bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of irinotecan, carboplatin, and bevacizumab in patients with limited-stage small cell lung cancer
Authors: Zubkus J. D. , Spigel D. R. , Greco F. A. , Yardley D. A. , Burris H. A. , Vazquez E. , Farley C. , Patton J. F. , Hart L. , Hainsworth J. D. 
Published: March 2020

18133 Background: In a previously reported phase II trial bevacizumab (B) was used as maintenance therapy following induction with irinotecan (I), carboplatin (C) and radiotherapy (RT) in patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). 1-year progression- free survival (PFS) and overall survival (OS) were 53% and 70%, respectively. In the present multicenter community-based trial B is given with induction chemoradiotherapy and as maintenance therapy. Methods: The primary endpoint is to assess the median PFS. Eligibility criteria: newly diagnosed LS-SCLC, measurable disease, ECOG PS 0–1, and informed consent. Exclusion criteria: hemoptysis and therapeutic anticoagulation. Treatment: I 60mg/m2 IV D1, 8, 15, C AUC=4 IV D1, and B 10 mg/kg IV D1 and 15 every 28D. Pts received concurrent RT to 61.2 Gy starting with the 3rd cycle, and were restaged every 8 weeks. If no progressive disease (PD) or excessive toxicity after 4 cycles, pts received B x 6 months. Prophylactic cranial irradiation was used at M.D. discretion. This 2-stage trial was designed to achieve a 40% improvement in historical median PFS of 12–14 months. Results: 20 pts were enrolled from 4/06 to 12/06 (trial ongoing, n=50 planned). Data are available for 14 pts in this analysis. Baseline features: median age 64 years; male/female, 21%/79%; and ECOG PS 0/1, 64%/36%. The objective response rate was 78% (95% CI 45%-94%) - all partial responses. No pt had PD. 7 pts were not evaluable: too early, 5 pts; off study (toxic megacolon, 1 pt; intercurrent illness, 1 pt). With a median follow-up of 5 months, the median PFS has not been reached. Grade (G) 3/4 non-hematologic toxicity with induction occurring in more than 2 pts: diarrhea (29%) and esophagitis, fatigue, pain (21% each). G3/4 hematologic toxicity: leukopenia (21%), neutropenia (14%), and thrombocytopenia (43%). There have been 2 G3/4 bleeding events with induction: suspected tracheoesophageal fistula with death (possibly treatment-related), 1 pt; and hematochezia, unrelated, 1 pt. Conclusions: This trial continues to be closely monitored for safety. Further accrual and longer follow-up are necessary to assess if B can be safely combined with chemoradiotherapy and improve efficacy. No significant financial relationships to disclose.
Gefitinib (G) treatment outcome after progression on erlotinib (E) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Grossi F. , Brianti A. , Defferrari C. , Loprevite M. , Catania G. , Pronzato P. 
Published: March 2020

18138 Background: Two case reports describe a response to E after failure of G (Garfield DH, J Clin Oncol 2005) or to G after failure of E (Choong NW et al, Nat Clin Pract Oncol 2006) in patients (pts) with advanced NSCLC. Otherwise, a limited experience in 5 pts suggests that E is not effective in pts progressing on G (Viswanathan A et al, Lung Cancer 2005). Aim of this study was the evaluation of response and time to progression (TTP) in advanced NSCLC pts treated with G after failure of E. Methods: Pts received G 250 mg/day after disease progression (PD) with E 150 mg/day. Pts accrual was stopped on August 2006 after the approval of E for use in Italy and the consequent closure of the G compassionate-use program. Results: From May 2005 to August 2006, 15 pts were enrolled. Median age 65 years (50–85); males= 14 pts (93%); never/former smokers= 4/10 pts (26/67%); adenocarcinoma= 10 pts (67%); PS 0/1= 5/10 pts (33/67%); in 2 pts (13%) E was administered as first-line therapy, 8 pts (53%) received 2 prior lines of chemotherapy (CT) and 3 pts (20%) received CT between E and G. One patient (7%) had a partial response (PR) and 5 pts (33%) had disease stabilization (SD) with E; with G no PR and 6 SD (40%) were obtained. Five out of 6 RP/SD pts with E, had SD with G; 8 out of 9 PD pts with E, had PD with G; 1 SD patient with E, progressed with G and 1 vice versa. TTP in RP/SD pts was 7.2 and 3.4 months for E and G respectively; in PD pts TTP was 1.7 and 1.6 for E and G respectively. Conclusions: Our data suggest that there is a benefit with G in pts who had RP/SD with E and that is associated with a good TTP. Conversely G is not recommended in pts that immediately progressed after E. Moreover these results support the rationale of treating PD pts with an EGFR TKI with another one; it may be worthwhile to collect more data on E. No significant financial relationships to disclose.
Ca-15.3 antigen as predictor of response to EGFR inhibitors in patients with bronchiolo-alveolar carcinoma
Authors: Bearz A. , Talamini R. , Vaccher E. , Spina M. , Simonelli C. , Berretta M. , Spazzapan S. , Tirelli U. 
Published: March 2020

