bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salvage vinorelbine (VNR) in the 2nd to 4th line setting in advanced non-small cell lung cancer (NSCLC): A retrospective review at the Fox Chase Cancer Center (FCCC)
Authors: Devlin J. G. , Langer C. J. 
Published: March 2020

17072 Background: Published literature has demonstrated minimal activity for VNR in the salvage treatment of NSCLC, with response rates of only 0.8% (Fossella, et al, JCO 2000; 18(12), 2354–2362). However, in our clinical experience, we have observed a number of patients (pts) with clinical benefit. Methods: Retrospective evaluation was performed of all pts with NSCLC who had received VNR at FCCC from 6/02–6/05 in the salvage setting. Pts were evaluable if full medical records (including radiographic imaging for disease assessment) were available, had received ≥2 cycles of VNR, and had advanced, recurrent or metastatic NSCLC. Primary endpoint was response rate (RR); secondary endpoints included safety, median overall survival (OS), and median time to progression (TTP). Results: 52 pts were included, 28 pts were ultimately evaluable (13 pts received <2 cycles of VNR, 7 pts did not have NSCLC, and 4 pts received VNR with RT or other agents). Median age was 64 yrs, 64% were female; ECOG-PS 0–18%, 1–50%, 2–28.5%, 3–3.5%. 82% exhausted 2 lines of systemic therapy before VNR; 32% exhausted 3; 21.4% received prior EGFR-TKI; 18% received other prior protocol therapies. 96.3% of pts had stage IV, stage IIIB, or recurrent disease. 21.4% had bone mets; 25% had brain mets; and 42.8% had visceral metastases. 85.8% had significant comorbidities. Median number of VNR cycles was 4. RR:PR 10.7%, SD/MR 35.7%, and PD 50%. 25% required dose reductions, predominantly for gr 4 hematologic toxicities. Non-hematologic toxicities were generally mild, and included neuropathy, fatigue and GI distress; there were no Tx-related deaths. 32% were able to receive other systemic therapy after VNR. Median OS was 5 months, and median TTP was 3 months. Conclusions: Vinorelbine is active and relatively well-tolerated in the salvage treatment of NSCLC, including heavily pretreated pts. Response rates exceed that observed in the literature. [Table: see text]
Prognostic quantification of non-small cell lung cancer metastases to the lung
Authors: Oh Y. , Srivastava G. , Rana V. , Munden R. , Bekele B. N. , Karp D. 
Published: March 2020

17080 Background: Lung is the most frequent organ site of metastases from non-small cell lung cancer (NSCLC), yet the impact of these metastases on the natural history of the disease has not been well elucidated. Part of the difficulty of evaluating the prognosis of lung metastases in NSCLC patients is the effect of metastases to other organ sites. Here we have studied the survival of patients with lung as the solitary or dominant site of metastases and correlated it with number and maximal size of tumors. Methods: Data from the M.D. Anderson Cancer Center Tumor Registry during 1998 to 2002 was interrogated. Of 1280 patients registering as new patients, 87 were evaluable as having lung as the only site of metastases on initial staging evaluation. Excluding 13 patients who had bronchioloalveolar carcinoma (BAC) or BAC features on histology, the remaining 74 patients’ baseline CT scans were reviewed and scored for 1) the maximal linear measurement of the largest lung tumor and 2) the number of lung nodules that were growing and consistent with lung metastases. Results: In non-BAC patients with lung only metastases, an inverse correlation is seen between maximal linear measurement of a patient’s largest lung metastasis on baseline staging and their subsequent survival. A similar inverse correlation is seen between the number of lung metastases and survival. When patients with subsequent development of other metastatic sites are excluded from the analysis, these correlations are strengthened. Also, in BAC patients with lung only metastases, a trend toward longer survival with fewer metastases was seen, but only 13 patients were evaluable. Formal statistical analysis of these results is pending. Conclusions: The number and size of lung metastases from NSCLC appear to be independent predictors of survival. This might be explained by lead-time bias where fewer lesions represent an earlier stage of metastatic disease, however, increasing number and size of metastases may also be multiplying the source for further metastatic spread of disease. This interpretation of data may justify the local therapy of individual lung metastases in oligometastatic disease by surgery, stereotactic radiosurgery, or radiofrequency ablation. No significant financial relationships to disclose.
Clinical outcomes of a phase I/II study of stereotactic radiotherapy for metastatic lung cancer
Authors: Nagata Y. , Hiraoka M. , Norihisa Y. , Takayama K. , Matsuo Y. , Mizowaki T. , Sakamoto M. 
Published: March 2020

