bluuebunny/crossref_metadata_2025 huggingface dataset:
The economical impact of subcutaneous amifostine in the Kaiser Permanente health care system
Authors: Wang R. , Hastings J. , Tome M. A.
Published: April 2020

18526

Background: We have previously shown that Subcutaneous amifostine (SQ A) was safe and effective in decreasing the early and late complications of patients (PTS) treated with radiotherapy (RT) or chemoradiotherapy (CRT) for head and neck cancer (HNC). We have further observed that the QOL is better for many PTS treated with SQ A compared with historical controls (HC). Although we believe we cannot put a price on QOL, we hypothesized that the use of SQ A could result in cost savings to our institution because of the observed decrease in treatment-related complications. Methods: From May 2001 to October 2004, we treated 52 consecutive HNC PTS with RT or CRT and daily SQ A. PTS treated in our SQ A protocol received 500 mg of SQ A at least 30 minutes prior to daily RT. In order to be included in our present study, SQ A PTS had to have completed at least 80% of the prescribed SQ A dose. These PTS were then matched with HC based on age, sex, stage, primary site, smoking status, co-morbidiites, and treatment (RT or CRT). Fourteen PTS treated with SQ A (SQ A Group) were successfully matched with HC (Control Group). The entire costs of these 28 PTS to our institution (including the cost of SQ A) was obtained using our Management Accounting and Analysis database. Cost data was obtained at 6 months and 12 months after the completion of treatment. The median follow-up is 18 months (range 12–31). The economical impact of SQ A on xerostomia and dental care were not addressed in this study. Results: Ten PTS received RT and 18 received CRT. At 6 months of follow-up, the total cost for the Control Group was $196,789 versus $211,711 for the SQ A Group (p= 0.59). At 12 months, the total cost in the Control Group and SQ A Group were $287,594 and $275,654 respectively (p = 0.51). Within the SQ A Group, the cost was lowest in PTS who had never smoked or had a remote (>5 years) smoking history (p < 0.01). Conclusions: This study primarily addresses one of SQ A’s cytoprotective properties, mucositis. Our analysis suggests that we were able to offset the cost of SQ A in most PTS because of fewer complications observed in this group. The cost benefit of SQ A appears to be greater at 12 months vs. 6 months after treatment, suggesting continued cytoprotection. QOL is better in the SQ A Group. We plan to continue to follow these PTS and accrue new ones in a prospective fashion.

[Table: see text]
Spirituality, quality of life, and locus of control in a palliative care setting
Authors: Thaker P. H. , Sun C. , Bodurka D. C. , Palmer J. , Pei B. , Willey J. , Bruera E. , Ramondetta L.
Published: April 2020

18529

Background: A patient’s spirituality/religious beliefs have a profound role on how one copes with disease & on quality of life (QOL). Perceptions of control play an important role in coping not only with stressful experiences, but also in health outcomes. Therefore, the primary objective was to determine whether patients’ spirituality/ religiosity correlates with quality of life and locus of control. Methods: As part of a pilot study, pts presenting for initial outpatient evaluation in the Department of Symptom Control & Palliative Care were enrolled and completed self-report measures: Functional Assessment of Chronic Illness Therapy-General (FACT-G), FACT-Spiritual Well-Being Scale (FACT-Sp), Duke University Religion Index (DUREL), Locus of Control (LOC), Herth Hope Scale (HHS), Predestination (PDQ), and Hospital Anxiety & Depression Scale (HADS). LOC contained 3 subscales: perceived occurrence of chance, dependence on powerful others, and internal control. Pearson correlation coefficients were calculated to explore the relationship between measures. The Mann-Whitney t-test was used to compare patient scores. Results: One hundred patients (48 men & 52 women) completed the surveys & 90% reported a Christian affiliation. QOL was positively correlated with FACT-Sp (p ≤ 0.001, r = .614) and the DUREL which measures both external/internal religiosity (p ≤ .01, r = .291). Interestingly, there was no gender difference in spirituality as measured by FACT-Sp; however, by the DUREL women engaged more frequently in private religious activity when compared with men (p < 0.001). Men had more perceived internal control with less emphasis on the occurrence of chance events or dependence on powerful others on LOC (p = 0.07), as well as a positive correlation with controlling of one’s own fate as measured by the PDQ (p = 0.1). Conclusions: As oncologists committed to providing comprehensive care, we need to be receptive to the spiritual needs of our patients since it augments their QOL and to empower them to have a sense of control. Future studies need to further define these complex relationships and to recognize possible gender differences.

No significant financial relationships to disclose.
Effect of zoledronic acid (Zol) compared with placebo on overall disease and bone lesion progression in patients (pts) with bone metastases from certain solid tumors: Stratification by baseline characteristics
Authors: Ucar K. , Tchekmedyian N. S. , Shrina N. , Chen Y. , Xie T. , Hei Y.
Published: April 2020

