bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of palonosetron 0.25 mg IV daily and incidence of nausea and vomiting in patients undergoing bone marrow transplantation (BMT)
Authors: Adel N. G. , Khan A. , Lucarelli C. 
Published: March 2020

16510 Background: Preparative regimens for BMT are associated with a high incidence of nausea and vomiting, which can negatively affect quality of life. It is important to evaluate the incidence of nausea and vomiting and understand which antiemetic regimens are most effective in these patients in order to improve outcomes. Methods: A retrospective review of patients admitted to the adult BMT Unit at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1/1/05 and 12/31/05 was performed. Currently at MSKCC, palonosetron (0.25 mg IV daily) is used as the main antiemetic agent during the preparative regimen; dexamethasone 20 mg IV is occasionally combined with palonosetron when there is no other contraindication to its use with some preparative regimens. The electronic medical records, as well as the pharmacy computer system, were used to collect demographics, primary diagnosis, BMT type, preparative BMT regimen, days of regimen, whether radiation was included, antiemetic used, and incidence of nausea and vomiting, which were assessed 3 times daily during the administration of the preparative regimen. Results: 176 pts (75 women, 101 men) received BMT; mean age was 50 yrs (18–73). All patients received a highly emetogenic preparative regimen for which the mean duration was 5 days (1–9 days). Over a 1–12 day period the incidence of nausea and vomiting were 78% and 39% in those undergoing an allogeneic transplant compared with 51% and 18% in those undergoing an autologous transplant. Patients with leukemia had the highest incidence of nausea (85%) and vomiting (45%). The rates of nausea and vomiting in those receiving radiation were 81% and 33%, while in those not receiving radiation, the rates of nausea and vomiting were 51% and 20%, respectively. Of patients receiving palonosetron alone, 87% experienced nausea and 41% had vomiting, compared to 48% and 15% for those receiving both palonosetron and dexamethasone. Conclusions: Radiation therapy and allogeneic transplant had higher incidences of nausea and vomiting when compared to autologous transplant. Nausea and vomiting were better controlled in patients receiving palonosetron and dexamethasone compared with those receiving palonosetron alone. No significant financial relationships to disclose.
Acute heart failure in bone marrow transplantation: Impact of intravenous immune globulin as adjuvant therapy
Authors: Salcedo P. , Shpall E. , Yusuf W. , Roberson S. , Woods M. , Lenihan D. , Durand J. 
Published: March 2020

16512 Background: Little is known regarding management or treatment of cardiac failure after bone marrow transplantation. We investigated the management, treatment and outcome of new onset acute decompensated heart failure (ADHF) after bone marrow transplantation (BMT) with beta blockers, ace-inhibitors and adjuvant intravenous immune globulin (IVIG) therapy. Methods: We retrospectively examined 25 patients with ADHF. Eleven of these patients developed congestive heart failure within 100 days of BMT. Baseline echocardiograms were normal prior to admission and all patients were hospitalized and evaluated for left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class. Patients with acute heart failure were treated with standard heart failure medications and patients post-BMT were treated with standard heart failure therapy plus adjuvant (IVIG) (500mg/Kg/day) for 48 hours. Baseline LVEF and NYHA class of 11 patients pre- and post-BMT were compared with LVEF and NYHA class of 14 patients with ADHF that did not receive a BMT. Results: The baseline diagnosis for all patients in the BMT group was NYHA class 4 and post-therapy improved to class 1.2. The baseline diagnosis for all patients in the non-BMT group were NYHA class 3.7 and improved to class 1.2 with medical therapy. The mean LVEF in the BMT group at diagnosis of ADHF was 27.5% and the mean post-therapy with IVIG was 57.6%. The mean baseline LVEF in the group not undergoing BMT and at diagnosis of ADHF was 28.2% and improved post-therapy to 45.2%. Conclusions: Acute decompensated heart failure in the cancer patient is highly treatable with aggressive medical management. Patients with ADHF after BMT and treated with IVIG may have potential clinical benefits with IVIG and standard medical therapy. Significant improvement in LVEF and NYHA were present in the BMT group versus the non-BMT group. These data suggest that BMT outcomes may be improved with routine heart failure management. Further randomized studies should be conducted. [Table: see text] No significant financial relationships to disclose.
Controlled study to evaluate physical and psychosocial effects of a standardized in-patient rehabilitation program for patients after allogenic stem cell transplantation
Authors: Bartsch H. , Auclair P. , Mumm A. , Weis J. 
Published: March 2020

