = 68%). Conclusions: This multicenter trial testing trimodality therapy in MPM showed that it is feasible with a high rate of chemotherapy delivery. One pCR was observed. Preliminary survival is below that reported by single institutions for patients undergoing EPP but with a high censorship rate at this early time point. Further analyses are necessary to identify a cohort of patients most likely to benefit. This study was sponsored by Eli Lilly & Company. No significant financial relationships to disclose.
A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): A trial of the Eastern Cooperative Oncology Group
Authors: Sandler A. , Szwaric S. , Dowlati A. , Moore D. F. , Schiller J. H. 
Published: March 2020

7564 Background: Scientific evidence supports the concept that the growth of solid tumors, including SCLC, is dependent on angiogenesis. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to improve survival when combined with chemotherapy in non-small cell lung cancer. PE is a standard regimen for use in SCLC. Thus, we proposed this study of PE plus B in patients (pts) with previously untreated extensive stage SCLC. Methods: Pts with previously untreated extensive SCLC with a performance status 0–2, received P (60 mg/m2) IV followed by E (120 mg/ m2) IV followed by B (15 mg/kg) IV infusion on day 1, with E repeated on days 2 and 3 of a 21-day cycle for 4 cycles or until progressive disease (PD). Pts not experiencing PD continued bevacizumab until disease progression or unacceptable toxicity. The primary endpoint was per cent of patients alive at 6 months. Results: From 6/8/04 to 8/18/06 (includes a ten month accrual suspension to evaluate data), 64 eligible pts were accrued. Patient characteristics: median age of 65.5 years (range: 45–83), 44% males, 95% Caucasian and 9% were performance status = 2. A median of 6 cycles of treatment were administered (range: 1–12). There is toxicity data on 58 pts. The most common treatment-related grade 3 & 4 toxicities were: neutropenia (7 & 26 pts), thrombocytopenia (8 & 2 pts), fatigue (10 pts, grade 3 only), hypertension (4 pts, grade 3 only), febrile neutropenia (2 pts) and dehydration (3 pts, grade 3 only). Two pts experienced grade 5 toxicities (hypotension and infection with grade ¾ neutropenia). There were no grade ≥3 hemorrhagic events. Response information is available on 39 pts. There have been 4 complete responses and 23 partial responses for an overall response rate of 69% (90% exact CI: (55%, 81%). The proportion of pts alive and progression- free at 6 months was 33% (95% CI: 17%, 49%). Conclusions: Preliminary results indicate that the addition of B to the combination of PE in patients with previously untreated extensive stage SCLC appears promising. A randomized phase III trial comparing PE to PE + B is under consideration. No significant financial relationships to disclose.