18541

Background: Zol has been shown to significantly reduce the risk of skeletal complications compared with placebo in pts with bone metastases from a wide range of solid tumors including a delay of bone lesion progression in pts with renal cancer. To assess whether Zol may reduce the risk of overall disease or bone lesion progression in pts with solid tumors other than breast, non-small cell lung, and prostate cancers, we conducted a retrospective analysis of pts enrolled in a large, randomized, controlled trial. Methods: Pts treated with Zol or placebo were retrospectively stratified by baseline characteristics, including Brief Pain Inventory (BPI) composite pain score, time from initial cancer diagnosis to development of bone metastases, and duration of cancer. The relative risk (RR) of disease progression during 25 months on study was analyzed using the Cox proportional hazards model (stratified log rank). Results: Median baseline BPI pain score was 2.75, median time with cancer was 15 months, and median time to development of bone metastases was 8.5 months. In pts with a baseline BPI score ≥ 2.75 (n = 236), Zol treatment significantly reduced the RR of disease progression by 34% (hazard ratio [HR] = 0.657; P = .014) and the RR of bone lesion progression by 32% (HR = 0.680; P = .028) compared with placebo. Additionally, in pts with cancer duration <15 months (n = 193), Zol treatment reduced the RR of disease progression by 45% (HR = 0.547; P = .002) and the RR of bone lesion progression by 40% (HR = 0.605; P = .016) compared with placebo. Similarly, among pts who developed bone metastases < 8.5 months from initial diagnosis of cancer (n = 193), Zol treatment significantly reduced the RR of disease progression by 39% and the RR of bone lesion progression by 48% compared with placebo (HR = 0.611; P = .009 and HR = 0.519; P = .004, respectively). Conclusions: This exploratory analysis suggests that Zol has potential antitumor effects that may reduce the risk of overall disease and bone lesion progression in pts who have higher pain scores and shorter time to development of bone metastases. Prospective studies are needed to confirm this result.

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Patient burden, resource utilization, and treatment outcomes of grade 3/4 chimeric or humanized monoclonal antibody-associated infusion reactions
Authors: Fortner B. V. , Zhu L. , Tsong W. , Burns C. , Schwartzberg L. S.
Published: April 2020

18544

Background: Treatment with chimeric and humanized monoclonal antibodies (MAb) is associated with infusion reactions that may limit their usage. Despite growing use and importance of MAb regimens, there is a dearth of information describing MAb-associated infusion reactions (MAb-IRs) outside of clinical trials. The purpose of this study is to describe the patient burden, resource utilization, and treatment outcomes of grade 3 and 4 chimeric or humanized MAb-IRs in a community sample. Methods: We obtained a convenience sample of charts from 8 US outpatient oncology practices for patients who were treated between Feb 2004 to Dec 2005 with bevacizumab, cetuximab, or rituximab and experienced a grade 3 or 4 MAb-IR during their treatment. Results: Data were abstracted for 30 (n = 3 bevacizumab, 4 cetuximab, 23 rituximab) adult cancer patients who experienced a grade 3 (26, 87%) or grade 4 (4, 13%) MAb-IR. Of these, 63% (19) of patients were male; the mean age was 62 yrs. Twenty (67%) of these patients received premedication before experiencing their grade 3/4 MAb-IR. Twenty (67%) MAb-IRs occurred during the first cycle, 6 (20%) occurred at or beyond cycle 4. The most common MAb-IRs were rigors/chills (13, 43%), bronchospasms (5, 17%), and dyspnea (6, 20%). Grade 4 MAb-IRs were sinus bradycardia (2), severe pain (1), and apnea, seizure, ventricular arrhythmia (1). The consequences of MAb-IRs required increased utilization of resources as shown in the table . Additionally, 9 (30%) required antihistamines, 19 (63%) corticosteroids, 1 (3.3%) an H2 blocker, 3 (10%) an H3 blocker, 4 (13%) epinephrine, 14 (47%) intravenous fluids, 4 (13%) antiemetics, 10 (33%) narcotics, and 17 (57%) oxygen. Conclusions: Grade 3 and 4 chimeric or humanized MAb-IRs result in substantial patient symptom burden, numerous clinical interventions, and changes to subsequent MAb treatment. Further analyses will be required to estimate the direct medical costs and long term consequences of MAb-IRs, and the impact of less severe infusion reactions.

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Presentation of non-small cell lung cancer (NSCLC) in octogenarians
Authors: Velcheti V. , Viswanathan A. , Sainani N. , Grove L. , Suresh R. , Baggstrom M. Q. , Govindan R.
Published: April 2020

18555

Background: Lung cancer is the most common cause of cancer related death in the United States. Non-small cell lung cancer (NSCLC) accounts for over 80% of all new cases of lung cancer. Lung cancer is a disease of the elderly. There are only limited data available on NSCLC in octogenarians. Methods: From our institutional tumor registry, we identified all patients with NSCLC from 1995 to 2002 who were 80 years or older at the time of initial presentation. Data regarding overall stage, histology, date and extent of surgery, and co-morbidities were analyzed. Co-morbidity determination was based on the Adult Co-morbidity Evaluation (ACE-27) test, which ranges from 0 to 3 depending on severity of co-existing conditions. Results: At the time of initial presentation with NSCLC, 236 pts were 80 years or older. The distribution of stages were: stage I in 93 pts (39.5%), stage II in 15 pts (6.5%), stage III in 66 pts (28%) and stage IV in 62 pts (26%). Of the 236 patients the co-morbidity score was known for 223 pts. The distribution of the known scores was: 0, 39 pts (17.5%); 1, 79 pts (35%); 2, 68 pts (30.5%); and 3, 37 pts (17%). Only 35 patients in this cohort underwent surgery. Conclusions: 1. Despite a high proportion (46%) of early stage NSCLC, only a few elderly patients 80 years or older undergo surgical resection, likely because of co-morbid conditions. 2. Innovative non-surgical local modalities of therapy need to be studied in this population.

