bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial safety and efficacy results of erlotinib in previously treated patients with advanced non-small cell lung cancer
Authors: Zhou S. , Zhou C. , Yan L. , Xu Q. , Xu J. 
Published: March 2020

18183 Background: Erlotinib is an orally available selective HER1/EGFR tyrosine kinase inhibitor. In the BR.21 trial, erlotinib significantly improved survival and quality of life in non-small cell lung cancer(NSCLC) patients (pts). The study evaluated the initial efficacy and safety of erlotinib in previously treated advanced or metastatic NSCLC patients in Shanghai, China. Methods: Eligibility criteria included stage IIIb/IV or recurrent NSCLC pts who failed from prior chemotherapy, PS = 0–2, weight loss less than 5%, and no urgent symptoms. Pts received oral erlotinib 150 mg po/day until objective or symptomatic progression. Results: 50 pts were enrolled from Oct 1 to Sept 30. Demographics: M 68%/F 32%; median age 55 y [range 28–68]; stage IV 86%; PS 0/1/2:2 (4%)/44 (88%)/4 (8%); adenocarcinoma/non-adenocarcinoma 39 (78%)/11 (22%); smoking status: 26 (52%) /no 24 (48%). The major toxicity was rash: 48 (96%), 10 (20%) of them are grade 3/4; other toxicity included grade 1/2 diahhrea: 5 (10%); grade 1/2 liver dysfunction: 4 (8%); grade 2 leucocytopenia: 2 (4%); grade 1 thrombocytopenia: 1(2%); fatigue and dyspnea. 3 patients discontinued for dyspnea, pneumonitis and fatigue respectively. No pts had pulmonary fibrosis and dose reduction. 47 pts were followed long enough for efficacy evaluation, which indentified 18 (38%) with PR, 21 (45%) with SD, 8 (17%) with PD. Subgroup analysis showed the resposes to erlotinib have no relation with gender, age, smoking status, performance status, histology and stages, however, significant difference existed in the subgroup patients with severe rash and less symptoms such as dyspnea and fatigue ( Table 1 ). Conclusions: Erlotinib is active and well tolerated in patients with advanced NSCLC failed to previously chemotherapy. Preliminary results suggest patients with severe rash, less dyspnea and fatigue are accociated with better response. The study in ongoing. Table 1 Response of erlotinib in advanced treated NSCLC pts. * P values less than 0.05. [Table: see text] No significant financial relationships to disclose.
Oral vinorelbine in first line treatment of NSCLC in elderly: Updated results of a low dose schedule in a single institution experience
Authors: Tomirotti M. , Galassi B. 
Published: March 2020

18192 Background: Oral Vinorelbine has been reported as an effective treatment option for advanced NSCLC in patients not suitable for CDDP containing schedules. Methods: With the aim to improve the toxicity profile of oral Vinorelbine therapy in the elderly setting, from 01/2004 to 05/2006, 31 patients with stage IIIB-IV NSCLC were treated with single agent oral Vinorelbine at the dose of 60 mg/m2 day 1,8,15 every 3 weeks. Median age of patients was 75 (range 65 to 82) and M/F ratio 1,6. All patients were untreated and received oral Vinorelbine as first line chemotherapy. 24/31 pts were first diagnosed and not suitable for surgery (14/24 locally advanced, 4/24 not operable for comorbidity, 6/24 stage IV at diagnosis), 7/31 recurring after surgery. Pathology reports 15/31 adenocarcinoma, 9/31 squamous, 7/31 non-small cells (citology). Sites of distant metastases were as follow: liver in 13%, bone in 16%, mediastinal lymph nodes in 71%. Median Karnofsky performance status was 80 (range 60–90). Results: Adverse event were experienced by 35% of patients, but were generally mild (grade 1–2). In particular fatigue was reported by 13%, parhestesias by 16%, gastrointestinal disconfort (mild nausea/diarrea) by 26%, costipation/abdominal pain by 10%, trombocytopenia by 6%; no patient experienced anorexia, emesis nor febrile neutropenia. Dose reduction was never required.Complete reversal of adverse effects was always documented. No patient experienced CR; 6/31 (19%) PR and 8/31 (26%) SD were reported with clinical benefit in 14/31 patients (45%). Median time to progression and overall survival were 4,2 and 9 months, not different from data reported in recent literature for higher intensity schedule (Gridelli C, et al.: Eur J Cancer 40:2424–43, 2004) Conclusions: Treatment with oral Vinorelbine at the 60 mg/m2 day 1,8,15 every 3 weeks schedule has a low toxicity profile and seems to be better tolerated than the conventional dose of 80 mg/m2, representing a valide alternative for elderly patients with advanced NSCLC. No significant financial relationships to disclose.
Phase I study of combination chemotherapy with amrubicin and paclitaxel in relapsed small cell lung cancer
Authors: Tanaka J. , Yoshizawa H. , Ito R. , Hayashi Y. , Kuriyama H. , Tanaka H. , Kagamu H. , Gejyo F. 
Published: March 2020

