bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of presurgical exercise training on exercise capacity in operable lung cancer: A pilot study
Authors: Peddle C. J. , Eves N. D. , Courneya K. S. , Haykowsky M. , Mackey J. R. , Joy A. A. , Reiman T. J. , Winton T. W. , Jones L. W.
Published: March 2020

17047

Background: Exercise capacity is a strong independent predictor of surgical outcome in patients with operable NSCLC and thus an established clinical tool to assess preoperative eligibility. The purpose of this study was to determine the effects of preoperative exercise training on exercise capacity in operable lung cancer. Methods: Using a single-group design, participants with suspected operable lung cancer were screened for eligibility at the time of diagnosis. Twenty-six patients were recruited and offered exercise training until surgical resection. Exercise training consisted of 5 endurance cycle ergometry sessions per week at 60 to 100% of patient’s baseline exercise capacity. Patients underwent cardiopulmonary exercise testing (CPET) including peak oxygen consumption (VO2peak), six minute walk distance (6MWD), and a pulmonary function test at baseline, immediately prior and 30 days post surgical resection. Results: The mean time from diagnosis to resection was 67 ± 27 days. During this time, 6 patients were deemed ineligible and were removed from the analysis. Of the remaining 20 patients, 18 completed exercise training and 13 performed CPET post resection. The overall adherence rate was 72% (range 0%–100%) with patients completing a mean of 30 exercise sessions (range 0–75). Intention-to-treat analysis indicated that VO2peak and 6MWD increased by 2.3 mL · kg−1 · min−1 [95% CI, 1.0 to 3.7; p = .002] and 40m [95% CI, 16 to 64; p=.003] respectively, from baseline to presurgery but decreased from pre to post resection [VO2peak, −2.7 mL · kg−1 · min−1, 95% CI, −3.9 to −1.6; p < .001; 6 MWD, −44 m, 95% CI, −94 to 6.4; p = .082]. There were no differences between baseline and postsurgical exercise capacity. Per protocol analyses indicated that patients who achieved acceptable exercise adherence (≥80% of prescribed sessions, n = 12) increased VO2peak and 6MWD by 3.2 mL · kg−1 · min−1 [95% CI, 1.1 to 5.4; p = .005] and 49 meters [95% CI, 12 to 85; p = .013], respectively. Conclusion: Preoperative exercise training is associated with improvements in exercise capacity in patients with operable NSCLC, particularly if acceptable adherence is achieved. This benefit may have important implications for surgical outcome and postsurgical recovery in this population.

No significant financial relationships to disclose.
Clinical outcomes of a multi-institutional retrospective study for 419 patients with locally advanced non-small cell lung cancer (NSCLC)
Authors: Ichikawa M. , Mio T. , Teramukai S. , Nakagawa M. , Nagata Y. , Fujita S. , Yanagihara K. , Ishiguro H. , Hiraoka M. , Mishima M.
Published: March 2020

17058

Background: Chemo-Radiotherapy (CRT) is considered the standard of care in locally advanced NSCLC. However, regimen of chemotherapy (CT), schedule of radiotherapy (RT), and application for surgical interventions (OP) are still controversial. We performed a study to establish clinical outcomes of NSCLC patients treated with CRT in Japan. Methods: A total of 373 consecutive patients (CRT: 307, OP after CRT (OP/CRT): 66) with stage III NSCLC, PS 0–2, no indications of OP at the initial evaluation, treated with CRT between January 1997 and December 2002 were analyzed. We also investigated 46 patients treated with RT alone as control. Results: We investigated a total of 419 patients (354 men and 65 women; average age: 64.5 ± 9.5 years) from nine institutes. Distributions of pathological subtypes were: squamous cell carcinoma: 225; adenocarcinoma: 154; large cell carcinoma: 14; non-small cell carcinoma: 26. In 189 stage IIIA patients, median survival time (MST) was 21.2 M, and MST of CRT, OP/CRT and RT were 19.1 M, 61.7 M, and 18.0 M, respectively. Multivariate analysis with Cox proportional hazards model indicates age, PS, existence of double cancer, existence of diabetes mellitus, stage IIIB, white blood cell counts increase, hemoglobin decrease as significant prognostic factors in CRT or OP/CRT patients. Multivariate analysis in stage IIIA patients indicated BMI decrease, double cancer, body weight loss, white blood cell increase, hemoglobin decrease as prognostic factors. There was a statistically significant difference between overall survival of CRT and OP/CRT in stage IIIA patients (p = 0.038 after adjustment for the effect of prognostic factors). However, there were no differences between CRT and RT, and among any schedules of CRT therapy. Conclusions: This clinical study suggests that OP after CRT could results in good survival compared with CRT alone, and BMI, double cancer, body weight loss, white blood cell, and hemoglobin could be prognostic factors in locally advanced NSCLC.