No significant financial relationships to disclose.
Poor risk assessment in the elderly receiving cloretazine induction for AML or MDS
Authors: Geller R. , Rizzieri D. , Vey N. , O’Brien S. , Johnson B. , Karp J. , Mufti G. , Giles F.
Published: April 2020

18562

Background: Elderly patients (pts) ≥60 years with acute myelogenous leukemia (AML) have lower response rates, and higher morbidity and mortality than younger pts when treated with cytotoxic induction therapy. Common disease-related factors that predict poor response in the elderly are adverse cytogenetics and secondary leukemia (following antecedent hematologic disorder or exposure to chemotherapy). Pt-related factors such as ECOG performance status (PS) and organ dysfunction affect treatment decisions due to poor tolerability and early death. Cloretazine, a novel alkylating agent has significant activity in AML and MDS with a favorable safety profile. A Phase II study of monotherapy induction was conducted in elderly pts with AML or high risk MDS (N = 105, median age 72, range 60–88), with a 31% complete response rate and minimal non-hematologic toxicity. To describe the pts in this study considered “unfit” for 7+3 induction, disease-related and pt-related information was obtained. The Hematopoietic Cell Transplantation Comorbidity Index (Sorrer et al, 2005) (HCT-CI) is a modification of the Charlson Comorbidity Index (Charlson et al.1987), for pts considered for stem cell transplant. Seventeen medical conditions are included with weighted values predicting non-relapse mortality (NRM). Methods: Baseline demographic and pt-related data was obtained from case report forms. In addition to disease-related prognostic indicators, pt-related data was scored by the HCT-CI. Pts were grouped in risk categories for NRM by HCT-CI scores (low = 0, intermediate = 1 or 2; high ≥3). Results: Either or both disease-related poor risk factors were present in 68 pts (65%): 42 pts (40%) had unfavorable cytogenetics and 45 pts (43%) had secondary AML. No pt had favorable cytogenetics. Ninety-four (89%) pts had at least one HCT-CI comorbidity. The most common were cardiac (46%), psychiatric (28%); hepatic (25%) and controlled infection (24%). By HCT-CI, the risk for NRM was low in 10%, intermediate in 32%, and high in 57% of pts. Conclusions: The majority of these elderly pts were poor-risk by disease-related criteria or comorbidities measured by the HCT-CI. This index warrants further testing for determining NRM risk of induction regimens for elderly pts with AML.

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Diagnostics and therapy of Merkel cell carcinoma (MCC) in Germany— Guidelines and reality
Authors: Becker J. C.
Published: April 2020

18564

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly. Due to its low incidence, current guidelines for diagnostic and therapeutic interventions are based on low levels of evidence. Moreover, it is unclear how strictly these guidelines are followed in the management of MCC patients. Methods: A review of MCC patients treated in 15 selected centres of the Dermatologic Cooperative Oncology Group between 1998 and 2004, i.e. when the initial version of national guidelines were valid, identified 150 patients of whom tumor- and treatment-related factors were analyzed for association with recurrence. Results: Initial tumour staging was completed in about 1/3rd of MCC patients in accordance with the guidelines (i.e. ultrasound of the abdomen and the regional lymph nodes, chest X-ray), in 1/3rd using an intensified regimen, and in the remaining patients was incomplete. Staging revealed that 82.5% of the patients were in stage I, 16.1% in stage II and 1.4% in stage III at the time of primary diagnosis of MCC. With respect to initial therapy, the mean surgical excision margin was 1.86 cm (instead of 3 cm) and adjuvant radiation was applied in 40% of the patients. Pathologic staging of the draining nodal basin was performed in 37 patients (24.6%), and 24.2% of these had node-positive disease. 56 patients (37.3%) recurred and the median time to recurrence was 10 months. Local and/or loco-regional recurrence developed in 29 and 33 patients, respectively; in 22 patients distant metastases occurred. While age, gender, tumour diameter and histological type were not significantly correlated with recurrence, therapeutic measures were, i.e. lower surgical margins and lack of adjuvant radiation were associated with an increased recurrence rate. Conclusions: Our study demonstrates that the current guidelines were only partially implemented in the clinical routine. This is particularly worrisome as our data indicate that MCC treatment in accordance to the guidelines results in an improved control of the disease.

No significant financial relationships to disclose.
What are the important health-related quality of life issues in patients diagnosed with indolent lymphoma?
Authors: Mathias S. D. , Cimms T. A. , Colwell H. H. , Lubeck D. P. , Dawson K. L. , Huang J. E.
Published: April 2020

18574

Background: Numerous treatment options are available for indolent lymphoma (IL), including watchful waiting, each with unique, longer term therapeutic and health-related quality of life (HRQL) issues. No validated HRQL questionnaire currently exists to assess the full range of issues that impact an IL patient’s QoL. We sought to fully assess these important areas to inform decisions about the use of a HRQL questionnaire in clinical studies. Methods: Five focus groups (n = 33), supplemented by in-depth one-on-one telephone interviews (n = 19) were conducted with IL patients across the US. Results: A total of 52 IL patients (65% female; mean age 53 years) participated and completed a questionnaire. Mean time since diagnosis was 51 months; 83% had received active treatment since diagnosis. Participants belonged to one of the following treatment categories: Watchful Waiting (17%), Actively Being Treated (50%), and Previously Treated (33%). Patients identified 4 domains and issues (see Table ) common across all patients regardless of treatment category. Treatment-specific issues included lack of control over the disease with watchful waiting vs. taking control, and actively fighting the disease with a specific treatment. Results from the questionnaire will be presented. Conclusions: Further elucidation of these issues is needed to facilitate HRQL evaluation in future studies and better inform treatment decisions.

