bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combination phase I study of topotecan with carboplatin for relapsed small cell lung cancer: Results of West Japan Thoracic Oncology Group trial (WJTOG0202)
Authors: Kashii T. , Kurata T. , Takeda K. , Seki N. , Tsuboi M. , Miwa T. , Morinaga R. , Kobayashi M. , Satoh T. , Fukuoka M. 
Published: March 2020

18126 Background: Topotecan is an active agent for relapsed or recurrent SCLC. Combination chemotherapy of topotecan and carboplatin for relapsed SCLC has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a phase I study was conducted. Method: Patients with measurable disease and one prior chemotherapy regimen excluding topotecan were enrolled in this study. Topotecan was administered through days 1 to 5, whereas carboplatin was administered on day 5. Courses were repeated every 3 weeks. The starting doses of topotecan and carboplatin were 0.50 mg/m2/day and AUC=5, respectively. The dose levels examined are shown in the table below. Results: A total of 32 patients with relapsed SCLC have been enrolled. Patient characteristics are as follows: median age, 64 yrs (range 43–74); male/female, 23/9; ECOG PS 0/1, 15/17 patients. Dose-limiting toxicities (DLTs) were observed in 1 patient at dose level 1 (infection), level 3 (diarrhea), and level 5 (thrombocytopenia), respectively. Three of 6 patients have experienced DLTs at dose level 6 (thrombocytopenia). MTD of topotecan and carboplatin were determined to be 0.85 mg/m2 and AUC=5, respectively. Five of 29 (17 %) assessable patients have responded to treatment with a partial response (PR), and 13 (45 %) patients have had stable disease (SD) at best response. Conclusions: The recommended doses are 0.75 mg/m2 of topotecan and AUC=5 of carboplatin. The combination of topotecan and carboplatin shows an acceptable activity and toxicity profile in relapsed SCLC patients. Further study in the phase III setting is warranted. [Table: see text] No significant financial relationships to disclose.
Targeting Na+/K+-ATPase in non-small cell lung cancer (NSCLC)
Authors: Nilsson B. , Mijatovic T. , Mathieu A. , Roland I. , Van Quaquebeke E. , Van Vynckt F. , Darro F. , Kiss R. 
Published: March 2020

18144 Background: Non-small cell lung cancer patients that present with grade IIIB or stage IV disease have a median survival of 5–7 months if left untreated. With modern chemotherapy overall survival may be 11–12 months, but still no patients are cured. We have investigated the impact of modulation of the a-1 subunit of Na+/K+-ATPase in NSCLC. Methods: Cancer tissue from 59 patients with NSCLC (30 adenocarcinomas and 29 squamous cell cancers) and 25 normal lung samples as well as four human NSCLC cell lines (A549, Cal-12T, NCI-H727, A427) were assessed with regard to expression of the a-1 subunit of Na+/K+-ATPase (sodium pump) by use of immunohistochemistry. In addition, A549 cells were transfected with specific a-1 siRNA for study of a-1 subunit expression and of cell proliferation and migration. Protein expression was analyzed by Western blotting. Cell proliferation was assessed by MTT and cell migration by video microscopy. Cell lines were exposed to varying concentrations of ouabain, digoxin, digitoxin and UNBS1450, a novel cardenolide targeting the a-1 subunit of Na+/K+-ATPase for study of proliferation, migration, and inhibition of the target. Results: Expression of the a-1 subunit of Na+/K+- ATPase was elevated in almost half of the tissue samples from patients with NSCLC compared to normal controls. The a-1 subunit was also overexpressed in A549, Cal-12T and NCI-H727 cells. Transfection of A549 cells with siRNA resulted in markedly decreased expression of the a- 1 subunit and also to reduced migration and proliferation of such cells. UNBS1450 at 10 and 100 nM for 72 hours reduced A549 cell migration and proliferation similar to that observed with anti- a-1 siRNA. Digoxin had no activity at these concentrations. Conclusions: Inhibition of the a-1 subunit of Na+/K+-ATPase is associated with significant decrease of cell migration and proliferation and has potential as a therapeutic strategy in NSCLC. No significant financial relationships to disclose.
Gemcitabin (G) plus cisplatin (P) versus etoposid (E) plus cisplatin in advanced/metastatic non-small cell lung cancer (NSCLC): Preliminary results of a randomized monocentric study
Authors: Bousahba A. , Bereksi-Reguig F. 
Published: March 2020

