bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated serum level of sialylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib
Authors: Fujiwara Y. , Kiura K. , Toyooka S. , Hotta K. , Tabata M. , Takigawa N. , Soh J. , Kato K. , Date H. , Tanimoto M.
Published: March 2020

18162

Background: The Factors affecting survival after gefitinib treatment in patients with non-small cell lung cancer (NSCLC) remain to be fully elucidated, although epidermal growth factor receptor (EGFR) mutation is a substantial prognostic factor. KL-6 has been studied as a useful indicator for interstitial lung diseases, however, it was first discovered as a pulmonary adenocarcinoma-related antigen. The aim of this study was to investigate the prognostic value of the serum KL-6 levels in advanced NSCLC patients treated with gefitinib and thus determine its association with the EGFR mutation status. Methods: Between September 2002 and September 2005, 41 patients with NSCLC were treated with gefitinib after having their serum KL-6 levels measured at Okayama University Hospital. EGFR mutations were analyzed by direct sequence methods. Results: The serum KL-6 levels ranged from 199 to 9080 U/ml (median, 550 U/ml), and 54% of 41 patients showed a level higher than the cut-off level of 500 U/ml. The median progression-free survival (PFS) time and the median overall survival (OS) time were 4.7 months and 13.9 months, respectively. Multivariate analyses revealed that the elevated KL-6 level was an independent adverse prognostic factor for PFS (hazard ratio: 2.278, p = 0.040) as well as OS (hazard ratio: 4.858, p = 0.002) in NSCLC patients treated with gefitinib. The EGFR mutation status was analyzed in 22 patients (54%). Among those with wild-type EGFR, the patients with high serum KL-6 levels also had a worse survival than those within normal serum KL-6 levels (6.5 months versus 13.3 months, p = 0.0194). Conclusions: Our data suggest that NSCLC patients with high serum KL-6 levels tended to have a poor clinical outcome when treated with gefitinib.

No significant financial relationships to disclose.
Gefitinib (ZD-1839) with concurrent docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel/gefitinib for patients with stage III NSCLC: A phase I study
Authors: Blackstock A. , Petty J. , Oaks T. , Porosnicu M. , Clark H. , Lovato J. , Miller A.
Published: March 2020

18165

Background: The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent gefitinib/docetaxel chemotherapy in patients with inoperable stage III NSCLC has not been evaluated. Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily gefitinib (250 mg given orally). Patients recieved concurrent thoracic radiation to a dose of 70 Gy utilizing 3-D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative docetaxel (75 mg/m2) given q 21 days and gefitinib 250 mg p.o. for 1 year or until disease progression. Results: Beginning December 2003, 15 patients have been entered to date to this IRB approved phase I trial to determine the maximum tolerated dose of weekly docetaxel when given concurrent with gefitinib and thoracic radiation. The dose-limiting toxicities (DLT) observed were primarily non-hematologic and occured at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in a grade III dehydration, a second patient experienced grade III diarrhea while a third patient suffered a grade V interstitial pneumonitis, believed to be related to the gefinitib. While 14 of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy, 4 patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent gefitinib/docetaxel thus far appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 docetaxel dose level concurrent with 250 mg of daily gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca.

No significant financial relationships to disclose.
VEGF-D expression in lung adenocarcinoma with or without acquired resistance to gefitinib and normal lung
Authors: Wang Z. , Wu Y. , Zhang G. , Guo A. , Su J. , Chen Z.
Published: March 2020

18166

Background: VEGF-D is related with pathogenesis and metastasis of lung cancer, however, its relationship with resistance to gefitinib in NSCLC remains unknown. Methods: Lung adenocarcinoma, normal lung tissues adjacent to the carcinoma and adenocarcinoma with acquired resistance to gefitinib including some metastastic lymph nodes were obtained during operation. Relative quantitation of VEGF-D gene expression was performed by SYBR Green real-time PCR with beta actin gene as the endogenous control. VEGF-D expression of each group was analyzed by comparing them qualitatively and quantitatively. The expression ratios were compared by Fisher’s exact test and expression levels were compared by two-related-samples nonparametric test. Results: CVEGF-D expression ratio of lung adenocarcinoma with acquired resistance to gefitinib (16.7%, 1/6) was not different from lung adenocarcinoma (50%, 7/14, P=0.325) but was significantly lower than that of normal lung (93.8%, 15/16, P=0.001). The logarithmically transformed VEGF-D relative expression levels in six lung adenocarcinomas and the matched normal lung tissues, which were 2.214±0.376 and 3.388±0.209, were found to be significantly different from each other by the analysis of Wilcoxon signed ranks test (P=0.028). Conclusions: VEGF-D expression is in a high-level state in normal lung tissues while in low-level or absent in lung adenocarcinoma with or without acquired resistance to gefitinib, suggesting that the role VEGF-D plays in normal lung tissue could be different from in lung adenocarcinoma with or without acquired resistance to gefitinib.