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[Table: see text]
The efficacy of hyperbaric oxygen therapy (HBOT) in the treatment of pelvic radiation-induced late side effects
Authors: Inbar M. , Grisaru D. , Fishlev G. , Lessing J. , Almog R. , Gall N. , Safra T.
Published: April 2020

18576

Background: The treatment of pelvic malignancies (uterine, cervix, rectum, etc) often include radiation. Radiation-induced late side effects (longer than 3 months) are developed in 5–10% of those patients. We wanted to investigate the efficacy of hyperbaric oxygen therapy (HBOT) in the management of those patients. Methods: Thirteen women were evaluated. The primary cancer sources were: cervix (7), vagina (2), uterus (2), rectum (1) and bladder (1). All patients were treated with a full pelvic dose of radiotherapy. Eight patients also underwent post-radiation surgery (4 post-hysterectomy, 1 post-colectomy, 1 post-vaginectomy, 1 post-cystectomy and 1 post-exanteration). Eleven patients suffered from pelvic pain, 7 from chronic cystitis (including 2 with vesico-vaginal fistulas), 7 had chronic proctitis (including 2 with recto-vaginal fistulas), 3 had long-standing vaginal ulcers, and one presented with a long-standing open skin wound following surgery. All patients underwent imaging studies and biopsies to rule out active malignant disease, and all received HBOT 100% oxygen, at 2 absolute atmospheres, for 90 minutes (2ATA 90 min). Results: The mean patient age was 61 years (range 32–88). The mean time between completion of radiation therapy and onset of symptoms was 32 months (range 4–60). The patients received an average of 27 HBOTs (range 16–40). Twelve patients reported improvement in pelvic pain, bladder and bowel symptoms and decrease in vaginal discharge. One patient developed lung metastasis and another developed pelvic recurrence. No patient reported side effects associated with HBOT. Conclusion: HBOT appears to be safe and effective in the management of pelvic radiation-induced late side effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas.

No significant financial relationships to disclose.
Assessing rectal toxicity in a pilot study using intrarectal amifostine and concurrent radiation
Authors: Simone N. L. , Soule B. P. , Menard C. , Albert P. , Guion P. , Smith S. , Godette D. , Coleman C. N. , Singh A. K.
Published: April 2020

18579

Background: There is evidence that daily intrarectal amifostine can protect rectal mucosa during prostate cancer treatment. Instruments more sensitive than the RTOG score may discriminate small but clinically important reductions in proctitis, however these tools need further evaluation. This study used both the RTOG GI toxicity score and expanded prostate cancer index composite (EPIC), a patient-administered quality of life instrument, to evaluate toxicity. Methods: In this pilot study, patients with localized prostate cancer were given daily amifostine (MedImmune, INC., Gaithersburg, MD) which was placed per rectum 30–45 min before 3D conformal radiation (66–76 Gy in 2 Gy fractions to a volume based on PSA, Gleason score and clinical stage). The first 18 patients enrolled received 1gram of amifostine and the next 12 patients were given 2 grams. Toxicity was assessed at baseline, 5, and 7 weeks during treatment and 3, 6, 12, 18, and 24 months after radiation and amifostine treatment. RTOG grading, an EPIC score and proctoscopic examination were done. The EPIC questionaire is a validated instrument that consists of 50 quality of life questions related to urinary, bowel, sexual and hormonal domains. Two subsets of the bowel domain were used: “bowel function” (BF) targets symptom severity and “bowel bother,” (BB) assesses quality of life subscales. Results: Previously reported results demonstrate a clear trend towards protection from rectal toxicity using 2 gm as compared to a 1 gm amifostine dose. Here, we report that the EPIC-BF and EPIC-BB scores are both highly correlated with the RTOG toxicity score with a pearsons coefficient of 0.98 and 0.97 respectively at a median follow up of 24 mos. There was no significant change in the RTOG GI toxicity score over the course of treatment for either amifostine dose group. There was a statistically significant decrease in EPIC-BF score at 7 weeks (p = 0.04) and the EPIC-BB score showed a trend toward improvement (p = 0.07) at the same time point. The EPIC scores at all other time points were not statistically different from baseline. Conclusions: The EPIC score may be a more sensitive measure to detect acute toxicity associated with prostate cancer treatment but needs further investigation in the acute setting.

No significant financial relationships to disclose.
Loading dose ibandronate in rapid pain management of metastatic bone disease (MBD)
Authors: Pendharkar D. , Goyal H.
Published: April 2020

18580

Background: MBD is common complication in many malignancies. Pain is common presentation of MBD. It is major cause of morbidity, major determinant of quality of life and an important reason for emergency medical referral. Acute pain necessitates emergency pain relief measures. Besides conventional radiation and pain killers, bisphosphonates are indicated in MBD. They contribute towards pain relief. Literature suggests that ibandronate may be effective in acute pain relief. The aim of this study was to study the efficacy of ibandronate in acute pain relief. This should obviate the need for local radiation and or increase in dose of pain killers. Methods: Patients with severe pain were given inj. ibandronate 6 mg iv over 2 hrs for 3 consecutive days. Pain was assessed by direct questioning the patient . Pain was assessed on first four days and after four weeks. Patients were continued with single dose ibandronate once in a month there after. Response was assessed as excellent-more than 90% disappearance of pain, good -more than 50% but less than 90%, satisfactory -between 25– 50% and no response-if less than 25%. Results: A total 9 patients were treated using loading dose ibandronate. There were 4 patients of carcinoma prostate, 3- carcinoma lung, 2- multiple myeloma. All had intolerable bone pain and this was the main reason for this particular admission to hospital. All patients had shown satisfactory response on day 2. On day three 6/9 patients shown a good response. On day four, 4/9 patients shown an excellent response, 4/9 -good response and 1/9 satisfactory response. At the end of four weeks 6/9 patients shown an excellent response, 2/9 good response and 1/9 satisfactory response. The pain response improved over four weeks. On questioning, all patients communicated there strong willingness to continue the same treatment. Conclusion: Loading dose, consecutive three day administration of ibandronate appears to be the ideal strategy for rapid pain relief in patients with MBD. There is an excellent response to such an intervention. In compromised patients with reduced bone marrow reserves this may form the standard of care. Broader data acquisition is warranted.

