bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine and vinorelbine followed by weekly docetaxel in patients with advanced non-small-cell lung cancer
Authors: Cobo Dols M. , Villar Chamorro E. , Alés Díaz I. , Gil Calle S. , Alcalde García J. , Gutiérrez Calderón V. , Carabantes F. , Carabantes F. , Montesa Pino Á. , Bretón García J. J. , Benavides Orgaz M. 
Published: March 2020

17129 Background: This trial was designed to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM)/vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Eligibility criteria: stage IV NSCLC, Performance status ≤2, adequate renal, hepatic and bone marrow function. Treatment: VNR 25 mg/m2 plus GEM 1000 mg/m2, on days 1 and 8 of each 21-day cycle, followed by DOC 36 mg/m2 weekly until progression or unacceptable toxicity. Results: 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patient (5%) and squamous cell carcinoma in 12 patients (57%). Most of the patients had ECOG PS of 1. 8 patients (38%) did not complete 6 cycles of GEM-VNR. The median number of cycles of GEM-VNR was 4 (range 2–6) Of the 13 patients (61%) who completed 6 cycles of GEM-VNR, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3–16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6–25 months). The median survival time (MST) was 7,9 months, and the 1-year survival was 30 %, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patient (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with DOC, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with DOC. Conclusions: The sequential triplet nonplatinum chemotherapy consisting of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease. No significant financial relationships to disclose.
EGFR inhibitor gefitinib in advanced pretreated non-small cell lung cancer patients: Experience from a centre in north India
Authors: Talvar V. , Vaid A. K. , Doval D. C. , Gupta S. , Sharma J. B. , Sarin J. 
Published: March 2020

17141 Background: Gefitinib is an orally active EGFR-TKI (Epidermal Growth Factor Tyrosine Kinase Inhibitor) that demonstrated, clinically meaningful anti tumor activity, favorable toxicity profile in phase II trials involving patients with advanced pretreated NSCLC. The aim of this study was to assess the antitumour activity (time to disease progression) and toxicity profile of Gefitinib. Methods: Twenty five patients of NSCLC advanced were included in this study who have failed at least one chemotherapy regimen and completed at least one month Gefitinib (250 mg/day) therapy. The study included 18 male and 7 female patients with, a median age of 60 years (32–80 years) and performance status ECOG 0-I 64%. The histologically included were Adenocarcinoma 56%, Squamous Cell Carcinoma 40% and Large Cell Carcinoma 1%. 64% patients had failed to response to 1 (CT) chemotherapy regimen, 28% to 2 CT and 8% to 3 CT regimens. Results: A total of 25 patients (18 male, 7 female) were evaluated for response. 2 Complete Response (CR) and 1 Partial Response (PR) were observed with an Overall Response Rate (ORR) of 12% (CR+PR). All the three patients were with Adenocarcinoma histology. A total of 14 patients (56%) had Stable Disease (SD). This led to an Overall Disease Control Rate (CR+PR+SD) of 68% (17 patients). The Median Time to Progression (TTP) was 3.8 months using the SAS method for statistical analysis (95% CI 4.4–9.3). The number of previous chemotherapy regimens did not alter the response to therapy. All the patients were evaluated for toxicity profile assessment (25 patients). The most frequent toxicity observed was Asthenia in 52% of patients. Other toxicities were Diarrhaea 24%, Skin Disorders 32%, Anorexia 32%, Vomitings 44%. Only 1 patient had grade IV skin related toxicity. No deaths related to Gefitinib treatment were reported. Conclusion: Gefitinib shows antitumour activity in pretreated patients of advanced NSCLC. Gefitinib therapy of (250 mg/day) has a favourable toxicity profile and is well tolerated. Gefitinib is a viable therapy in NSCLC patients who have limited treatment options. No significant financial relationships to disclose.
Renal impairment in multiple myeloma patients following zoledronic acid or ibandronate treatment
Authors: Antràs L. , Smith M. , Neary M. , Green J. , Wintfeld N. , Duh M. 
Published: March 2020

