bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vandetanib with pemetrexed in patients with previously treated non-small cell lung cancer (NSCLC): An open-label, multicenter phase I study
Authors: De Boer R. , Vansteenkiste J. , Humblet Y. , Wolf J. , Nogova L. , Ruffert K. , Smith R. , Godwood A. , Milenkova T. 
Published: March 2020

7654 Background: Vandetanib (ZD6474) is a once-daily oral anticancer drug that selectively inhibits VEGF-dependent tumor angiogenesis and EGFR- and RET-dependent tumor cell proliferation and survival. Methods: Eligible patients had locally advanced or metastatic NSCLC (stage IIIB/IV) after failure of 1st-line chemotherapy. An initial cohort of 10 patients received once- daily oral vandetanib (100 mg) with pemetrexed (500 mg/m2 i.v. infusion every 21 days). If <2 patients experienced a vandetanib- related dose-limiting toxicity (DLT), an additional cohort received vandetanib 300 mg + pemetrexed. The planned duration of treatment was =6 weeks. The primary objective of the study was to establish the safety and tolerability of vandetanib + pemetrexed. Secondary objectives included an assessment of pharmacokinetic (PK) interaction and preliminary assessment of efficacy (RECIST). Results: Twenty- one patients (14 male, 7 female; mean age 60 years, range 44–77) received vandetanib 100 mg + pemetrexed (n=10) or vandetanib 300 mg + pemetrexed (n=11). One DLT was reported in each cohort: QTc prolongation (>100 ms from baseline, but absolute QTc <500 ms) in a male patient who had electrolyte imbalance and short baseline QTc interval of 318 ms (100 mg cohort); and interstitial lung disease, which resolved after steroid therapy, in a Caucasian female patient with bronchoalveolar carcinoma and a long smoking history (300 mg cohort). The most common adverse events (AEs) were rash, anorexia, fatigue and diarrhea (all n=10; 48%). The most frequent CTC grade 3/4 AEs were increased gamma-glutamyltransferase (n=4), anorexia (n=3) and dyspnea (n=3), which are generally consistent with previous experience with vandetanib and pemetrexed as monotherapies. There was no apparent PK interaction between vandetanib and pemetrexed. In 18 patients evaluable for efficacy, there was one confirmed partial response (female; 100 mg cohort) and 13 stable disease =6 weeks. Conclusions: In patients with advanced NSCLC, vandetanib + pemetrexed was generally well tolerated, with no apparent PK interaction. A Phase III trial of vandetanib 100 mg + pemetrexed in 2nd-line NSCLC has begun. No significant financial relationships to disclose.
Expression of protein kinase C beta (PKCß) as a prognostic marker in non-small cell lung cancer (NSCLC) and mesothelioma
Authors: Faoro L. , Loganathan S. , Husain A. , Westerhoff M. , Janamanchi V. , Vokes E. , Salgia R. 