18155 Background: we performed a randomized monocentric study to compare the treatment response of two chemotherapy doublets EP versus GP. Survival rates and toxicity are the secondary endpoints. Methods: from December 2003 to October 2006, patients with non-operable stage IIIB /IV histological or cytological proven NSCLC, ECOG PS = 2, were randomized to: (A) gemcitabin 1250 mg/m2 on d 1, 8 plus cisplatin 80 mg/m2 on d1 q3w for 6 cycles or (B) cisplatin at same dose followed by etoposid 100 mg / m2 on d1, 2, 3 q3w. The sample size was estimated at 64 patients per treatment arm to provide a power of 0.80 to detect a 20% difference in response rate between the two groups at the 5% level. Results: one hundred thirteen chemonaïve patients were enrolled (A: 57, B: 56), median age 61 years (arm A) and 57.5 years (arm B), stage IIIB (42.1% A vs 41.1% B), two or more metastatic sites (34% A, 39% B), PS 1 (68.4% A, 69.6% B). 360 cycles were administered 187 (A) and 173 (B) with a median of 3 cycles per patient in each group. Two patients were excluded from analysis. One hundred one patients were evaluable for toxicity, 90 for response. 47 pts were evaluable in A and 43 pts in B with treatment response in intent to treat principle respectively: complete response (1.8% - 0%), partial responses (29.1% and 20.7%). The objective response rate was 30.9% (95% CI 18.8%-43.2%) in A, 20.7% (95% CI 9.8%-31.6%) in B, no change (36.4% and 37.7%) and progressive disease (18.2% and 22.6%). Median duration of objective response 8.2 months (A) and 8.3 months (B), median time to progression : 8.0 months (A) and 7.5 months (B). Incidences of grade 3–4 toxicities were respectively in arms A and B: nausea-vomiting (37%-12.5%), leucopenia (5.6%-14.6%), neutropenia (13%-37.5%), thrombopenia (0–2.1%), anemia (13%-6.3%). Febril neutropenia occurred in 1.9% (A) and 8.3% (B). One toxic death occurred in arm B. Conclusions: preliminary analysis indicates that GP had a more favourable toxicity profile and a higher activity is suggested for the GP regimen. The enrolment is continued. No significant financial relationships to disclose.
A feasibility study of adjuvant carboplatin (C) plus gemcitabine (G) in completely resected stage IB-III non-small-cell lung cancer (NSCLC)
Authors: Horiike A. , Ohyanagi F. , Okano Y. , Satoh Y. , Okumura S. , Ishikawa Y. , Nakagawa K. , Horai T. , Nishio M. 
Published: March 2020

