bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vatalanib (V) for patients with previously untreated advanced malignant mesothelioma (MM): A phase II study by the Cancer and Leukemia Group B (CALGB 30107)
Authors: Jahan T. M. , Gu L. , Wang X. , Kratzke R. A. , Dudek A. Z. , Green M. R. , Vokes E. E. , Kindler H. L. 
Published: March 2020

7081 Background: Targeting both vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) may be an appropriate therapeutic strategy in MM. MM express VEGF, PDGF, and their receptors, suggesting autocrine growth-stimulating loops. VEGF inhibitors and PDGF inhibitors have in vitro activity in MM. In MM patients (pts), high VEGF levels correlate with poor outcome. Vatalanib inhibits VEGF and PDGF receptor tyrosine kinases. Methods: We conducted a phase II trial of V in pts with unresectable, histologically-confirmed MM, measurable disease, no prior therapy, ECOG performance status (PS) 0–1. Primary endpoint: 3-month (mo) progression-free survival (PFS). V 1250 mg, was given orally daily. CT scans were obtained Q6 weeks. Baseline serum VEGF, PDGF were determined. Results: 47 eligible pts (46 evaluable) enrolled at 19 sites from 7/03–11/04. Pt characteristics: male 92%, median age 75 (range 51–92; 64% were >70). Histology: epithelial 80%, sarcomatoid 11%, biphasic 9%. Site of origin: pleura 87%, peritoneum 6%, other 6%. PS 0/1: 21%/ 79%. 261 cycles were administered, median 3, range 1–32; 2 pts continue treatment. Grade 3/4 toxicities: neutropenia 2%, lymphopenia 2%, nausea/vomiting 15%/9%, increased ALT/AST 9%/6%, hypertension 2%, gastrointestinal bleed 2%. Partial response: 11% (5 pts), stable disease 66%. 3-mo PFS: 55% (95% CI: 40%, 68%), median PFS: 4.1 mo; median survival 10.0 mo. Median baseline serum levels in 40 pts: VEGF 425 pg/mL, PDGF 22754 pg/mL. There was no correlation between baseline VEGF or PDGF levels and response, PFS, or survival. Conclusions: The study did not achieve the protocol-specified 3-mo PFS of 75%. However, the objective response rate of 11% and median survival of 10 months are similar to other active single-agents for MM, which suggests that V may warrant further study in this disease. [Table: see text]
Pneumonectomy following induction chemoradiotherapy (CRT) in NSCLC at Fox Chase Cancer Center (FCCC): Peri-operative mortality rate is lower than expected
Authors: Brown K. M. , Scott W. J. , Langer C. , Feigenberg S. , King E. , Goldberg M. 
Published: March 2020

7107 Background: Induction CRT is used commonly prior to resection for NSCLC. Selected data cite increased operative mortality in patients (pts) requiring pneumonectomy following induction CRT (> 25% in RTOG 9309). We reviewed the FCCC experience with pneumonectomy for NSCLC and compared operative outcomes in pts who had induction CRT to those who had surgery (S) as initial treatment. Methods: Retrospective review of pts undergoing pneumonectomy for NSCLC from 1993–2005. Perioperative variables were analyzed for impact on operative mortality and complications. Results: 169 pts were analyzed: 110 (65%) were male; median age was 64 (range 39–84). 39 had induction CRT; 16 had preoperative chemo only and 3 had preoperative radiation only. Overall operative mortality was 13/169 (7.7%); for CRT pts, mortality was 5/39 (12.8%) compared to 7/111 (6.3%) for S pts (p = NS). In the CRT group, one pt died from respiratory failure due to radiation pneumonitis of the remaining lung; one pt died from complications of pneumonia, and the remainder died of respiratory failure. In the S group, 3 pts died of respiratory failure, 2 died after discharge of unknown causes, and one each died of pulmonary hypertension and empyema. Complications occurred in 19/39 (48.7%) of CRT pts compared to 39/111 (35%) in S patients (p = NS). Cardiac arrhythmias and pneumonia were the most common complications in both groups. A pre-op DLCO <60% predicted was associated with increased operative death (p = 0.045) and complications (p = 0.066) in the CRT group; this association was not present in the S group. There was no difference in DLCO between the groups. Age, diabetes, tobacco, laterality of surgery, and pre-op FEV1 did not predict operative complications or death in any group. Conclusions: Induction chemoradiotherapy pre-pneumonectomy is not associated with a statistically significant increase in perioperative morbidity or mortality vs those undergoing surgery alone. Mortality rate for CRT appears lower than that seen in RTOG 9309. DLCO <60% is a risk factor in pts with induction CRT, but not in our pts undergoing surgery alone. No significant financial relationships to disclose.
