bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biweekly paclitaxel as second-line treatment in advanced non-small cell lung-cancer (NSCLC). A phase II study of the Lung Cancer Galician Group
Authors: Vazquez-Estevez S. , Fírvida J. , Huidobro G. , León L. , Lázaro M. , Salgado M. , Mel J. , Grande C. , Pérez E. , Campos B. 
Published: March 2020

18120 Background: Paclitaxel is an active drug for NSCLC. Our purpose was to evaluate the efficacy and toxicity of biweekly administration of this drug in previously treated patients with advanced NSCLC. Methods: Patients with stage IIIB and IV NSCLC, which progressed after or during first-line chemotherapy, measurable disease, ECOG PS=0–1 and adequate organ function were included. Paclitaxel was administered at 150 mg/m2 iv, days 1 and 14, every 28 days, for a maximum of six cycles. Both, toxicity and efficacy analyses, were performed on the intent-to-treat (ITT) population. Results: Between September 2004 and November 2006, 42 patients (M/F, 39/3) were included, with median age 64 years (39–79). Tumor histology mainly included epidermoid (40.5%) and adenocarcinoma (35.7%). Tumor stage was IIIB (23.8%) and IV (76.2%). Median number of metastatic lesions was 1 (55%), located mainly in lymph nodes (30%), lung (25%), adrenal glands (16%) and bone (11%). Previous chemotherapy included platinum (76.1%), docetaxel (66.6%) and gemcitabine (52.4%). A total of 167 cycles (median 4, range 1–6) were administered. Median relative dose intensity was 94%. Toxicity: Grade III/IV hematologic toxicities per patient were neutropenia (2.5%) and anemia (2.5%). Grade III/IV non-hematologic toxicities were asthenia (2.5%), arthralgias/myalgias (2.5%) and peripheral neuropathy (2.5%). Efficacy: Of 39 ITT patients (3 patients have just begun chemotherapy), 7 achieved PR, 11 SD and 16 progressed, resulting in an ORR of 17.95% (95% CI: 5.9–30%). Five patients could not be evaluated for response due to early withdrawal (4 tumor-related exitus and 1 PS deterioration). Median TTP and OS were 174 days (95% CI: 115.52–232.48) and 332 days (95% CI: 261.18–402.82), respectively. Conclusions: Biweekly paclitaxel is an active and very well tolerated regimen in previously treated patients with advanced NSCLC. No significant financial relationships to disclose.
Phase II trial of imatinib (I) and docetaxel (D) in recurrent non-small cell lung cancer (NSCLC)
Authors: Huang C. H. , Williamson S. , Van Veldhuizen P. J. , Hsueh C. T. , Smith H. , Mayo M. , Allen A. , Kelly K. 
Published: March 2020

18132 Background: Second line monotherapy for NSCLC produces a response rate of 9% and a median survival of 7–8 months, regardless of the agent used. Emerging data suggest that combining an approved agent with an anti-angiogenesis inhibitor may improve efficacy in the salvage setting. Platelet Derived Growth Factor Receptor alpha (PDGFR-alpha) is involved in angiogenesis and its expression has been reported in 100% of adenocarcinoma (11/11) and 89% of squamous cell (16/18) lung cancer specimens in a small group sample. Preclinical models have shown that I inhibits PDGFR and may subsequently inhibit angiogenesis. In addition, I + D have additive anticancer activity. We initiated a phase II trial of I +D to evaluate the efficacy and safety of this combination regimen in recurrent NSCLC. Methods: Patients (pts)with pathologically confirmed NSCLC, measurable disease, no more than 1 previous platinum-based chemotherapy regimen, PS 0–1, clinically stable brain metastases and adequate organ function were eligible. Tumor samples, when available, were tested for PDGFR expression by immunohistochemistry. All pts received D 30mg/m2 intravenously weekly x 3 every 4 weeks and oral I 600mg daily for 4 cycles. Non- progressors after 4 cycles continued with I alone for a total of 12 months or until progression. Tumor response was assessed every 2 cycles. The primary endpoint was response rate. A Simon two-stage design was used with 16 patients in the first stage and accrual of a total of 32 patients planned. Results: Currently 15/16 patients for stage I of the protocol have been enrolled. A total of 24 cycles of combined I+D were given. Patient characteristics and toxicity data are described in the table below. Efficacy data is premature. Conclusion : I +D combination has been well tolerated in this relapsed population. A detailed toxicity, efficacy and PDGFR analysis will be presented. [Table: see text] No significant financial relationships to disclose.
Changes in high FDG-avid tumor volumes during radiation therapy differ from that of CT gross tumor volumes in patients with non-small cell lung cancer
Authors: Zhao L. , Ten Haken R. K. , Kong F. 
Published: March 2020