18158 Background: In recent randomized phase III trials in early-stage NSCLC, cisplatin-based adjuvant chemotherapy resulted in a 4.1–15% 5-year survival benefit versus observation. However, only 56–74% of patients completed planned treatment, suggestive of poor compliance. C plus G (CG), one of the standard regimens for advanced NSCLC, is considered more tolerable than other platinum-based regimens because it is associated with less nausea/vomiting, sensory neuropathy, and alopecia. The objective of this study was to assess the feasibility and safety of adjuvant CG in patients with completely resected NSCLC. Methods: Eligibility criteria included histologically confirmed NSCLC, age 20–74 years, complete surgical resection, post-operative pathological stage IB-III, 4–8 weeks post-surgery, ECOG performance status (PS) 0–1, adequate organ function, and informed consent. Patients were treated with adjuvant CG (C, AUC=5 on day 1; G, 1,000 mg/m2 on days 1 and 8) every 3 weeks for 4 cycles. The primary endpoint was treatment compliance, and the planned sample size was 35 patients (Simon’s minimax design). Results: From October 2004 to July 2006, 35 patients (17 males, 18 females; median age, 64 years) were enrolled. All patients had PS=0. Histologic types included adenocarcinoma (n=27), squamous cell carcinoma (n=3), large cell neuroendocrine carcinoma (n=3), large cell carcinoma (n=1), and adenosquamous carcinoma (n=1). Pathological stages included stage IB (n=7), stage IIA (n=7), stage IIB (n=4), stage IIIA (n=13), and stage IIIB (n=4). Resection consisted of lobectomy (n=33) and pneumonectomy (n=2). All patients received =2 cycles of chemotherapy, with 29 patients (83%) completing 3 or 4 cycles. Primary G3/4 toxicities were leukopenia (51%), neutropenia (83%), thrombocytopenia (71%), and anemia (38%). Nonhematologic toxicities were very mild: 6% G3/4 febrile neutropenia, 3% infection, and 3% rash. No treatment-related deaths occurred. Conclusion: Adjuvant CG in patients with completely resected NSCLC is well tolerated, and treatment compliance is very good. No significant financial relationships to disclose.
A phase II study of weekly docetaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer
Authors: Son C. , Kim K. , Lee K. , Yang D. , Lee S. , Choi P. , Cho S. 
Published: March 2020

18174 Background: Combination chemotherapy has been shown to extend survival and improve symptoms for patients with advanced stage, unresectable non-small cell lung cancer (NSCLC). However, chemotheraputic agents sometimes show significant toxicities that restrict their usefulness and not well tolerated in elderly and/or poor performance status patients. Docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy in advanced stage NSCLC. We performed this study to explore the efficacy and safety of weekly docetaxel plus carboplatin in patients with advanced NSCLC aged 60 years or older. Methods: From January 2005 to August 2006, 45 patients with advanced NSCLC patients aged 60 years or older were enrolled in the study. Patients received docetaxel 25mg/m2 by IV infusion over 30–60 min and carboplatin, AUC = 2, infused IV over 15–30 min weekly. Treatment was continued until disease progression or unacceptable toxicity occurred, at which time the patient was taken off treatment. Maximum doses were 18 and evaluated the patients received at least 9 doses. Results: Of 45 patients, 24 patients received at least 9 dose of study drug. 21 patients stopped the treatment before the completion of 9 cycles; 9 (42.9%) due to poor general condition, 7 (33.3%) due to disease progression, and 5 (23.8%) due to volitional withdrawal. Of the 24 patients who received more than 9 cycles, final results were complete response in 1 (4.2%) patient, partial response in 16 (66.7%) patients, stable disease in 1 (4.2%) patient, and progressive disease in 6 (25%) patients. The most common hematological grade 3/4 adverse event was neutropenia(25%). There was no treatment-related death. Conclusion: Weekly docetaxel at low doses plus carboplatin in elderly patients with advanced non-small cell lung cancer provides acceptable response rate and toxicity. However, further study with large population will be needed to confirm its effectiveness and toxicity. No significant financial relationships to disclose.
Clinical Responses to EGFr-TKI’s characterized by drug-induced cell death in human NSCLC primary cultures
Authors: Nagourney R. A. , Paulsen M. , Mc Connell D. , Shuman R. 
Published: March 2020

