bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of gefitinib (G) on bone metatases (BMs) in non-small cell lung cancer patients
Authors: Garfield D. , Zampa G. , Cadranel J. , Bell D. W. , Moscato M. , Normanno N. 
Published: March 2020

17147 Background: Selected pts with advanced NSCLC might have particular benefit from EGFR tyrosine kinase (TK) inhibitor treatment. We have identified 4 NSCLC pts with BMs who had major responses to G. Methods: Pts characteristics: Pt 1, 62 y/o female, never-smoker (ns), NSCLC, brain and BMs with bone pain; pt 2, 51 y/o male, former smoker (fs), ADC and BMs; pt 3, 51 y/o male, ns, ADC and BMs; pt 4, 50 y/o male, fs, ADC, pleural effusion, BMs and bone pain. Pts 1 and 4 had mixed osteolytic-sclerotic BMs; pts 2 and 3 had osteolytic BMs. Pts were treated with 250 mg/day of G; the dose was increased to 375 mg/day in pt 1 for maximum CNS control. Pts 1 and 4 received G as first-line therapy, pts 2 and 3 as second-line following failure of platinum-containing therapy. Pts 1–3 also received zoledronic acid. Results: Pts 1 and 4 experienced significant decrease in bone pain with G, within hours in pt 1 and by day 3 in pt 4. Pts 1–3 developed rash. Objective regression of primary tumor was observed in all 4 pts. After 3 months of G the bone scan did not change in pt 1 but many lesions became more sclerotic. Bone scans became negative after one year of treatment in pts 2 and 3. Pt 2 had resection of the primary tumor with no recurrence, 26+ months (mos) from diagnosis, 9+ mos from surgery. Pt 1 has had disease control for 7+ mos, pt 3 for 15+ mos. Pt 1 had CNS regression with G. Pt 3 was found to have asymptomatic CNS mets at 6 mos of G, received whole-brain radiation, and remains on G at >1 year. Pt 4 died 6 weeks after starting G from unrelated causes but showed dramatic BMs response by PET. Tumor tissue was available for molecular analyses for pts 2 and 4, who respectively showed EGFR-TK domain G719C mutation in exon 18 and L858R mutation in exon 21. Both mutations have been previously described in NSCLC patients responding to G. Conclusions: G may be effective in the treatment of BMs in some NSCLC patients. [Table: see text]
Modified gemcitabine regime in advanced lung cancers
Authors: Agarwal S. , Agarwal P. 
Published: March 2020

17148 Background: Gemcitabine is established treatment modality for NSCLC. However it’s introduction on day 8 is sometimes delayed because of low counts or poor patient acceptance because of effects of d1 dose. Methods: We have used gemcitabine 10000 mg/m2 as d1,d10 regimen in 32 patients of advanced lung cancer incombination with either cisplatin or carboplatin .Colony stimulating factors were required in 2 patients. Results: The patients tolerated the chemotherapy (4 to 6 cycles) satisfactorily and none of the patient required delaying of the d10 therapy. Complete regression was seen in 2 patients,partial regression in 22 patients.the median survival was 10.2 months. Conclusions: The d1–10 schedule of gemcitabine based chemotherapry is safe,effective and better tolerated then the d1-d8 schedule. No significant financial relationships to disclose.
Predictors for toxicity profiles of weekly docetaxel in non-small cell lung cancers
Authors: Chen J. P. , Lo Y. , Yu C. J. , Hsu C. , Shih J. Y. , Cheng A. , Yang P. C. , Yang C. H. 
Published: March 2020