18139 Background: To study whether changes in Fluorodeoxyglucose (FDG)-avid tumor volumes (VPET) correlate with changes in CT gross tumor volumes (CTGTV) during the course of radiation therapy (RT). Methods: Patients with stage I-III non- small cell lung cancer (NSCLC) were prospectively enrolled in this pilot study and were treated with fractionated RT based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within 2 weeks prior to RT (pre-RT), after 45 Gy of irradiation (during-RT), and 3 months after completion of RT (post-RT). The scans were co-registered within our treatment planning system using the CT portion of each scan. Fused CTGTVs were delineated for each CT dataset. Fused VPETs were auto-contoured using 20%, 30%, 40% and 50% of maximum FDG activities within the tumors as threshold (VPET20, VPET30, VPET40, and VPET50, respectively) for each PET dataset. Paired T test and linear correlation were used for statistic analysis with all P values obtained using a 2-tailed test. Results are reported as Mean ± StDev. Results: Fifteen patients were enrolled in this pilot study. Pre-RT CTGTVs averaged 130.3 ± 194.7 cm3 and reduced to 91.7 ± 155.3 cm3 3 months after RT (P = 0.027). A mean PET threshold of 20.0 ± 10.6% matched best with the CTGTVs pre-RT. For the during-RT PET scans, the best-matched threshold increased to 30.0 ± 10.2% (P < 0.001). No significant correlation was found between changes of VPET and reduction of CTGTV during-RT. During-RT changes of higher FDG-avid VPET significantly correlated with the reduction of CTGTV Post-RT (P values were 0.735, 0.189, 0.022, and 0.029 for VPET20, VPET30, VPET40, and VPET50, respectively), but during-RT changes of CTGTV did not (P = 0.113). Conclusions: Changes of high FDG-avid tumor volumes during-RT differ in magnitude from CTGTV changes. High FDG-avid tumor volume changes (instead of CTGTV changes) during-RT are correlated with CTGTV changes Post-RT. Further study in a large number of patients is needed to verify these findings. No significant financial relationships to disclose.
Phase II and pharmacokinetic (pk) study of induction docetaxel/cisplatin followed by pulsed docetaxel chemoradiation for stage III non-small cell lung cancer (NSCLC)
Authors: Chen Y. , Pandya K. J. , Smudzin T. , Strychor S. , Sidone B. , Zamboni W. C. 
Published: March 2020