18206 Background: Amrubicin (AMR) and paclitaxel (PTX) are promising agents for advanced non-small cell and small cell lung cancer (SC). However, the combination of these drugs for relapsed SC has never been reported. The aim of this study was to determine the maximum tolerated dose (MTD) of AMR and PTX, thus to investigate the recommended dose (RD) of this combination chemotherapy for relapsed SC patients. Methods: Relapsed SC patients after 1 or 2 regimens with age younger than 70 and good performance status (PS) were eligible. The treatment consisted of AMR (escalating from 30 to 40 mg/m2 by 5 mg/m2 increment) as a one- shot iv on days 1 through 3, and PTX (escalating from 70 to 90 mg/m2 by 10 mg/m2 increment) as a 60-minute infusion on days 4 and 11, repeated every 21 days. The dose-limiting toxicities (DLTs) were defined as grade 3/4 non-hematological toxicities, grade 4 thrombocytopenia, and grade 4 leukocytopenia / neutropenia for 4 days or more. Results: Nine relapsed SC patients were enrolled. All of them were sensitive-relapsed cases with mean age of 60.1 and PS of 0 - 1, and received one or more cycles of chemotherapy (mean: 2.7 cycles). Six patients were treated at level 1 (AMR 30mg/m2, PTX 70 mg/m2) with two of them on DLT of grade 4 neutropenia for 4 days or more. Three patients were treated at level 2 (AMR 35 mg/m2, PTX 70 mg/m2) with all of them on DLTs; grade 4 neutropenia for 4 days or more, grade 3 febrile neutropenia, and grade 3 pneumonia. Overall response rate was 63%. Conclusion: The MTD was identified to be level 2, and the RD for this regimen with AMR and PTX was considered to be 30 mg/m2 and 70 mg/m2, respectively. Treatment was well tolerated and the preliminary activity observed warrants further investigation. A phase II study is currently under investigation for relapsed and refractory SC patients. No significant financial relationships to disclose.
Dose-seeking study of the combination of GM-CSF with pegfilgrastim plus CHOP-rituximab in patients with aggressive non- Hodgkin lymphoma (NHL)
Authors: Cabanillas F. , Pavia O. , Rivera E. , Liboy I. 
Published: March 2020