No significant financial relationships to disclose.
Intensified treatment might improve survival in small cell lung cancer (SCLC) limited disease (LD). The STING study
Authors: Brodin O. , Wagenius G.
Published: March 2020

18167

Background: Intensified treatment in SCLC is not used, in spite of 19% improved 2-year survival from high dose or dose densified treatment according to a comprehension of 20 randomised studies. (Annals of Oncology 13:1519, 2002). What would happen if both the doses were increased, one further drug was given and dose density increased? Methods: A standard (ST) and an intensified treatment (INT) schedule were given in a phase II study in which 42 patients were included, 18 of which with LD. Patients up to 75 were included. The ST consisted of 6 courses of carboplatin, 5 AUC and etoposide 100 mg/m2 iv day 1–3 with 3 weeks interval. Thoracic radiotherapy was given 1.5 Gy bid to 45 Gy in patients with LD, starting concommitantly with course two. INT consisted of carboplatin 6 AUC, etoposide 120 mg/m2 and ifosfamide 5,000 mg/m2 course 1 and 3,000 mg/m2 in courses 2–6. Treatment was given with 2 weeks interval, which was possible by the addition of filgrastim. Radiotherapy was given in the same way as in the ST. Results: There was more problems with trombocytopenia and fatigue in the INT arm but not more problems with leucopenia. Two year survival in the ST was 4/11 (37 %) and in the INT 5/7 (72%). We now also have reached 5 year survival and there are 3/11 (27%) survivors in the ST and 4/7 (57%) in the INT. One further patient with limited disease, not included in the study was also treated according to the INT schedule and she has now reached two year survival, thus 6/8 patients treated according to that schedule are 2 year survivors. Concerning extensive disease patients there was 0/13 ST and 2/11 (18%) surviving 2 years and no 5 year survivors. Conclusion: There were too few patients with LD in this study to prove a superiority of INT, however, we consider the results very promising. The INT treatment is possible to give to patients up to 75 years and the toxicity is feasible. INT earns further studies in SCLC. We plan to start a phase III study with the same treatment arms in patients with LD during the spring 2007 and would like to get in contact with other groups that might be interested to participate, who could contact ola.brodinkarolinska.se.

No significant financial relationships to disclose.
Initial safety and efficacy results of erlotinib in previously treated patients with advanced non-small cell lung cancer
Authors: Zhou S. , Zhou C. , Yan L. , Xu Q. , Xu J.
Published: March 2020

18183

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

[Table: see text]

No significant financial relationships to disclose.
Oral vinorelbine in first line treatment of NSCLC in elderly: Updated results of a low dose schedule in a single institution experience
Authors: Tomirotti M. , Galassi B.
Published: March 2020

18192

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

No significant financial relationships to disclose.
Phase I study of combination chemotherapy with amrubicin and paclitaxel in relapsed small cell lung cancer
Authors: Tanaka J. , Yoshizawa H. , Ito R. , Hayashi Y. , Kuriyama H. , Tanaka H. , Kagamu H. , Gejyo F.
Published: March 2020