18184 Background: Small molecule inhibitors of the EGFr have proven effective in advanced NSCLC but response rates in unselected populations remain low. Certain subsets of patients appear favored including females, non-smokers and Asians. Molecular profiles suggest that gene amplification or EGFr mutations (codons 19–21) may underlie responses. Our prior observations (Proc. AACR 2002, Abs.3902) indicated that gefitinib and erlotinib induced cell-death in human tumor microspheroids isolated from surgical specimens of some NSCLC patients, suggesting programmed cell death to be an important mechanism of action for these molecules. As part of an IRB-approved clinical trial, patients whose tumors were found sensitive to the EGFr-TKI’s by laboratory analysis, received 1st line single agent oral erlotinib at 150 mg/day. Methods: Following informed consent, NSCLC patients participating in the trial provided tissue for analysis as previously described (J Clin Oncol, 2000 18: 2245–2249). Dose response curves provided LC50 values by interpolation. Modified Z-score analysis identified patients sensitive to the EGFr-TKI’s by comparison with a database of over 900 EGFr-TKI analyses. Results: Three female caucasian patients were found more sensitive to EGFr-TKI’s than cytotoxic chemotherapy (2 non- & 1 former smoker). All 3 responded to erlotinib, 2 near-CR by PET, 1 lasting 19 months, the 2nd continuing at 10 months, with a 3rd patient in continuous PR at month 6. Toxicities have been moderate. One near-CR had virtually no skin rash. The molecular profile of 1 near-CR revealed no known gain of function mutation but instead a novel mutation in the EGFr domain. Conclusions: Exposure of human NSCLC microspheroids to EGFr-TKI’s in short term culture results in cell death events associated with clinical response, suggesting that programmed cell death is an important determinant of clinical response to these agents. This is consistent with the concept of oncogene addiction, in tumors driven by EGFr upregulation. Accrual to this trial continues. Supported by the Memorial Medical Center Foundation. [Table: see text]
NETS of the lung (non SC): Experience of lung cancer working group E. Morelli Hospital Sondalo
Authors: Valmadre G. , Delfanti R. , Robustellini M. , Rossi G. , Della Pona C. , Epis R. , Pastorini A. , Buscemi A. 
Published: March 2020

18191 Background: pulmonary NETS are typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNC), and SCLC. Purpose: to evalue prognosis of pulmonary NET (non SC) according by histotype, treatment and serum CgA. Methods: From 1996 to 2006 our lung cancer working group followed 42 pulmonary NETs, none carcinoid syndrome and 1 metastatic (CgA 100xN) at diagnosis. 39/42 underwent radical surgical resection with adenectomy. 2/42 TC had endobronchial laser, the metastatic any treatment. 31/42 (73.8%) are TC. 10/42 (23.8 %) are AC, 1/42 (2%) undetermined. Results: In dec 06 we reviewed 37/42 cases (20 clinical examination and 17 by phone). 2/5 missing were dead: 1 AC 7 years later with liver metastasis, high CgA without syndrome and 3 years of octreotide. 2 TC, 1 AC drop-out. Of 20 pts seen, 3 had high CgA, but Octreoscan negative. 32 pts (86.5%) had only surgery: 15 with more than 5 years DFS. 7 had preoperating CgA: 4 normal, 2 high (1 had hepatic metastasis, in 1 normalized and 36 months DFS), 1 ongoing. 2 pts without surgery are alive after 17 and 8 months. The metastatic pt has PR with octreotide. 1 TC had gastric carcinoma at 7 years. 3 TC had progressive disease. 1 TC (IA and high pre-lobectomy CgA), had persistent high CgA and positive octreoscan hepatic lesion 4 months later: PR after 6 months of octreotide. Another with normal pre-lobectomy CgA (TC IB) had carcinoid syndrome with high CgA and octreoscan positivity, 4 months later: negative restaging at 22 months with one-year of octreotide. A sixteen girl - TC IB - with high CgA (normal after pneumonectomy) developed octreoscan positive thoracic lesions, 18 months later. PR after 44 months with radiometabolic therapy. Conclusion: NETS are heterogeneous and with better prognosis (except SC) than other lung cancers. AC radically resected had good prognosis (1/10 metastasis ), sometimes TC gave metastasis and progression (2/31). For the 2 subtypes OS is high. Octreotide- and radiometabolic therapy can control the metastatic disease. CgA is not indicative of relapse but well correlates with the extension of metastatic disease. High CgA values are not predictive of carcinoid syndrome. It is important to evalue CgA before and 2–3 months after surgery. Carcinoid syndrome is rare in lung NET. We don’t have any LCNL. No significant financial relationships to disclose.
Phase I study of cisplatin/carboplatin/irinotecan (CPI) regimen in patients with ED small-cell lung cancer
Authors: Ichiki M. , Yoshida Y. , Ishimatsu A. , Minami S. , Taguchi K. , Tachibana K. , Aizawa H. 
Published: March 2020