18501 Background: Therapy for aggressive B cell NHL includes CHOP-rituximab (CHOP-R)q 14 days with G-CSF support. We are now investigating CHOP-R plus pegfilgrastim (Neulasta [N]) and low dose GM-CSF (Leukine). The rationale for low dose GM-CSF is based on its stimulation of ADCC which appears to be the most important mechanism of action of R and upregulation of CD20 on B cells, in addition, to other immunomodulating effects. Some of these are seen at lower levels of GM-CSF and appear to be lost at higher doses. N is given in order to allow delivery of chemotherapy q. 2 weeks. Methods: The goal was to determine the optimal dose of GM-CSF needed to support absolute neutrophil count (ANC) recovery >1,000 by day 14 without inducing marked leucocytosis when combined with N. R is given on day 1, CHOP on day 2 and growth factors start on day 3. We used a single fixed low dose of N 3 mg s.c. on day 3 and an escalating dose of GM-CSF starting at 75 mcg s.c. on day 3. GM-CSF was repeated every Monday, Wednesday and Friday. Results: So far we have delivered 65 evaluable courses to 18 pts (16 evaluable) whose median age was 58 (range 26–87). The plan was to escalate GM-CSF as necessary to support ANC recovery by day 14 without inducing severe leucocytosis. GM-CSF was to be escalated in cohorts of 5 patients at: 75, 125 and 250 mcg. The first cohort of 5 was treated at 75 mcg and all 5 recovered their ANC to >1,000 by day 14 and none exceeded ANC >50,000 before day 14. Therefore the next cohort of 5 received the same dose of 75 and all 5 were able to recover by day 14. Subsequently the next 6 were also treated at the same dose of 75 mcg. During 65 total courses, all but 3 pts recovered ANC to >1,000 before day 14. Chemotherapy doses were not reduced unless severe infection (i.e. septic shock or bilateral pneumonia). Because of prolonged or severe neutropenia, intrapatient dose escalations of GM-CSF were done in 2 pts (to 125 mcg) during the 2nd course and to 250 mcg in 1 pt during the 3rd. Conclusions: GM- CSF 75 mcg on Mondays, Wednesdays and Fridays is adequate and safe to support ANC recovery if combined with 3 mg N. However, in view of encouraging data of McLaughlin et al with 250 mcg of Leukine plus R in indolent NHL, in the next study we will attempt to escalate Leukine to 250 mcg. [Table: see text]
Non-pegylated lyposomal doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-COMP) as initial treatment for patients with splenic marginal zone lymphoma (SMZL): A GISL study
Authors: Iannitto E. , Luminari S. , Mammi C. , Minardi V. , Merli F. , Angrilli F. , Stelitano C. , Cesaretti M. , Franco G. , Carella A. M. , Federico M. 
Published: March 2020

18502 Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associated with intrasinusoidal bone marrow infiltration. The encapsulation of doxorubicin into non-pegylated liposomes allows targeting of the drug to affected organs including spleen, lymphnodes and bone marrow. Methods: In 2005, the GISL started a phase II study for the treatment of patients with histologically confirmed SMZL, investigating safety and clinical profile of 6 courses of a modified R-CHOP regimen in which standard doxorubicin was substituted with non pegylated lyposomal doxorubicin (NPLD) used at the same doses (50 mg/m2) (R-COMP). Main inclusion criteria were age >18 yrs, normal cardiac function and active disease (at least one of the following; Hb <10 g/dl; plt <100,000/mmc, symptomatic splenomegaly, elevated LDH, B symptoms, extrasplenic disease, LDT <12 months). Splenectomy was allowed prior to treatment start only in case of symptomatic spleen enlargement. The study was planned according to a two-stage Simon design using overall response rate as primary endpoint. We present the results of the analysis performed after the completion of study stage 1. The access to stage 2 is allowed if at least 12 responses are recorded among among the first 19 evaluable cases. Results: As of January 2007, 20 patient were enrolled with the following characteristics; median age 63 years (30–80), Hb <10 g/dl in 20%, Lymphocytes > 5,000/mmc in 65%, elevated LDH in 65%; 2 patients were splenectomized before treatment start. One patient was not available for response assessment. A clinical response was observed in all remaining 19 cases (ORR 100%); 12 (63%) cases obtained a CR. So far only one patient progressed at +1 month from treatment. Treatment was well tolerated with grade III/IV neutropenia in 8 patients (42%), grade 3 pulmonary toxicity in 1 patient and grade 2 peripheral neuropathy in 5 cases. In one case a reversible cardiac failure was reported after 1 month from the end of treatment. Conclusions: In conclusion 6 cycles of R-COMP combination represent a safe and promising treatment option for patients with clinically active SMZL. No significant financial relationships to disclose.
Factors associated with long-term survival following stem cell transplantation (SCT) for non-Hodgkin lymphoma
Authors: McQuellon R. P. , Russell G. B. , Jesse M. T. , Thomas C. R. , Keung Y. 
Published: March 2020