17081 Background: The clinical significance of three-dimensional stereotactic radiotherapy (SRT) for primary lung cancer has been demonstrated by a few studies. This study was performed to evaluate the clinical outcomes of SRT for treating metastatic lung cancer using a stereotactic body frame. Methods: Of the forty-one patients who were treated between October 1998 and December 2004, thirty-four patients were evaluated in this study. All patients had less than two lung solitary metastases without any other metastases and primary recurrence. Fifteen patients were metastasis from primary lung cancer. The other 9 had metastasis from colo-rectal cancer, 5 from head and neck cancer, 3 from renal cancer, 1 from breast cancer, 1 from osteosarcoma of femur. All tumor size was less than 4 cm in diameter. Three-dimensional treatment planning using 5 to 8 non-coplanar beams was performed to maintain the target dose homogeneity and to decrease the irradiated lung volume >20 Gy. All patients were irradiated using a stereotactic body frame and 18 received 4 single 12 Gy, 16 recieved 5 single 12Gy of radiation at the isocenter over a period of 4–18 (median = 12) days. Results: Four patients (4/34%) completely disappeared after treatment (CR) and nine (9/34%) decreased in size by 30% or more (PR), eighteen had no tumor progression in clinically (SD). Three had progress disease (PD). Twenty-eight (82%) of 34 tumors were locally controlled during the follow-up period. Local recurrences and new metastase occurred in one and six of lung cancer patients, one and three of colo-rectal cancer patients, respectively. For recurrent primary lung cancer, the overall survival rates after one and three years were 100 and 63%, respectively, while for secondary lung cancer from colorectal cancer, the overall survival rates were 100 and 71%, respectively. During the follow-up of 10.5–80.6 (median = 27.3) months, no pulmonary complications greater than an CTC-AE V3.0 criteria of grade 4 were noted. Conclusions: Sterotactic radiotherapy using a stereotactic body frame was useful for the treatment of metastatic lung tumors. No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF) is a survival factor for neuropilin-1-expressing lung tumour cells
Authors: Barr M. P. , Pidgeon Dr G. P. , O’Byrne Dr K. J. 
Published: March 2020

17084 Background: Lung cancer is the leading cause of cancer mortality in Ireland. The formation of new blood vessels, angiogenesis, is essential for tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). Several studies have suggested a role of VEGF as a survival factor for endothelial and some tumour cells. We investigated the effect of VEGF on lung tumour cell survival and examined the VEGF receptor profile of these cells. Methods: A panel of lung cancer cell lines, H460, H647, A549 and SKMES1 were treated with recombinant VEGF (100 ng/ml). Tumour cell survival was assessed using the BrdU proliferation assay. Apoptosis was examined by flow cytometry using Annexin-V and PI staining. VEGF receptor profiles for Flt-1 (VEGFR-1), KDR (VEGFR-2), Neuropilin-1 (NP1) and Neuropilin-2 (NP2) were examined at the mRNA and protein level by RT-PCR and Western blotting, respectively. Tumour cell expression of the Plexin family of signalling receptors was investigated, in addition to the class III Semaphorins which have been shown to bind the Neuropilin receptors. Results: All lung cancer cells expressed NP1 with the exception of the H460 cell line. Using endothelial cells as a positive control, neither VEGFR-1 or VEGFR-2 were identified on the panel of lung cancer cell lines examined at the mRNA and protein level. A dose-response in tumour cell proliferation was observed with the addition of VEGF at 10ng and 100ng/ml. This increase in tumour cell proliferation was significant in all NP1-positive cells, with no effect on NP1-negative H460 cells. VEGF decreased apoptosis in cells expressing NP1, with no effect observed in H460 cells. Our preliminary data show that in addition to NP1, lung cancer cells also express NP2, Plexin-A1, Sema-3A and Sema-3C mRNA which are potential mediators of the NP1 signalling cascade. Conclusions: These results demonstrate that VEGF promotes survival of lung cancer cells, potentially through NP1 signalling. We are currently examining VEGF/VEGFR signalling and the downstream anti- and pro-apoptotic pathways activated in response to VEGF on lung cancer cells. Blockade/inhibition of VEGF and its receptors may offer potential as a therapeutic biological strategy in lung cancer. No significant financial relationships to disclose.
Phase II study of gemcitabine and carboplatin plus bevacizumab for stage III/IV non-small cell lung cancer: Preliminary safety data
Authors: Kraut M. J. 
Published: March 2020