17153 Background: Weekly docetaxel has been proved recently to be safer and equivalently effective compared with traditional tri-weekly docetaxel as second-line treatment for NSCLC. However, the risk factors for toxicity of weekly docetaxel in this group of patients are still unknown. Methods: We reviewed advanced NSCLC patients receiving 2nd line or 3rd line weekly docetaxel from 1999 to 2003 from cancer registry and pharmacy records in our hospital. Clinical characteristics, previous chemotherapy regimens, laboratory data, docetaxel administration schedules/dosage, and treatment efficacy were retrospectively collected. Logistic regression was performed to identify risk factors for adverse outcomes. Cox’s proportional hazards model was used to analyze cumulative-dose related adverse events. Results: A total 155 patients were analyzed for treatment effect and toxicity. The overall response rate of weekly docetaxel (36–40 mg/m2) was 5.16% and median survival of all patients was 8.1 months. The incidence of treatment withdrawal due to adverse events was 43.23 % and significantly related to previous anthracycline use (odds ratio 4.582; P = 0.0144) and chronic hepatitis B or C virus (HBV/HCV) infection(odds ratio 3.928; P=0.0058). The incidence of grade 3 or 4 neutropenia was 23.2% and was significantly associated with old age (odds ratio 7.232; P < 0.001), lower baseline white count(odds ratio 5.57; P < 0.05), and chronic HBV/HCV infection(odds ratio 3.25; P < 0.05). The incidence of fluid retention was 41.29% and the median cumulative dose of docetaxel at onset was 327 mg/m2. Abnormal liver function significantly increased the risk for fluid retention(odds ratio 2.368; P < 0.05); steroid premedication (odds ratio 0.184; P < 0.01), higher albumin(odds ratio 0.237; P < 0.01), and previous surgical resection(odds ratio 0.341; P < 0.05) decreased the risk. Conclusions: Salvage weekly docetaxel for NSCLC patients in Taiwan remains toxic. Part of the reasons for the significant toxicities is that chronic HBV/HCV infection, which occurs in around 20% of general populations in Taiwan, represents a significant risk factor for neutropenia, fluid retention, and treatment withdrawal. The role of prophylactic anti-viral agents in these patients should be explored in the future. [Table: see text]
Gemcitabine, cisplatin and methylprednisolone (GEM-P) in patients with T-cell lymphoma: Results from The Royal Marsden Hospital
Authors: Arkenau H. , Trumper M. , Sirohi B. , Chong G. , Chau I. , Wotherspoon A. , Norman A. , Horwich A. , Matutes E. , Cunningham D. C. 
Published: March 2020

17507 Background: There is a need for novel, effective therapies for T-cell non-Hodgkin’s lymphoma (NHL). The combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) has shown activity in patients (pts) with relapsed Hodgkin’s disease and NHL (Chau I et al. Br J Haematol 2003, Baetz T et al. Ann Oncol 2003). We report a single institution retrospective analysis of GEM-P for pts with T-cell NHL. Methods: Sixteen pts with T-cell NHL treated at the Royal Marsden Hospital between June 2001 and March 2005 with GEM-P (gemcitabine 1 g/m2 D1, 8, 15; cisplatin 100 mg/m2 D15; methylprednisolone 1 g D1–5, repeated every 28D) were identified. Results: 16 pts (9 males and 7 females) were analysed. Histological subtypes were: angioimmunoblastic (n = 5), T-cell enteropathy (n = 2), NK/T cell nasal-type (n = 2), T-cell anaplastic (n = 3) and peripheral T-cell unspecified (n = 3). Median age was 55 years (range: 18–71 years), 69% had IPI-score ≥ 2 and 69% had stage III/IV disease. 15 /16 pts were pre-treated: median number of prior treatments: 1 (range: 0–4). At the start of GEM-P treatment pts presented with: primary refractory disease (n = 3), 1st relapse (n = 6), 1st relapse refractory (n = 3), 2nd relapse (n = 2) and 4th relapse (n = 1). Median time from diagnosis of T-cell NHL to start of GEM-P was 8.9 months(m) and median number of cycles given was 3 (range: 1–6). Of 16 evaluable patients, 3 pts (19 %) achieved complete remission (CR), 8 pts (50 %) achieved partial remission (PR), (ORR= 69%; CI-95% 41.4–89.0) and 5 pts (31%) progressed while on GEM-P. One pt received high dose chemotherapy (melphalan/etoposide) after CR to GEM-P. After a median follow up of 17.4m the mean progression free survival (PFS) was 9m (range 1.15–37.5). The median overall survival (OS) has not been reached and the survival probability at 1 year was 68.2% (95% CI: 40–85). The main grade 3/4 toxicities were myelosuppression (leucopenia 62%, neutropenia 62% and anaemia 12%) and required granulocyte colony stimulating factor (GCSF) in 3 pts with neutropenic sepsis and in 1 pt with neutropenia. Conclusion: GEM-P has encouraging efficacy with an acceptable toxicity profile in pts with previously treated T-cell NHL. [Table: see text]
Phase I trial of combination therapy with 90Y ibritumomab tiuxetan and gemcitabine in patients with non-Hodgkin’s lymphoma
Authors: Borghaei H. , Smith M. , Millenson M. , Krieger K. , Rogatko A. , Schilder R. 
Published: March 2020