16519 Background: Allogeneic stem cell transplantation (HSCT) involves somatic restrictions as well as psychosocial problems. We devolped a specific, standardized in-patient rehabilitation program (RP) for pts after HSCT. Main goals of this combined medical and psychosocial RP are the accelerated increase of physical strength and the decrease of psychosocial distress to improve health related quality of life (QoL).The purpose of this study was to evaluate this RP and define prognostic factors to discriminate between groups of pts. who might differentially benefit by the program. Methods: 132 pts. after HSCT were prospectively enrolled in the treatment group and compared to 22 pts. after HSCT who did not receive the specific RP. Besides an elucidated medical and physical assessment all pts. answered different standadized questionaires for evaluation of treatment related symptoms, fatigue (MFI), QoL (QlQ), and psycosocial distress (HADS). All measurements were repeated at different time points. RP-Pts received the first questionnaire at their admission to our center, controls during the first control after HSCT at their respective treatment center (T1). T2 was at discharge from the hospital or four to six weeks after T1. T3 was six months and T4 twelve months after T2. A matched-pairs strategy was chosen to compare the smaller group of 22 control patients with matching partners selected from the treatment group. Results: The analyses reveal that the rehabilitation patients as a group had significant poorer initial values compared to controls, particularly in physical parameters and fatigue. At T2 and T3 both groups did improve significantly compared to T1 in different physical and psychosocial measures. However the matched pair analysis is still ongoing and data will be presented. Conclusions: Our data show that pts who are obviously more impaired following HSCT were preferentially transferred to our in-patient RP and benefit significantly from a standardized RP in physical as well as psychosocial conditions. The improvement increases over time and reaches after one year values comparable to those of healthy people. No significant financial relationships to disclose.
Preoperative gemcitabine (G) and docetaxel (D) in patients (pts) with stage IB, II, or III non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network
Authors: Spigel D. R. , Hainsworth J. D. , Yardley D. A. , Burris H. A. , Thompson D. S. , Zubkus J. D. , Litchy S. , Silverberg D. , Thomas J. R. , Greco F. A. 
Published: March 2020

17007 Background: Preoperative chemotherapy may improve outcomes for pts with resectable NSCLC compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative G/D for pts with resectable NSCLC. Methods: The primary endpoint was to assess the response rate (RR) of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station ≤2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Treatment included: D 30 mg/m2 IV and G 1000 mg/m2 IV D1,8 Q 21D × 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. Eligibility included: measurable disease, ECOG PS 0–1, adequate organ function, informed consent. Analysis was by intent to treat. Results: Fifty-four pts were enrolled between 4/04 and 9/05. Baseline features include: median age 62 years (42–82); male/female, 44%/56%; ECOG PS 0/1: 50%/50%; adenocarcinoma (28%), squamous (43%), large cell (9%), mixed/not specified (20%); IB (30%), IIA (5%), IIB (19%), IIIA (33%), IIIB (13%). Forty-eight pts (91%) completed preoperative treatment and 32 pts (60%) underwent resection. Grade 3/4 hematologic and non-hematologic toxicities were limited to neutropenia (20%) and infection (8%), respectively. All other toxicities were <5%. There were no treatment-related deaths. Complete/partial responses for all pts were observed in 1 pt/16 pts, respectively, for an overall RR of 31% (95% CI 20%–44%). Twenty-five pts (46%) had stable disease, and 11% had progression (6 pts were unevaluable.) No pathological complete responses were observed in 32 resected pts. After a median follow-up of 12 months, actuarial 1-year progression-free survival and overall survival (OS) are 54% and 79%, respectively. Median OS has not been reached. Conclusions: G/D is a well-tolerated preoperative regimen for pts with resectable NSCLC with activity rivaling platinum-based regimens. Further follow-up and additional studies comparing preoperative and adjuvant treatment are needed to assess the benefit of this regimen. [Table: see text]
NOV-002, a chemoprotectant/immunomodulator, added to first-line carboplatin/paclitaxel in advanced non-small cell lung cancer (NSCLC): A randomized Phase 1/2, open-label, controlled study
Authors: Pazoles C. J. , Gerstein H. 
Published: March 2020

