tbuckley/cabot-search huggingface dataset:
The addition of prednisone (Pr) to the combination of docetaxel (T) and perifosine (P) decreases the severity of gastrointestinal (GI) toxicity
Authors: B. Bernhardt, J. J. Nemunaitis, B. Ebrahimi, A. Cervera, R. Birch, D. A. Richards, G. B. Smith, J. P. Allerton, I. C. Henderson
Journal: Journal of Clinical Oncology (2006)

13142 Background: Miltefosine (M) is an alkophosholipid with activity as a topical treatment for cutaneous breast cancer lesions. Severe GI toxicity limited its development as a systemic anticancer treatment. P is an equipotent derivative of M with less GI toxicity, but nausea,(N), vomiting (V) &amp; diarrhea (D) are still dose limiting. Methods: This phase 1 study evaluated whether the addition of Pr would enhance the tolerability of P &amp; T in combination. Twenty-five patients (pts) were enrolled. The dose of T was 75 mg/m 2 on day 8 of a 21 day cycle and half of the pts were randomized to also receive Pr, 5 mg bid. 50 mg of P was given orally 1, 2 or 3 times a day in successive cohorts on days 1 - 14 of each cycle. Results: Disease sites included lung 9, prostate 7, pancreas 3, ovary 2, breast 1 and other 4. The median age was 63 (range 41 - 80). 18 pts were male &amp; median ECOG performance status was 1 (range 0–2). 22 pts had received a median of 2 prior chemotherapy regimens, 15 a prior taxane and 16 prior radiotherapy. Forty-two cycles of T+P were given without Pr (median 3 &amp; range 1 - 18 per pt) and 84 cycles were given with Pr (median 4.5 cycles &amp; range 1 - 17 per pt). The percentage of pts experiencing various grades (Gr) of N, V &amp; D without and with prednisone are shown in the table below: Five of 12 pts not receiving Pr had gr 2 or 3 toxicities compared to 1 of 13 given Pr. (p&lt;0.05) There were 7 pts evaluable for response not receiving Pr of whom 2 patients with prostate cancer had stable disease for 4+ and 10+ months. There were 9 evaluable pts receiving Pr; 3 partial responses (1 lung &amp; 2, prostate pts) were seen and 1 prostate cancer was stable for 10 months. Patients given prednisone increased their average time on treatment by 50%, and this might be the reason that more responses were seen in this group. Conclusions: These data show that Pr decreases the severity of GI toxicity seen with T &amp; P together and provide a rationale for further studies evaluating the effects of Pr on the toxicities of P either alone or in combination with other drugs. [Table: see text] [Table: see text]
Activation of Akt correlates with resistance to endocrine therapy for metastatic breast cancer
Authors: E. Tokunaga, Y. Kimura, E. Oki, K. Mashino, A. Kataoka, S. Ohno, Y. Kakeji, H. Baba, Y. Maehara
Journal: Journal of Clinical Oncology (2005)

9500 Background: In breast cancer, the PI3K/Akt pathway can be activated by membrane receptors, including the HER family of growth factor receptors. Akt promotes breast cancer cell survival and it has been suggested that Akt promotes resistance to chemotherapy, trastuzumab, and tamoxifen. This suggests that targeting the PI3K/Akt pathway may increase the therapeutic efficacy of breast cancer therapy. Methods: 1. We analyzed the activation of Akt by immunohistochemical analyses of expression of phosphorylated Akt (pAkt) in breast cancer, from 253 patients who underwent surgery at our department. We also evaluated the expression of HER2, estrogen receptor (ER), and progesterone receptor (PR) by immunohistochemistry. 2. Thirty-five patients with metastatic breast cancer received 44 endocrine therapies. We evaluated the correlation of pAkt expression with effect of the endocrine therapy in those patients. Results: 1. Expression of pAkt was positive in 85 samples (33.6%). Expression of pAkt significantly correlated with overexpression of HER2 (p<0.0001) and inversely correlated with PR expression (p<0.05). There was no correlation between of ER expression and pAkt expression. 2. Endocrine therapies for recurrent cases were as follows; Aromatase inhibitor for 21 cases, LH-RH agonist for 7 cases, SERM for 15 cases and MPA for one case. We defined CR, PR, and SD as effective and PD as not effective. High expression of pAkt and HER2 in primary tumor well correlated with resistance of endocrine therapy (p=0.0045 and p=0.0229) (Table). Conclusion: Activation of Akt correlated with HER2 overexpression and inversely correlated with PR expression. Activation of Akt correlated with endocrine therapies for metastatic breast cancer. This study suggets that pAkt may be used as a predictor of resistance of endocrine therapy for breast cancer and that inhibition of Akt may increase the efficacy of endocrine therapy. No significant financial relationships to disclose.
Can telehealth offer care delivery alternatives for oncology patients?
Authors: B. H. Weinerman, A. Kazanjian, J. den Duyf, M. Loyola, M. L. Fyfe, V. Ashworth, J. Stephen, N. Macpherson Dr
Journal: Journal of Clinical Oncology (2008)