18142 Background: We have previously reported that docetaxel (Doc) demonstrates longer G2/M arrest and better synergistic effects with irradiation when compared with paclitaxel in human lung cancer cell lines. We designed a phase II clinical study targeting micrometastasis using upfront induction chemotherapy (CT) with Doc/cisplatin (CP) followed by sensitizing Doc chemoradiation (CRT) for patients (pts) with stage III NSCLC. Methods: Pts with inoperable stage III NSCLC were eligible. Induction CT consisted of Doc 75 mg/m2 and CP 75 mg/m2 on d 1 followed by rhG-CSF (150 ug/m2 sq on d 2 to 10). The CRT consisted of sensitizing Doc 12 mg/m2 twice per wk with daily RT (64.8 Gy to gross tumors and 45–57.6 Gy to subclinical disease). PK studies of Doc were performed during CT and CRT in each pt. The clearance (CL) and area under the plasma concentration versus time curve (AUC) were estimated. Results: 26 pts were enrolled and 16 completed study. Overall response rate was 69% [50% (8/16) PR and19% (3/16) CR]. 2-year survival was 57 %. During induction CT, primary grade (G) 3 toxicities were allergic reaction (10%), non-neutropenic infection (20%), nausea/vomiting (N/V) (10%), fatigue (10%), hypertension (5%) hyperglycemia (5%), dyspnea (5%) & fatigue (5%). There was no G3/4 hematologic toxicity. During CRT, 50% (4/8) of pts developed G3 esophagitis after Doc at 12 mg/m2. The next 8 pts received Doc at 10 mg/m2 with only 1 pt developing G3 esophagitis. Other G3 toxicities from CRT were N/V (28%), fatigue (14%), loss of appetite (14%), flushing (7%), chest pain (7%), & diarrhea (7%). No G3 or 4 pneumonitis or any G4 toxicity. Mean ± SD Doc CL at 75 and 10 mg/m2 were 20 ± 5 and 22 ± 10 L/h/m2, respectively. Ratio of Doc CL at 75 to 10 mg/m2 within a pt was 1.0 ± 0.4. Doc AUC at 75 and 10 mg/m2 were 3,933 ± 1,028 and 566 ± 257ng/ml·h, respectively. Conclusions: One-cycle full- dose Doc/CP with rhG-CSF followed by pulsed low-dose Doc CRT is associated with promising antitumor activity and low hematologic toxicity. Grade 3 esophagitis was associated with dose intensity of radiosensitizing Doc, and was minimized by dose reduction. Results suggest that this regimen should be further evaluated in pts with NSCLC. The PK disposition of Doc was similar at 75 and 10 mg/m2. No significant financial relationships to disclose.
A phase II trial of weekly cisplatin and docetaxel in advanced non-small cell lung cancer (NSCLC)
Authors: Sovak M. A. , Lutzker S. , Guensch L. , Joyce M. , Schwartz S. , Wu Y. , Zheng L. , Aisner J. 
Published: March 2020

18150 Background: Every 3-week cisplatin doublets used to treat advanced NSCLC carry a significant risk of renal and other toxicities and can be difficult for patients with co-morbidities. To reduce these toxicities, we conducted a phase II study to evaluate the efficacy and toxicity of weekly cisplatin and docetaxel in advanced NSCLC. Methods: Eligibility included patients with advanced or recurrent NSCLC, ECOG PS of 0–1, and no prior chemotherapy for metastatic disease. This Cancer Institute of New Jersey network, single stage phase II clinical trial was designed to give 3 weekly doses of cisplatin at 25 mg/m2 and docetaxel at 35 mg/m2, followed by 1 week of rest, for a total of 6 cycles of therapy. Toxicity was monitored weekly, and disease evaluation was performed every 2 cycles. The primary endpoint was response rate (RR); secondary endpoints included time to progression (TTP), median and 1-year survival. Results: From 12/03 to 11/06, 36 patients were enrolled so far. The median age of patients is 63 (range 47–78), the majority is white (n=33), 29 have stage IV disease, and half (n=18) are women. Fourteen have an ECOG PS=0 and 22 with PS=1. Histologic subtypes are: adenocarcinoma (n=24), NSCLC NOS (n=7), squamous (n=5). Eleven patients received = 4 cycles of therapy; median number of cycles delivered is 2.5. Reasons for treatment discontinuation include completion of therapy (n=5), progression of disease (n=16), adverse events (n=8), and patient preference (n=4). Three patients continue on therapy at this time. No complete responses were yet observed; 8 patients (22%) achieved a partial response; 10 patients had stable disease, 10 patients progressed, and 8 came off study before first disease evaluation. Median TTP was 3.1 months (mo) (95% CI 2, 5.5), median survival is 8.3 mo (95% CI 5,16.2) and 1-year survival is 39% (95% CI 20, 57). Most toxicities were mild but also included neutropenia (grade 3, n=1; grade 4, n=1), neutropenic fever (n=1), renal toxicity (grade 3, n=2), nausea (grade 3, n=1), fatigue (grade 3, n=3), diarrhea (grade 3, n=4) and metabolic abnormalities (grade 3, n=3). Conclusion: Weekly cisplatin and docetaxel is well tolerated with a low incidence of toxicity and demonstrates activity similar to every 3-week treatment in patients with advanced NSCLC. No significant financial relationships to disclose.
IMRT and cetuximab in stage 3 non-small cell lung cancer: The NEAR trial (NCT00115518)
Authors: Jensen A. D. , Münter M. W. , Bischoff H. G. , Herpel E. , Haselmann R. , Timke C. , Haberkorn U. , Huber P. E. , Thomas M. , Debus J. , Herfarth K. K. 
Published: March 2020