17501 Background: Although bisphosphonates prevent skeletal complications, agents differ with respect to renal safety. Ibandronate (IB) is a single-nitrogen, noncyclic bisphosphonate that has shown a renal safety profile comparable to placebo in phase III trials. This retrospective study aimed to compare renal impairment rates in multiple myeloma (MM) patients treated with IB or zoledronic acid (ZO). Methods: Medical records in a German oncology clinic (Praxisklinik für Hämatologie und Onkologie Koblenz, Koblenz, Germany) from May 2001 to December 2005 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before ZO or IB treatment) to last evaluation for each patient. Renal impairment was defined as (1) a serum creatinine (SCr) increase of ≥0.5 mg/dL or ≥1.0 mg/dL from baseline values of <1.4 mg/dL or ≥1.4 mg/dL, respectively, or (2) a ≥25% decrease in glomerular filtration rate (GFR; abbreviated MDRD formula) from baseline. Patients treated sequentially with both ZO and IB were included as separate observations. Andersen-Gill extension of the Cox model was used for multiple-event analysis. Results: In 84 MM patients, 69 received ZO and 40 received IB, with 25 patients receiving both drugs. Compared with IB, the ZO group had a significantly better baseline renal function (mean SCr 1.01 vs 1.34, p = 0.007; mean GFR 75.9 vs 57.3, p = 0.0002). Data analysis showed that ZO treatment increased the relative risk (RR) of renal impairment by ∼3-fold compared with IB (renal impairment rates: ZO 39.1% vs IB 10.8%, RR = 3.6, p = 0.002 [SCr]; 62.3% vs 24.3%, RR = 2.6, p = 0.0002 [GFR]). The incidence rate of renal impairment was higher for ZO than IB (SCr: 1.14 vs 0.48 events per person-year, p = 0.169; GFR: 2.65 vs 0.87 events per person-year, p = 0.007). Multiple-event analysis found significantly higher hazards ratios for ZO over IB (SCr = 5.3; GFR = 2.7; both p < 0.0001). Conclusions: In this retrospective review, MM patients were significantly more likely to experience renal impairment with ZO than with IB. A prospective randomized study is warranted for further validation. [Table: see text]
A phase II study of cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin (Myocet), and prednisone plus rituxmab (R-COMP) in elderly patients with diffuse large B-cell lymphoma (DLBCL)
Authors: Federico M. , Caballero D. M. , Thiel E. , Bologna S. , S. Dyer M. J. , Luminari S. 
Published: March 2020

17506 Background: The majority of patients (pts) with diffuse large B-cell lymphoma (DLBCL) are elderly and may have limited tolerance to intense chemotherapy. Myocet has an improved therapeutic index in comparison to doxorubicin, resulting in less myelosuppresion, lower GI toxicity and reduced risk of cardiotoxicity. The aim of this study was to assess the efficacy and safety of the R-CHOP modified by replacing doxorubicin with Myocet (R-COMP) in pts ≥ 60 years with newly diagnosed, advanced DLBCL. Methods: Sample size was defined with the level of no interest P0 = 40% of CRs and the level of interest P1 = 60% of CRs. After assessment of the first 25 evaluable pts accrual continued to 75 pts, sample size estimated to include 66 evaluable pts. R-COMP regimen: d1 every 3 wks Myocet 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (max. 2 mg), rituximab 375 mg/m2 (d3 C1, d1 thereafter) and prednisone 100 mg/d d1–5. After 3 cycles pts with an objective response received 5 additional cycles. Results: Between Oct 2002 and Apr 2005, 75 pts were registered. This analysis includes the first 51 evaluable pts: median age was 71 (60–83); 56% of pts had an intermediate or high risk IPI score (≥ 3); median LVEF at baseline was 60% (50–89). Relative dose intensity was 89.8%. Median treatment of 8 cycles (1–8). Thirty-four pts (67%) achieved CR (95% CI = 51, 5–79,3) and 10 pts (20%) PR; Five percent of cycles were delayed and 9% were dose reduced due to toxicity. Toxicity: Grade (G) 3–4 neutropenia in 22% of cycles (52% of pts), febrile neutropenia in 3% of cycles (12% of pts), G 3–4 thrombocytopenia in 2 cycles, one episode of neutropenic sepsis, mucositis and related infections in 1% of the cycles each. Median final LVEF was 60% (40–79). Four pts were withdrawn due to decrease in LVEF. One pt had acute pulmonary oedema (considered related to the drug in absence of other reasons). No pts had congestive heart failure related to study drug. Conclusions: The R-COMP regimen is a well-tolerated and effective treatment for aggressive NHL in elderly pts. Both, the general tolerability and the low incidence of cardiac events warrants further studies in order to confirm the clinical benefit of R-COMP in elderly population. [Table: see text]
R-DHAOX as salvage treatment in CD20+ relapsed/refractory (R/R) non-Hodgkin lymphomas (NHL). An institutional experience
Authors: Rupolo M. , Spina M. , Michieli M. , Simonelli C. , Gattei V. , Bulian P. , Mazzucato M. , Abbruzzese L. , Tirelli U. 
Published: March 2020