17519 Background: Telehealth is a means of delivering consultation in underserved areas.60% of our referrals come from communities outside Victoria. Objectives were to assess to compare a) patient and b) provider satisfaction with face-to-face(ff) oncology consultation and teleoncologic (th) consultation. Methods: Seventy-one encounters with 71 patients and occurred in the ff and126 encounters involving 109 patients in the th. All patients and physicians filled out standardized questionnaires about both types of encounters. Results: 8 of 20 oncologists took part in the th trial. There were 63 new patients and 8 follow-ups in the ff and 62 follow-ups and 8 new patients in the th (not all data in from video). To all questions the mean response from Patients was over 4.9 (out of 5) in the th group (identical to ff). There was no difference in responses in terms of sex, age (in decades), the 3 main cancer types (colorectal, lung and breast), or the remote location. If physicians saw patients ff they often felt a physical exam was needed but not if they saw the patients via th. Physicians rated all the questions on ff exams at 4.9, slightly higher then the 4.85 the th. Nonetheless, they rated the question “nothing important was missing -an average of 4.85 and “I would do it again” at a mean of 4.88. Patients stated that there median cost of travel was $50;meal costs $40; and parking was $4.43. Ten patients reported accommodation costs of an average of $103.40 and some reported other costs. About 20% of patients reported a cost of the visit at $200. Eighty-two patients reported a total of 27510 kilometres traveled, and about 7571 kg/km of greenhouse gases would have been saved (kg/km × 0.2752006). Conclusions: Patients overwhelming liked the th experience, felt that intimacy and contact with the physician could be established and saved money and gas emissions. Physicians were less enthusiastic. Only 8 of 20 oncologists participated in the th, and they overwhelmingly chose to do follow up visits through th. Although telehealth meets an unmet need and patients like it, barriers still remain despite costs, time and money meant to patients. No significant financial relationships to disclose.
Outcome in 41 patients with late relapse germ cell tumors (GCT) treated with high-dose chemotherapy (HDCT)
Authors: A. Lorch, O. Rick, J. T. Hartmann, B. Metzner, A. Glasmacher, W. Berdel, R. Schirren, C. Bokemeyer, J. Beyer
Journal: Journal of Clinical Oncology (2007)