18206

Background: Amrubicin (AMR) and paclitaxel (PTX) are promising agents for advanced non-small cell and small cell lung cancer (SC). However, the combination of these drugs for relapsed SC has never been reported. The aim of this study was to determine the maximum tolerated dose (MTD) of AMR and PTX, thus to investigate the recommended dose (RD) of this combination chemotherapy for relapsed SC patients. Methods: Relapsed SC patients after 1 or 2 regimens with age younger than 70 and good performance status (PS) were eligible. The treatment consisted of AMR (escalating from 30 to 40 mg/m2 by 5 mg/m2 increment) as a one- shot iv on days 1 through 3, and PTX (escalating from 70 to 90 mg/m2 by 10 mg/m2 increment) as a 60-minute infusion on days 4 and 11, repeated every 21 days. The dose-limiting toxicities (DLTs) were defined as grade 3/4 non-hematological toxicities, grade 4 thrombocytopenia, and grade 4 leukocytopenia / neutropenia for 4 days or more. Results: Nine relapsed SC patients were enrolled. All of them were sensitive-relapsed cases with mean age of 60.1 and PS of 0 - 1, and received one or more cycles of chemotherapy (mean: 2.7 cycles). Six patients were treated at level 1 (AMR 30mg/m2, PTX 70 mg/m2) with two of them on DLT of grade 4 neutropenia for 4 days or more. Three patients were treated at level 2 (AMR 35 mg/m2, PTX 70 mg/m2) with all of them on DLTs; grade 4 neutropenia for 4 days or more, grade 3 febrile neutropenia, and grade 3 pneumonia. Overall response rate was 63%. Conclusion: The MTD was identified to be level 2, and the RD for this regimen with AMR and PTX was considered to be 30 mg/m2 and 70 mg/m2, respectively. Treatment was well tolerated and the preliminary activity observed warrants further investigation. A phase II study is currently under investigation for relapsed and refractory SC patients.

No significant financial relationships to disclose.
Dose-seeking study of the combination of GM-CSF with pegfilgrastim plus CHOP-rituximab in patients with aggressive non- Hodgkin lymphoma (NHL)
Authors: Cabanillas F. , Pavia O. , Rivera E. , Liboy I.
Published: March 2020

18501

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

[Table: see text]
Non-pegylated lyposomal doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-COMP) as initial treatment for patients with splenic marginal zone lymphoma (SMZL): A GISL study
Authors: Iannitto E. , Luminari S. , Mammi C. , Minardi V. , Merli F. , Angrilli F. , Stelitano C. , Cesaretti M. , Franco G. , Carella A. M. , Federico M.
Published: March 2020

18502

Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associated with intrasinusoidal bone marrow infiltration. The encapsulation of doxorubicin into non-pegylated liposomes allows targeting of the drug to affected organs including spleen, lymphnodes and bone marrow. Methods: In 2005, the GISL started a phase II study for the treatment of patients with histologically confirmed SMZL, investigating safety and clinical profile of 6 courses of a modified R-CHOP regimen in which standard doxorubicin was substituted with non pegylated lyposomal doxorubicin (NPLD) used at the same doses (50 mg/m2) (R-COMP). Main inclusion criteria were age >18 yrs, normal cardiac function and active disease (at least one of the following; Hb <10 g/dl; plt <100,000/mmc, symptomatic splenomegaly, elevated LDH, B symptoms, extrasplenic disease, LDT <12 months). Splenectomy was allowed prior to treatment start only in case of symptomatic spleen enlargement. The study was planned according to a two-stage Simon design using overall response rate as primary endpoint. We present the results of the analysis performed after the completion of study stage 1. The access to stage 2 is allowed if at least 12 responses are recorded among among the first 19 evaluable cases. Results: As of January 2007, 20 patient were enrolled with the following characteristics; median age 63 years (30–80), Hb <10 g/dl in 20%, Lymphocytes > 5,000/mmc in 65%, elevated LDH in 65%; 2 patients were splenectomized before treatment start. One patient was not available for response assessment. A clinical response was observed in all remaining 19 cases (ORR 100%); 12 (63%) cases obtained a CR. So far only one patient progressed at +1 month from treatment. Treatment was well tolerated with grade III/IV neutropenia in 8 patients (42%), grade 3 pulmonary toxicity in 1 patient and grade 2 peripheral neuropathy in 5 cases. In one case a reversible cardiac failure was reported after 1 month from the end of treatment. Conclusions: In conclusion 6 cycles of R-COMP combination represent a safe and promising treatment option for patients with clinically active SMZL.