18151 Background: Bronchiolo-alveolar carcinoma (BAC) is a subtype of non-small cell lung cancer (NSCLC). Incidence of pure BAC ranges between 2% and 5% of NSCLC although a BAC histotype may be present in up to 20%. There is no established treatment for BAC, although promising results have been achieved from the use of inhibitors of the Epidermal Growth Factor Receptor (EGFR). It has been demonstrated that there is a very close relationship between responsiveness to EGFR inhibitors Erlotinib and Gefitinib and some factors, including female gender; adenocarcinoma histotype, with BAC features; Asian origin; and never having smoked. No tumor marker has been validated in the diagnosis and follow-up of lung cancer. Ca 15–3 antigen serum levels are reported to be pathologically abnormal in adenocarcinoma of the lung, although it does not seem to be related to the EGFR pathway. We studied this tumor marker in relation with the treatment with EGFR inhibitors in patients affected by BAC. Methods: We collected data from 16 caucasian, female and never smoker pts with BAC. All pts received EGFR inhibitors as first-line therapy. In compliance with the EAP, dosage of Gefitinib and Erlotinib was 250 mg/day and 150 mg/day, respectively. Results: One (6%) pt had a complete response and 6 (38%) showed a partial response to EGFR inhibitors, 1 (6%) pt remained stable for 4 months, while 8 (50%) pts progressed. All 7 pts with normal Ca 15–3 levels before treatment with EGFR inhibitors’ achieved a partial or complete response, but the 8 pts with abnormal Ca 15–3 levels did not (p=0.0001). Among the responders we noticed an increase of Ca 15–3 serum levels at progression. In particular, 5 pts had an increase of Ca 15–3 serum levels up to normal value when their disease progressed; 2 pts have not progressed yet and Ca 15–3 serum levels remain normal. Conclusions: We suggest that Ca 15–3 levels may be a prognostic factor to predict the response to EGFR inhibitors in pts with BAC. We are studying its role in a larger population with BAC and in other NSCLC subtypes as well. No significant financial relationships to disclose.
A phase I/II study of pemetrexed plus cisplatin in Japanese patients with malignant pleural mesothelioma
Authors: Gemba K. , Yamazaki K. , Kunitoh H. , Hida T. , Nakagawa K. , Shinkai T. , Ichinose Y. , Nambu Y. , Saijo N. , Fukuoka M. 
Published: March 2020

18152 Background: Pemetrexed (pem) is globally used for the treatment of malignant mesothelioma (MPM) in combination with cisplatin (cis). Pharmacokinetic (PK) difference of pem/cis between Western and Asian population (pop) so far remains unknown. To investigate safety/efficacy of pem/cis therapy and PK profiles of pem/cis for Japanese (Jpn) MPM patients (pts), we designed a phase I/II study. Methods: Primary objectives in phase (Ph) I part were to determine a recommended dose (RD), and in Ph II part were to examine the efficacy of the RD and safety. PK profiles were to be analyzed as a secondary objective. A cohort of 6 pts, starting from a dose of pem 500 mg/m2 and cis 75 mg/m2 (level 1: LV1), was used in the dose-escalation Ph I. The efficacy of the RD was to be evaluated in at least 18 pts in the study. Key eligibility criteria were: histologic diagnosis of MPM incurable by surgery, no prior systemic chemotherapy, and a performance status 0–1. Under full vitamin supplementation, pem was administered as a 10-min. infusion on day 1 of a 21-day cycle, followed by cis administration as a 2-hr. infusion 30 min. after pem administration. For comparison of PK profiles, PK data of this study and a Western phase III study were analyzed by pop PK approach. Results: In Ph I, 13 pts were enrolled: 7 in LV1 and 6 in level -1 (LV-1: pem 500 mg/m2 and cis 60 mg/m2). Two dose-limiting toxicities were observed in LV1: pneumonitis and neutropenia. The RD were then determined to be LV1. In Ph II, 12 pts were enrolled in LV1. For safety, one drug-related death was reported among 25 pts due to worsening of underlying pneumonia observed before enrollment. The most common G3/4 toxicities were neutropenia and hemoglobin decrease. For efficacy, a partial response was achieved for 7 of 19 pts who received LV1. Response rate was 36.8% (95% CI: 16.3- 61.6). PK profiles of pem/cis in Jpn pts were similar to those in Western. The results of other secondary objectives, e.g., progression-free survival, QOL, and pulmonary function test, will be presented in the conference. Conclusions: The profiles of efficacy/safety/PK shown in this study are almost comparable to those in Western pts, and indicate that pem/cis therapy will be a promising therapy for Jpn MPM pts. No significant financial relationships to disclose.
Gemcitabine in combination with oxaliplatin as second-line therapy of advanced and metastatic NSCLC
Authors: Alencar A. J. , Blaya M. , Raez L. , Farfan N. , Lopes G. , Walker G. , Flores A. , Macintyre J. , Rocha-Lima C. 
Published: March 2020