5086 Background: The management of patients (pts) with late-relapse GCT and unresectable tumors or very high tumor markers is controversial. Methods: A total of 41 late-relapse pts were identified among a group of 216 pts with refractory or relapsed GCT who were treated in an open, prospective, randomized, multicenter phase III trial. Late relapse was defined as any relapse occurring more than 2 years after completion of initial chemotherapy for GCT. Treatment consisted of either one cycle cisplatin 100 mg/m 2 , etoposide 375 mg/m 2 and ifosfamide 6 g/m 2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m 2 and etoposide 1,500 mg/m 2 (CE, arm A) or of three cycles of VIP plus one cycle high-dose carboplatin 2,200 mg/m 2 , etoposide 1,800 mg/m 2 and cyclophosphamide 6,400 mg/m 2 (CEC, arm B). Each HDCT was followed by reinfusion of autologous peripheral blood progenitor cells. Results: Overall 20 pts with late-relapse GCT received sequential HDCT and 21 pts single HDCT when the study was stopped due to excess treatment-related mortality in arm B; median time to late relapse in 41 pts was 5.4 years (range 2–18 years); 8/41 (20%) pts had seminomatous GCT, 32/41 (78%) pts had nonseminomatous GCT with or without teratoma; one pt (2%) had unknown GCT histology. No non-GCT histologies were included. The retroperitonum was most commonly involved in 30/41 (73%) pts. 29 of 41 (71%) pts had unresectable, multifocal disease and 20/41 (49%) pts also had very high markers. A complete remission to chemotherapy alone was achieved in 4/41 (10%) pts, 16/41 (39%) pts achieved a partial remission with negative tumor markers. The remaining 21/41 (51%) either had a transient or no response despite HDCT. Residual tumor resections were performed in 17/41 (41%) pts. Residual tumor histology was viable cancer in 8/17 (47%) pts, teratoma in 4/17 (24%) pts and necrosis in 5/17 (25%) pts. With a minimum follow-up of 1 year and a median follow-up of 3 years the estimated Kaplan-Meier rates are 17%, 20% and 32% for event-free, progression-free and overall survival. Conclusion: Treatment outcome after HDCT was inferior in late-relapse pts compared to the group of pts who relapsed within less than 2 years. Despite an overall poor prognosis, HDCT can still result in long-term remissions in selected late-relapse GCT pts. No significant financial relationships to disclose.
Inflammatory cytokines and toxic effects of oxaliplatin-based chemotherapy in patients with colorectal cancer.
Authors: X. S. Wang, C. S. Cleeland, V. E. Johnson, J. M. Reuben, D. R. Fogelman, M. Malekifar, K. E. Liao, P. Liu, E. N. Cohen, K. R. Gilmore, C. Eng
Journal: Journal of Clinical Oncology (2011)

9094 Background: Oxaliplatin-based chemotherapy (FOLFOX or FOLFIRI), a standard first-line chemotherapy for patients with colorectal cancer (CRC), is not only associated with dose-limiting toxicity, such as cumulative sensory neuropathy, but also with debilitating general symptom burden, such as fatigue, pain, and distress. The lack of effective mechanism-driven patient care to prevent or treat symptoms and improve adherence to therapy is of great concern. This prospective study investigated the potential inflammation-related mechanism underlying these treatment-related toxic effects. Methods: Patients with newly diagnosed CRC undergoing oxaliplatin-based chemotherapy (N=31) rated symptoms weekly via the M. D. Anderson Symptom Inventory (MDASI) for up to 12 months. Serum samples were collected repeatedly at the patient’s clinic visits. An ordinal regression model was used to assess the correlation between symptom scores (used as ordinal responses) and independent variables: age, gender, ECOG performance status, staging, and concentrations of serum cytokines (IL-1RA, IL-6, IL-8, MCP-1, sIL-6R, sTNF-RI, sTNF-RII), and C-reactive protein (CRP). Results: Overall, the 5 most severe symptoms reported by patients were numbness, fatigue, disturbed sleep, drowsiness, and distress. On the basis of 175 observations, sTNF-RI was significantly and positively associated with severity of pain, distress, drowsiness, numbness, and all interference items (p<.05 for all models) and poor memory and sadness (p<.0001). Increased IL-6 was related to poor sleep, distress, and mood interference (p<.01). Increased IL-1RA was related to diarrhea (p<.00001). CRP was negatively associated with distress and numbness (p<.05). Conclusions: Using longitudinal analysis, we observed a significant relationship between increased patient-reported symptom burden and dynamic change of circulating inflammatory cytokines including sTNF-RI, IL-6, and IL-1RA during and after oxaliplatin-based chemotherapy in patients with CRC. Our results warrant further study with the intent to analyze mechanism-driven interventions for symptom reduction as a primary outcome in CRC patients undergoing standard therapy.
Multicenter phase II study evaluating docetaxel, CDDP, and cetuximab as induction regimen prior to surgery in chemotherapy-naive patients with NSCLC stage IB-IIIA (INN06-study): Preliminary results.
Authors: W. Hilbe, G. Pall, T. Schmid, B. Forstner, A. Zabernigg, H. Jamnig, A. Gaechter, M. Freund, D. Kendler, E. Woell
Journal: Journal of Clinical Oncology (2010)