Analysis of prognostic factors in chemo-naïve patients with advanced NSCLC and poor performance status (PS): Cox regression analysis of two phase III trials
Authors: O’Brien M. , Bonomi P. , Langer C. , O’Byrne K. , Bandstra B. , Ross H. , Sandler A. , Socinski M. , Paz-Ares L. 
Published: March 2020

7113 Background: Two phase III trials in chemo-naïve PS2 patients with advanced NSCLC compared paclitaxel poliglumex (PPX) to either gemcitabine or vinorelbine (STELLAR 4), or PPX/carboplatin to paclitaxel/carboplatin (STELLAR 3). While overall survival (OS) was similar between treatment arms in both studies, individual patient characteristics may be predictive of benefit. Methods: STELLAR 3 and STELLAR 4 enrolled 400 and 381 chemo-naïve PS2 patients, respectively. The impact of pre-defined baseline characteristics on OS was evaluated by univariate and step-wise multivariate Cox regression analysis. Treatment differences between subgroups were also estimated by Cox analysis. Results: Univariate Cox analysis of potential risk factors showed pre-baseline weight loss, extra-thoracic metastasis, and a low lung cancer symptom (LCS) score to be highly significant (p < 0.001). In STELLAR 4, tobacco use was also a highly significant risk factor. Important primary baseline factors predicting survival as determined by multivariate analysis are summarized in the table . Other baseline factors evaluated but not predictive of survival included gender, number of comorbidities, age, and history of tobacco use. Treatment differences between subgroups were not statistically significant; however, a strong trend towards improved survival was observed for women receiving PPX in STELLAR 4 compared to those in the control-arm (HR = 0.65; p = 0.069). In contrast, men had similar survival between treatment arms (HR = 1.08; p = 0.579). Conclusion: In this large PS2 patient population, weight loss, presence of extra-thoracic metastasis, low LCS scores, and high LDH were found to be important clinical determinants of survival. In addition, significant differences in survival based on geographic region in STELLAR 3 highlight the importance of stratification by region. [Table: see text] [Table: see text]
Are age and comorbidity independent prognostic factors in the treatment of metastatic NSCLC? A review of prospectively randomized national cancer institute of Canada Clinical Trials Group (NCIC CTG) trials
Authors: Asmis T. R. , Ding K. , Whitehead M. , Seymour L. , Shepherd F. A. , Winton T. , Leighl N. , Goss G. 
Published: March 2020

7117 Background: This study analyzed all patients enrolled in two large prospectively randomized trials of systemic chemotherapy to determine whether age and/or co-morbidity are independent predictors of outcome. Methods: Baseline information was recorded, including ongoing medical problems and current medications. This information was extracted and scored using the validated Charlson co-morbidity scale. Scores were then correlated with other clinical data, which included age, gender, race, performance status, histology, stage, weight, LDH, chemotherapy (type, total dose, dose intensity), response and survival. Results: A total of 1,255 patients (481 in BR10 and 774 in BR18) were included in this analysis, the median age was 61.2 years (range 34.2 to 88.7), 827 were less than 65yrs, and 428 65yrs or older. 391 had other medical conditions besides the primary disease of lung cancer, 310 with a Charlson co-morbidity score of 1, and 81 with a cumulative score of 2 or higher. There were more male patients with co-morbidity (35% vs. 21%, p < 0.0001); fewer patients with histologic subtype of adeno with co-morbidity (26% vs. 35%, p = 0.001); and more older patients with co-morbidity (42% vs. 26%, p < 0.001). There was no difference in overall survival in the elderly (≥65) as compared to the younger patients (<65). In contrast, patients with co-morbidity were associated with a shorter survival (p = 0.01). A cumulative Charlson score of 1 was associated with a hazard ratio of 1.28 (95% CI 1.09–1.5; p =0.003), and a cumulative score of 2+ was associated with a hazard ratio of 1.09 (95% C.I. 0.83 -1.44, p = 0.52). Conclusions: From these two large randomized NCIC CTG trials, one observes that age over 65 is not associated with a worse outcome. However, the presence of co-morbidity does appear to be a negative prognostic factor and co-morbity is more common in older patients. No significant financial relationships to disclose.