No significant financial relationships to disclose.
Phase I trial of TS-1 plus carboplatin in patients with advanced non-small cell lung cancer: A Central Japan Lung Study Group Trial-CJLSG0402
Authors: Saka H. , Kitagawa C. , Ichikawa M. , Yamada Y. , Saito H. , Taniguchi H. , Yamamoto M. , Shimokata K.
Published: March 2020

17065

Background: TS-1, a novel oral antimetabolite, is active against advanced non-small cell lung cancer (NSCLC). A response rate of 21.3% was reported in a monotherapy trial. In combination with cisplatin, TS-1 demonstrated a response rate of 47.3% in NSCLC. To develop a clinically relevant combination, we investigated TS-1 plus carboplatin in patients (pts) with advanced NSCLC. This is a report of the phase I section of a phase I/ II trial. In the phase I section, primary endpoints were to determine the maximum tolerated dose (MTD), the recommended dose for the phase II section, and to evaluate the toxic profile. Methods: Pts were enrolled who were chemo-naïve, in stages IIIB and IV, with ages between 20 and 74, PS (ECOG) of 0 or 1, and with adequate bone marrow and major organ functions. Post-surgical relapses and asymptomatic brain metastases were accepted. Pts received a fixed dose of carboplatin (6 mg/mL min) via IV infusion on day 1, once every 3 weeks. TS-1 was given at the initial dose of 60 mg/m2 (level 1) with dose escalation in 10 mg/m2 increments from day 1 to day 14, repeated every 3 weeks. Severe toxicities occurring in cycle 1 were considered dose-limiting toxicities (DLTs). Results: Sixteen pts were enrolled in 3 cohorts receiving 60 (n = 3), 70 (n = 7), and 80 (n = 6) mg/m2. Median age was 65 years (range, 37 to 74 years) and median performance status was 1. Ten pts had stage IV, and 4 pts had stage IIIB disease. Two pts had post-surgical relapses. Adenocarcinoma (n = 11) was the dominant histology. DLT was observed in 1 pt in level 1, 2 pts in level 2 (TS-1, 70 mg/m2), and 3 pts in level 3 (TS-1, 80 mg/m2). DLTs were grade-4 thrombocytopenia (n = 3), grade-4 neutropenia (n = 1), grade-3 liver dysfunction (n = 1), and grade-3 anorexia (n = 1). Conclusions: The MTD was level 3 (TS-1 80 mg/m2, carboplatin 6 mg/mL min). According to the total delivered doses, the recommended dose for phase II study was determined to level 2 (TS-1 70 mg/m2, carboplatin 6 mg/mL min). The phase II study is currently underway.