17514 Background: Zevalin (Z) is an effective therapy in patients with relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). Gemcitabine (gem) also is active against NHL and is a potent radiation sensitizer. We are conducting a phase I trial to assess the safety of concomitant administration of Z and gem in patients with NHL. Methods: The starting gem dose is 250 mg/m2 on days 1 and 8. Nine patients in three cohorts will be treated with 250 mg/m2 of gem with 0.2, 0.3 or 0.4 mCi/kg of Z. The next cohort can accrue after all patients in the prior cohort have hematologic toxicity has recovered to grade 2 or after 60 days from the date of the last treated patient in the previous cohort. Once it is confirmed that a Z dose of 0.4 mg/kg can be safely administered with gem 250 mg/m2, gem will be escalated according to a Bayesian based system. Response evaluation is based on the International Workshop on Standardized Response Criteria for Non-Hodgkin’s lymphomas. Eligibility criteria include: any histology of recurrent NHL (not candidates for high dose therapy), platelets ≥ 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to < 25% radiation of bone marrow and no prior bone marrow or stem cell transplant. Results: Five patients have been treated thus far, two with follicular NHL (FL) and three with diffuse large B cell (DLBCL). Median age is 75 (range 55–82). The median number of prior treatments is 2 (range 1–6). One patient with DLBCL is not evaluable. The first three patients received 0.2 mCi/kg and next two patients 0.3 mCi/kg of Zevalin. Toxicity consists of grades 2 & 3 myelosuppression in the first 3 weeks in 3 pts. due to gem and then of grade 2 in 1 pt. at 6 to 8 weeks as is usually seen with Z. One grade 3 leukopenia and one grade 2 thrombocytopenia have been observed resolving within one week. One grade 3 infection occurred, unrelated to the protocol or the study drugs. No grade 3 or 4 non-hematologic toxicity has been seen. In follow up, two patients with FL and one with DLBCL achieved CRu. One patient with DLBCL has progressed and one is not yet evaluable. Conclusions: Our preliminary findings suggest that Z can be safely combined with gem 250 mg/m2 in the treatment of patients with NHL. Dose escalation to full dose Zevalin and then of gemcitabine is continuing. [Table: see text]
Comparison of engraftment in patients undergoing peripheral blood stem call transplantation (PBSCT) with or without support of G-CSF on day +5: A prospective cohort study results
Authors: Arpaci F. , Baskoy K. , Ataergin S. , Ozet A. , Komurcu S. , Ozturk B. 
Published: March 2020