18168 Background: For stage 3 non-small cell lung cancer (NSCLC), RCHT is the treatment of choice with sometimes marked side- effect. Hence, patients with co-morbidities may not be eligible for combined treatment. Based on the results at other tumor sites, a combined- modality treatment with the EGFR antibody cetuximab and IMRT should be evaluated in a prospective phase II trial. Methods: Pts with inoperable stage 3 NSCLC ineligible for RCHT are included in the trial. Treatment consists of cetuximab weekly and concurrent IMRT with 50 Gy to CTV and subsequent boost to GTV to 66 Gy. Staging and f/u include CT, FDG-PET, and lung function prior to/after completion of treatment (response assessment) plus CT scans in 3 mo intervals. Overall treatment time is 4 months. Side-effects and efficacy were assessed. Results: So far, 17 of 30 pts (median 70 yrs; 57–82 yrs) have been enrolled. The median f/u from treatment start was 6 months (1–17). 3 pts are still being treated, 13 pts have completed, and one pt died prior to completion of treatment. Where available, EGFR staining yielded a median receptor score of 2 (0–3) in 12 pts. 3/12 pts showed strong (3+), 2/12 showed no EGFR expression. The treatment was well tolerated with only 1 treatment-related °3 morbidity (esophagitis). All pts showed acneiforme skin rash (°I), but no significant reduction of lung function. 2 pts with underlying heart disease developed thrombembolic complications (arterial & pulmonary embolisms). We observed PR in 10/13 and SD in 3/13 pts (RECIST). All pts showed a marked reduction of SUV in PET even if CT did not show PR. Conclusion: Preliminary results of IMRT combined with cetuximab suggest a reasonably safe treatment with only mild side-effects and encouraging local response. Addition of cetuximab does not seem to increase toxicity of RT. [Table: see text]
Outcome of treatment with 2nd and 3rd generation platinum-based chemotherapy in advanced non-small cell carcinoma (NSCLC): A single institute experience
Authors: Khodadad K. , Malekzadegan M. R. , Hashemi N. , Azadi A. , Abdollah Shamshirsaz A. H. , Padyab M. , Emami H. 
Published: March 2020