[Table: see text]

No significant financial relationships to disclose.
A phase II study for selection of clinical and molecular predictors for survival in patients (pts) with advanced NSCLC treated with erlotinib
Authors: Rohr U. P. , Rohrbeck A. , Schwalen A. , Kliszewski S. , Haas R. , Kronenwett R. , Kappes R. , Von Haeseler A. , Rosskopf M. , Meckenstock G.
Published: March 2020

17066

Background: The primary objective of the ongoing phase II study was to find clinical and molecular predictors for survival. Consequently, we prospectively examined gene and protein expression and EGFR mutation profiles of tumor cells, and clinical variables. Methods: Pts with advanced NSCLC (stage IIIb/IV) previously treated with platinum-based chemotherapy received 150mg/day erlotinib (Tarceva an EGFR tyrosine-kinase inhibitor) orally until disease progression. For molecular analyses, biopsies were taken from the primary lung tumor prior to erlotinib treatment. Pure tumor cells were isolated using laser-capture microdissection. For expression analysis, a microarray of 8793 genes (Human Focus Array, Affymetrix) was used. Data were analyzed using VSN method and significance analysis of microarrays. Results: In an interim analysis, clinical data were available for 36 of 43 so far included pts in the ongoing phase II study. For 36 pts, the tumor responses were: 1 CR (3%), 4 PR (11%), 11 SD (30%) and 19 PD (53%), and the median survival was 20 wks. Overall survival was significantly better in pts with rash than without rash: 9.2 vs 4.3 months. In a 14 months follow up, all of the responding pts survived while the median survival for pts with SD or PD was 11.4 and 4.0 months, respectively. Comparing gene expression profiles of tumors from 6 pts with a response or SD with those from 13 pts with tumor progression, we could not identify genes that were differentially expressed with sufficient significance. In 20 tumor samples evaluated for EGFR protein expression and mutation analysis, 19 expressed EGFR (IHC). A base exchange in exon 18 (2166G>A; A722A) and 20 (2547A>G; Q787Q) of the EGFR already described as a single nucleotide polymorphism was seen in 4 samples performing SSCP gel electrophoresis and sequencing. Conclusions: Rash, a side effect with erlotinib, was significantly associated with better survival. No activating EGFR mutations were found indicating that the response in 14% of pts is independent of mutations. For identification of genes predictive for response to erlotinib, a larger sample number is necessary.

No significant financial relationships to disclose.
The benefits of a restaging PET scan after two cycles of neoadjuvant chemotherapy for resectable non-small cell lung cancer
Authors: Tanvetyanon T. , Eikman E. , Robinson L. , Sommers E. , Cantor A. , Bepler G.
Published: March 2020

17092

Background: Neoadjuvant chemotherapy can potentially improve the outlook of resectable non-small cell lung cancer (NSCLC). Whole-body 2-deoxy-2-[18F] fluoro-D-glucose (FDG)-PET is often used as an initial test to determine tumor resectability, but its role as a restaging test after neoadjuvant chemotherapy is unclear. Restaging PET after neoadjuvant chemoradiation helps identify unexpected distant metastasis and avoid unnecessary thoracotomy. We explored its benefits after neoadjuvant chemotherapy. Methods: Patients with stage IB-IIIA and selected IIIB resectable NSCLC received induction gemcitabine (1,000 mg/m2) and vinorelbine (25 mg/m2) on days 1, 8, 22, and 29. PET and CT scan were performed before enrollment and between day 43–50. Response from CT scan was defined by RECIST criteria; from PET, defined as >20% reduction in the SUVmax (a decrease of > 2 SD of spontaneous change in FDG uptake, previously validated). This abstract explores patients participated in a published prospective trial with available both pre- and post-treatment PET scans. Results: There were 19 patients: stage IB-7, stage IIB-2, and stage III-10. Median age was 67 years. Mean interval between staging and restaging PET scan was 59 days. By PET, 10 patients responded. By RECIST criteria, complete response occurred in 0, partial response in 6, and stable disease in 13 patients. Most successfully underwent a complete resection, but positive margins were present in 3; multi-station lymph node involvement was found intraoperatively in 1 patient. Overall median survival was 20.5 months. We found that restaging PET did not help identify any distant metastasis. Moreover, no survival difference was observed between PET responders and non-responders, though PET responders had more advanced stage than their counterparts: median survival 16 months vs. not reached (p = 0.08 adjusted for stage). PET response was correlated with RECIST response (p = 0.05) as well as the response as obtained by SUV max divided by the activity of contralateral lung or aorta ratio. Conclusion: Based on this small group of patients, a restaging PET scan obtained after two cycles of neoadjuvant chemotherapy among patients with resectable NSCLC did not appear to impact the decision on a planned thoracotomy.