17091 Background: The current standard of care for stage III/IV non-small cell lung cancer (NSCLC) is platinum-based chemotherapy. Bevacizumab (BV) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody that improves survival when used in combination with chemotherapy. In a randomized, phase II study of patients (pts) with advanced NSCLC, the addition of bevacizumab 15 mg/kg to paclitaxel/carboplatin (PC) resulted in prolonged survival and progression-free survival compared with PC alone (Sandler AB et al, ASCO 2005). In the present study, we are using BV 15 mg/kg in combination with gemcitabine/carboplatin (GC) for the treatment of NSCLC. Preliminary safety findings are summarized. Methods: Eligible pts with stage IV NSCLC, PS 0–1, and adequate hematologic, renal and hepatic function, were enrolled; pts with squamous cell carcinoma, tumor in the central airways, baseline hemoptysis, or brain metastases were excluded. GC/BV treatment was given in q 3-weekly cycles for 6 cycles, with BV continued in stable and responding patients. G 1250 mg/m2 was given on days 1 and 8 and C AUC 5 was given on day 1. BV 15 mg/kg was given on day 1. After 7 pts were enrolled, the study was amended to reduce the dose of G to 1000 mg/m2 on days 1 and 8 due to unacceptable neutropenia. Primary endpoint of the study is time to progression. Results: To date, 9 pts have received treatment; we report here the hematologic toxicity of the first 8, and non-hematologic toxicity of the first 7. There are 6 men and 2 women, median age 61.5 years. There was one episode of grade 4 thrombocytopenia, and Grade 3 events have been reported a number of patients: leukopenia (5 pts); neutropenia (4 pts); thrombocytopenia (4 pts); infection (1 pt); hemoglobin toxicity (1 pt); fatigue (1 pt); diarrhea (1 pt); dyspnea (1 pt); and dehydration (1 pt). Adverse events possible related to BV include Grade 3 hypertension (1 pt) and Grade 1 epistaxis (2 pts). No thrombosis or proteinuria has been reported. There have been no fatal toxicities. Conclusions: To date, the addition of BV to GC in pts with NSCLC is generally well tolerated and no unexpected adverse events possibly related to BV were observed. Enrollment is ongoing. [Table: see text]
Phase II study of UFT, vinorelbine and gemcitabine as first-line treatment in advanced non-small-cell lung cancer
Authors: Atagi S. , Kawahara M. , Takada M. , Kawasaki M. , Tamura A. , Saitou R. , Fukai S. , Komatsu H. 
Published: March 2020

17100 Background: Vinorelbine (VNR)/gemcitabine (GEM) is active and well tolerated chemotherapy regimens for the treatment of patients (pts) with advanced non-small-cell lung cancer (NSCLC). UFT is composed of uracil and tegafur in a molar ratio of 4:1, and tegafur is a prodrug of 5-FU. Sequential exposure to 5-FU followed by GEM has been reported to give additive effects in vitro. For these reasons, we conducted a phase II study of triple treatment with these 3 drugs for advanced NSCLC. The objectives were to determine the tumor response rate, survival, safety and toxicity of this combination chemotherapy. Methods: Eligible pts were required to have histologically or cytologically comfirmed measurable or evaluable stage IIIB or IV NSCLC, age <75 years, no previous chemotherapy, a Karnofsky performance status (PS) 0–1, and adequate organ function and bone marrow reserve. In this study, pts received UFT (300 mg/m2 orally on days 1-5, 8–12) plus VNR (25 mg/m2 IV on days 6 and 13) and GEM (1000 mg/m2 IV on days 6 and 13). Treatment was repeated every 3 weeks. Results: Between September 2002 and November 2004, 32 pts were enrolled on this study. Characteristics of this study were as follows: male/female = 20/12; median age = 65 years (range 46–74); PS 0/1 = 11/21; stage IIIB/IV = 5/27. Median # of cycles = 2 (range 1–10). Response: PR = 7 (21.9%), SD = 14, PD = 10, NE = 1. Median survival time was 13.9 mos. 1-year survival rate was 56.7% (95% confidence interval, 38.9–74.4%). Gr 3/4 toxicity (% of pts) was as follows: leukocytes 40.6%, neutrophils 56.3%, platelets 3.1%, infection 9.4%, hypoxia 6.3%, dyspnea 3.1% and ALT/AST 3.1%. There were no treatment-related deaths. Conclusions: The combination of UFT, VNR and GEM appears effective with acceptable toxicity. No significant financial relationships to disclose.
A multicentric phase II trial of gemcitabine (Gem), oxaliplatin (Oxa) and vinorelbine (VNB) in untreated stage IIIB and IV non-small cell lung cancer (NSCLC) patients (pts): Preliminary results of GON triplet regimen
Authors: Tredaniel J. , Becht C. , Bekradda M. , Culine S. , De Cremoux H. , Misset J. , Alexandre A. , Goldwasser F. , Chomy F. , Ecstein-Fraisse E. , Cvitkovic E. 
Published: March 2020