Published: March 2020

7656 Background: The protein kinase C (PKC) family of serine-threonine protein kinases has been shown to be involved in tumor cell growth, survival, and progression. Tumor-induced angiogenesis requires activation of PKCs, particularly PKCβ, through vascular endothelial growth factor (VEGF) pathways. PKCβ-2 appears to be a major down-stream signaling protein for the VEGFR. This makes PKCβ an attractive target in treatment of malignancies, including lung cancer. Methods: 135 tumor samples (111 Non-small cell lung cancer tissues (52 adenocarcinomas (AC), 34 large cell (LC), 25 squamous cell carcinoma (SCC)) and 24 mesotheliomas (MT)) arranged in tumor microarrays (TMAs) were subject to immunohistochemical staining of PKCβ-1 and PKCβ-2. Results were analyzed manually and scored for intensity (1+, 2+, 3+). Clinical information was available for the AC, LC, and SCC group. Survival curves were generated and median survival between groups was compared utilizing the Log-rank methodology. Results: In NSCLC the expression of PKCβ1 was negative in 1% (1/107), 1+ in 14% (15/107), 2+ in 43% (46/107), 3+ in 42% (45/107); PKCβ2 immunostaining was negative in 28.4% (29/102), 1+ in 12.7% (13/102), 3+ in 23.6% (24/102) and 3+ in 35.3% (36/102). Median survival was superior for patients who expressed PKCβ1 (2+ or 3+) as compared to non-expressors (median survival 1258 days versus 124 days, p<0.001). There was no difference in median survival in patients whose tumors expressed PKCβ2 and those that did not express it. In mesothelioma, staining for PKCβ1 was negative in 0, 1+ in 0, 2+ in 8.3% (2/24) and 3+ in 91.7% (22/24). For PKCβ2, tissues stained negative in 56.5% (13/23), 1+ in 21.8% (5/23), 2+ in 8.7% (2/23), 3+ in 13% (3/23). Median survival was superior for patients whose tumors did not express PKC-beta 2 (0 or 1+) as compared to expressors (median survival 604 days versus 103 days, p<0.001). Conclusions: PKCβ is expressed in NSCLC and mesothelioma. PKCβ1 expression is a favorable prognostic factor in NSCLC, whereas expression of PKCβ2 is an adverse prognostic factor in mesothelioma. Therapeutic targeting of this molecule would be useful for the future. No significant financial relationships to disclose.
Study of three weekly nab-paclitaxel regimens in combination with carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC)
Authors: Hawkins M. J. , Manikhas G. , Makhson A. , Cheporov S. , Orlov S. , Yablonsky P. , Bhar P. , Socinski M. 
Published: March 2020

7659 Background: We previously reported that 130-nM albumin-bound form of paclitaxel (ABI-007, nab paclitaxel) 225 - 340 mg/m2 and carboplatin AUC of 6 mg/min·ml (C6), both administered on day (d) 1 every 3 weeks (q3w), produced an objective (PR/CR) response rate (ORR) of 27% in first line patients (pts) with NSCLC with median progression-free (PFS) and overall survivals of 6.0 and >10.3 months respectively [Hawkins et al., ASCO, 2006]. Grade 2 and 3 sensory neuropathy (SN) was 36–56%. The aim of the current study was to obtain clinical experience with weekly schedules of nab- paclitaxel in combination with C6 in NSCLC prior to initiating large scale clinical trials. Methods: 75 Pts with previously untreated, stage IIIB or IV NSCLC with measurable disease and a life expectancy of over 12 weeks were recruited into 3 cohorts (n = 25 each) of successive pts and received nab paclitaxel weekly using 3 different regimens (see table ). Results: Patient Characteristics: 75 pts (100% Caucasian; 84% male; median age, 60; performance status score: 0 [16%], 1 [84%]. Accrual was completed in each cohort and serious adverse events reviewed prior to accrual at the next dose level. The primary efficacy endpoints are provided in the table . Grade 3/4 hematologic toxicities were: neutropenia 32%/35%; thrombocytopenia, 19%/11%; anemia, 24%/3%. The most common non- hematologic toxicities (any grade) were fatigue, 48%; SN, 48%; nausea, 37%; alopecia, 40%; and vomiting, 26%. Grade 2 and 3 SN was 12–28%. Graded toxicity data by regimen will be presented. Conclusions: When combined with C6, the ORR was higher and there was less peripheral neuropathy for weekly nab-paclitaxel compared to our previous experience using q3w administration. [Table: see text] [Table: see text]
Phase II trial of gemcitabine/carboplatin (GC) followed by paclitaxel (P) in patients with performance status = 2,3 or other significant co-morbidity (HIV infection or s/p organ transplantation) in advanced non-small cell lung cancer (NSCLC)
Authors: Bridges B. B. , Thomas L. , Hausner P. , Doyle L. A. , Bedor M. , Smith R. , Brahmer J. , Edelman M. J. 