17521 Background: The role of G-CSF administration on day +5 after PBSCT in terms of hematologic engraftment and supportive treatment need has been evaluated. Methods: Forty-two consecutive patients with solid and hematological malignancies were enrolled in two cohort groups depending on G-CSF administration. Twenty-seven patients were given G-CSF (5 μg/kg/day) from day +5 after the transplantation until the achievement of neutrophil engraftment. Posttransplant G-CSF was not given to the control arm of 15 patients. A number of at least 2 × 106 CD34+ cells per kilogram collected by cytapheresis were given to all patients. Results: A significant difference was found between the two groups in favor of G-CSF receiving group, in terms of neutrophil engraftment time (10.56 ± 1.22 vs 11.93 ± 2.89 day; p = 0.04), number of days with fever (3.33 ± 2.66 vs 5 ± 2.95 day; p = 0,03) and number of the days requiring antibiotic therapy (7.07 ± 3.46 vs 11.87 ± 3.74 day; p < 0,001); whereas, no statistically significant difference was noted in terms of hospitalization period (13.30 ± 4.79 and 13.53 ± 2.56 day; p = 0.26), platelet engraftment time (12.22 ± 2.79 and 13.40 ± 3.89 day; p = 0.26) and erythrocyte transfusion need; however, platelet transfusion need was statistically significant between the groups with and without G-CSF support (1.27 ± 0.96 vs 0.56 ± 0.75, p = 0.01) Conclusions: This study reveal that starting G-CSF on day +5 may fasten the neutrophil engraftment, decrease the number of days with fever, as well as a the need for antibiotic therapy in posttransplant period. No significant financial relationships to disclose.
A phase I study of G3139 in combination with RICE chemotherapy in relapsed non-Hodgkin’s lymphoma (NHL)
Authors: Smith S. M. , Van Besien K. , Conner K. , Gajewski T. , Kuna T. , Karrison T. , Wade Iii J. L. , Zwiebel J. , Vokes E. E. 
Published: March 2020

17529 Background: Aggressive lymphomas are chemosensitive, but frequently relapse. Bcl-2 protein overexpression promotes tumor cell survival via anti-apoptosis, and is clinically correlated with shortened remission duration and decreased survival. The antisense oligonucleotide oblimersen sodium (G3139) downregulates bcl-2, has activity in NHL, and may be synergistic with chemotherapy. Methods: Pts had histologically confirmed aggressive NHL that relapsed after one prior anthracycline-based regimen. G3139 was given as a continuous infusion on Days 1–8 (168 hours) every 14 days, with stem cell collection following cycle 3. Standard RICE chemotherapy was given on Days 4–6, allowing 72 hrs pre- and 48 hrs post-chemo G3139. Dose-limiting toxicity (DLT) was defined as grade 3 or greater non-hematologic toxicity, grade 4 thrombocytopenia, duration of neutropenia <500/mL greater than 7 days despite growth factors, grade 3 hemolytic anemia, or prolonged severe anemia. Pharmacodynamic endpoints included measurement of bcl-2 protein in peripheral blood (FACS analysis) and tumor (IHC), and bcl-2 RT-PCR in blood and tumor. Results: 8 pts were enrolled. At dose level 1 (G3139 3 mg/kg/day), both enrolled pts had grade 4 thrombocytopenia. The next 6 patients were treated with G3139 2.5 mg/kg/day (Dose Level -1) without any DLT’s. There were no grade 3 or 4 non-hematologic toxicities. 7 evaluable pts had successful stem cell collections: median CD34+ 4.2 × 106/kg (range, 1.3–8.72 × 106/kg). Responses: 4 CR/CRu, 2 PR, 1 SD, 1 too early. There was no detectable decrease in bcl-2 protein in the blood using flow cytometry or RT-PCR. Conclusion: The maximum tolerated dose of G3139 given over 8 days in combination with RICE chemotherapy is 2.5 mg/kg/day. It is unlikely that this dose sufficiently suppresses bcl-2 levels. The protocol will thus be amended to shorten the G3139 infusion to 5 days with renewed efforts to escalate the dose. No significant financial relationships to disclose.
The role of FDG-PET in low-grade non-Hodgkin lymphoma (NHL): Impact of histology
Authors: Kassar M. , Go A. , Fung H. , Venugopal P. , Ali A. , Kumar M. , Farhat M. , Batus M. , Shammo J. , Gregory S. A. 
Published: March 2020