17508 Background: Second line chemotherapeutic regimens in NHL are mainly based on cisplatin (DDP) and are frequently employed as cytoreductive regimens for preparation to high dose chemotherapy (HDC). The substitution of DDP with oxaliplatin in DHAP-like regimens can result in a lower toxicity and higher activity. In R/R CD20+ NHL the synergistic activity of Rituximab with chemotherapy has been shown to improve the outcome. We assessed the tolerability and efficacy of R-DHAOX (Rituximab 375 mg/m2, i.v. day 1, Dexametasone 40 mg i.v. days 1–4, Oxaliplatin 130 mg/m2 i.v. day 2 and Cytarabine 2000 mg/m2 i.v. twice a day, day 3) regimen in a fase II study including 35 pts (M/F = 22/13; median age 55 yrs, range 38–74) affected by R/R CD20+ NHL and enrolled from November 2002 until September 2005. 34 (97%) pts were staged III-IV. 31 pts (89%) were relapsed and 4 (11%) refractory. International Prognostics Index at relapse (s-IPI) was >2 for 10 (71%) DLBCL, 2 (14%) FL and 2 (29%) MCL. A total of 147 cycles were administered (range 1–7). Dose reduction due to Oxaliplatin neuropathy or Cytarabine haematological toxicity occurred in 13% and in 58% of pts, respectively. NCI G3-G4 toxicities were thrombocytopenia (58%), neutropenia (55%), anaemia (13%), infection (10%) and neurotoxicity (3%). No renal failure was observed. Results spitted according to histology were summarised in the table . R-DHAOX had significant clinical activity both in FL and MCL patients (overall response rates (OR) of 93% and 86%, respectively), as well as in DLBCL (OR of 79%) despite the very high S-IPI score observed. R-DHAOX allowed adequate stem cell harvest with G-CSF mobilisation in 25/35 (71%) pts. Three-yrs projected overall survival, according to the histology, were 71% for FL, 67% for MCL and 28% for DLBCL. These data suggested that the R-DHAOX is a novel combination highly effective for R/R CD20+ NHL. [Table: see text] No significant financial relationships to disclose.
The combination of gallium nitrate, rituximab and dexamethasone is effective and safe as a salvage regimen for diffuse large B-cell lymphoma
Authors: Smith S. E. , Toor A. , Klein J. , Rodriguez T. , Stiff P. J. 
Published: March 2020