Published: March 2020

7661 Introduction: The role of chemotherapy (Rx) in patients (pts) with advanced NSCLC and poor performance status (PPS) defined as PS = 2 or 3 is unclear. While survival appears to be enhanced, serious toxicity may occur. In addition, no treatment options have been defined for the growing population of pts with HIV infection or post organ transplantation. Based on a prior study (Cancer 2001;92:146–152), we evaluated the efficacy of sequential, dose attenuated GC followed by P in patients with PS=2,3, HIV infection or s/p solid organ transplantation. Patients and Methods: Rx naive patients with PPS and adequate organ function received G: 1,000 mg/m2 d 1,8 C: AUC=5 d 1 q 21d × 2 followed by P 80 mg/m2 q wk × 6 followed by a 2 wk break and then repeated until progression. Results: 47 of a projected 47 pts have been enrolled. Stage IIIb/IV: 8/39, PS 2/3= 26/19, HIV infection=2, solid organ transplantation=2. 12 (25%) had brain metastases. Thirty-nine pts completed two cycles of GC and 29 pts received at least one cycle of P. Overall response rate:19% (95% CI 1.2%-31.7%). Median survival: 5.8 mo. One year survival: 8.4%. Median event free survival: 3.3 months. Toxicity rates for GC: Grade (gr) 3 neutropenia, anemia and thrombocytopenia = 29.8%, 14.9%, 23.4% respectively, gr 4 neutropenia=19% and 10.6% had gr 4 thrombocytopenia. There were 2 gr 1 bleeding episodes, two pts received platelets and 8 pts received red cells. 8.5% had gr 3 fatigue and 10.6% had gr 3 febrile neutropenia, 4.3% had grade 3 nausea, vomiting. Gr 4 nonhematologic toxicities: Thromboembolism = 1 pt (2.1%), Fever = 1 (2.1%). Toxicity rates for P phase: 2.1% had gr 3 neutropenia and anemia. 4.3% had gr 3 neuropathy. There was 1 episode of gr 4 hemoptysis. Two patients received red cells. Conclusions: 1) Sequential GC to P is well tolerated and active in this population. 2) Survival is comparable to that of other regimens utilized in PS = 2 pts with superior tolerability. 3) The prognosis for these pts is very poor even with Rx.4. This is the first trial to prospectively evaluate Rx for pts with HIV disease or organ transplantation and NSCLC. Supported by Bristol Myers Squibb. No significant financial relationships to disclose.
Elderly subgroup analysis of a randomized phase 3 trial of gemcitabine (G) in combination with carboplatin (Cb) or paclitaxel (P) compared to paclitaxel plus carboplatin in advanced (stage IIIB, IV) non-small cell lung cancer (NSCLC)
Authors: Ansari R. H. , Gonin R. , Socinski M. , Edelman M. , Catalano R. , Marinucci D. , Comis R. , Obasaju C. , Treat J. A. , Belani C. P. 
Published: March 2020

7665 Background: Efficacy and safety of platinum-based chemotherapy doublets in elderly (ELD) NSCLC pts with good PS have been reported to be similar to those in younger pts (N-ELD). However, little data exists about which of the standard regimens are suitable for the ELD. To compare efficacy and safety of doublet regimens in the ELD, we conducted a retrospective age-specific subgroup analysis of our Phase 3 randomized trial comparing 3 regimens for advanced NSCLC (Treat, et al: Abst#7025, Proc ASCO 2005). Methods: A Phase 3 study in advanced (Stage IIIB/IV) NSCLC chemonaive patients with ECOG PS <2 was designed to compare the efficacy of a G-containing platinum regimen GCb (G 1000 mg/m2 IV D 1, 8 plus Cb AUC 5.5, D 1) to a nonplatinum G doublet GP (G 1000 mg/m2 IV D 1,8 plus P 200 mg/m2, D 1) and a reference regimen of PCb (P 225 mg/m2 plus Cb AUC 6.0, D 1). Outcome data of ELD pts (age =70) vs. N-ELD pts (age <70) were compared. Survival (OS) was the primary endpoint with