No significant financial relationships to disclose.
Factors associated with long-term survival following stem cell transplantation (SCT) for non-Hodgkin lymphoma
Authors: McQuellon R. P. , Russell G. B. , Jesse M. T. , Thomas C. R. , Keung Y.
Published: March 2020

18504

Background: Psychosocial variables have been associated with survival in stem cell transplantation recipients. The purpose of this study was to examine the relationship between clinical, psychosocial, and demographic variables and long-term survival. Methods: Autologous SCT recipients with NHL (n=315) from 1/92 - 4/05 (mean age = 51.6 yrs (±12); 35% F; 7% AA; median survival/follow-up = 4.4/ 6.1 yrs) completed the Center for Epidemiologic Studies-Depression Scale, Functional Assessment of Cancer Therapy- BMT (FACT-BMT; physical well-being, PWB), Profile of Mood States, and the Medical Outcomes Study Social Support Survey (MOS-SS) prior to transplantation. Clinical and demographic data were abstracted from the patient’s record. Cox’s proportional hazards regression models were used to assess the effect of the following variables on survival: clinical - histological subtypes (HS) [anaplastic large cell (ALC), diffuse large B-cell (DLBC), mantle cell (MC), indolent, and aggressive], grade, stage, type of conditioning regimen (TC), chemosensitivity (CS), number of chemotherapy regimens (1–7) prior to SCT (NCR); demographic - age, race, gender; and psychosocial - depressed mood, general distress, quality of life, and social support. Measures with a univariate p-value <0.2 were fit in a backwards stepwise regression; remaining variables had a p-value < 0.05. Results: The included univariate model variables (p-values) were: HS (0.0004), grade (0.004), TC (0.14), CS (0.0001), NCR (0.02), PWB (0.03), FACT-BMT subscale (0.16), SS-Emotional (0.05), SS-affection (0.13). In the regression model, predictors of survival were: HS (<0.0001), median survival = ALC 1.9, DLBC 2.7, aggressive 3.3, MC 5.1, indolent 8.4 yrs; CS (0.008); NCR (0.03), and PWB(0.03). Conclusions: Clinical variables were the most predictive of survival. Psychosocial variables were not associated with survival.

No significant financial relationships to disclose.
Factors influencing tymic function in 55 patients with lymphomas: Candidates to autologous stem cell transplantation (ASCT)
Authors: Simonelli C. , Pratesi C. , Zanussi S. , Talamini R. , Rupolo M. , Abbruzzese L. , Gattei V. , Vaccher E. , Michieli M. G. , De Paoli P. , Tirelli U.
Published: March 2020

18512

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

No significant financial relationships to disclose.
Ifosfamide or trofosfamide for intraocular lymphoma: Long-term results of a prospective study
Authors: Thiel E. , Jahnke K. , Bechrakis J. , Wagner T. , Fischer L. , Kiewe P. , Korfel A.
Published: March 2020

18524

Background: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. In a prospective study, ifosfamide (IFO) or trofosfamide (TRO) have been assessed for treating IOL. Here, long-term results are presented. Patients and Methods: Patients with histologically proven isolated IOL were included. The median age of the patients was 74 years (range 46–83 years); 4 patients had a newly diagnosed disease and 6 a relapse. IFO was administered intravenously at a dose of 1.5 - 2.0 g/m2/day for 3 days every three weeks. TRO was given at a dose of 150 or 400 mg/day (continuous or intermittent administration) to 4 patients considered unable to receive intensive intravenous hydration. IFO, TRO and their active 4-hydroxy (4-OH) metabolites were measured in aqueous humor of 9 patients. Results: The median number of IFO courses was 6 (range 2–8), the median duration of TRO therapy was 8.5 months (range 6–18 months). All patients responded. Toxicity > WHO grade 2 was: anemia grade 2 in 2 patients, leukopenia grade 2–3 in 2 patients, nausea/vomiting grade 2 in 2 patients, thrombopenia and cystitis grade 2 in 1 patient each. Thus far, three patients each have developed cerebral and ocular relapse. Median progression-free survival from the study treatment was 9.5 months (range 6 - 24+ months), median overall survival was 15.5 months (range 6–34 months). Both patients retreated with IFO on ocular relapse responded. In 6 of 6 patients, 4-OH metabolites were detected in the aqueous humor immediately after IFO infusion with an aqueous/serum ratio of 0.19–0.54. Three to 16 hours after ingestion of TRO, 4-OH metabolites could be detected in one of 3 patients. Conclusions: Response rate of IOL to IFO or TRO is high with a tolerable toxicity even in elderly patients. However, long-term remissions are infrequent. Combining IFO/TRO with other cytostatics seems reasonable to improve long-term disease control.