18504 Background: Psychosocial variables have been associated with survival in stem cell transplantation recipients. The purpose of this study was to examine the relationship between clinical, psychosocial, and demographic variables and long-term survival. Methods: Autologous SCT recipients with NHL (n=315) from 1/92 - 4/05 (mean age = 51.6 yrs (±12); 35% F; 7% AA; median survival/follow-up = 4.4/ 6.1 yrs) completed the Center for Epidemiologic Studies-Depression Scale, Functional Assessment of Cancer Therapy- BMT (FACT-BMT; physical well-being, PWB), Profile of Mood States, and the Medical Outcomes Study Social Support Survey (MOS-SS) prior to transplantation. Clinical and demographic data were abstracted from the patient’s record. Cox’s proportional hazards regression models were used to assess the effect of the following variables on survival: clinical - histological subtypes (HS) [anaplastic large cell (ALC), diffuse large B-cell (DLBC), mantle cell (MC), indolent, and aggressive], grade, stage, type of conditioning regimen (TC), chemosensitivity (CS), number of chemotherapy regimens (1–7) prior to SCT (NCR); demographic - age, race, gender; and psychosocial - depressed mood, general distress, quality of life, and social support. Measures with a univariate p-value <0.2 were fit in a backwards stepwise regression; remaining variables had a p-value < 0.05. Results: The included univariate model variables (p-values) were: HS (0.0004), grade (0.004), TC (0.14), CS (0.0001), NCR (0.02), PWB (0.03), FACT-BMT subscale (0.16), SS-Emotional (0.05), SS-affection (0.13). In the regression model, predictors of survival were: HS (<0.0001), median survival = ALC 1.9, DLBC 2.7, aggressive 3.3, MC 5.1, indolent 8.4 yrs; CS (0.008); NCR (0.03), and PWB(0.03). Conclusions: Clinical variables were the most predictive of survival. Psychosocial variables were not associated with survival. No significant financial relationships to disclose.
Factors influencing tymic function in 55 patients with lymphomas: Candidates to autologous stem cell transplantation (ASCT)
Authors: Simonelli C. , Pratesi C. , Zanussi S. , Talamini R. , Rupolo M. , Abbruzzese L. , Gattei V. , Vaccher E. , Michieli M. G. , De Paoli P. , Tirelli U. 
Published: March 2020

18512 Background: Signal joint T cell receptor excision circles (sjTRECs) have been reported to be a clinical marker to evaluate the tymic reservoir after immunosuppression treatments. Methods: We studied the sjTRECs levels in a mono-institutional series of a cohort of 26 HIV-positive and 29 HIV-negative pts with relapsed or refractory lymphomas, candidates to ASCT, considering important biological and clinical characteristics, virological parameters and immunological settings including age, type of lymphoma, number of first line CT cycles, time from the end of first line chemotherapy to the enrolment (TECT), HIV infection and T subpopulations. Results: The overall study subjects, showed lower sjTRECs levels than healthy donors (p<0.01), but no differences in the sjTRECs content were seen between HIV-negative and HIV-positive pts (536 vs. 401 TRECs/106 PBMCs, respectively) as well as in the T cell naive count. We found a significant correlation between the sjTRECs decay and the increase of age (r=-0.32, p=0.02), CD4 and CD8 naive cell count and the sjTRECs level; on the contrary we did not observe any significant correlation between CT cycles number TECT, lymphoma type in both subgroups. HIV-positive viremic pts showed significant lower level of sjTRECs level than averimic pts. Conclusions: Our analyses suggest that de novo T cell generation is partially maintained in lymphoma pts’ candidates to ASCT and could contribute to restore the immune function after transplantation. Chemotherapeutic treatments seem to induce a similar influence on thymic output despite their intensity and, surprisingly, HIV infection is not a detrimental factor on thymic reservoir at the time of lymphoma relapse, and a good control of HIV replication seems to preserve thymic reservoir. No significant financial relationships to disclose.
Ifosfamide or trofosfamide for intraocular lymphoma: Long-term results of a prospective study
Authors: Thiel E. , Jahnke K. , Bechrakis J. , Wagner T. , Fischer L. , Kiewe P. , Korfel A. 
Published: March 2020