secondary endpoints being response rate (RR), time to progression (TTP) and toxicity. Data from all 3 arms were pooled for this analysis. Results: A total of 314 ELD and 746 N- ELD pts were analyzed (GCb 111/245, GP 100/251, PCb 103/250). There were no significant differences in the OS or TTP distributions in ELD compared to N-ELD pts ( Table 1 ). In general, the incidence and grade of toxicity in ELD vs. N-ELD were comparable. ELD experienced moderately higher incidences of Grade 3–4 constitutional (12.6% vs. 7.1%), neurologic (16.1% vs. 8.9%), and pulmonary (12.3% vs. 7.9%) toxicities compared with N-ELD pts. Conclusion: Use of G-containing doublets as first-line chemotherapy showed similar efficacy to the standard PCb regimen in ELD and N-ELD patients with advanced/metastatic NSCLC as defined by OS, RR, and TTP. ELD tolerated these regimens well despite experiencing slightly more toxicity than younger patients. No significant financial relationships to disclose. [Table: see text]
Sex differences in non-small cell lung cancer (NSCLC) patients (p) participating in Spanish Lung Cancer Group (SLCG) trials
Authors: Isla D. , Felip E. , Garrido P. , Viñolas N. , García-Campelo R. , Lianes P. , Bover I. , Terrasa J. , Sánchez J. J. , Rosell R. 
Published: March 2020

7679 Background: Previous findings about differences by sex in lung cancer have prompted us to undertake a retrospective analysis of clinicopathologic and genetic features in women (W) with advanced NSCLC participating in first-line chemotherapy (CT) SLCG trials. Methods: Data on age, histology, PS, CT schedule, XRCC3 (DNA repair capacity gene) single nucleotide polymorphisms (SNPs) assessment in DNA from peripheral blood lymphocytes and CT outcomes were obtained. Smoking history was not available. Results: 1,191 p included in 4 SLCG trials from 2001 to 2005 treated with CT based on CDDP/GEM, CDDP/DOC or DOC/GEM were analysed. 163 p (14.9%) were W. W were significantly younger than men (M) (median, 57 yrs vs 61 yrs, P<0.0001). Adenocarcinoma was the most frequent histology subtype for W but not for M (77.3% vs 46.8%, P<0.0001). There were not significant differences by sex considering PS (0/1) (P<0.85), stage (IIIB/IV)(P<0.18) or overall response rate (P<0.45). Median time to progression (TTP) was 6.8 months (m) vs 5.3 m (P<0.009) in favour of W. Median overall survival (OS) was 12.9 m for W vs 9.3 m for M (P<0.001). XRCC3 SNPs were distributed similarly between sexes. Both SNPs genotyping of XRCC3 241Met/Met and Thr/Met conditioned better survival in W vs M (P<0.05 and P<0.008). In a multivariate analysis, sex was an independent predictive marker for both OS (HR 1.5, 95% CI 1.2–1.9, P<0.0001) and TTP (HR 1.4, 95% CI 1.1- 1.7, P<0.001), others independent variables found were PS, age, type of CT (only for OS), but not XRCC3 241 genotype. Conclusions: Significant differences have been detected in advanced NSCLC by sex in this retrospective first-line SLCG trials analysis according to age, histology and survival favouring W that are in agreement with previous data. Undertaking prospective sex-specific research is crucial in order to determine the best treatment choice and it could be considered gender as a stratification factor in future phase III trials. No significant financial relationships to disclose.
DN101–004: A multicenter, open label, dose ranging study of DN-101 and docetaxel in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) after platinum-based chemotherapy
Authors: West H. J. , Lee S. , Reyno L. , Fehrenbacher L. , Cohn A. L. , Hopkins J. O. , Irwin D. H. , Smith D. A. , Boyd T. E. , Olsen M. R. 