18157 Background: Single agent gemcitabine is active as second line therapy in NSCLC. Oxaliplatin may be non-cross resistant with the other platinum-containing agents used as first-line therapy in NSCLC. The combination of gemcitabine and oxaliplatin (GEMOX) is synergistic in pre-clinical models. Methods: A phase II, non-randomized trial was designed to assess the efficacy and tolerability of gemcitabine 1,000 mg/m2 over 100 min in combination with oxaliplatin 100 mg/m2 over 2 hours both given on days 1 and 15 of each 28-day cycle. Patients with NSCLC were eligible if they had progressed after first line treatment. Primary endpoint was tumor response rate. Planned sample size is 30 patients over a period of 2 years. Functional Assessment of Cancer Therapy- Lung (FACT-L) v.4 questionaire was used to assess quality of life of patients on therapy. Results: Twenty-two patients have been enrolled. 13 males (59%) and 9 females (41%). 15 Hispanic (68%), 4 Caucasian (18%), and 3 African-American (13%). Median age is 55 yrs. Histologic subtypes are as follows: adenocarcinoma, 12; NSCLC not otherwise specified 7; squamous cell carcinoma, 3. Nine patients had an ECOG performance status (PS) of 0 (41%) and 13 had a PS of 1 (59%). Two patients were never smokers. A total of 56 cycles have been administered (median 2, range 1 to 6). GEMOX as second-line therapy was given to 18 patients (81%), third-line to 4 patients (18%). Two patients died on study from disease progression leading to respiratory and multi-organ failure. The following Grade 3 and 4 adverse events were seen in 2 patients each: fatigue, dyspnea, anemia, and multi-organ failure. Cancer pain was seen in 1 patient. Twenty patients are available for assessment of response. Two patients had a confirmed partial response (10%) and another eight had stable disease (40%). Preliminary results of FACT-L analysis in 19 pts shows improvement in Lung Cancer Subscale (LCS) score in 25% of the patients after 2 cycles of therapy. Conclusions: Combination gemcitabine and oxaliplatin is active and well tolerated as second line treatment for NSCLC. Improvement of LCS score after 2 cycles suggests a clinical benefit that is beyond the observed response rate of 10%. No significant financial relationships to disclose.
Topotecan and etoposide as salvage chemotherapy in patients with irinotecan- and platinum-failed small-cell lung cancer: A phase II study
Authors: Choi H. , Choi B. , Shin S. , Cheon S. , Cheon S. , Jung J. , Kim Y. , Sohn J. , Kim J. , Kim J. 
Published: March 2020

18177 Background: The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. Methods: From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan 1mg/m2 (day 1–5) followed by intravenous etoposide 80mg/m2 (day 1–3). Treatment was repeated every 21 days for a maximum of 6 cycles. Results: Twelve patients were refractory to first-line chemotherapy. Seventeen patients (73.9%) were male and the median age was 63 years. ECOG performance status was 0–1 in 13 (56.5%) patients. The median cycles of chemotherapy was 3. Twenty one patients were assessable for response evaluation. The overall response rate was 17.4% (0 CR, 4 PR, 7 SD, 10 PD) under the intent-to-treat analysis. After a median follow- up of 20.8 months, median progression free survival was 4.7 months and median overall survival was 9.5 months. The estimated 1-year survival rate was 38.7%. In sensitive relapsed patients, 2 achieved tumor response and median progression free survival and overall survival were 5.5 months and 14.5 months. All patients were assessable for toxicity and major toxicities were myelosuppression. Grade 3/4 neutropenia and thrombocytopenia occurred in 18 (78.3%) and 12 (52.2%) patients, respectively. Grade 3/4 febrile neutropenia occurred in 2 patients (8.7 %) and infection in 3 patients (13.0%). There was one treatment-related death due to pneumonia. Conclusions: This salvage regimen failed to demonstrate a considerable response rate compared with monotherapy for relapsed or refractory SCLC. However, the combination of topotecan and etoposide could be further studied for sensitive relapsed patients pretreated with irinotecan and platinum No significant financial relationships to disclose.
Investigation on the serum antibodies levels against Epstein-Barr virus in pulmonary lymphoepithelioma-like carcinoma
Authors: Niraula S. , Zong Y. S. , Zhai L. Z. , Guo C. C. , Lin T. Y. 
Published: March 2020