No significant financial relationships to disclose.
Rituximab, ifosfamide, carboplatin, and etoposide (RICE) compared with ICE in relapsed diffuse large cell lymphoma (DLCL) before autologous stem cell transplantation
Authors: Case D. C. , Aronson F. R. , Ebrahim K. S. , Hedlund J. A. , Boyd M. A. , Ault K. A.
Published: March 2020

18532

Background: Retrospective cohort analysis suggests that the addition of rituximab to the ICE regimen (RICE) improved the complete response (CR) rate in relapsed DLCL and progression-free survival after transplantation (Blood 103:3684, 2004). We reviewed the results of two consecutive cohorts of patients treated with ICE and RICE prior to stem cell transplantation for CR rate, percent patients able to go to transplantation, and progression-free survival after transplantation. Methods: Adult patients (1996–2000) with relapsed DLCL received ICE chemotherapy [ifosfamide 1800 mg/m2 IV q.d. x3, carboplatin 250 mg/m2 IV day 1, and etoposide 75 mg/m2 IV q.d. x3 along with mesna] every 28 days to maximum response. Responding patients who were clinically stable and able received high-dose chemotherapy with autologous stem cell support. Adult patients (2001–2004) with relapsed DLCL received ICE along with rituximab 375 mg/m2 IV on day 1 of each cycle of chemotherapy. Patients in CR received autologous stem cell transplantation. Results: In the ICE series, 49 patients were treated with a 20% CR rate, and 10% went to transplant. Progression-free survival in those transplanted was 9, 12, 24, 36, and 81+ months (median 24 months). In the RICE series, 24 patients were treated with a 33% CR rate, and 25% were transplanted. Progression-free survival was 12, 18, 24+, 36, and 46+ months (median 24+ months). Myelosuppression was similar in each series. All patients were able to tolerate rituximab. The CR rate, percent of patients transplanted, and progression-free survival after transplantation appeared better with RICE but these differences were not statistically significant (P>.05). Conclusions: In our small series, Rituximab added to ICE did not have a statistically significant impact.

No significant financial relationships to disclose.
Conserved epigenetic changes in sporadic and HIV-associated high-grade B-cell lymphomas
Authors: Crook T. , Smith P. , Syed N. , Stebbing J. , Griffin B. , Bower M. , Naresh K.
Published: March 2020

18540

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

No significant financial relationships to disclose.
A simplified staging system in cutaneous melanoma to select patients for adjuvant trials
Authors: Beam S. L. , Elias E. G.
Published: March 2020

19003

Background: Most clinical trials with adjuvant therapy in melanoma concentrate on high-risk patients including those with metastases to regional lymph nodes (LN), stage III and locally advanced T4, i.e., stage IIB and IIC. These trials may be missing the advantageous results in the relatively earlier stages. Methods: We reviewed the new American Joint Committee on Cancer (AJCC) for cancer staging of cutaneous melanoma and Balchs’ data for the prognostic factors. The data was correlated to patients’ survival expressed by the natural history of the disease. Results: We grouped the reported survival data into 3 risk groups, excluding patients with distant metastases. Group 1: 2–4mm deep primary with ulceration, >4mm deep primary without ulceration, micrometastases to 1–3 LN, primary not ulcerated; Group 2: >4mm deep primary with ulceration, micrometastases to 1–3 LN ulcerated primary, macrometastases to 1–3 LN, primary not ulcerated intransit metastases/satellitosis, without LN metastases; Group 3: macrometastases to 1–3 LN, ulcerated primary, metastases to 4 or more LN, matted LN, and/or intransit, metastases/satellitosis with LN metastases. The table summarizes the results. Conclusions: 1. Over one-third of the patients in group 1 died of disease in the first 5 years. They should be considered at intermediate risk and should receive adjuvant therapy. 2. Patient prognosis should determine the intensity of target therapy utilized in the adjuvant arena. While anti-CTLA-4 may be sufficient for group 1, the addition of anti-kinases may be required in group 2 and more so in group 3.