Published: March 2020

7685 Background: DN-101 is a high-dose oral formulation of calcitriol, the most potent natural ligand of vitamin D receptor. Calcitriol has various anti-neoplastic effects on malignant cells and increases activity of cytotoxic agents, including taxanes. DN-101 in combination with docetaxel was associated with improved survival in a phase II study in androgen-independent prostate cancer and ASCENT 2, a phase III confirmatory study is underway. The objective of the study was to determine the maximum tolerated dose, response rate (ORR), progression-free survival (PFS), and overall survival (OS) of DN-101 in combination with docetaxel in advanced NSCLC patients (pts). Methods: Eligible pts had Stage IIIB or IV NSCLC that progressed on or after platinum-based chemotherapy, ECOG = 1, and measurable disease by RECIST criteria. DN-101 was administered on day 1 in doses of 45 (n=5), 75 (n=4), 135 (n=3), or 180 μg (n=53) in the q21d group, or 180 μg on day 1, followed by 45 (n=5), 90 (n=4), or 180 μg (n=12) on days 8 and 15 in the q7d group. Docetaxel (75 mg/m2 BSA) was given on day 2 q21d for all pts. Results: A total of 86 pts were treated. No unexpected toxicities were reported with DN-101. Grade 3/4 (G3/4) toxicities and fatal adverse events (AEs) were consistent with the reported toxicity of docetaxel alone. Stomatitis (0% in q7d, 9% in q21d) and G3/4 asthenia and fatigue (5% in q7d, 14% in q21d) were less frequent on DN-101 compared to published reports on docetaxel. No pt on DN-101 q21d developed hypercalcemia while 2 pt on DN-101 q7d (180 μg cohort) developed G3/4 hypercalcemia. Three fatal AEs included 2 on DN-101 q21d (1 lung infiltration, 1 pneumonitis) and 1 on DN-101 q7d (intestinal perforation). The ORR was 5.9% (CI 0.1%, 28.7%) and 6.6% (1.8%, 15.9%), median PFS 14.1 (6.0, 20.0) and 11.6 (8.4, 17.4) weeks, median OS 8.8 (7.1, NA) and 6.9 (5.5, 9.7) months, and 1 year survival rate 40% (15.2%, 64.8%) and 31% (18.9%, 42.2%) for the q7d and q21d group, respectively. Conclusions: DN-101 in combination with docetaxel is well-tolerated in advanced NSCLC. The observation of improved PFS, OS, and 1 year survival with weekly DN-101 administration supports further investigation. [Table: see text]
Exclusive high dose rate brachytherapy (HDR-BT) for early stage non-small cell lung carcinoma: Results of a retrospective study in 226 patients
Authors: Aumont M. , Mahe M. A. , Prevost B. , Sunyach M. P. , Peiffert D. , Maingon P. , Thomas L. , Begue M. , Willaume D. , Lerouge D. , Campion L. 
Published: March 2020

7688 Objective: To evaluate efficacy and toxicity of HDR BT in non operable endobronchial carcinoma from a retrospective multicentric study. Patients and Methods: Criteria for selection: non small cell carcinoma accessible to fiberoptic bronchoscopy, no extrabronchial extension on CT, contraindication to surgery and external radiation therapy (ERT). Statistical analysis: survival curves calculated with the Kaplan-Meier method and compared with the Logrank test; Cox model to evaluate in uni and multivariate analysis the impact on survival and complications of these parameters: location of tumor: lobar or segmental vs main stem bronchus, previous ERT vs no, total dose:= 30 Gy vs less, dose per fraction:= 5 Gy vs more, number of catheter(s):1 vs = 2. Results: Between 1991 and 2006, 226 patients from 9 radiotherapy departments were included. Main characteristics of tumors: squamous-cell histology: 96%, stage Tis: 60, T1: 153, T2: 9, Tx 4; lobar or segmental location: 91%. 51 patients (22.5%) had received ERT for previous lung cancer(s). Characteristics of HDR BT were: total dose = 30 Gy: 70%, dose per fraction = 5 Gy: 66%, 1 catheter: 46%. Dose was prescribed at 1 cm from the radius. Mean follow-up was 30.4 months (9- 116). Histologic evaluation was performed at 3 months in 137 patients. 92% had a complete response. 128 patients were died: intercurrent disease 45, local failure 35, complications 13. Two and 5-year survival: overall: 57%, 29%; specific (death of lung cancer) 81%, 56%; local- relapse free (LRF) 68%, 50%. Toxicity included 1.3% pneumothorax, hemoptysis 6.6% (5% fatal), bronchitis 20%. In univariate analysis: overall, specific and LRF survival were better for lobar or segmental location vs main stem bronchus (p=0.0001), overall and specific survival were higher with no previous ERT (p=0.006). In multivariate analysis, lobar or segmental location was associated with improved overall (p=0.0001) and LRF (p=0.003) survival. LRF survival was better in patients treated with = 2 catheters (p=0.007). No factor influence frequency of complications. Conclusion: This large retrospective study confirmed that HDRBT is efficient and safe in medically inoperable patients particulary with lobar or segmental endobronchial carcinoma. No significant financial relationships to disclose.