18524 Background: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. In a prospective study, ifosfamide (IFO) or trofosfamide (TRO) have been assessed for treating IOL. Here, long-term results are presented. Patients and Methods: Patients with histologically proven isolated IOL were included. The median age of the patients was 74 years (range 46–83 years); 4 patients had a newly diagnosed disease and 6 a relapse. IFO was administered intravenously at a dose of 1.5 - 2.0 g/m2/day for 3 days every three weeks. TRO was given at a dose of 150 or 400 mg/day (continuous or intermittent administration) to 4 patients considered unable to receive intensive intravenous hydration. IFO, TRO and their active 4-hydroxy (4-OH) metabolites were measured in aqueous humor of 9 patients. Results: The median number of IFO courses was 6 (range 2–8), the median duration of TRO therapy was 8.5 months (range 6–18 months). All patients responded. Toxicity > WHO grade 2 was: anemia grade 2 in 2 patients, leukopenia grade 2–3 in 2 patients, nausea/vomiting grade 2 in 2 patients, thrombopenia and cystitis grade 2 in 1 patient each. Thus far, three patients each have developed cerebral and ocular relapse. Median progression-free survival from the study treatment was 9.5 months (range 6 - 24+ months), median overall survival was 15.5 months (range 6–34 months). Both patients retreated with IFO on ocular relapse responded. In 6 of 6 patients, 4-OH metabolites were detected in the aqueous humor immediately after IFO infusion with an aqueous/serum ratio of 0.19–0.54. Three to 16 hours after ingestion of TRO, 4-OH metabolites could be detected in one of 3 patients. Conclusions: Response rate of IOL to IFO or TRO is high with a tolerable toxicity even in elderly patients. However, long-term remissions are infrequent. Combining IFO/TRO with other cytostatics seems reasonable to improve long-term disease control. No significant financial relationships to disclose.
Rituximab, ifosfamide, carboplatin, and etoposide (RICE) compared with ICE in relapsed diffuse large cell lymphoma (DLCL) before autologous stem cell transplantation
Authors: Case D. C. , Aronson F. R. , Ebrahim K. S. , Hedlund J. A. , Boyd M. A. , Ault K. A. 
Published: March 2020