17021 Background: NOV-002 is a proprietary formulation of oxidized glutathione that modulates production of cytokines and hematopoietic growth factors. A randomized, multi-site advanced NSCLC trial conducted in the Russian Federation showed a one-year survival rate of 63% with NOV-002 + cytotoxic chemotherapy compared to 17% with cytotoxic chemotherapy alone. Methods: Forty-four chemotherapy-naïve, Stage IIIB/IV NSCLC patients (ECOG 0–2, stratified by disease stage) were randomized to one of three groups for six months of treatment: Groups A and B: NOV-002 in combination with carboplatin and paclitaxel (C+P). For each nominal 21-day chemotherapy cycle, these groups received 60 mg of NOV-002 i.v. daily for the first 4 days, then 60 mg i.m. (A) or s.c. (B) weekdays for the next 17 days. Group C: C+P alone. Initial doses of C and P in all three groups were 225 mg/m2 and AUC 6, respectively. Initiation of repeat C+P cycles required an absence of hematologic and other toxicities in excess of pre-defined values. Primary study endpoints included tumor response (scans performed at baseline and then every two months) and safety. Results: An intent-to-treat analysis of the best overall objective tumor response (WHO criteria), showed that 11 out of 16 (69%) Group B patients demonstrated greater than 50% tumor shrinkage versus 5 out of 15 (33%) in the control group (C) (p = 0.044, logistic regression stratified on disease stage). Six out of 13 (46%) patients in Group A demonstrated an objective response. 100% of NOV-002 treated patients in Group B and 85% in Group A were able to complete four cycles of C+P compared to 50% of control patients (Group C) (p = 0.004, chi square). NOV-002 was well-tolerated in this patient population. Conclusions: These data continue to suggest increased efficacy of NOV-002 plus cytotoxic chemotherapy compared to chemotherapy alone in advanced NSCLC. [Table: see text]
Impact of RASSF1A methylation on survival of stage IIIb and IV NSCLC patients treated with gemcitabine
Authors: Fischer J. R. , Ohnmacht U. , Rieger N. , Stoffregen C. , Manegold C. , Lahm H. 
Published: March 2020

17028 Background: The epigenetic inactivation of genes plays an important role in lung cancer carcinogenesis. We have investigated the methylation status of seven genes (APC1A, DAPK, FHIT, p14ARF, p16INK4a, RARβ, RASSF1A) in serum DNA of NSCLC patients and analyzed their potential prognostic value. Methods: Blood samples were drawn pretherapeutically. Genomic DNA was purified from serum and subjected to sodium bisulfite treatment to convert unmethylated cytosine bases. Epigenetic alteration was detected by a nested methylation-specific PCR. Results: We have investigated a group of 92 patients with histologically confirmed NSCLC (60 males, 32 females; 21 stage IIIb, 71 stage IV; median age 60.9 years, range 34–78). All patients received gemcitabine first-line alone or in combination with other drugs. The vast majority of samples (n = 87) showed at least one methylated gene. More than half of the tested genes were hypermethylated in 20 samples (21.7%). The methylation frequencies of individual genes were 30.8% (APC1A), 26.1% (DAPK), 47.3% (FHIT), 30.4% (p14ARF), 25.9% (p16INK4a), 44.6% (RARβ) and 33.3% (RASSF1A). The hypermethylation status of none of the genes altered median overall survival (11.0 ± 1.4 mo) of the total population significantly. However, patients with a methylated RASSF1A gene who showed a partial response (n = 27) survived significantly longer (33.6 ± 10.4 mo) compared to those with a wild-type allele (16.1 ± 4.7 mo, P = 0.0045). This difference was not seen in patients with stable (n = 40) or progressive (n = 20) disease. Conclusions: Our results show that the hypermethylation frequency of single genes and the accumulation of epigenetic alterations in individual samples of NSCLC patients may vary considerably. Molecular parameters such as RASSF1A hypermethylation may be useful prognostic markers in subpopulations. [Table: see text]
Pemetrexed overcomes primary and secondary resistance to erlotinib in human non-small cell lung cancer (NSCLC) cell lines
Authors: Li T. , Ling Y. , Perez-Soler R. 
Published: March 2020