17510 Background: More than 56,000 new cases of non-Hodgkin’s lymphoma (NHL) will be diagnosed this year in the United States. As our aging patient population develops worsening performance status and co-morbidities, it seems appropriate to develop effective lymphoma treatments, which have fewer toxicities and lower costs for administration. One approach is to combine non-myelosuppressive therapies. One non-myelosuppressive agent, which has efficacy in lymphoma, is gallium nitrate. Investigation of gallium nitrate for cancer treatment dates back to the 1970’s and it has been shown to inhibit ribonucleotide reductase and bind transferrin and potentially complex with transferrin and/or transferrin receptor, which is highly expressed in intermediate and aggressive histology lymphomas. It appears that the binding of the transferrin receptor on the lymphocyte as well as its inhibition of ribonucleotide reductase, eventually impairs iron metabolism, which is a necessary component of the intracellular cytochrome systems/mitochondrial function and ultimately oxidative phosphorylation. Methods: The current study is a phase II clinical trial investigating the combination of gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. The gallium nitrate is given at 200mg/m2 CIV days 1–7, rituximab 375mg/m2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients must have proven relapsed or refractory disease and have a SWOG PS ≤3. Patients may have failed prior ASCT or allogeneic SCT. The accrual goal was 37 patients however the study was stopped after 22 patients were accrued as the primary endpoint was reached after the initial interim analysis. Results: ORR 12/22 (55%); CR/CRu 6/22(27%); PR 6/22(27%); SD 3/22 (14%); and PD 7/22 (32%). Most of these patients were refractory to prior salvage regimens 15/22 (68%), including ESHAP, DHAP or high-dose cyclophosphamide. No patients developed grade 3 or 4 toxicities, with the exception of grade 4 lymphopenia. Conclusions: Gallium nitrate, rituximab and dexamethasone (GaRD) appears to be an effective and non-toxic salvage regimen for patients with relapsed DLBCL [Table: see text]
Marked activity of bortezomib, rituximab, and dexamethasone (BORID) in heavily pretreated patients with mantle cell lymphoma
Authors: Drach J. , Kaufmann H. , Pichelmayer O. , Sagaster V. , Seidl S. , Chott A. , Zielinski C. , Raderer M. 
Published: March 2020

17522 Background: Bortezomib (B) belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma (MCL). Preclinical studies suggest that B has synergistic activity with rituximab (R), which provides a rationale for the exploration of treatment combinations. Methods: We have initiated a phase II study in relapsed/chemotherapy refractory MCL to evaluate the activity and safety of B in combination with R and dexamethasone (BORID). A treatment cycle consists of B at 1.3 mg/m2 administered on days 1, 4, 8, and 11, R at 375 mg/m2 administered on day 1, and dexamethasone 40 mg orally on days 1 to 4. Cycles are repeated every 3 weeks for a total of 6 treatment cycles. Patients (pts) with progressive MCL after at least one prior line of therapy (including CHOP or a CHOP-like regimen) are eligible. Results: Up to now, we have enrolled 10 pts (median age, 69 years; range, 48 to 75 years) after a median of 3 lines of prior therapies (range, 1 to 6) including R in 8 pts, high-dose therapy in 3 pts, and thalidomide in 5 pts. Median time between start of frontline therapy and study inclusion was 43 months (range, 11 to 98 months). Severe adverse events (> grade II) included infections (herpes zoster in 2 pts, bacterial pneumonia, mucosal candidiasis), peripheral neuropathy (3 pts), fatigue (2 pts) and vasculitic skin infiltrates in 3 pts. Thrombopenia (< 50 G/L) occured in 2 pts. All adverse events were managable by standard means of supportive care and prolongation of the treatment interval between cycles. Of 8 pts evaluable for efficacy, 7 have achieved a response (3 CR, 4 PR), and 1 pt experienced stable disease. Pts in CR were also negative for disease activity by PET scanning. Skin infiltrates (histologically proven T-cell infiltrates) preceded achievement of CR in 2 pts. 6 of 6 pts are still progression-free at 6 months after treatment initiation. Recruitment of patients is ongoing, and updated results will be presented. Conclusions: Data obtained thus far indicate that BORID has promising activitiy and managable toxicity in patients with heavily pretreated MCL, and development of a vasculitic rash may be an early indicator of a favorable response. [Table: see text]
The adjuvant role of low dose total body irradiation following chemoimmunotherapy in elderly high risk patients with diffuse large B-cell lymphoma (DLBCL)
Authors: Safwat A. , Specht L. , Hansen F. , Hansen M. , Boesen A. , Jurlander J. , D’Amore F. 
Published: March 2020