18532 Background: Retrospective cohort analysis suggests that the addition of rituximab to the ICE regimen (RICE) improved the complete response (CR) rate in relapsed DLCL and progression-free survival after transplantation (Blood 103:3684, 2004). We reviewed the results of two consecutive cohorts of patients treated with ICE and RICE prior to stem cell transplantation for CR rate, percent patients able to go to transplantation, and progression-free survival after transplantation. Methods: Adult patients (1996–2000) with relapsed DLCL received ICE chemotherapy [ifosfamide 1800 mg/m2 IV q.d. x3, carboplatin 250 mg/m2 IV day 1, and etoposide 75 mg/m2 IV q.d. x3 along with mesna] every 28 days to maximum response. Responding patients who were clinically stable and able received high-dose chemotherapy with autologous stem cell support. Adult patients (2001–2004) with relapsed DLCL received ICE along with rituximab 375 mg/m2 IV on day 1 of each cycle of chemotherapy. Patients in CR received autologous stem cell transplantation. Results: In the ICE series, 49 patients were treated with a 20% CR rate, and 10% went to transplant. Progression-free survival in those transplanted was 9, 12, 24, 36, and 81+ months (median 24 months). In the RICE series, 24 patients were treated with a 33% CR rate, and 25% were transplanted. Progression-free survival was 12, 18, 24+, 36, and 46+ months (median 24+ months). Myelosuppression was similar in each series. All patients were able to tolerate rituximab. The CR rate, percent of patients transplanted, and progression-free survival after transplantation appeared better with RICE but these differences were not statistically significant (P>.05). Conclusions: In our small series, Rituximab added to ICE did not have a statistically significant impact. No significant financial relationships to disclose.
Conserved epigenetic changes in sporadic and HIV-associated high-grade B-cell lymphomas
Authors: Crook T. , Smith P. , Syed N. , Stebbing J. , Griffin B. , Bower M. , Naresh K. 
Published: March 2020

18540 Background: Transcriptional silencing represents a major mechanism of tumour suppressor gene inactivation in human tumours, including lymphoma. Here, we have compared patterns of aberrant methylation in sporadic and HIV-associated B cell lymphomas. Methods: We used methylation reversal/ micro-array analysis to seek novel genes subject to methylation-dependent transcriptional silencing in B cell lymphoma cell lines and primary B cell lymphomas from immune competent and HIV positive patients. Results: We describe the identification from these studies of a number of genes previously unreported as human tumour suppressors that are subject to transcriptional silencing in B lymphomas. Analysis of a subset of these genes, together with a panel of previously identified transcriptionally-silenced genes in primary B lymphomas, both sporadic and HIV-associated, revealed that patterns of aberrant methylation were highly conserved between the two patient groups. In contrast, we found no epigenetic changes in any of the analysed genes in EBV-immortalised B lymphoblastoid cell lines. Conclusions: These studies show that a similar subset of genes is subject to methylation-dependent transcriptional silencing in B lymphomas in sporadic and HIV-associated cases, implying that the same tumour suppressor pathways are inactivated and arguing that, at least epigenetically, these disorders are very similar disease entities. No significant financial relationships to disclose.
A simplified staging system in cutaneous melanoma to select patients for adjuvant trials
Authors: Beam S. L. , Elias E. G. 
Published: March 2020

19003 Background: Most clinical trials with adjuvant therapy in melanoma concentrate on high-risk patients including those with metastases to regional lymph nodes (LN), stage III and locally advanced T4, i.e., stage IIB and IIC. These trials may be missing the advantageous results in the relatively earlier stages. Methods: We reviewed the new American Joint Committee on Cancer (AJCC) for cancer staging of cutaneous melanoma and Balchs’ data for the prognostic factors. The data was correlated to patients’ survival expressed by the natural history of the disease. Results: We grouped the reported survival data into 3 risk groups, excluding patients with distant metastases. Group 1: 2–4mm deep primary with ulceration, >4mm deep primary without ulceration, micrometastases to 1–3 LN, primary not ulcerated; Group 2: >4mm deep primary with ulceration, micrometastases to 1–3 LN ulcerated primary, macrometastases to 1–3 LN, primary not ulcerated intransit metastases/satellitosis, without LN metastases; Group 3: macrometastases to 1–3 LN, ulcerated primary, metastases to 4 or more LN, matted LN, and/or intransit, metastases/satellitosis with LN metastases. The table summarizes the results. Conclusions: 1. Over one-third of the patients in group 1 died of disease in the first 5 years. They should be considered at intermediate risk and should receive adjuvant therapy. 2. Patient prognosis should determine the intensity of target therapy utilized in the adjuvant arena. While anti-CTLA-4 may be sufficient for group 1, the addition of anti-kinases may be required in group 2 and more so in group 3. [Table: see text] No significant financial relationships to disclose.