17104 Background: Oxa, Gem and VNB are active agents against NSCLC and have shown synergy in combination. VNB plus Gem showed efficacy comparable to platinum combinations with a more favorable toxicity profile, while Oxa/VNB and Oxa/Gem combinations have established recommended doses. Platinum given on day 2 after Gem appears safer and more active. A fixed Gem infusion rate of 10 mg/m2/min is a pharmacologically optimized dosing intended to provide plasma concentrations (≈20 μmol/L) sufficient to maximize the rate of Gem triphosphate accumulation. The aim of the trial was to assess the efficacy (response rate) and safety of GON regimen. Methods: Chemo naive pts with stage IIIB and IV NSCLC received VNB 25 mg/m2, 20-min IV followed by Gem 700 mg/m2 in 10 mg/m2/min IV on day 1, and Oxa 85 mg/m2, 2h IV, on day 2, cycles repeated every 2 weeks. 88 pts are planned in a two-stage design. Results: From February 2004 to November 2005, 39 pts were eligible and treated: 26M/13F; median age: 58 (36–75) years; PS 0/1: 17/22; stage IIIB/IV: 6/33; 21 adenocarcinoma, 9 squamous, 9 large cell carcinoma. Metastatic sites were 67% lung, 21% liver, 36% bone. 229 cycles (cyc) were administered; median cycles/pt 8. Relative dose intensity: Oxa 89%, VNB 94%, Gem 100%. Thirty-four pts were assessable for response (RECIST, external radiological panel review), 5 pts too early: 1 CR, 14 PR (44% ORR, 95% CI 27–62%) with a median OR duration of 12.5 months (range: 3.1–19+), 9 SD, 10 PD. Median follow-up of 6 months (1–21) with median TTP of 4.6 months (95% CI: 1.0–8.3, range: 1–19+); estimated 6-month survival: 80%. Safety is assessable in 38 pts with grade 3–4 toxicities (pts/cyc): neutropenia 6/18, febrile neutropenia 1/1, anemia 1/2, neurotoxicity 3/4, diarrhea 2/3, vomiting 1/1, transaminitis 2/3. Conclusions: The GON triplet is a safe and active outpatient regimen in advanced NSCLC. If these promising results are confirmed in the full cohort, the regimen warrants comparison with standard doublet regimens. [Table: see text]
Percutaneous laser-induced thermoablation (LIT) of non-resectable lung metastases and primary lung tumors: A preliminary evaluation of technical aspects and local efficiency
Authors: Sponza M. , Aprile G. , Gasparini D. , Iaiza E. , De Pauli F. , Giovannoni M. , Meduri S. , Piccoli G. , Morelli A. , Fasola G. 
Published: March 2020

17106 Background: Surgical resection remains the standard of care for solitary lung metastasis from colorectal cancer or primitive lung tumors. Nevertheless only a small part of patients can be radically resected. Thermal ablation is a mini-invasive local treatment that can be considered an alternative approach in non-resectable lesions or inoperable patients. Methods: We present a consecutive series of thirteen patients treated with LIT from March 2004 to March 2005. Nine patients had a small (maximum diameter smaller than 5 cm) non-resectable lung carcinoma while four patients had a solitary metastasis from colorectal cancer. Median age was 70-yrs (range 55–87), male-female ratio was 2:1. After mild sedation and local anaesthesia, optical fibers were inserted directly into the tumor with CT-guided percutaneous needle placement. Each optical fiber was connected to a neodymium:yttrium-aluminium-garnet (ND:YAG) laser, which delivers concentrated light at a wave-length of 1064 nm, with a 5-Watt power and a 1800-Joule energy per single fiber. A minimum of two and a maximum of four needles were used, with a 5 to 8 mm distance from one needle to another. Results: All the patients tolerated LIT procedure well, developing a minimal pneumothorax, which did not require any treatment. Easy manageable local side-effects occurred in two cases (a mild self-limiting haemoptysis and a pleural empyema). Post-treatment CT-scan demonstrated complete thermonecrosis in all the lesions smaller than 3 cm and almost complete in the bigger ones (3 to 5 cm). All the patients are still alive, with a local tumor control rate of 100% at radiological follow-up: no local progression was observed in 10 pts with a follow-up of at least 12 months and in 3 pts with a follow-up of at least 6 months. Conclusions: Percutaneous LIT permitted a complete ablation of lung metastases and lung carcinomas with an optimal local tumor control rate at 1-year and a low complication rate. Complete necrosis was achieved only in lesions with maximum diameter smaller than 3 cm. No significant financial relationships to disclose.
A phase II study of vinoreline (VNR) and carboplatin (CBDCA) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Takatani H. , Kinoshita A. , Fukuda M. , Soejima Y. , Nagashima S. , Narasaki F. , Soda H. , Oka M. , Kohno S. 
Published: March 2020