[Table: see text]

No significant financial relationships to disclose.
Elevated interleukin-6 levels correlation with anemia, symptom burden, and neurocognitive deficit in cancer patients receiving chemotherapy: Effects of darbepoetin-alfa administered once per cycle for prevention of anemia
Authors: Vadhan-Raj S. , Bueso-Ramos C. , Trent J. , Patel S. , Zhou X. , Benjamin R. S. , Meyers C. A.
Published: March 2020

19505

Background: Chemo-naïve sarcoma pts experience severe anemia during chemotherapy (CT) with adriamycin and ifosfamide (AI) resulting in PRBC transfusions (Tx) in >90% of pts. Anemia has a negative impact on quality of life (QOL) and neurocognitive (NC) functions (fx). Preclinical studies suggest that treatment with erythropoietic stimulating agent (ESA) may protect NC fx. The purpose of this study was to evaluate the effects of darbepoetin (Initial dose 500mcg) administered once per cycle on prevention of anemia, transfusions, symptom burden and NC fx. Methods: Pts underwent assessment for neuropsychological tests, symptoms (MDASI), and quality of life (QOL). To determine if NC deficits and Hb were correlated to cytokine levels, serum IL-1, IL-6, and TNF were measured at baseline, after 3 cycles and completion. Results: Baseline median hemoglobin (Hb) was 13.2 g/dL (n=49); however, significantly more NC deficits and symptoms were seen in pts as compared to normal. Interestingly, serum IL-6 levels were significantly elevated as compared to normal at baseline and during treatment (p<0.001), and were negatively correlated with baseline Hb (p=0.003) and significantly associated with NC deficits, QOL and symptoms. Of 45 pts that received > 1 cycle of CT, 38% avoided PRBC Tx. Pts with higher baseline Hb had less sadness and shortness of breath (p<0.01). Pts with higher Hb nadir had lower tingling/numbness (p=0.006). Pts who avoided transfusions had less distress (p=0.032), less sadness (p=0.01), and better motor fx (p=0.005). Conclusions: These findings suggest that cancer pts can have NC deficits prior to CT. Prevention/early intervention with ESA may avoid transfusions, reduce symptom burden, and NC deficit. Significant correlation of anemia, symptoms, and NC deficit with elevated IL-6 levels suggest that anti-IL-6 treatment may improve response to ESA and NC functions.

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No significant financial relationships to disclose.
Clinical outcomes of 203 adult patients receiving highly (H) and moderately (M) emetogenic (E) chemotherapy (C) following an institutional antiemetic guideline update incorporating aprepitant (A) and palonosetron (P)
Authors: Timoney J. P. , Chan W. W. , Culkin A. E. , Flaherty A. M. , Giacalone W. F. , Lucarelli C. D. , Murphy D. J. , Schumann M. L. , Major M. A. , Kris M. G.
Published: March 2020

19506

Background: A quality improvement project targeted at chemotherapy induced nausea (N) and vomiting (V) was initiated in 2004. The project included an antiemetic guideline update consisting of replacing ASCO 1998 3 tier guidelines with a 4 tier system similar to ASCO 2006. Following implementation of the guidelines an evaluation phase began. Methods: Adult chemotherapy-naïve patients receiving HEC or MEC were asked to participate. HEC patients received P 250 mcg IV each day of chemotherapy, A 125 mg PO day 1 and 80 mg PO days 2 and 3 and dexamethasone (D) 12 mg PO days 1, 2 and 3. MEC patients received P 250 mcg IV and D 12 mg PO on the day of C. Participating patients were asked to complete a 7 question NV tool at least 5 days following C to report on the 5 days following C. Outcomes reported include % of patients without N, % without V and N score using a 0–10 visual analog scale (VAS). Patient satisfaction with the the control of N and V was also assessed using a 0–10 VAS. Results: A total of 151 patients received HEC and 89% and 44% were protected from V and N respectively. A total of 52 patients received MEC and 90% and 56% were protected from V and N respectively The median N score for all patients who reported nausea was 3. The median and mean score for satisfaction with N and V control was 10 and 8.7 respectively. Patient outcomes for the most commonly used C regimens are reported in the table below. Conclusion: Implementation of revised AEG provided patients receiving HEC and MEC a high level of protection from vomiting, low nausea scores and a high level of overall satisfaction with prevention of N and V. Although N scores were low, the incidence of N reported offers an opportunity for further improvement.