17534 Background: FDG-PET scan was proved important diagnostic and prognostic tool in patients with aggressive (NHL). The objective of this study is to investigate the correlation between the histology subtype in low-grade NHL and the sensitivity of the FDG-PET. Methods: We included all patients who presented to our institution during the period from April 2001 till April 2004 and underwent staging evaluation by FDG-PET during the course of their disease. All patients had histologically confirmed low-grade NHL. Patients with history of active malignancy, other than NHL, within the last five years were excluded. Correlation was made with the CT-scan findings. Results: 53 patients were included. Age (range 30–82, median 54), 57% of them were male. 34 patients had follicular lymphoma (FL), 9 patients had marginal zone lymphoma (MZL), and 10 patients had small lymphocytic lymphoma (SLL). 24/34 patients with FL underwent FDG-PET during the initial evaluation of their disease, and 10/34 patients underwent FDG-PET as part of their restaging assessment. 33 patients had true positive FDG-PET findings when compared to CT-scan results. One patient had negative FDG-PET with CT-scan findings suggestive of pathologic lymphadenopathy (sensitivity 97%). The highest SUV was in the range of 3.5–15 (median = 7). 8/9 patients with MZL had true positive FDG-PET findings and one had false negative FDG-PET result (sensitivity 89%). The highest SUV was in the range of 2–6.30 (median 2.6). Among the ten patients with SLL, 5 had FDG-PET during the initial evaluation and 8 patients during re-staging workup. 13 FDG-PET results were available for analysis. 5 cases were false negative, 1 case was false positive, 5 cases were true positive, and 2 cases were true negative (sensitivity 50%). The highest SUV was in the range of 1.8–6.2 (median of 2.5). Conclusion: Histology in low-grade NHL has a major impact on the sensitivity of the FDG-PET imaging results. Whereas it is a highly sensitive diagnostic method in patients with FL, and to a lesser degree in patients with MZL, it has poor sensitivity in patients with SLL. No significant financial relationships to disclose.
A phase IV, open-label trial using bortezomib for retreatment of patients (pts) with multiple myeloma (MM) following an initial response to bortezomib
Authors: Druck M. , Walters I. B. , Carloss H. , Sood R. , Leblanc A. L. , Noga S. J. 
Published: March 2020

17539 Background: Bortezomib (VELCADE; Vc) has substantial single agent activity in heavily pretreated patients. Response rates have been shown to improve when used in combination with other agents. Since some pts experience long durations of response with treatment-free periods, this open-label, single-arm study was designed to determine the utility of retreatment with Vc alone or in combination with dexamethasone, thalidomide or liposomal doxorubicin. Methods: Pts who previously responded to Vc alone or in combination are eligible for this study. Up to 78 pts will receive Vc alone or in combination at the finishing dose of their initial Vc treatment (0.7, 1.0, or 1.3 mg/m2) as a bolus, intravenous injection on days 1, 4, 8, and 11 of a 21-day treatment cycle. Responses are assessed by the investigators and also calculated from percentage reduction in serum or urine M-protein. Results: To date, 15 pts have been treated and 12 are evaluable for response (having received at least 2 cycles of therapy). 8/12 patients had dexamethasone added to their regimen. The population is representative of pts with relapsed and refractory MM: mean age, 68 years; 4 males, 8 females; median of 5 prior lines of therapy; and 67% IgG MM. Median treatment-free period between the end of first Vc treatment and the start of retreatment: 11.1 months (range 5–21 months). Investigator-assessed responses show that 50% of pts have achieved a PR or CR. Only 1 pt had progressive disease. One pt has developed new peripheral neuropathy, while pre-existing neuropathy has worsened in 4 pts. No Vc-related serious adverse events have been reported. Conclusions: Preliminary results show that retreatment with Vc alone or in combination has encouraging activity with manageable toxicity even in pts who are heavily pretreated. These data suggest that repeated use after a treatment break may achieve prolonged disease control. This is the first report of Vc retreatment for MM. [Table: see text]
Vinorelbine-based salvage therapy for patients with aggressive leukemias and non-Hodgkin’s lymphomas
Authors: Morar S. , Larson J. , Qazi S. , Uckun F. 
Published: March 2020