Navelbine (NVB) oral (o) with cisplatin (CDDP) as induction and concomitant to radiotherapy (RT): Final results of an international phase II trial in stage III non-small cell lung cancer (NSCLC)
Authors: Utracka-Hutka B. , Krzakowski M. , Provencio M. , Villa E. , Codes M. , Kuten A. , Riggi M. , Caux N. , Longerey B. , Dubray B. 
Published: March 2020

7691 Background: NVB i.v. with CDDP has reported an optimal activity/tolerance ratio when used in combination with RT. The new oral formulation of NVB should be easier to use assuming a similar activity profile. An international phase II trial with NVBo + CDDP as induction followed by NVBo+CDDP+RT was implemented in order to evaluate the efficacy of this combination. Methods: Patients (pts) between 18 and 70 years, with histologically proven untreated locally advanced inoperable stage IIIA/IIIB (supraclavicular LN and pleural effusion excluded) NSCLC, adequate bone marrow, hepatic and renal function, KPS ≥ 80% were treated with NVBo D1,8 60 mg/m2 cycle 1 and 80 mg/m2 cycle 2 (if no haematological/non-haematological grade 3–4 toxicity) and CDDP 80 mg/m2 every 3 weeks for 2 cycles as induction. OR/NC pts received NVBo D1,8 40 mg/m2 and CDDP 80 mg/m2 every 3 weeks for 2 more cycles and RT 66 Gy in 6.5 weeks. Results: Between 12/01 and 12/03 54 pts were enrolled; stages IIIA 48%, IIIB 52%; squamous 59%; median age 57 years (range 41;71), median KPS 100% (range 80; 100%) 7% pts ≥ 5% weight loss at baseline. RDI of NVBo/CDDP were 86%/93% and 97%/98% at induction and in combination with RT, respectively. Forty-one pts (76%) during induction increased NVBo from 60 to 80 mg/m2. Reasons for non- escalation: haematological 7 pts, non-haematological 2, mistake 4. After 2 cycles of CT induction, OR (ITT) in the 54 pts was 37%. Toxicity during induction: G3–4 Neutropenia (28%), febrile neutropenia (7%), G3 nausea (11%), G3–4 vomiting (9%), G3 anorexia (4%) G4 diarrhoea (2%); G3 constipation (2%). Forty-seven out of 54 pts received CT-RT. Median RT delivered dose: 66 Gy. Tolerance: 9% G3 Neutropenia; no G3/4 oesophagitis; 2% G3 radiation dermatitis. Late pulmonary fibrosis 1 pt. One month after CT-RT completion the overall RR (ITT) in the 54 pts was 54% (95% CI: 40%; 67%). Median PFS/OS: 12.5 (95% CI: 9.6; 16.4) /23.4 (95% CI: 17.6; 29.8) months, respectively. Conclusion: NVB Oral with CDDP is effective in stage IIIA/IIIB pts. The excellent tolerance profile allowed to complete the CT/RT treatment in 94% of pts. NVB oral is a new and promising option which facilitates the concomitant administration of CT/RT. [Table: see text]