18202 Cisplatin/irinotecan(IP) is standard regimen for ED-SCLC in Japan. Cisplatin (CDDP)-based treatment requires copious hydration, which can lead to a deterioration of outpatients’ quality of life. CDDP and carboplatin (CBDCA) have a common active form, but are associated with different adverse reactions. We considered that the combined use of these two agents could increase the dose intensity of active form platinum complexes without enhancing their toxicities. The IP was modified to nearly half the dose of CDDP/CBDCA to facilitate outpatient administration. We conducted a phase I study to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of this modified regimen for patients with ED-SCLC and stage IV NSCLC. Eligibility criteria included: PS 0–1, age <75 yrs, no prior therapy, measurable disease, adequate organ functions. DLT was defined as follows: 1) grade 4 neutropenia lasting 4 days or febrile neutropenia, 2) grade 4 thrombocytopenia, 3) prolongation of treatment due to toxicity, 4) grade 3 or worse non-hematological toxicity. Three patients were enrolled at level 1(CDDP/CBDCA: 25 mg/m2/AUC2), 3 patients at level 2 (25 mg/m2/AUC 2.5) and 3 patients at level 3 (30 mg/m2/ AUC 2.5), respectively. DLT was not observed at level 1, 2, 3. At dose level 4 (30 mg/m2/AUC3), two of three patients experienced DLT, suggesting this level to be the MTD. The recommended dose for phase II study is CDDP 30 mg/m2 on day 1, CBDCA AUC 2.5 on day 1 and irinotecan 60 mg/m2 on days 1, 8, 15. A phase II study of this regimen in ED-SCLC is ongoing. No significant financial relationships to disclose.
Phase I study of amrubicin (AMR) for patients (pts) with previously treated small cell lung cancer (SCLC)
Authors: Katakami N. , Hata A. , Yoshioka H. , Higashi Y. , Nishimura T. , Sakaguchi S. , Hayashi M. , Tomii K. , Naya R. , Ishihara K. 
Published: March 2020

18209 Background: Amrubicin, a totally synthetic 9-amino-anthracycline, has been demonstrated to have excellent antitumor activity against previously untreated SCLC. However, severe hematological toxicities were observed in previously treated SCLC when given at doses of 40 to 45 mg/m2, days 1–3. We sought to determine the maximum tolerable dose (MTD) and toxicity of amrubicin for pts with previously treated SCLC. Methods: Pts with confirmed SCLC, ECOG PS 0–1, and 20 to 74 years of age, with a history of receiving one or two regimens were eligible for the study. Pts were divided into two groups. Group R (-) consisted of pts without history of radiotherapy except prophylactic cranial irradiation. Group R (+) consisted of pts with history of irradiation up to two fields including thoracic radiotherapy. AMR was initially given at 35 mg/m2, iv, days 1–3, every 3 weeks in both groups. The dose was then increased to 40 and 45 mg/m2. Three pts were treated at each dose level in the absence of a dose limiting toxicity (DLT). All pts received prophylactic hG- CSF between days 8–13. DLT was defined as neutrophil nadir <500/μL lasting more than 4 days, neutropenic fever and neutrophil nadir <1000/μL, platelet nadir <20,000/μL or ≥ grade 3 non-hematologic toxicities. Results: Fourteen pts were enrolled, 10m/4f. The median age was 62 years (range 34–82). Two of 6 pts in the first cohort in group R (-) had dose-limiting neutropenia. The dose escalation is ongoing. Three pts in the first cohort in group R (+) had no dose-limiting toxicities. A subsequent 5 pts were treated at dose-level 2, and 3 pts had dose-limiting neutropenia. The MTD in group R (+) was 40 mg/m2. A response rate of 62% was observed. Median survival time was 12 months. No treatment-related death was observed. Conclusions: The MTD in group R (-) was not determined. The MTD in group R (+) was determined as 40 mg/m2. Further data will be presented. No significant financial relationships to disclose.
Comparison of metabolic activity in mantle cell lymphoma at biospy site and other tumor sites using 18F-FDG PET
Authors: Chundru S. , Nguyen M. , Jaiyesimi I. , Wong O. , Douglas-Nikitin V. , Nadeau L. , Balon H. , Mardis N. , Fink-Bennett D. 
Published: March 2020