17040 Background: Erlotinib (E) and pemetrexed (P) have proven single agent activity in advanced NSCLC after first-line chemotherapy. The presence of K-Ras or EGFR T790M mutations in NSCLC tumors has been associated with primary or secondary resistance to erlotinib. We have previously reported that sequential administration of P followed by E results in synergistic cytotoxicity in NSCLC cells that contain the wild-type EGFR gene. In this study, we evaluate the cytotoxic effects of E and P in E-resistant human NSCLC cell lines that have either EGFR or K-Ras mutations and validate predictive biomarkers for drug sensitivity. Methods: E-resistant NSCLC cell lines [H1650 (EGFRdel E746-A750), H1975 (EGFRL858R/T790M), and A549 (K-RasG12S)] were exposed to E and P continuously for 72 hrs. Combinations of E and P were compared with E or P alone. Cellular effects assayed include cell survival by cell count and MTT assay, cell cycle distribution and apoptosis by flow cytometry after propidium iodide staining, and expression of different elements of the EGFR axis by immunoblots. The degree of cytotoxic synergism was expressed by the combination index (C.I.). Results: P and E have significant cytotoxic synergism (C.I. <1) in these E-resistant NSCLC cell lines. The cytotoxic synergism is, at least in part, mediated by the inhibitory effect of E on the P-induced activation of EGFR-mediated proliferation and/or survival responses (mainly via the PI3K/AKT pathway). Sensitivity of NSCLC cells to P and E might be predicted by the ratio of (p-EGFR:EGFR) to (p-AKT:AKT), reflecting tumor dependency on the EGFR axis for growth and survival. Conclusions: Together with our previous data, we have demonstrated that the combination of P and E is synergistic in E-resistant NSCLC cell lines that have either a wild-type or mutant EGFR gene, or a mutant K-Ras gene. This combination deserves further evaluation in a clinical trial for the treatment of advanced NSCLC. No significant financial relationships to disclose.
Tumor volume changes on serial imaging with megavoltage CT for non-small cell lung cancer during conformal radiotherapy
Authors: Siker M. L. , Tome W. A. , Mehta M. P. 
Published: March 2020

17041 Background: Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intra-treatment imaging capabilities on radiotherapy devices. This study assesses non-small cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage CT (MVCT) scans. Methods: MVCTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in 5 fractions) and 17 on a dose-per-fraction escalation protocol (57–80.5 Gy in 25 fractions). Four patients were treated palliatively (22–30 Gy in 8–10 fractions). Gross tumor volumes (GTVs) were contoured on serial MVCTs at weekly intervals, by individuals other than the treating physician, to minimize bias. Each patient had 3–25 scans including one at the beginning, mid-way, and one at the end of treatment. Initial GTVs ranged from 1.4 - 565.5 cm3 (mean = 70 cm3). Results: At completion of treatment, no patient demonstrated a complete response (CR). Partial response (PR) defined as a >65% decrease in tumor volume occurred in 3 (12%) and marginal response (MR) defined as a 35 - 65% reduction in tumor volume was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease (SD) defined as <35% reduction or <40% increase in size. The minimum “scorable threshold” for volume discrepancy between scans to account for inter-scan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Conclusions: Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, as there is no way to document histologic tumor clearance and therefore field reductions during radiotherapy cannot be recommended. [Table: see text]
A phase II trial of amrubicin (AMR) for recurrent or refractory small cell lung cancer (SCLC)
Authors: Kudoh S. , Yoshimura N. , Kimura T. , Mitsuoka S. , Hirata K. 
Published: March 2020