No significant financial relationships to disclose.
Comparison of the use of cefepime (cefp) monotherapy vs. piperacillin/tazobactam (pip/tazo) plus a fluroquinolone or aminoglycoside for the empiric treatment of febrile neutropenia (FN)
Authors: Gordon S. , Stuntebeck E. , Collins C. , Streetman D. , Ward A. , Erba H.
Published: April 2020

18581

Background: Practice guidelines for empiric therapy of FN were created and implemented at our institution in January 2003, prior to which empiric therapy often included the use of cefp. These guidelines recommend the combination of pip/tazo with gentamicin or levofloxacin for most patients. This retrospective chart review compared the efficacy of pip/tazo combination therapy versus historical controls treated with cefp. Methods: 183 patients met eligibility criteria. 87 patients were treated with pip/tazo, with 92% receiving levofloxacin as the second agent. 75 patients received cefp, 16 of which initially also received either a fluoroquinolone or an aminoglycoside. Endpoints included a difference in the addition of vancomycin and antifungals, incidence of breakthrough infections, trends in antibiotic resistance, and survival until discharge. Groups were compared using chi-square or Student’s t-test as appropriate. Results: The two groups were not significantly different in any measured demographic or clinical characteristic. No statistical difference was found between groups for the addition of vancomycin (cefp 43%, pip/tazo 41%; p = 0.9898) or antifungals (cefp 45%, pip/tazo 51%; p = 0.1346). The incidence of breakthrough infections was comparable (cefp 25%, pip/tazo 26%; p = 0.7461), and microorganism eradication rates were not different between groups (cefp 48%, pip/tazo 54%; p = 0.41). However, of those who developed a breakthrough infection, survival was lower in the cefp group (37% vs. 63%; p = 0.0389). Additionally, the rate of overall survival to discharge was significantly lower in patients initially treated with cefp (83% vs. 94%; p = 0.0193). The antibiograms of the hematology floors were compared for the 2 years prior to and after implementation of our FN guidelines; no change in susceptibilities was observed. Conclusions: From these results, we conclude that pip/tazo combination therapy is a reasonable alternative to cefp for empiric treatment of FN.

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A prospective, observational study of the effectiveness, safety and impact on quality of life (QoL) of a weekly fixed dose of darbepoetin alfa (DA) for the treatment of chemotherapy-induced anemia (CIA) in patients (pts) with non-myeloid malignancies
Authors: Mel J. R. , Salar A. , Rodríguez C. A. , Alegre A. , González A. , Cassinello J. , Montesinos J. , Gasquet J. A. , Sánchez J. , Saigí E.
Published: April 2020

18588

Background: CIA in cancer pts results in fatigue and reduction of QoL. DA is a unique erythropoiesis-stimulating agent (ESA) effective for the treatment of CIA when administered weekly (QW), every 2 weeks (wks, Q2W) or every 3 wks(Q3W).Fixed dosing of DA is routinely used in clinical practice, but little data are available on its patterns of use and effectiveness. Methods: Prospective, observational, multicenter study performed in 30 centres across Spain. Eligible pts: ≥18 yrs, anemic(Hb ≤11 g/dL), with non-myeloid malignancies, and scheduled to receive ≥12 wks of chemotherapy. Data were collected from pts starting treatment with DA 150mcgQW for a maximum of 16 wks (dose to be doubled if Hb increased <1 g/dL after 4 wks). Primary endpoint: hematopoietic response (Hb increase ≥2 g/dL or Hb ≥12 g/dL without transfusions in the previous 28 days). Secondary endpoints include QoL measured by FACT-F score and safety. QoL was evaluated by changes in FACT-F score from baseline to 6 wks (sc0-sc6), 12 wks (sc0 - sc12) and to the end of treatment (EOT) (sc0-sc16). Results: A total of 293 pts were recruited. Most pts were women (56.4%), median age: 64.9 yrs (range: 20.6–88.4), median weight: 67.0 Kg (range: 40.5–115.0) with lymphoproliferative malignancies (44.3%) and solid tumours (55.7%). Stage III/IV: 75.6%. Most (83.7%) pts had baseline Hb between 9–11 g/dL; 16.3% with Hb <9 g/dL. DA was administered for a median of 15.0 wks (range: 1–16). At wk 5, 21% pts had dose doubled to 300 mcg QW. Hematopoietic response: 63.8% (95% CI: 58.1; 69.4). Proportion of pts transfused from wk 5 to EOT: 12%, median: 2 units (range 1–3). DA was well-tolerated with only 6 pts experiencing adverse events considered related to the study drug (thromboembolic events, 3pts (1.03%)). Changes in FACT-F score showed significant improvement in sc0-sc6 (mean difference: −1.73, p = 0.0083), in sc0-sc12 (−1.98, p = 0.0088) and particularly in sc0-sc16 (−3.75, p < 0.001). Conclusions: Fixed dose of DA is an effective and well-tolerated treatment for CIA in pts with non-myeloid malignancies. DA significantly improved health-related quality of life in this clinical practice-based study.

[Table: see text]
The safety profile of eltrombopag, a novel oral platelet growth factor, in thrombocytopenic patients and healthy subjects
Authors: Provan D. , Saleh M. , Goodison S. , Rafi R. , Stone N. , Hamilton J. M. , Hassani H. , Mayer B. , Uhl J. , Jenkins J.
Published: April 2020