No significant financial relationships to disclose.
Predisposing factors of blood brain barrier penetration from docetaxel during lung cancer treatment: Preliminary study
Authors: Zarogoulidis K. , Chatzopoulou A. , Kontakiotis T. , Theodoridis G. , Pousinis P. , Patakas D.
Published: March 2020

17102

Background: Patients with lung cancer account for approximately 50% of brain metastasis cases. On the other hand the majority of active cytotoxic agents (like taxanes) in lung cancer treatment, are unable to penetrate blood brain barrier (BBB) so the role of chemotherapy in management of brain metastasis from lung cancer remain controversial. To investigate predisposing factors (if any) of penetration of BBB from cytotoxic agents we measured concentation levels of Docetaxel in serum and cerebrospinal fluid (CSF) during first line chemotherapy. Methods: Twelve lung cancer patients receiving chemotherapy consisted of Docetaxel (100 mg/m2) and Carboplatin AUC 6 were included in this study. CSF and plasma samples were withdrawn half an hour after termination of chemotherapy infusion. Measurements were performed with high performance liquid chromatography and UV detection was at 227 nm. Results: Mean levels of docetaxel in blood was 2,5530 ± 0,53 mg/l and in CSF 0,7397 ± 0,22 mg/l. Three out of twelve patient had SCLC (2 with ED and 1 with LD) and 9 with NSCLC (2 stage IIIB and 7 stage IV). In three patients without metastasis no detectible level of docetaxel was measured. We were also unable to detect Docetaxel in CSF of the patient with NSCLC and metastasis in the ipsilateral lung. On the other hand in 9 patients with metastatic disease (4 brain metastasis 2 with bone metastasis 1 with metastasis in liver and adrenal and 2 with liver and bone metastasis) had detectable levels of docetaxel in CSF. There was not statistically significant correlation of docetaxel in plasma and CSF. Only one patient without any evidence of metastasis had a detectable level of Docetaxel in CSF (0,33229) but in 6 weeks a brain metastasis was apparent in brain MRI. Conclusions: Metastasis development seems to be associated with a modification of BBB penetration. If Docetaxel penetrates BBB (especially in the presence of brain metastasis) it would be probable to accelerate radiotherapy sensitivity of brain metastasis.

No significant financial relationships to disclose.
Hb-level stabilisation with epoetin alfa in patients with advanced NSCLC undergoing concurrent neoadjuvant chemo-radiation therapy (phase III study)
Authors: Wagner W. , Granetzny A. , Hilejan L. , Marra A. , Koch O. M. , Krukemeyer M. G. , Wiedemann G. J.
Published: March 2020

17110

Background: Patients suffering from advanced stage IIIA/B NSCLC still have a bad prognosis despite the development of new and more effective treatment methods. Improved therapy options include multi-modal treatment approaches with sequential and/or concurrent chemo-radiation therapy and, alternatively, subsequent surgery. The patients have to accept a higher incidence of side effects and longer therapy cycles, which can last up to six months. This means that most patients spend a considerable part of their survival time undergoing therapy, where, in the short or medium term, they are likely to die of a relapse or haematogenous metastatic spread. Therefore we have decided to offer patients with unfavourable prognostic factors (poor general health, high age, comorbidity) a shortened, three-week neoadjuvant and concomitant chemo-radiation therapy plus possible surgery. This form of treatment is expected to produce more positive outcomes than the purely palliative radiation therapy at 40–50 Gy. Preventive dosing with Epoetin alfa as part of an intensive therapy regimen might lead to higher compliance, increased quality of life and possibly even to a better prognosis as a result of stabilising patients’ Hb levels. Methods: 51 stage IIIA/B NSCLC patients received neoadjuvant concurrent chemo-radiation therapy (daily cisplatin (6 mg/m2), 45 Gy hyperfractionated accelerated radiotherapy). 25 patients received additional treatment with Epoetin alfa 3 times a week (10,000 IU sc). Results: While Hb levels dropped significantly (−0.54 g/dL) during therapy in the control group, the Epoetin-alfa group showed a significant rise after only three weeks (+1,35 g/dL). There were no significant differences in remission rates between the goups. Conclusions: In this patient group, preventive treatment with Epoetin alfa stabilises Hb levels at a target level of around 12 g/dL even under intensive therapy. To what extent treatment with erythropoietin affects prognosis should be examined in further studies.