18169 Background: The cornerstone of treatment in patients with advanced NSCLC is chemotherapy. During past years 3rd generation cytotoxic drugs have replaced 2nd generation drugs in combination with platinum. Although some trials suggest that newer agents are less toxic and with better response rates compared to older ones, but overall survival outcomes are similar. Methods: Between 1999- 2005, 275 patients with advanced NSCLC (unresectable IIIA, IIIB and IV) have been treated in our center with either frontline 2nd (204 pts.) or 3rd (71 pts.) generation, platinum-based regimens. Retrospectively we analyzed the outcome of treatment (i.e. response rate and overall survival) in these patients according to the generation of chemotherapy regimen. Results: Male/female ratio was 3.6/1 and mean age 58.9. Pathology subtypes includes: adenocarcinoma (49.8%), squamous cell carcinoma (28%), undiff. NSCLC (21.8%) and large cell carcinoma (0.4%). The RR was higher with 3rd generation protocols compared to 2nd generations (47.9% vs 26.5%, P = 0.001) but the median OS in both groups was statistically non-significant (12.07 vs 10.57 m). Analyzing RR and OS in different pathology subtypes shows that in adenocarcinoma and squamous cell ca. the RR is higher with 3rd generation compared to 2nd generation (40.5% vs 20%, P=0.01 & 72.8% vs 27.3%, P=0.005 respectively), but the OS between these two generations was not statistically significant in both pathology subtypes. In undiff. NSCLC the outcome between 2nd and 3rd generation is non-significant in terms of OS and RR. The distribution of different stages in both study groups was statistically similar. Conclusions: Based on this study the 3rd generation protocols in the treatment of advanced NSCLC is superior to 2nd generation protocols in term of RR, although the median OS is statistically non-significant. No significant financial relationships to disclose.
TGFBR1*6A germline deletion in gemcitabine (gem)/cisplatin (cis)-treated stage IV non-small cell lung cancer (NSCLC) patients (p)
Authors: Domine M. , Alberola V. , Muñoz-Langa J. , Muñoz-Quintana M. A. , Molina M. A. , Viñolas N. , Gonzalez-Larriba J. , López- Brea M. , Sanchez J. J. , Taron M. 
Published: March 2020

18171 Background: An in-frame germline deletion variant (TGFBR1*6A) in the TGFBR1 gene results in loss of three alanines within the 9-alanine (*9A) repeat in the receptor. Compared with *9A, *6A is a less effective mediator of TGFB antiproliferative signals. Methods: We examined the germline deletion TGFBR1*6A in 107 gem/cis-treated stage IV NSCLC p. DNA was extracted from peripheral lymphocytes and deletion was analyzed by length analysis of fluorescently labeled PCR products. Results: Median age, 65 (range, 32- 81); male, 100 p (93%. Performance status (PS) 0, 39 p (37%); PS 1, 52 p (48.5%); PS 2, 26 p (24.5%). Adenocarcinoma: 56 p (52%). 71.6% of p had the *9A/*9A genotype; the remaining 28.4% had the *6A/*9A genotype. Response was observed in 37 p (34.5%). Overall median survival (MS) was 8 months (m). There were no differences in response or MS between p harboring the *9A/*9A genotype and those with the *6A/*9A genotype. There was a trend towards longer MS in p with PS 0 with *9A/*9A genotype (11 m) than in thoase with *6A/*9A (3 m) (P=0.06). Conclusions: Although the findings of this study do not identify significant differences between *6A and *9A, the fact that the shorter signal sequence could confer a tumor growth advantage merits further investigation. No significant financial relationships to disclose.
Detection of prognostically distinct subpopulations in non-small cell lung cancer patients treated with epidermal growth factor receptor (EGFR) inhibitors
Authors: Stewart D. J. 
Published: March 2020

18178 Hypothesis: In patient survival curves that follow 1st order kinetics, prognostically distinct subpopulations will be identified by inflection points in plots of log % survival vs time. Prognostically important dichotomous variables (present vs absent, or above vs below a threshold) will give inflection points while important continuous variables will shift curve slope without giving inflection points. Methods: For overall and progression-free survival curves from 35 published clinical trials of EGFR inhibitors, curve height at different times was measured manually and converted to % of height at time 0. Curve nonlinear regression analyses were performed using the Pharsight WinNonlin 5.0.1 program. Results: In assessments done to date, the most common survival curve pattern was conformity to a 2-compartment model, indicating a single inflection point and ≥ 2 prognostically distinct subpopulations. The second most common pattern was conformity to a 1-compartment model, suggesting that some populations are relatively homogenous. Only a minority of curves could be fit to 3-compartment models that would have indicated ≥ 3 distinct subpopulations. In different studies, EGFR inhibitors shifted some patients from poorer to better prognosis compartments compared to placebo, and/or decreased the slope (ie, increased the t1/2) of one or both individual compartments. Similarly, factors that have been found to be associated with prognosis in these studies were associated with formation of prognostically homogeneous groups or with alterations of relative compartment sizes or slopes. Conclusions: It is feasible to perform nonlinear regression analysis of log-linear survival plots to define prognostically distinct subpopulations. Preliminary assessments suggest that EGFR inhibitors and factors known to be important prognostically are associated with alteration of size and survival t1/2 of these subpopulations. Helpful data that could potentially be obtained from such analyses include minimum number, size and t1/2 of prognostically distinct subpopulations, and impact of a therapeutic modality or potential prognostic factor on each subpopulation. No significant financial relationships to disclose.
Epidermal growth factor receptor mutations and stat3 phosphorylation in surgically resected non-small cell lung cancer
Authors: Yang F. , Zhou Z. , Wang J. 
Published: March 2020