18596

Background: Eltrombopag (SB-497115) is an oral, non-peptide, small molecule, thrombopoietin receptor agonist being tested as a potential treatment for thrombocytopenia. Eltrombopag has been shown to increase platelet counts in both healthy subjects and thrombocytopenic patients. Methods: Safety and tolerability data for eltrombopag (3–75 mg for up to 6 weeks) is presented from randomized, placebo-controlled, parallel group clinical trials involving 115 healthy subjects and 104 immune thrombocytopenic purpura (ITP) patients. Safety and tolerability endpoints involved assessment of adverse events (AE) and clinical laboratory parameters, including ECGs and platelet function. Results: In 3 Phase I trials, 98 healthy males received active eltrombopag QD for up to 10 days at 3–75 mg. In the Phase II dose ranging study, 78 chronic ITP patients (28 male/50 female) received active eltrombopag QD for 6 weeks at doses of 30–75 mg. There was no apparent relationship between active and control arms, the dose of eltrombopag and the incidence or severity of AEs, changes in laboratory values, platelet function or cardiac parameters in any of the studies. There were no serious adverse events (SAEs) reported by subjects in the 3 Phase I studies. 5 SAEs were reported in 1 patient in the ITP study that were considered by the investigator as possibly associated with administration of 50 mg eltrombopag. No SAEs were related to 30 mg or 75 mg eltrombopag, and 2 SAEs in 2 patients were related to placebo. Conclusions: There was no apparent relationship between eltrombopag dose and safety endpoints in these studies. These encouraging safety and tolerability data support the further testing of eltrombopag in phase II and III studies involving patients with ITP and chronic liver disease, and cancer patients receiving thrombocytopenic chemotherapy.

[Table: see text]
Pulmonary lymphangitis and cancer: Prospective series of 37 patients in palliative care
Authors: Dettino A. A. , Negri E. M. , Pagano T.
Published: April 2020

18600

Background: Lymphangitis of the lungs is an uncommon type of metastasis, mainly in breast, lung and gastric cancers, and has major impact in quality of life and an unfavorable prognosis. Survival is very poor: 50% in 3 and 15% in 6 months. Our objective was to evaluate prospectively quality of life in cancer patients with pulmonary lymphangitis, under palliative care. Methods: Patients with pulmonary lymphangitis, diagnosed either by lung biopsy (major criteria) or 3 minor criteria (cyto or histotologically proven cancer, clinical picture and image exam) were followed in 3 tertiary services, in a cohort series study. Primary end point was quality of life (QoL), measured with questionnaires in the beginning of the study and monthly afterwards (Saint George Respiratory Questionnaire -SGRQ- and Medical Outcomes Study 36-Item Short-Form Health Survey -SF36). Clinical and complementary aspects were also followed, in addition to treatment and outcome. Results: Thirty-seven patients were included from Aug/2004 to Jan/2006 - 23 female and 14 male; age from 41 to 84 (mean: 62) years. Primary tumors were: lung (20), breast (11), esophagus (2), pancreas, rectum and bone. Of those patients, 33 were able to respond QoL questionnaires in the beginning of follow-up and monthly thereafter. Median follow-up was of one month (range: 0–13); at the moment, 9 patients are still alive. Median survival was 2.5 months (range: 0,1–33), with 38% with a survival of at least 6 months. In general, QoL was poor, but improved after palliative care. Notice that values get higher as QoL improves in SF-36; however, they get lower as QoL improves in SGRQ - values were 61.5, 50.5, 61.7, and 47.5% for SGRQ and 38.1, 32.1, 32.8, 61.6 for SF36 in 0, 1, 3 and 6 months, respectively. Palliative care included: corticosteroids (65%), oxygen (51%), opioids (51%), diuretics (47%), inhalations with beta2-agonists and/or ipatropium (57%), chemo and/or hormonotherapy (51%), physical therapy (43%), antidepressants and benzodiazepines (37% each), thoracocentesis (35%), and blood transfusions. Conclusions: Even though QoL is poor and survival is short for patients with cancer lymphangitis in lungs, some improvement is possible with active palliative care.

No significant financial relationships to disclose.
Linac-stereotactic radiosurgery (LSRS) in the management of trigeminal neuralgia
Authors: Gurley S. , Mark R. , Anderson P. J. , Neumann T. , Nair M.
Published: April 2020

18603

Background: Stereotactic Radiosurgery (SRS) with the Gamma Knife (GK) has been used successfully in the treatment of Trigeminal Neuralgia (TN). Results have been comparable to open surgery. There have been few reports with the use of LSRS in the management of TN. We report our updated results with LSRS in the treatment of TN. Methods: Between 2000 and 2006, 37 patients with medically refractory TN were treated with LSRS. Prior neurosurgical intervention had been performed in 28 patients. Ten patients had one procedure, 10 patients two, and 3 patients three interventions. All patients had typical TN. LSRS was given to the cranial nerve V entry root zone into the brainstem. Targeting was defined by CT and MRI Scans, and CT Cisternogram, utilizing axial, coronal, and sagittal images. Treatment planning was accomplished thru the Radionics Treatment Planning System. The dose was 87 Gy to Dm, in one fraction using the 5 mm collimator and 6 arcs with the 20% Isodose line just touching the brainstem. This dosimetry is similar to Gamma Knife. The dose rate was 400 MU/min. Average Arc length was 130 degrees. Response to treatment was defined as excellent (no pain, off analgesics), good (no pain, with analgesics), and poor (continued pain despite analgesics). Results: With a median follow-up of 40 months (range 6–72 months), 73% (27/37) of patients have reported an excellent or good result after LSRS. One patient has sustained permanent ipsilateral facial numbness. Conclusions: LSRS offers comparable results to Gamma Knife SRS, with respect to both pain relief and complications, in the management of TN.