17053 Background: AMR, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for previously untreated extensive stage SCLC (Yana et al., Proc. ASCO, 1998, abstr.No.1734). The aim of this trial was to evaluate clinical activity of AMR in the treatment of patients with recurrent or refractory SCLC. Methods: Eligibility criteria were patients having histologically or cytologically proven measurable SCLC, had relapsed after one or two previous systemic chemotherapies, an Eastern Cooperative Oncology Group performance status (PS) of 0–2 and adequate organ function. AMR (40 mg/m2) was administered on days 1–3 every 3 weeks. This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true response rate was >30%, and 5% significance to deny the hypothesis is the true RR was <10%. Results: Between July 2003 and October 2005, 19 patients were enrolled with the following characteristics: male/female, 15/4; median age, 66 years (range 47–78); PS 0/1/2, 0/16/3; sensitive relapse/refractory case, 7/12. Median number of treatment cycles was 3. A total of 59 courses were assessable for safety. The principle toxicity was myelosuppression. Grade 3/4hematologic toxicities were leukopenia (53/32%), neutropenia (32/53%), thrombocytopenia (32/0%) and anemia (42/0%). Non-hematologic toxicities weremild with no grade 4 toxicities; grade 3neutropenic fever (16%), infection (11%), diarrhea (5%), constipation (5%), and AST/ALT (11%) were observed.Responses included 7PR (3 sensitive cases and 4 refractory cases) and 8SD; for an objective RR of 37% (95% CI 16–59%). Conclusions: AMR is well tolerated and promising for treatment of recurrent or refractory SCLC. This regimen warrants further evaluation in a phase III trial. No significant financial relationships to disclose.
Epidermal growth factor receptor mutations and gene amplification in Japanese non-small cell lung cancer patients treated with gefitinib
Authors: Kawaguchi T. , Sasaki H. , Kawahara M. , Takeuchi H. , Iuchi K. , Matsumura A. , Isa S. , Kubo A. , Kitaichi M. , Kasai K. , Takada M. 
Published: March 2020

17063 Background: To evaluate relationship between epidermal growth factor receptor (EGFR) gene status and clinical outcome in patients with non-small-cell lung cancer (NSCLC) treated with gefitinib. Also, to examine an involvement of human papilloma virus (HPV) in EGFR status of these patients. Methods: Twenty seven patients with NSCLC who had relapsed after surgery and received gefitinib were included. Genomic DNA was extracted from the 12 paraffin and the 15 frozen surgical specimens. PCR and sequencing for genotyping were done for EGFR (exon 18–21) and ERBB2 (exon 19–22) and KRAS (exon 1). Gene amplification for EGFR was analyzed by quantitative real-time PCR. HPV was detected by PCR and in-situ PCR. Results: Nine patients (33%) had EGFR mutations; seven patients had deletion mutations in exon 19, one patient had missense mutations (L858R) in exon 21. Two patients had missense mutations (G719S, exon 18 and L838P, exon 21) No mutations were identified in ERBB2 and KRAS. EGFR copy number in the tumor cells ranged from 1.1 to 9.7, and increased EGFR copy numbers (≥3) were observed in six patients ( 22.2%). Two patients (7%) had HPV, and had no mutation and no amplification. Response rate (67% {six of nine patients} v 18% {three of 17 patients}; p = 0.012) was significantly better in patients with EGFR mutations than in patients with wild-type EGFR. Overall survival (median 17 v 9 months) was better in patients with EGFR mutations than in patients with wild-type EGFR. EGFR copy number and presence of HPV were not associated with clinical outcome. Conclusions: EGFR mutations were significantly associated with better clinical outcome in gefitinib treated NSCLC patients. No significant financial relationships to disclose.