[Table: see text]

No significant financial relationships to disclose.
Ibandronate reduces radiotherapy-resistant metastatic bone pain in patients with solid tumors: A comparison of i.v. and oral formulations
Authors: Mystakidou K. , Stathopoulou E. , Parpa E. , Hatzipli I. , Touroutoglou N. , Vlahos L.
Published: March 2020

19517

Background: Bisphosphonates are used to treat metastatic bone disease (MBD). However, some bisphosphonates are associated with renal toxicity. Ibandronate (IA) is a single-nitrogen, noncyclic bisphosphonate with a renal safety profile similar to placebo in phase III trials. This study compares the effects of i.v. IA 6mg and oral IA 50mg on bone pain, analgesic intake and renal safety. Methods: Recruited patients fulfilled the following criteria: age ≥18, solid tumors with at least one bone lesion, normal renal (serum creatinine ≤1.5mg/dL) and hepatic function, WHO performance status 0, I or II, life expectancy ≥6 months, normal serum calcium or asymptomatic hypercalcemia. Patients were excluded if they were pregnant or lactating, taking nephrotoxic drugs or osteoclast activity modulators. Eligible patients (n=52) were recruited for a two-arm study, with 26 patients per group treated over 6 months. Groups were matched for age, gender, weight, height, blood pressure, site of primary tumor, site and number of bone metastases and number of irradiated sites. Intravenous IA 6mg was administered over 15 minutes every 4 weeks. Oral IA 50mg was administered as a single, daily tablet before breakfast. Studies were ceased on occurrence of new bone events. Primary endpoint was reduction in bone pain and reduced analgesic use. Results: There were no significant differences in patient demographics between the two treatment arms. The percentage of patients receiving i.v. IA that achieved stable or progressive disease was 15.4%; those receiving oral IA attained 11.5% stable or progressive disease. Pain (Brief Pain Inventory questionnaire) and analgesic intake were assessed at baseline, 3 and 6 months. Both i.v. and oral IA caused a significant and sustainable decrease in each of the pain indices (p<0.0005) with no significant difference between i.v. and oral groups. Both i.v. and oral IA treatment led to a trend in decrease of analgesic use. Conclusions: Oral and i.v. ibandronate have comparable efficacy for palliation of bone pain in MBD patients.

No significant financial relationships to disclose.
Association of physical and psychological symptom burden with time to death among palliative cancer outpatients
Authors: Zimmermann C. , Barmala N. , Zarinehbaf S. , Le L. W. , Cheung W. Y.
Published: March 2020

19523

Background: Patients with terminal cancer have a high symptom burden, which tends to increase as death approaches. Previous studies have assessed the association of symptom burden with time to death (TTD) among inpatients or using baseline data for patients enrolled in a trial. Our purpose was to determine the association of symptom burden with TTD in patients who were followed by an outpatient palliative oncology clinic (OPOC). Methods: Cancer patients seen in the OPOC between January 2005 to June 2006 and who subsequently died were identified from the palliative care database. The last outpatient Edmonton Symptom Assessment Scale (ESAS) score completed in clinic was compared among patients in the last 4 months of life. Multiple linear regression was used to determine the association of ESAS total symptom distress score (SDS), physical subscore (PHS), psychological subscore (PSS) and individual symptom scores with demographic parameters, disease characteristics and TTD. Results: In total, 198 patients were identified. All patients had stage IV cancer, the mean age was 63.8 years (SD 12.9) and 55% were male. Median survival time from initial assessment was 6.6 weeks (range 0.3 to 16.7) and mean SDS was 46.0 (SD 18.0). Sites of cancer included gastrointestinal (36%), lung (12%), genitourinary (10%), hematological (8%), gynecological (8%), breast (7%) and others (19%). There was no significant association between symptom burden and gender, age or cancer site. TTD was significantly associated with SDS (p<0.001) and PHS (p<0.001), but not with PSS (p=0.19). Individual symptoms most strongly associated with TTD were fatigue (p=0.001), appetite (p=0.001), drowsiness (p=0.0005) and shortness of breath (p=0.0008). There was no significant association between TTD and depression (p=0.24) or anxiety (p=0.20). Conclusions: In this outpatient palliative cancer population, the association between TTD and symptoms held true only for physical symptoms, particularly constitutional symptoms and shortness of breath which are amenable to therapy. Symptoms in palliative patients should be rigorously assessed and treated, regardless of prognosis and especially at end-of-life.