18186 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) belongs to large cell sub-type of non-small cell lung cancer (NSCLC) with just about 160 cases reported previously. Its epidemiology, prognosis and therapeutic approach is evidently different from other NSCLCs. EBV infection is seen in 100% of Asian PLELC patients whenever tested. The aim of this study was to analyze serum antibodies level against EBV in PLELC patients. Methods: Sera of all seven patients with re-confirmed PLELC from a single institute in Canton, China in the past 4 years were collected. Serum levels of 8 different antibodies against EBV (Epstein-Barr virus): EBNA1 (EBV nuclear antigen 1- IgA and IgG), Zta (Bam Z transactivator antigen-IgA and IgG), VCA-p18 (Viral capsid antigen-p18-IgA and IgG), VCA-antigen complex (VCA-IgA) and Early antigen complex (EA-IgA ) were measured in each of these patients using enzyme-linked immunosorbent assay and Immunoenzymatic assay respectively. Results: Out of 7 cases, 6 showed high EBNA-1 level, 4 showed high zta, 3 showed high VCA-p18, 3 showed high titer of VCA complex and 2 showed high EA complex titer ( Table 1 ) Conclusions: Though small sample size, this is the first study in this depth ever to conclude that sera of all Asian patients with pulmonary LELC have high antibody titers against EBV. The infection mainly is latency II type as seen in Nasopharyngeal carcinoma and Hodgkin’s disease as well. A small portion of PLELC express lytic products such as Zta, EA and VCA. The authors assume that pre-therapeutic measurement of serum levels of anti-EBV antibodies (at least 2 kinds) is highly warranted in suspected Asian NSCLC patients. Positive result strongly puts PLELC into differential diagnosis. [Table: see text] No significant financial relationships to disclose.
Gemcitabine and cisplatin double as neoadjuvant chemotherapy for operable 1B-IIIB stage NSCLC patients
Authors: Gorbounova V. , Polotsky B. , Marenich A. , Breder V. , Laktionov K. , Gerasimov S. , Dgebuadze E. , Fedenko A. , Kolesnik A. , Rodnikova E. 
Published: March 2020

18190 Background: the ongoing open-label, nonrandomized clinical trial on the evaluation of the efficiency and safety of gemcitabine/cisplatin as neoadjuvant chemotherapy of operable NSCLC. Methods: 37 chemonaive patients (male- 30 (81%) and female- 7 (19%), median age 54), ECOG 0–1 with morphologically verified NSCLC recieved gemcitabine 1250 mg/m2 IV on days 1,8 plus cisplatin 75 mg/m2 IV on day 1. The follow-up period was 3 years after the surgery. Results: Most of patients recieved 3 cycles in neoadjuvant setting. IB stage had 5 (13.5%) patients, IIB- 3 (8.1%), IIIA- 23 (62.2%) and IIIB- 6 (16.2%) patients. At baseline 12 (32.3%) patients had ECOG 0 and 25 (67.7%) ECOG 1. CR was registered in 3 (8.1%) patients, PR in 12 (32.3%), SD in 19 (51.3%) and PD in 2 (5.4%) and 1 patient was not assessed. The most common hemotologic toxicity was mild/moderate neutropenia that didn’t need dose reduction or intercycle interval prolongation. 25 patients underwent curative surgery with median survival of 30 months, 1-year survival of 81%, 2-year survival- 60% and 3-year survival - 40%. There was no statistically significant dependance between the level of pathomorphosis and the intensity of clinical response.6 patients recieved explorative thoracotomy and 6 didn’t recieve any surgery. Conclusions: Preliminary results show that gemcitabine/cisplatin combination is an effective and well-tolerable neoadjuvant regimen for patients with operable NSCLC. No significant financial relationships to disclose.
Pemetrexed in second-line therapy in patients with malignant pleural mesothelioma
Authors: Serke M. , Bauer T. 
Published: March 2020