Vinorelbine (NVB) oral (NVBo) in combination with carboplatin (CBDCA) followed by maintenance therapy with single agent vinorelbine oral in stage III/IV non-small cell lung cancer (NSCLC): Final results of a multicenter international phase II trial
Authors: Abratt R. P. , Macha H. , Del Barco S. , Aubert D. , Mitrovic M. , Parlier Y. , Gatzemeier U. 
Published: March 2020

7126 Background: NVB i.v. day 1 (25 mg/ m2) & NVBo day 8 (60 mg/ m2) and CBDCA AUC 5 have been previously studied in chemonaive NSCLC patients (pts) (O’Brien et al, Ann Oncol 2004; 15: 921). We investigated the efficacy and safety of NVBo weekly with CBDCA AUC 5 q3w for 4 cycles(Cy) followed by maintenance therapy with single agent NVBo in non progressive pts. Methods: Inoperable NSCLC stage IIIB, stage IV or delayed relapse of any stage becoming unresectable, KPS ≥ 80%, treated with combination therapy every 3 weeks for 4 Cy: NVBo 60 mg/m2 on days 1, 8 and 15 (Cy1), 80 mg/m2 (Cy2–4) in absence of neutropenia NCI CTC V2 G3/4; CBDCA AUC 5 day 1, administered over 1 hour. Maintenance therapy if pts did not have a PD: NVBo 60 mg/m2 for the first three weekly administrations, followed by NVBo at 80 mg/m2/week until PD. Results: from December 2003 to January 2005 57/56 pts have been registered/treated: median age 61 yrs (37–71); median KPS 90%; male 71.4%; Squamous cell 30%, Adenocarcinoma 50%; Stage III/IV 32.1/62.5% ; median dose intensity NVBo (% RDI) : combination, 50.1 mg/m2/w (67.3%), maintenance 56.2 mg/m2/w (70.2%); pts with NVBo dose escalation from 60 to 80 mg/m2 during combination : 36/52 (69.2%). Tolerance (% of pts with G3/4 NCI CTC V2) : Neutropenia 23.2/44.6; Platelets 16.1/1.8; Hb 19.6/3.6; Nausea 7.1/0; Vomiting 7.1/0; Diarrhea 5.4/0. No G3/4 toxicity was reported for Infection, Bilirubin, Creatinine, Stomatitis, and motor/sensory Neuropathy. Febrile Neutropenia was reported in 5 patients (8.9%). Efficacy: (RECIST) Percent Overall Response rates (n =56 pts) PR 17.9, SD 53.6, PD 23.2, NE 5.4; Progression-Free Survival 4.3 (95% CI [3.1–5.1]) months; Overall Survival 9.7 (95% CI [7.7–11.9]) months. Conclusions: NVBo on a weekly schedule and CBDCA AUC5 in combination therapy for 4 Cy followed by NVBo in maintenance therapy is an effective and safe treatment regimen for advanced NSCLC. The avoidance of further CBDCA administrations after 4 Cy and the use of NVBo as a maintenance therapy until PD has promise as an alternative to the 6 Cy option and calls for further comparative studies. [Table: see text]
A phase II evaluation of the combination of paclitaxel protein-bound and carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Allerton J. P. , Hagenstad C. T. , Webb R. T. , Smith G. B. , Birch R. , Goggins T. F. , Katakkar S. B. , Khan W. , Mehta N. D. , Greco F. A. 