No significant financial relationships to disclose.
Randomized trial of acupuncture versus sham control for prevention of myelosuppression in patients with gynecologic malignancies
Authors: Matulonis U. , Lee H. , Lu W. , Goodman A. , Rosulek A. , Doherty A. , Kornblith A. , Atkinson T. , Gibson C. , Dean-Clower E. , Penson R.
Published: March 2020

19524

Background: CIM is a significant toxicity that is treated with cytokine growth factors, dose reductions and/or delays. Preliminary uncontrolled Chinese studies suggest that acupuncture lessens CIM. Methods: Patients (pts) with newly diagnosed or recurrent gyn cancers receiving chemotherapy were eligible. Trial design was a double blinded, randomized trial of active acupuncture or sham for 5 weeks (administered 3x per week). Primary endpoints were first nadir WBC and ANC levels at chemo cycle 2; other endpoints were recovering counts following the cycle 2 nadir, QOL, G-CSF levels, and feasibility. Results: >460 patients were screened. 21 pts were randomized to either active acupuncture (n=11) or sham control (n=10). Median age of the pts was 55 yrs (range: 28–81). 15 pts have completed the acupuncture treatment to provide the baseline and nadir WBC and ANC. Toxicities related to either sham or active acupuncture were minimal. The active pts group showed higher baseline WBC (median: 3,600 vs. 2,600, NS) and ANC (median: 2,269 vs. 1,922, NS) values. The nadir WBC was higher in the pts receiving acupuncture (median 3,600 vs. 2,300) but the difference was not statistically significant after adjusting for the baseline difference (p=0.16). Nadir ANC was higher among the pts receiving acupuncture (median: 2,424 vs. 1,274) but the difference was not statistically significant after adjusting for the baseline difference (p=0.1107). Recovering WBC in the pts receiving acupuncture was higher (median: 8,600 vs. 4,400) after adjusting for the baseline difference (p=0.045). The recovering ANC in the pts receiving acupuncture was higher (median: 6,530 vs. 4,038) but this difference was not statistically significant after adjusting for the baseline difference (p=0.0919). QOL and G-CSF data will be presented at ASCO. Conclusions: Although a larger randomized trial is necessary to determine the effects of acupuncture on CIM, there were consistent trends, and recovering WBC counts were significantly higher in patients receiving acupuncture. Formal evaluation of CAM is vital to confirm potentially clinically meaningful benefits.

No significant financial relationships to disclose.
Adherence to anemia treatment guidelines in U.S. community oncology practices
Authors: Friedman L. , Naeim A. , Pasta D. J. , Elkin E. P. , Viswanathan H. , Kallich J. , Glaspy J.
Published: March 2020

19525

Background: Adherence to anemia guidelines may improve patient outcomes including health-related quality of life. This analysis presents baseline guideline adherence among community-based oncology practices prior to an educational intervention targeted to health care providers to improve adherence to anemia guidelines. Methods: Medical records of a sequential sample of adult cancer patients receiving chemotherapy from 47 participating sites during the year prior to site randomization to an educational intervention were abstracted. Each chart was analyzed to determine (1) whether or not the patient met the criteria for anemia treatment with an erythropoiesis- stimulating agent (ESA) or a blood transfusion, and (2) whether the patient received anemia treatment. A complex algorithm was developed to evaluate whether treatment adhered to guideline recommendations. Results: This baseline analysis included 2463 patient charts. Most patients were female (66%); with a mean duration of cancer of 14.5 months and a mean age of 61.8 years. According to guidelines, 523 patients (21%) met the criteria for anemia treatment and of these, 286 (55%) received an ESA or transfusion. In 1103 patients (45%), guidelines suggested that anemia treatment may be inappropriate. However, 216 (20%) of the 1103 patients for whom guidelines recommend against treatment received an ESA or transfusion. For 837 patients (34%), the guidelines did not provide a definitive recommendation and 242 (29%) of such patients received an ESA or transfusion. Conclusions: Baseline assessment found that many patients did not receive treatment consistent with anemia guidelines. This study will evaluate whether a year long educational intervention can improve clinician adherence to guideline recommendations, thereby improving patient outcomes.

No significant financial relationships to disclose.