17563 Background: We treated 26 patients with aggressive lymphohematopoietic malignancies, including 3 chronic myeloid leukemia (CML) patients in blast crisis, 2 chronic lymphocytic leukemia (CLL) patients with rapidly progressive leukemia, 10 acute lymphoblastic leukemia (ALL) patients in therapy refractory relapse, and 11 non-Hodgkin’s lymhoma (NHL) patients (9 in relapse with progressive lymphoma) with vinorelbine-based outpatient salvage chemotherapy. Methods: Patients received vinorelbine-based salvage therapy regimens NND-I (Vinorelbine [Navelbine] 25 mg/m2 d1,d8, Mitoxantrone [Novantrone]10 mg/m2 d1, Dexamethasone [Decadron] 20 mg BID d1 through 7, or NND-II (Vinorelbine 25 mg/m2 d1, Mitoxantrone 10 mg/m2 d1, Dexamethasone 20 mg BID d1 through 7, Fludarabine 25 mg/m2 d1,d2,d3). Rituximab (Rituxan, 375 mg/m2 d1,8,15,29) was used in combination with chemotherapy in patients with CD20 antigen positive malignancies. Treatment responses were evaluated by peripheral blood and bone marrow examinations in patients with leukemia and CT/MRI-PET fusion imaging in patients with non-Hodgkin’s lymphoma using standard response criteria. Results: All patients completed their salvage therapy as an outpatient without infectious disease complications or hospitalizations. Of the 26 patients, 20 (77%) had objective responses, including 14 complete remissions (CR). All 3 CML patients and both CLL patients achieved a CR. Of the 10 ALL patients, 5 achieved a CR and one achieved a partial remission (PR). Of the 11 NHL patients, 4 achieved a CR and 5 achieved a PR. Conclusions: Taken together, these findings demonstrate that patients with high risk/poor prognosis leukemias and non-Hodgkin’s lymphomas can achieve meaningful objective responses in an outpatient setting using vinorelbine-based salvage regimens. No significant financial relationships to disclose.
Working Formulation (WF) and Revised European-American classification of Lymphoma (REAL): Inter-observer agreement in conflicting lymphoma cases
Authors: Latifzadeh S. , Riahi T. , Entezari V. 
Published: March 2020

17567 Background: Immunophenotypic and genetic studies play an increasingly important role in diagnosis and classification of lymphoid neoplasm. This study tried to re-evaluate a number of conflicting lymphoma cases which were reported by WF previously, with REAL classification and to measure the agreement between these two methods of classification. Methods: In a three year period, a panel of expert pathologists evaluated referral cases by WF. Those cases (n = 60, Mean age = 40.9 ± 16.4) whose evaluations did not reached to a definitive pathologic diagnosis or there was a discrepancy between their pathologic and clinical findings were reviewed in Keil institute of hematopathology in Germany based on REAL classification. The primary and secondary diagnoses each were classified in five subgroups with equivalent clinical risks (see Table ). Results: Disagreement was detected in 23 cases (38%), while exact kappa statistic was 0.50. Sixteen cases (70%) of difference belonged to group of low grade lymphoma (kappa = 0.35) in which 11 cases (69%) changed to aggressive lymphoma and one case changed to highly aggressive subgroups. Four cases (25%) of difference occurred in the group of low probability lymphoma in which neoplasia was documented. High grade and Hodgkin lymphoma subgroups showed a high level of agreement (kappa = 0.84 and 0.74 respectively). Conclusions: Based on this study’s results, it can be concluded that there is a moderate agreement between WF and REAL classifications in conflicting lymphoma cases. WF underestimates clinical risk of low grade lymphoma in a considerable amount of patients but in high grade lymphoma the disagreement is not so high. [Table: see text] No significant financial relationships to disclose.