7062 Background: Despite several theoretical advantages, neoadjuvant/perioperative chemotherapy in patients with early stage NSCLC has not proven to be superior to the standard adjuvant approach. The aim of this study has therefore been to increase the efficacy of neoadjuvant treatment by combining a platinum doublet (cisplatin/docetaxel) with a monoclonal antibody targeting the EGFR (cetuximab). Methods: Between 01/2007 and 12/2009, 33 patients (planned sample size = 40) with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2) and docetaxel (75 mg/m2) q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly). The primary endpoint was radiological response. Secondary endpoints included toxicity, metabolic response (PET), pathological response, recurrence-free survival and overall survival. Results: At the time of this interim-analysis 31 patients were evaluable for radiological response, 22 for PET-response. Toxicity data were complete for 25 patients. In total, 65 cycles of the study treatment were applied. The following grade 3/4 toxicities were reported (>5% of cases): Neutropenia 48%, electrolyte disorders 28%, nausea 12%, skin toxicity 8%. A severe anaphylactic infusion reaction was seen once. 18/31 patients (58%) achieved PR (RECIST criteria). 13/31 (42%) were classified as stable disease. No patient showed disease progression. A metabolic response (PET) was documented in 63% of the patients. All patients underwent surgery after completion of study treatment. Surgical morbidity was not increased compared to historical controls. Survival data are still immature. Conclusions: In this study, two cycles of cisplatin/docetaxel/cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC. Toxicities were manageable and as expected. Recruitment of this trial is ongoing and an updated analysis will be presented at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck, sanofi-aventis Merck, sanofi-aventis
Abstract 4319: Clinical significance and possible role of GPNMB in patients with breast cancer
Authors: Manabu Futamura, Masako Kanematsu, Atsuko Yamada, Kasumi Morimitsu, Akemi Morikawa, Ryutaro Mori, Kazuhiro Yoshida
Journal: Cancer Research (2015)

Abstract Glycoprotein non-metastatic B (GPNMB) is a type I transmembrane protein, which is isolated from differential expression assay using metastatic melanoma cells. The physiological function is very little known but may be supposed to be associated with cell invasion and motility particularly in breast cancer cells. Here we investigated the role of GPNMB in breast cancer. First we checked expression of GPNMB by RT-PCR and western blot in several cancer cell lines including breast, gastric, and colon cancer followed by establishment of GPNMB measurement by ELISA because it's reported that GPNMB is shed at extracellular domain by sheddase such as ADAM10. GPMNB expressed in breast (5/6:83%), gastric (3/6:50%), colon (1/7:14.3%) cancer cell lines. Of breast cancer cell lines, GPNMB was highly expressed in SK-BR3 (HER2 positive), BT474 (HER2/ER positive), MDA-MB-157 (Triple negative) cells. Shed GPNMB in culture medium was measurable and correlated with expression of each cell line. Next we evaluated serum GPNMB in patients with breast (n = 164; primary 119, metastatic 43), gastric (n = 38), and colorectal (n = 50) cancer in our institute from 2011.9-2014.2.) This study was approved by the central ethics committee of Gifu University. Serum GPNMBs were 9.403, 5.751, 6.550 ng/ml, respectively. GPNMB for breast cancer patients was statistically higher than those by colorectal cancer patients (p = 0.018). Of breast cancer patients, GPNMB for HER2-type patients was higher than those for Luminal type and DCIS patients (p = 0.0386, p = 0.0195, respectively). Those for triple negative patients was also higher than those for DCIS patients (p = 0.0459). Interestingly, serum GPNMB was dramatically reduced in accordance with chemotherapy in some patients. Based on these clinical observations, we further investigated relationship between GPNMP and HER2 in vitro. Blockage of GPNMB induced not only HER2 but also EGFR expression. On the other hand, inhibition of HER2 by trastuzumab increased expression of GPNMB. Depletion of GPNMB increased sensitivity of trastuzumab, suggesting that GPNMB may play an important role in crosstalk of signal transduction for breast cancer. These notions may suggest a novel therapeutic strategy to overcome HER2 positive breast cancer. Citation Format: Manabu Futamura, Masako Kanematsu, Atsuko Yamada, Kasumi Morimitsu, Akemi Morikawa, Ryutaro Mori, Kazuhiro Yoshida. Clinical significance and possible role of GPNMB in patients with breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4319. doi:10.1158/1538-7445.AM2015-4319
The role of 131-I-metaiodobenzylguanidine (<sup>13I</sup>I-MIBG) therapy in irresectable and compromising localized neuroblastoma
Authors: R. A. Schoot, G. Bleeker, H. A. Heij, B. L. van Eck, H. N. Caron, J. de Kraker
Journal: Journal of Clinical Oncology (2009)