Published: March 2020

7127 Background: Abraxane (A) is a cremophor free, albumin-bound nanoparticle of paclitaxel (P) approved for the treatment of metastatic breast cancer. Belani et al. (JCO 21: 2933–2939, 2003) reported that P 100 mg/m2 days 1, 8 and 15 q 28 days with C AUC 6 on day 1 led to a 32% response rate in 132 patients (pts) with NSCLC. The median time to progression (TTP) was 35 weeks (wks) for stage IIIB and 29 wks for stage IV. Methods: This study was designed to determine if substituting A for P at an identical dose would lead to an improved response rate, TTP or decreased toxicity. Results: Fifty-six pts with stage IIIB/IV NSCLC previously untreated with chemotherapy were enrolled. The median age was 66 (range 37 - 83); 37 were male and median ECOG performance status was 1 (range 0–2). Thirteen pts were stage IIIB. Metastases included bone (17), liver (7), brain (2) and lymph nodes (16). Currently a total of 239 cycles of therapy have been administered with a median of 4 (range 1–8) cycles per pt. In 194 (81%) full dose A was administered on days 1, 8 and 15. The table below shows toxicities compared to P: Seven pts (13%) experienced grade (G) 1 neuropathy and 3 pts (5%) experienced G 2 neuropathy. Five pts were inevaluable for response due to removal from study after <2 cycles of treatment (2 died from progressive disease, 2 because of toxicity - thrombocytopenia and neutropenia - and 1 refused). Of 51 evaluable pts 1 (2%) had a complete response and 23 patients (45%) achieved a partial response. Four of 10 evaluable stage IIIB pts obtained a PR. Twenty-one pts were stable for at least 12 weeks of whom twenty remain stable at 12–29 weeks and one progressed at 23 weeks. A total of 13 pts have progressed and 3 pts have died. The Kaplan-Meier estimate of median TTP is 23 wks and maximum follow up is 34 wks. Conclusions: We conclude that combining A and C is tolerable and active in the treatment of newly-diagnosed NSCLC and antitumor activity compares favorably to that of P/C. Further studies are warranted in this population. [Table: see text] [Table: see text]
Components of metabolic syndrome correlate with longer survival in NSCLC in bexarotene-treated patients with high hypertriglyceridemia in SPIRIT I and II trials: A retrospective analysis
Authors: Dziewanowska Z. , Zhang J. , Sun S. , Groves E. , Negro-Vilar A. 
Published: March 2020

7137 Background: Bexarotene activates RXR receptors regulating cell proliferation, differentiation, apoptosis and many aspects of lipid metabolism. Both SPIRIT I and II trials (ASCO 2005) showed that a large (36%) subgroup of bexarotene-treated patients showing high sensitivity to hypertriglyceridemia had a significantly longer survival in both studies. This subgroup included males, smokers, stage IV and weight loss, factors associated with poorer survival. A recent study in retinoid-treated patients revealed those developing high hypertriglyceridemia, as well as their parents, have a familial predisposition to hyperlipidemia and the metabolic syndrome (Ann Intern Med, 2002, 136:582). We evaluated baseline and in-treatment patient characteristics in relation to triglyceride responses and overall survival after bexarotene treatment to further extend that observation to NSCLC patients. Methods: A pooled analysis of 595 patients treated with bexarotene in SPIRIT I and II trials assessed factors related to metabolic syndrome (BMI, HDL, LDL and Total cholesterol [T-chol], T-chol/HDL ratio, triglycerides, glucose, blood pressure) at baseline and during treatment at the time of high-triglyceridemia. Individual and composite risk factor scores were evaluated by logistic and Cox-regression analysis in two subgroups, e.g., Responders (high trigs, long survival) and Non-responders (low trigs, shorter survival). Results: Among in-treatment risk factors, Responders (N = 215) had significantly higher (p < 0.0001) BMI, trigs, T-chol, T-chol/HDL ratio and lower HDL (p < 0.0001) than Non-responders (N = 380). A composite risk score (the sum of the individual in-treatment dichotomous risk scores) analysis also showed a significantly (p < 0.0001) higher score for metabolic risk factors in the Responder/longer survival subgroup. Hazard ratio analysis by Cox-regression showed a 13% survival benefit for each composite score increase. Conclusions: Baseline and in-treatment triglycerides and other key metabolic syndrome factors are important predictors and contributors to the beneficial survival impact of bexarotene in this important subgroup of NSCLC patients. [Table: see text]
Secondary primary cancer in the long-term survivors with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer
Authors: Takigawa N. , Segawa Y. , Kiura K. , Tabata M. , Ueoka H. , Yonei T. , Shibayama T. , Takata I. , Matsuo K. , Tanimoto M. 