No significant financial relationships to disclose.
Tolerability of a weekly schedule of docetaxel-cisplatin as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: Binder D. , Hackenthal M. , Graseck L. , Schweisfurth H. , Schäper C. , Temmesfeld-Wollbrück B. , Suttorp N. , Beinert T. , Hellriegel K.
Published: March 2020

17112

Background: Recent trials have shown that the combination docetaxel-cisplatin is an effective first-line treatment in locally advanced or metastatic NSCLC. However, the regimen can be associated with a marked rate of neutropenia. The present study tests the efficacy and tolerability of a weekly schedule of docetaxel and cisplatin. Methods: Patients (pts) with histologically confirmed NSCLC stages UICC IIIB (malignant effusion) or IV were treated with docetaxel (35 mg/m2, 30 min. infusion) and cisplatin (25 mg/m2, 30 min. infusion) on days 1, 8 and 15 repeated every 4 weeks for 4 to 6 cycles. This phase II study is scheduled to include 50 pts and primary endpoint is tumour response rate. Pts received 8 mg of ondansetron and 8 mg of dexamethasone i.v. preceding every day of therapy and oral dexamethasone 2 × 4 mg from the day before until the day after chemotherapy. NK1-antagonists were given at discretion of the investigator. In total, 2750 ml of volume were infused on each day of therapy. Most of the pts were treated in an outpatient department. Safety was assessed via common terminology criteria for adverse events v3.0 (CTCAE 3.0). Interim tolerability data is presented. Results: Currently, 28 pts were evaluable for this interim tolerability analysis. Pts received a median of 3 full cycles. There were no treatment-related deaths. Dose reductions of docetaxel and cisplatin due to poor tolerability were necessary in 3 pts (11%). No pts suffered from neutropenic fever while grade 3 neutropenia occurred in only 2 pts (7%). There was no grade 2/3/4 thrombocytopenia. 5 pts (18%) had grade 2 anemia, and 2 pts (7%) had an elevation of the plasma creatinine (both grade 1). Other toxicities were non-neutropenic infections (5/1/1 pts with grade 2, 3, 4, respectively), diarrhea (3 pts [11%] with grade 3), constipation (5 pts [18%] with grade 2) and mucositis (4 pts [14%] with grade 2/3). There was no grade 3/4 nausea or vomiting; 3 pts [11%] had grade 2 nausea/vomiting. Conclusions: In the present study, the combination of docetaxel and cisplatin appears well tolerated. It was associated with a very low frequency of severe hematologic toxicity or neutropenic fever. With relatively low hydration volumes it can be safely administered in an outpatient setting.

[Table: see text]
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.
Inhibiting TNFα with etanercept in relapsed/refractory follicular lymphoma
Authors: Jacobsen E. , Van Den Abbeele A. D. , Neuberg D. , Li S. , Fisher D. C. , Friedberg J. , Barnes A. S. , Yap J. T. , Kutok J. , Freedman A. S.
Published: March 2020