17108 Background: VNR is one of standard drugs for elderly NSCLC. The role of platinum- based combination chemotherapy for elderly pts is controversial. Methods: Based on our phase I study (Fukuda, et al, abstract 2763, ASCO 2002), we conducted a phase II single arm study of VNR combined with CBDCA for elderly NSCLC pts. Primary endpoints were response and toxicity. Eligibility criteria included: chemotherapy-naïve, good performance status (PS: 0–2), age ≥75, stage IIIB-IV, and adequate hematological, hepatic and renal function, written informed consent. Treatment consisted of VNR 20 mg/m2 i.v. on days 1 and 8 and CBDCA target AUC = 4 (Chatelut formula, Jaffe method) on day 1 of every 4 weeks. Planned sample size was 40. Results: A total of 40 pts were enrolled. Pts characteristics: male/female = 30/10, PS 0/1 = 18/22, median age (range) = 78 (75–86), Ad/Sq/Others = 30/9/1, stage IIIB/IV = 14/26. Forty pts were eligible and assessable for toxicity and survival, and 37 pts were assessable for response on the submission of this abstract. Thirty-three pts were treated with two or more courses of treatment. Overall response rate was 13.5% (95% CI, 4.5%-28.8%); CR= 0, PR= 5, SD = 23, PD = 9. Grade 3 or 4 leukopenia, neutropenia, and anemia were observed in 31.6%, 50.0%, and 7.1%, respectively. Treatment-related death did not occurred. Non-hematological toxicity was mild. The median survival time was 392 days (95% CI, 311–474) and the median time to progression was 114 days. Conclusions: This combination is well-tolerated and modest activity in pts with elderly NSCLC. No significant financial relationships to disclose.
Pemetrexed and carboplatin plus bevacizumab as first-line therapy for advanced non-squamous non-small cell lung cancer: preliminary safety results of a phase II trial
Authors: Patel J. D. , Hensing T. A. , O’Keeffe P. , Frantonius K. , Hart E. , Bonomi P. 
Published: March 2020

17111 Background: Bevacizumab is a novel antiangiogenic agent that has been shown to improve response rates and survival of patients with advanced non-squamous NSCLC when added to paclitaxel and carboplatin. Pemetrexed is a multitargeted antimetabolite that has shown activity in NSCLC as a single agent and when combined with carboplatin. Because the combination of pemetrexed and carboplatin has activity comparable to that of other standard platinum doublets and promising toxicity profile (Zinner, 2005), the addition of bevacizumab to this regimen is investigated. Methods: This single cohort, phase 2 study evaluates the safety and efficacy of the combination of pemetrexed and carboplatin plus bevacizumab in patients with untreated non-squamous NSCLC. Eligibility requires ECOG performance status 0–1, Stage IIIB (malignant effusion) or Stage IV non- squamous NSCLC, no evidence of CNS metastases, no anticoagulation. Treatment consists of pemetrexed 500 mg/m2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes. Treatment is repeated every 21 days for 6 cycles. For patients who have either stable disease or partial response, pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg are continued every 21 days until progression of disease or toxicity. All patients receive folic acid, vitamin B12 and steroid prophylaxis. Tumor response is assessed using RECIST every 2 cycles during treatment with carboplatin and then every 3 cycles during treatment with pemetrexed and bevacizumab alone. Results: From 8/2005 to 12/2005, 10 (of planned 50) patients with Stage IIIB and IV non-squamous NSCLC have been enrolled and treated. Patient characteristics are: median age: 65 (48–71), 20% female, 80% male, 30% stage IIIB, 70% stage IV. Median number of cycles delivered is 5 (range 1–9). No patient has discontinued therapy secondary to progressive disease or toxicity to date. 6 patients are evaluable for response: 1 PR, 1 minor response (24% reduction), 4 SD. No grade 3/4 toxicities have been experienced. Conclusions: This is a highly tolerable and active regimen with little toxicity to date. Updated response and toxicity data will be forthcoming. Supported by Genentech Inc and Lilly Pharmaceuticals. [Table: see text]