Published: March 2020

7147 Background: Although concurrent chemoradiotherapy (CT/RT) is associated with increased survival for patients (pts) with locally advanced non-small cell lung cancer (NSCLC), long-outcomes beyond 5 years have not been fully analyzed. Methods: Between 1994 and 1999, we conducted two phase II studies examining concurrent CT/RT for treatment of surgically unresectable stage IIIA or IIIB NSCLC. One regimen consisted of three cycles of 5-fluorouracil 500mg/m2 and cisplatin 20mg/m2, days 1–5, every 4 weeks and concurrent hyperfractionated thoracic RT (1.25Gy twice daily, total 62.5–70Gy) [FP-TRT] (Segawa et al. BJC 82, 2000). The other consisted of docetaxel 40mg/m2 and cisplatin 40mg/m2, days 1, 8, 29 and 36 and concurrent thoracic RT (2Gy daily, total 60Gy) [DP-TRT] (Kiura et al. BJC 89, 2003). Long-term data is presented. Results: In 50 pts treated with FP-TRT, the median survival time (MST) was 1.6 years (yr; 95% confidential interval [CI]: 0.91 - 2.25 yr) by a median follow-up time of 10.4 yr and the actual 5 yr-survival rate was 30%. In 15 long-term survivors, 3 and 2 pts died due to primary NSCLC and secondary primary cancer (SPC), respectively, 1 was lost to follow-up, and 9 are still alive. In 42 pts treated with DP-TRT, the MST was 2.1 yr (95% CI: 0.82 - 2.48 yr) by a median follow-up time of 6.3 yr and the actual 5 yr-survival rate was 31%. In 13 long-term survivors, 1 pt died due to primary NSCLC, 1 died due to SPC, 1 was lost to follow-up, and 10 are still alive. Overall, 7 of 92 pts enrolled in these studies developed SPCs (2 NSCLC, 1 small cell lung cancer, 2 esophageal cancers, 2 gall bladder cancers) although no pts developed leukemia or myelodysplastic syndrome. An observed incidence rate of SPCs was 2356.1/100,000 (95% CI: 947.6 - 4856.0). Cumulative incidence was 5.8% (standard error [SE] 4.0%) at 5 yr, 10.0% (SE 5.6%) at 8 yr and 60.8% (SE 18.9%) at 10 yr. The median time from the beginning of CT/RT to the diagnosis of SPC was 9.6 yr (95% CI: 8.1 - 11.1 yr). Conclusions: Approximately 30% of pts survived more than 5 years after concurrent CT/RT, however, they were still at risk of dying from primary NSCLC. Occurrence of SPC in long-term survivors should be concerned in follow-up. No significant financial relationships to disclose.
Patient attitude and survival in advanced non-small cell lung cancer (NSCLC): Results of a prospective observational study
Authors: Altug S. , Wang L. , Chu D. , Park K. , Hsu H. , Cok G. , Roubec J. , Patil S. , Damyanov D. , Reece W. 