17523 Background: Results from the RICOVER-60 trial indicated a better outcome in elderly DLBCL patients (pts) by adding rituximab (R) to CHOP and shortening cycle intervals 14 days. We tested the addition of low dose total body irradiation (LTBI) to what proved to be the best performing arm of the RICOVER-60 trial (6xR-CHOP-14 + 2xR). Methods: A phase II trial including pts>60 yrs with stage II-IV, CD20-positive DLBCL was started in 2003 and is still ongoing. Pts received 6x R-CHOP-14 and 2 x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Subpopulations of blood lymphocytes, monoctytes and dendritic cells were identified by multi-color flowcytometry during treatment. Results: 24 patients finished their treatment and were found to be predominantly high risk. Median age was 68 years; 50% had ≥ 1 extranodal lesion; 71% had stage III or IV; 63% had B symptoms; 58% had ECOG score ≥ 1; 75% had elevated LDH and 58% had IPI of >2. There were 3 toxic deaths (12.5%) due to sepsis occurring after 1st, 3rd and 5th chemotherapy cycle, respectively. One patient got off study because of disease progression. 14 pts achieved a CR or CRu at the end of chemotherapy, while 6 were in PR. After LTBI, all 6 PR pts converted to CR. 3 pts relapsed within 7 months after achieving CR. All treatment failures occurred in patients with IPI 3&4. 94%, 100% and 98% of the administered R-CHOP-14, Rituximab and LTBI cycles respectively were given in full dose and on time. CTC Gr 3–4 neutropenia occurred following 22 of 135 R-CHOP-14 cycles (16%). CTC Gr. 3–4 thrombocytopenia was seen in 4 pts following the last LTBI cycle (16%). Preliminary data from multi-color flowcytometry of the first seven pts, showed depletion of circulating B-cells, but in some pts, a relative increase in the frequency of circulating dendritic cells during chemotherapy, which was enhanced by LTBI. Conclusion: In high-risk elderly DLBCL pts, R-CHOP-14 is associated with potential fatal infections. LTBI adds relatively little extra toxicities in the form of thrombocytopenia and may have the potential of converting PR patients to CR. Testing lymphocytic subpopulations in peripheral blood may help elucidating the immunomodulatory mechanisms of LTBI. No significant financial relationships to disclose.
Rituximab maintenenance therapy in CD20+ B-cell non-Hodgkin lymphoma - Interim results of a multicenter prospective randomised phase II study
Authors: Witzens-Harig M. , Hensel M. , Schmier J. W. , Neben K. , Benner A. , Dreger P. , Schmidt-Wolf I. G. , Krämer A. , Ho A. D. 
Published: March 2020

17524 Background: Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. Methods: To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) every 3 months for 2 years. Patients after first line therapy as well as relapse patients were included in the study. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. Results: So far 124 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were enrolled in this trial. Histological subtypes included diffuse large cell lymphoma (55 pts), follicular lymphoma (24 pts), mantle cell lymphoma (16 pts), primary mediastinal lymphoma (12 pts), marginal zone lymphoma (8 pt), Burkitt’s lymphoma (3 pt), immunocytoma (2 pt), primary intestinal lymphoma (1 pt), hairy cell leukemia (1 pt), chronic lymphocytic leukemia (1 pt) and unclassified B-cell lymphoma (1 pt). No severe adverse events were observed during rituximab maintenance therapy. Results from an interim analysis including event free survival and overall survival for the observation group and for the maintenance therapy group will be presented. Conclusions: We conclude that rituximab maintenance therapy is feasable, effective, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. No significant financial relationships to disclose.