No significant financial relationships to disclose.
Effect of melanoma on immune function in regional lymph nodes (LN)
Authors: Negin B. P. , Panka D. , Wang W. , Tawa N. , Mullen J. , Tahan S. , Mandato L. , Polivy A. , Mier J. , Atkins M.
Published: April 2020

8000

Background: Metastatic melanoma is associated with various measures of systemic and local immune suppression. We hypothesized that immune suppression in the regional LN basin exists and may facilitate melanoma progression. Methods: We collected portions of regional LNs from tumor uninvolved sentinel LNs (USLN) (remote from primary melanoma removal) and from macroscopically involved nodes (TILN) from therapeutic node dissections in successive melanoma patients. Lymphocytes were extracted, stained using surface and internal antibodies to T cell receptor zeta chain (TCRζ), T regulatory cells (CD4+CD25+ Fox 3p+) (Tregs) and tumor associated myeloid cells (CD11b+ CD14- CD15+) (TAMC), and analyzed via flow cytometer. Results from USLN specimens were compared with TILN. Results: 30 LNs (14 USLN/16 TILN) from 30 patients were evaluated. Median age of patients was 48 years (range 30–83); 20 were male. USLN patients were stage IB (12) or IIA (2); TILN patients were stage IIIB (5), IIIC (5), and IV (6). 7 patients with TILN and none with USLN have progressed. TILN had significantly less TCRζ chain expression than SLN (62% vs. 85%; p = 0.0001). This amounts to a localized decrease of 23% of TCRζ expression (95% CI 13%; 34%). No significant relationship between lymph node involvement and Treg or TAMC was documented. Conclusion: Regional LN involvement with melanoma is associated with a significant reduction in lymphocyte TCRζ expression indicating immune suppression. The mechanism for this is uncertain, but does not appear to be related to changes in Tregs or TAMC (arginase producing cells). We plan to further investigate TCRζ expression in microscopically involved SLNs and SLNs removed at time of primary excision to see if immune changes precede macroscopic tumor involvement. Supported by Harvard Skin SPORE Project 5 and Immune Monitoring Core P50CA93683–01

No significant financial relationships to disclose.
A phase III randomized trial of adjuvant biochemotherapy (BC) versus interferon-α-2b (IFN) in patients (pts) with high risk for melanoma recurrence
Authors: Kim K. B. , Legha S. S. , Gonzalez R. , Anderson C. , Papadopoulos N. E. , Eton O. , Plager C. , Roe A. , Liu P. , Bedikian A. Y.
Published: April 2020

8003

Background: High-dose IFN (HDI) is associated with significant toxicity, and its clinical benefit as an adjuvant therapy for melanoma has been often debated. BC is associated with higher response rates than other regimens, but it has never been tested in an adjuvant setting. Methods: We conducted a prospective randomized phase III study comparing the clinical benefit of IFN and BC in pts who had undergone lymphadenectomy within 56 days for melanoma metastatic to regional lymph nodes. Pts were randomized to receive BC (Cisplatin 20 mg/m2 IV [d1–4]; Vinblastine 1.5 mg/m2 IV [d1–4]; DTIC 800 mg/m2 IV [d1]; IFN 5 MU/m2 SQ [d1–5]; IL-2 9 MU/m2 continuous IV infusion [d1–4] every 3 wks for 4 courses) or IFN, and those who were randomized to IFN were further randomized to either HDI (20 MU/m2 IV for 5 d/week for 4 wks and 10 MU/m2 SQ 3 times a wk for 48 wks) or intermediate-dose IFN (IDI) (10 MU/m2 SQ 3 times a wk for 1 year). The primary end points were overall survival (OS) and relapse-free survival (RFS). Using 80% power and 5% significance level, 200 pts would be required to detect the difference in median RFS of 18 vs. 36 months and in OS of 40 vs. 80 months between IFN and BC groups. Results: An interim analysis was performed because of slow accrual. 138 pts were enrolled between 1995 and 2003, with 71, 33 and 33 in the BC, HDI and IDI group, respectively. There were no significant differences in both RFS and OS between HDI and IDI groups. With median follow up of 49.3 months, neither the BC or IFN had reached the median RFS and OS. Log-rank test was used to compare RFS (p=0.96) and OS (p=0.52) between 2 groups. RFS and OS data are presented below. Pts in the BC arm had more grade 3–4 fatigue, nausea, anorexia, capillary leak syndrome, diarrhea and myelosuppression. Conclusions: There were no significant differences in both OS and RFS between the BC and IFN groups. This interim analysis supports terminating this trial before achieving the specified target for patient accrual. Supported in part by Schering-Plough.

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XIAP is highly expressed in melanoma and is associated with chemotherapy resistance
Authors: Kluger H. M. , McCarthy M. , Alvero A. , Divito K. , Camp R. , Rimm D. , Mor G.
Published: April 2020

8008

Background: Chemoresistance is a major problem in treating melanoma. The X-linked inhibitor of apoptosis (XIAP) is associated with chemoresistance in other cancers. Here we characterize XIAP expression in primary and metastatic melanomas and determine whether XIAP plays a role in chemoresistance. We report differential expression of XIAP between primary and metastatic melanomas and benign nevi. We demonstrate that inhibition of XIAP expression by Phenoxodiol can reverse chemoresistance. Methods: We employed tissue microarrays containing specimens from 548 melanoma patients and 540 benign nevi. XIAP expression was evaluated by an automated method for in situ quantitative analysis of protein levels (AQUA). We use S100 to define pixels as melanoma (tumor mask) within the array spot, and measure intensity of XIAP expression using Cy5 conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathological variables. Cell viability after exposure to Carboplatin and Phenoxodiol was determined in 3 melanoma cell strains using the CellTiter 96 Assay. Apoptosis was measured using the Caspase-3/7 GloTM Assay, and levels of XIAP and Caspase 2 were assessed by Western blots. Results: XIAP expression was significantly higher in melanomas than in nevi (P<0.0001), and higher in metastatic than in primary specimens (P<0.0001). All three melanoma cell strains examined were highly resistant to Carboplatin, and moderately resistant to Phenoxodiol. Pre-treatment with Phenoxodiol prior to Carboplatin induced a significant decrease in XIAP expression, which correlated with remarkable sensitization to Carboplatin. Conclusions: XIAP expression is higher in malignant melanocytes than in their benign counterparts. Expression is higher in early stage disease specimens than in metastatic specimens, suggesting an association with disease aggression. Phenoxodiol is a well tolerated drug, and has been shown to inhibit XIAP expression in ovarian cancer. Here we demonstrate that melanoma is resistant to Carboplatin, possibly due to XIAP expression. In vitro inhibition of XIAP by Phenoxodiol sensitizes melanoma cells to Carboplatin. This drug combination warrants further investigation as a therapeutic approach for metastatic melanoma.