18529 Background: Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin’s lymphoma (NHL) with a variable clinical course ranging from indolent to aggressive. Treatment for MCL is complicated by this variability, as systemic chemotherapy for NHL is directed by the aggressiveness of the lymphoma. Previous attempts have been made to correlate clinical outcome in MCL with histologic features. More recently, measurement of metabolic activity using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) was found to be highly correlative with the aggressiveness of NHL. Given the clinical heterogeneity of MCL, the search for the true metabolic status in MCL is important in prognostication and management. We propose to study the metabolic activity in MCL by comparing the maximum SUV at the site of biopsy with the highest SUV in other MCL areas of the body. Methods: 12 patients with newly diagnosed MCL and having staging by FDG-PET were identified. PET(CT) body scans were obtained in the usual fashion. The SUVs, defined as tumor activity divided by dose injected per lean body mass, from the PET and PET-CT cameras were cross validated to produce the same value in a given phantom and patient. Maximum biopsy SUV was measured by searching the maximum value within a volume of interest over the known biopsy site, and highest body SUV was similarly searched in known tumor sites in other body areas. Results: One patient was excluded because the tumor at the biopsy site had been completely resected. The remaining 11 patients (M:F=8:3, age=63±8 yrs) were analyzed. The SUV at biopsy sites ranged from 2.1 to 9.8 (mean=5.2±2.3). The SUV in other tumor sites ranged from 4.8 to 18.6 (mean=8.9±4.1), which was significantly higher when compared to the respective biopsy site (p=0.0036). Conclusions: As the SUV of MCL at the biopsy site may not represent the highest SUV, it is important to search other tumor sites in the body for the highest SUV to help in grading, managing, and subsequent monitoring of MCL. Perhaps FDG-PET can direct biopsies to tumor sites with the highest SUV and subsequently provide useful histologic detail for predicting clinical course. Future study is needed to correlate the maximal SUV of MCL with histology and clinical course. No significant financial relationships to disclose.
Mutant P53 in non-Hodgkin lymphoma
Authors: El-Wahidy G. F. , Sharaf-eldin O. A. , Awad M. A. , Abdel Ghaffar H. A. , Salama M. S. 
Published: March 2020

18537 Background: *Chromosomal aberrations are important events in the pathogenesis of lymphoma & leukaemias P53 belongs to class of genes whose functions involves negative regulation of cell growth through certain protein synthesis which leads to arrest of the cell cycle at growth phase. *Elucidate the nature of P53 in cases with Non Hodjkins lymphoma presented in our province (North east Mediterranean) and the impact of its mutation on known prognostic factors as well as on survival of patients receiving treatment by different chemotherapy protocols. Methods: Study done on 34 patients and 10 normal contorls Conclusions: *P53 +ve mutations in patients with lymphoma outnumbered those with −ve mutations. *Positivity degree is increased in higher grade than lower grade lymphoma. *Dfs is prolonged in those with −ve mutations than in subgroups with +ve mutations. *Subgroups with negative Exon mutations carry better survival than those with +ve mutations. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text] No significant financial relationships to disclose.