18180 Background: Somatic mutations in the kinase domain of the epidermal growth factor receptor (EGFR) gene and EGFR downstream pathways in non-small-cell lung cancer (NSCLC) have generate enormous interest in the searching of biological predictors of EGFR inhibitor. Selective Akt and STAT3 pathways activation has been hypothesized from in vitro model. The goal of this study is to determine the association of EGFR mutations with phospho-STAT3 (p-STAT3) in resected lung adenocarcinoma samples. Methods: 94 consecutive lung adenocarcinoma specimens from Chinese patients were analyzed for activating EGFR mutations in exon 19 and 21 by direct sequencing and p-STAT3 expression by immunohistochemistry. Results: 18 (19%) samples harbored exon 19 deletions and 22 (23%) samples had exon 21 L858R mutaions. 46 (49%) samples were scored p-STAT3 positive defined as strong nuclear staining in more than 5% cancer cells. 25 (62%) cases with EGFR activating mutations showed positive p-STAT3 nuclear staining, compared with 21 (39%) p- STAT3 cases in the EGFR wild type group (p=0.024). Conclusions: Our data further support the hypothesis that EGFR mutations may selectively activate STAT3 pathway in NSCLC. No significant financial relationships to disclose.
Preliminary results from a phase II study of celecoxib plus chemotherapy in patients with untreated advanced NSCLC
Authors: Wang J. , Liu X. , Yang L. , Guo Q. , Yang L. , Zhao J. , Wu M. , An T. 
Published: March 2020

18188 Background: Preclinical studies indicated that cyclooxygenase-2(cox-2) inhibitor celecoxib may enhance antitumor efficacy of cytotoxics, and combination with chemotherapy had acceptable tolerability in a phase I trial. This phase II trial evaluated the efficacy and safety of the celecoxib plus platinum-based chemotherapy in advanced NSCLC as first-line chemotherapy. Methods: Patients: chemotherapy naïve, IIIB (w/malignant effusion) IV, PS 0–2; treated with platinum-based chemotherapy (Gemcitabine 1,200 mg/m2 d1, 2, Cisplatin 75 mg/m2 d1 Q3w or Docetaxel 35 mg/m2 d1,8,15, cisplatin 75 mg/m2 d1, Q4w), and plus celecoxib 400 mg p.o. bid., until evidence of disease progression or toxicity. Primary endpoint: median survival; secondary endpoints: response rate and toxicity. Results: From 3/05 to 6/06, 30 pts with cox-2 positive expression detected by ICH were treated; 27 evaluable for response and toxicity; M/F: 18/12; median age 64 (42–74); PS 0/1/2: 3/23/4; Path: adeno/squamous: 60%/40%; StageIII/IV: 35%/65%. Toxicity: Grade 3 or 4 neutropenia and thrombocytopenia were observed in 40% (11/27) and 30%(8/27) patients, respectively. One patient death was considered possible treatment related. Response: CR:0; PR: 14 (52%; 95% CI 32%-76%); SD: 6 (22%; 95% CI 14%-32%); PD:7 (26%; 95% CI 19%-36%). Median duration of response and stable disease: 6.4 (range 3.5–7.5) and 3.5 months (range 1.5–8.0), respectively. Survival is too early to evaluate. Conclusions: Celecoxib in combination with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients with previously untreated advanced NSCLC. Accrual is continuing to 40 patients and updated response and survival data will be presented. No significant financial relationships to disclose.