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A phase II pilot trial of low dose, continuous infusion, or “metronomic”, paclitaxel and oral celecoxib in patients with metastatic melanoma
Authors: McDermott D. F. , Cho D. C. , Merchan J. R. , Bhatt R. S. , Seery V. , Mosher J. L. , Farquhar M. B. , Mier J. W. , Atkins M. B. , Sukhatme V. P.
Published: April 2020

8010

Background: In patients (pts) with metastatic melanoma (MM), tumor angiogenesis has been associated with tumor progression and survival (Ugurel et al, JCO 19:577). Microtubule and cyclooxygenase (COX)-2 inhibitors, both alone and in combination, have been shown to have inhibitory effects on endothelial cells and tumor angiogenesis both in vitro and in vivo (Merchan et al, Int J Ca 113:490. Jones et al, Nat Med 5:1418). We tested the safety and efficacy of a regimen involving low dose, continuous infusion (CIV) paclitaxel and oral celecoxib in pts with MM. Methods: Pts received paclitaxel 10mg/m2 for 96 hours weekly by CIV and Celecoxib 400 mg po/bid. Systemic tumor response was assessed at 6 wk intervals (1 cycle (C)). Pts without unacceptable toxicity or clinically significant disease progression (PD) received additional cycles. Pts exhibiting PD after C 2 relative to end of C 1 were removed from study. Pts on anticoagulants, with recent MI or untreated brain metastases were ineligible. Results: 20 pts (12 M/ 8 F), median age 55 (range 44–65), ECOG PS 0/1/2 (5/13/2), M1a/M1b/M1c: 1/1/18 (90%), and prior systemic therapy regimens 0/1/2/3+: 1/7/5/7 were enrolled in the protocol. Sites of systemic disease included: lung (13 pts), LN (14), soft tissue (13), liver (9), bone (4), brain (6), other (11). 3 pts came of study prior to treatment with rapid disease progression. Treatment related grade 3–4 toxicities included line related (LR) bacteremia (3 pts), LR DVT (3 pts), LR PE (3). There were no grade 3–4 toxicities attributed to paclitaxel or celecoxib. No pt exhibited a major tumor response; 6/20 (30%) pts had stable disease for 17, 18, 18, 18+, 30+, 60 wks. Median TTP was 6 wks (range 3- 60); median overall survival was 6 months (range 1–29). Conclusions: Low-dose, CIV paclitaxel and oral celecoxib leads to disease stabilization in a significant portion of previously treated pts with MM. This suggests a role for combination anti-angiogenic therapy in MM. The incidence of LR toxicities indicates that alternative microtubule inhibitors, such as oral taxanes, should be considered in combination with COX-2 inhibitors for future studies. Results of biomarker studies will be presented at the meeting. Supported by Pfizer Inc. and NIH R21 CA097730.

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Temozolomide (TMZ) in combination with pegylated interferon alfa-2b for stage IV metastatic melanoma: A multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)
Authors: Spieth K. , Dummer R. , Leiter U. , Garbe C. , Gille J. , Becker J. C. , Hauschild A. , Tilgen W. , Kaufmann R. , Schadendorf D.
Published: April 2020

8017

Background: Modifying the pharmacokinetic profile of IFN alfa-2b (PegIFN) may improve its activity and tolerability. Specifically, the conjugation of recombinant IFN alfa-2b with a 12 kDa polyethylene glycol (Peg) chain results in a prolonged half-life and has been previously demonstrated to increase efficacy in hepatitis C patients compared to nonpegylated IFNs. We therefore evaluated the combination of TMZ with PegIFN in stage IV metastatic melanoma. Methods: This open-label, phase II study was conducted by the DeCOG at 10 study sites. Eligible pts were between 18 and 75 yrs, had a histologically confirmed diagnosis of metastatic melanoma (stage IV AJCC), no brain metastases and no prior chemotherapy. Pts were required to have a Karnofsky score of > 60% as well as adequate renal, liver and bone marrow function. Informed consent from all participants and approval from the corresponding ethic committees was provided. The regimen (28 d cycles) consisted of TMZ (200 mg/m2 d 1–5) in combination with PegIFN (100 μg sc d 1, 8, 15 and 21). Patients received 2 cycles before reevaluation (WHO response criteria). OR and OS were primary and TTP and toxicity were secondary endpoints of the trial. Results: 124 pts were accrued between 10/02 and 7/04, 8 pts were ineligible or withdrew consent, and thus 116 pts were treated per protocol. At the time of data analysis, 81.0% of pts had died from melanoma and median follow up time was 9.4 months. OR was 18.1% (2 CR, 1.7%; 16 PR; 16.4%); 25.0% of pts presented with SD and 54.3 % progressed (2.6% not evaluable). Median TTP was 2.8 months, median OS 9.0 months (95% CI 7,4;10,6). Grade (gr) 3/4 leucopenia occurred in 22.8% and gr 3/4 thrombocytopenia in 20.3%. Gr 1/2 nausea and emesis experienced 37.5% of the pts; severe nausea (gr 3/4) was rare (1.7%). Liver enzyme elevation occurred in 30.5 % (26.3% gr 1/2; 4.2% gr 3). Conclusions: Combination therapy with TMZ and pegylated interferon alfa-2b constitutes a manageable treatment option in the outpatient setting for advanced metastatic melanoma. Its primary advantage is an increased patient convenience as a result of oral intake of TMZ and once weekly application of PegIFN.

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