17525

Background: Follicular dendritic cells (FDC) support the survival of follicular lymphoma (FL). TNFα is overexpressed by FL cells and TNFα plays a central role in the development and maintenance of normal FDCs. TNFα may be an ideal target for therapy due to its pleotropic effects on FDCs. Inhibition of TNFα is possible with the decoy receptor, etanercept. Methods: Patients with relapsed/refractory FL received 8 weeks of etanercept, 25 mg SC on day 1 and 4 of each week. Patients with any response or stable disease (SD) received 16 more weeks of etanercept at the same dose/schedule. 7 patients enrolled from April 2002 to September 2005. Median age was 63. All patients had stage III/IV disease and had received multiple chemotherapy regimens (median 3); 2 had prior autologous stem cell transplant. FDG-PET was performed at baseline and after 8 (scan 1, n = 7 patients) and 24 weeks on therapy (scan 2, n = 3 patients). Maximum standardized uptake values (SUVmax) were measured in up to 3 lesions per patient (n = 17 lesions for scan 1; 7 lesions for scan 2). The summation SUVmax of all lesions was calculated at each time point. The percentage (%) change in SUVmax in individual lesions and the summed SUVmax for each patient was calculated relative to baseline. The % metabolic response (mR) was assessed using EORTC thresholds for % SUVmax change (mPR ≤ −25% < mSD < +25% ≤ PD). Results: All patients completed at least 8 weeks of etanercept. 2 patients completed 24 weeks. 5 patients had minor or mixed responses. At the 8 week evaluation 5 patients had SD and 2 had progressive disease (PD). Of the 5 with SD, 2 progressed at 9 and 12 weeks of therapy and 3 progressed by 24 weeks. PET scan 1 showed mPR in 5/7 pts, SD in 2/7 and no PD. PET scan 2 showed mPR in 2/3 pts, mSD in 1/3 and no mPD.All patients are alive at a median of 20+ months after therapy. 1 grade 3 toxicity (lymphopenia) and 3 grade 1/2 toxicities (rhinitis/URI and 2 injection site reactions) were reported. Conclusions: Etanercept was well tolerated and minor clinical responses were observed. By EORTC criteria for metabolic response, mPR occurred in 5/7 pts, mSD in 2/7 and there was no mPD. The significant number of metabolic PR’s suggest that targeting the microenvironment with agents like etanercept may be a novel treatment approach for FL.

No significant financial relationships to disclose.
Ten year retrospective analysis of BOP (bleomycin, vincristine, predinisone)—A novel non-myelosuppressive chemotherapy regimen for treatment of non-Hodgkin’s lymphoma
Authors: Chan A. , Nay D. , Hopman W. , Galbraith P. , Baetz T.
Published: March 2020

17560

Background: Non-Hodgkin’s Lymphoma (NHL) represents the most common hematological malignancy in North America. Patients with advanced NHL, particularly those with pancytopenia, often do not tolerate the myelosuppressive side effects of chemotherapy. BOP (Bleomycin 10 mg/m2 IV D1, Vincristine 1.4 mg/m2 (max 2 mg) D1 and Prednisone 100 mg PO on D1,3,5,) q weekly ± Rituximab 375 mg/m2 IV D1 has been used as a non-myelosuppressive chemotherapy regimen for patients with advanced NHL at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: This was a retrospective chart review of patients with NHL who have been treated with ≥1 cycle of BOP ± R at the CCSEO in the last 10 years. Primary endpoints included an assessment of patient demographics, clinical setting, clinical response, survival and toxicity. Results: Eighty-two patients were treated with BOP ± R (71 BOP, 11 R-BOP). The patient population was 59% male and 80% stage ≥3. The most common histology was Diffuse Large B cell Lymphoma (22%) and Follicular Lymphoma (19.5%). Eighty percent of patients had an IPI score ≥2. The median number of chemotherapy treatments prior to BOP was 2. Overall, the response rate (CR + PR) was 46.3% with a mean duration of response of 4.6 months. Median survival was 3.8 years. BOP was used successfully as a salvage regimen prior to stem cell transplant in three patients and as a first line treatment prior to myelosuppressive treatment in 19 patients. The regimen was generally well tolerated with no hematologic toxicity or infectious complication. Four patients experienced mild pulmonary toxicity. There were no deaths attributable to drug toxicity. Response rates and toxicities in the R-BOP population were not significantly different from those of BOP. Conclusions: Patients with advanced poor prognosis NHL have a favorable response rate associated with minimal toxicity to the non-myelosuppressive chemotherapy regimen BOP ± R.

No significant financial relationships to disclose.