18198 Introduction: Based on the study of Vogelzang (2003) standard treatment in patients with malignant pleural mesothelioma (MPM) is pemetrexed cisplatin with a medium survival of 12 months compared to 9 months with cisplatin therapy. As this treatment prolongs survival, but is not a curative treatment, many patients will relapse during the course of their disease. In sensitive relapses (within more than 3 months) our policy was to reintroduce pemetrexed therapy in unselected consecutive patients. Methods: Retrospective analysis of 17 consecutive patients treated in our hospital. Patient characteristics: 17 patients (pat), 14 males, 3 females, with MPM were included between April 2004 and November 2006 with an age between 45 and 82 years, with a median age of 65 years. Histologic subtypes were: 16 epithelial, 1 biphasic MPM. Pretreatment: 8 pat. had undergone palliative debulcing surgery (pleurectomy) 1 pat. underwent EPP. All patients were pretreated with platinum /pemetrexed, 5 pat. were pretreated with platinum/Gemcitabine before the availability of pemetrexed. 2nd line chemotherapy: 9 pat. were treated with carboplatin AUC5 / pemetrexed 500 mg/m2, 1 patient had cisplatinum 75 mg/m2/Pemetrexed 500 mg/m2 and 7 patients had pemetrexed single agent therapy (500 mg/m2 d1, WH d21), repeated on day 22 respectively. Results: Response: 6% (n=1) PR, MR: 12% (n=2 )., NC: 47% (n=8)., PD: 35% (n= 6), clinical benefit (PR, MR, NC) was seen in 65% of ou pat. Toxicity: Pemetrexed/Carboplatin or pemetrexed therapy were well tolerated, toxicity was mild: one patient developed mild sensory neurotoxicity (peripheral sensory neuropathy) (WHO II) under 6 cycles pemetrexed, 35% developed mild fatigue (Who I and II), one patient had mild renal impairment, no alopecia was seen. Survival: Only 3 patients had still died, median survival from start of second-line pemetrexed-therapy was not reached, time to progression was between 25 and 630 days, 4 pat. had not progressed until now. Conclusion: Second line therapy in MPM is not yet standard of care. Nevertheless patients with progressive disease following pemetrexed/platinum therapy may benefit from second line pemetrexed reintroduction therapy. Clinical benefit was seen in 65% with low toxicity. No significant financial relationships to disclose.
Anti-cancer gene expression profile of curcumin identifies new therapeutic targets in squamous cell lung carcinoma in vitro
Authors: Sen S. , Singh A. , Pal A. , Sharma C. , Kar R. , Singh N. 
Published: March 2020

18203 Background: Lung cancer is notorious for early metastasis and very high mortality, worldwide. Curcumin, a chemopreventive has also shown chemotherapeutic potential but its mechanisms are still not well understood. In this study, the genes targeted by Curcumin were investigated to identify new targets for the therapy of squamous cell lung carcinoma (SCC) in vitro. Methods: Lung squamous cell carcinoma cells (H520) were cultured in DMEM with 10% FCS. They were treated with Curcumin (25μM) for 24 hours. Apoptosis was detected by morphological examination, MTT assay, flowcytometry and TUNEL assay. Microarray analysis of gene expression profiles on curcumin treatment was done. Real time quantitative RT-PCR confirmed the results. Results: Curcumin (25μM for 24 hours) caused 29.8 ± 2.1% cytotoxicity (MTT assay). Apoptosis was corroborated by flowcytometry (23.7 ± 1.4%) and TUNEL (21.6 ± 1.8%). Using microarray analysis, 34 genes were seen to be upregulated and 31 genes downregulated after curcumin treatment. Several apoptosis related genes were upregulated including GADD45a (3.36 fold), transcription factor Egr-1 (2.2 fold) and Peroxiredoxin-I (2 fold). In addition, Angiopoietin-2 (Ang-2), an angiogenic factor that promotes angiogenesis and tumor invasion was downregulated (1.7 fold). Real time quantitative RT-PCR confirmed the results. Conclusions: This study helps to identify novel putative intervention sites as targets for curcumin in the therapy of squamous cell lung carcinoma (SCC) in vitro and can contribute to better understanding of lung tumorigenesis and anticancer therapy. No significant financial relationships to disclose.