10053 Background: According to current practice, observation only is justified in patients with localized, irresectable neuroblastoma with favorable biologic features. However, when organ or life threatening symptoms arise, therapy is required. Side effects of treatment should be minimal, since outcome is good. The aim of this study was to evaluate the response and outcome of neuroblastoma under these circumstances, when treated with 131-I-metaiodobenzylguanidine ( 131 I-MIBG). Methods: Between 1989 and 2008, 21 patients (8 boys/13 girls) with localized neuroblastoma were included. Median age was 1.6 years (range of 0–5.5 years). Patients were eligible when the primary tumour was irresectable and organ or life threatening. Diagnosis and staging were performed according to the International Neuroblastoma Staging System (INSS). Fixed dosages of 131 I-MIBG (50–200 mCi) were given with an interval of four weeks. The median number of infusions was two (range 1 to 7). 131 I-MIBG was given according to standard directions for targeted therapy. Response was graded according to the International Neuroblastoma Response Criteria (INRC). Results: Four patients were classified as stage I, three as stage II, and fourteen as stage III. Three tumors were NMYC amplified and two had loss of heterozygosity of 1p. Minimal pretreatment was given to nine patients, because of organ or life threatening symptoms. These patients responded insufficiently or showed return of tumor growth. After 131 I-MIBG treatment, 8/21 regressed. Resection became possible in 13/21 patients. In 10/13 patients resection was macroscopically complete. Three other patients had incomplete resection of their tumor. They had longterm progression free survival. At the end of treatment 16/21 patients achieved complete response (CR) and 3/21 had stable disease (2 very good partial response (VGPR), 1 partial response (PR)). Two patients died, one of progressive disease, one due to complications of surgery (CR). One patient was lost to follow-up. Ten years OS was 90.5%, 10 years EFS was 72.4%. Median follow-up was 7.5 years (range 1 to 17.4). Conclusions: 131 I-MIBG treatment is an effective treatment modality in irresectable, localized neuroblastoma, in case of organ or life threatening situations. No significant financial relationships to disclose.
Histoproliferative Effect of Rauscher Leukemia Virus on Lymphatic Tissue. III. Alterations in the Thymic-Dependent Area Induced by the Passenger Lactic Dehydrogenase Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. J. Snodgrass, M. G. Hanna, Jr.
Journal: JNCI Journal of the National Cancer Institute (1970)

Light and electron microscopic observation of the destruction of lymphocytes of thymic origin in splenic lymphoid nodules confirmed the presence and replication of lactic dehydrogenase virus (LDV) in the thymic-dependent area. Morphologically typical LDV particles were localized intercellularly and in single membrane-bound vesicles of phagocytic reticular cells in the marginal zone at the earliest intervals after inoculation with Rauscher leukemia virus (RLV) and/or LDV, corresponding to the well-known events of the exponential phase of the plasma virus titer. LDV particles were first seen in the thymic-dependent area, where they were associated with similar phagocytic reticular cells, 24 hours after inoculation. However, only complete, intercellular virus particles were observed throughout the experiment; incomplete, intracellular particles were not present. The virus population in this region increased until the 2d day, when cellular necrosis and macrophage infiltration were at a peak. On day 4 these effects were cleared, leaving the prominent reticulum, and very few virus particles were present. Although lymphocytes of thymic origin were adversely affected as the result of LDV infection, phagocytic reticular cells in the marginal zone and thymic-dependent areas appeared to be the target cell of this virus. The importance of cell-mediated immunity, which is suppressed by LDV, in the host defense against viral infection is supported by the augmented RLV-associated splenomegaly after infection with LDV. This phenomenon strongly implies a synergistic interaction between the passenger LDV and the RLV-induced disease process.
<i>Brca2</i> Deficiency Sensitizes Cells to PARP Inhibition
Journal: Cancer Research (2006)

In the article on how Brca2 deficiency sensitizes cells to PARP inhibition in the November 15, 2005 issue of Cancer Research ( 1), the grant support in the Acknowledgment should have read as follows: Association for International Cancer Research grant no. 03–336, KuDOS Pharmaceuticals Ltd., and Wales Gene Park.