Published: March 2020

7148 Background: A physician’s ability to accurately identify a patient’s attitude toward treatment is critical. The primary objective of this study (B9E-AA-JHSH) was to evaluate patient attitudes as predictors of survival independently of currently known predictive variables, and secondarily, whether physician-assessed patient attitudes differed from patient-assessed attitudes. Methods: This was a non-interventional, prospective, observational study of patients from 19 countries of Asia, Central Eastern Europe, and Latin America. Eligible patients had stage IIIB/IV NSCLC not amenable to curative surgery/radiotherapy, gemcitabine and cis/carboplatin as part of treatment, and were chemonaive. Physicians and patients used a 7-item questionnaire to assign patient attitudes to 1 of 4 categories using a pre-defined algorithm: A = Cure; B = Maximum extension of survival with acceptance of high toxicity; C = Maximum extension of survival only if coupled with normal lifestyle; and D = Symptom relief. Enrolled patients were followed until 18 months from enrolment, death, or loss to follow up. Results: From Sept 2002 to Dec 2003, 1,985 patients were enrolled; the majority were male (73.4%), <70 yrs (83.9%), and had stage IV disease (79.2%), PS 0–1 (79.2%), and tumor-related symptoms (89.2%). Distribution of patient-assessed attitudes were A = 0%, B = 55%, C = 25%, and D = 20%. From category B-D, median survival (B = 14.6 months, C = 13.5, D = 12.5) and 1-year survival (B = 57.6%, C = 56.2%, D = 51.2%) both decreased but the differences were not statistically significant. Adjustment for known predictive variables eliminated this decreasing trend. Physician-assessed patient attitudes were lower than patient-assessed attitudes (p < .0001); however, the difference was less for patients with disease-related symptoms (p = .03). Conclusions: This is the largest analysis to date of patient attitudes when treated with gemcitabine and cis/carboplatin. Patient attitudes were not significant predictors of survival; however, physicians do underestimate patients’ desire for extended survival compared to symptom relief. Also, it was interesting to see a comparatively longer median and 1-year survival in routine practice compared to reports in clinical trial settings. [Table: see text]
ECOG 3503: A pilot study to determine if downstream markers of EGFR linked signaling pathways predict response to erlotinib (OSI-774) in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)
Authors: Kolesar J. , Brahmer J. , Li S. , Guaglianone P. , Patel J. , Keppen M. , Hidalgo M. , Carbone D. , Siegfried J. , Schiller J. 
Published: March 2020

7162 Background: Markers of response and survival in patients (pts) who benefit from erlotinib (Elb) remain controversial. In another study, pts who developed a rash on Elb survived longer. The primary objective of this study is to prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response. The secondary objectives are to estimate response rate (RR), disease control rate, time to progression, survival, and if a grade (gr) 2 rash is a predictor of response and survival. Methods: Pts with advanced NSCLC (Stage IIIB with pleural effusion and IV, no prior systemic treatment, performance status 0–2, no symptomatic CNS metastasis, and adequate renal, hepatic and hematologic function) were accrued to this single arm study. Elb was taken orally once a day until disease progression or unacceptable toxicity. Starting at 150 mg per day, the dose was escalated by 25 mg once every 2 weeks until a gr 2 rash developed, other toxicities precluded escalation, or a maximum dose of 250 mg reached. Response was evaluated by RECIST criteria. Paraffin-fixed tumor tissue was collected on all patients for correlative studies. Results: Over 8 months, 137 pts (58 M, 79 F) were recruited with a median age of 70 (41–92). Most pts were Caucasian (92%) and had adenocarcinoma (54%). Dose escalation occurred in 53/117 of pts, with 11 getting a dose of 250mg. Only 58 pts have been evaluated for response so far. The preliminary RR is 1% (1/58) with stable disease rate of 18% (32/58). Pts have received a median of 4 cycles of treatment (range 0–10). Most pts went off trial because of progression of disease (38%, 52/137) with only 8% (11/137) stopping because of toxicities (42% unknown). Of the 123 pts evaluated for toxicity, 44 (36%) and 10 (8%) had a grade 1 / 2 and 3 rash respectively. Grade 1 / 2 diarrhea occurred in 16% (20/123) and Grade 3 diarrhea in 10% (13/123). One pt died of pneumonitis of unclear cause. Conclusions: Mature toxicity, response, and survival data as well as laboratory studies which include IHC, EGFR mutation and FISH analysis, and genotype and allele frequency will be available at the meeting. [Table: see text]