tbuckley/cabot-search huggingface dataset:
Phase II study of fludarabine, carboplatin, and topotecan with thalidomide (FCTT) for patients with relapsed/refractory or secondary acute myelogenous leukemia, chronic myeloid leukemia and advanced myelodysplastic syndromes
Authors: P. M. Barr, O. N. Koc, W. Tse, H. M. Lazarus, H. J. Meyerson, B. W. Cooper
Journal: Journal of Clinical Oncology (2005)

6630 Background: Limited treatment options are available for patients with AML that has relapsed or develops as a result of prior chemotherapy or hematologic disorders. Methods: We designed a phase II study of fludarabine (15mg/m2 x 5 days) given concurrently with carboplatin (AUC 12 by CIVI over 5 days) followed by topotecan (0.85 mg/m2 daily by CIVI over 72 hours) based on promising results of a phase I study. Thalidomide was given at a dose of 100mg daily for 1 week then 200 mg daily for potential anti-angiogenic activity as well as single agent response in myelodysplasia. 35 pts were enrolled with median age 60 years (range 40 to 78). 14 pts had AML secondary to cytotoxic chemotherapy or prior hematologic conditions and had not received prior therapy for acute leukemia (Group 1). 21 pts had relapsed or refractory AML (Group 2). Two patients had failed prior autologous stem cell transplantation. Results: Seven of 14 (50%) pts in Group 1 and 8 of 21 (38%) pts in Group 2 achieved bone marrow aplasia. Four of 14 (29%) pts in Group 1 and 5 of 21 (23%) pts in Group 2 achieved a CR or CR with persistent thrombocytopenia (CRp). Two pts required two cycles of FCTT to achieve remission. In pts who achieved CR or CRp, the median time to ANC > 500/uL was 31 days (range 20 to 48) and time to platelet transfusion independence was 40 days (range 23 to 82). Median remission duration was 153 days. Three pts subsequently underwent allogeneic stem cell transplantation. Six of the 35 pts required modification of the thalidomide dose and 7 of 35 discontinued thalidomide due to grade 3 neutropenic enterocolitis (3 pts), neuropathy (3 pts), thrombotic complications (2 pts), rash (4 pts) and persistent neutropenia (1 pt). There were 5 treatment related deaths. 4 pts died of infectious complications before bone marrow recovery and 1 died of cardiac tamponade. Grade 3 or greater extramedullary toxicity was comparable to other salvage regimens. Conclusion: FCTT appears to be an active, well-tolerated regimen for both untreated high-risk AML as well as relapsed or refractory disease. Combinations of FCTT with other promising biologic agents are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene
Influence of taxanes (docetaxel, paclitaxel) on response assessment in DCE MRI.
Authors: Simone Schrading, Christiane K. Kuhl
Journal: Journal of Clinical Oncology (2015)

132 Background: To prospectively investigate the influence of taxane-containing (T-CTx) vs. non-taxane containing neoadjuvant chemotherapy (NT-CTx) on contrast-enhancement of breast-cancers, of benign-enhancing-lesions (BEL), and of background-parenchymal-enhancement (BPE) in DCE-MRI. Methods: Prospective study on 62 patients with invasive breast-cancer who received neoadjuvant multi-agent chemotherapy with (n = 49) or without (n = 13) taxanes between 2008 and 2011, with 3 years of follow-up. Written informed consent was obtained. Patients underwent DCE-MRI according to a standardized protocol before and 2 weeks after completing neoadjuvant-CTx. The percent reduction of enhancement of breast-cancers, of BEL and BPE was calculated for patients receiving NT-CTx vs. T-CTx. Final surgical-pathology served as standard-of-reference. Changes of mean enhancement of breast cancers, BEL and background enhancement in patients under T-CTx vs. NT-CTx were compared. Results: Similar rates of pCR were observed after T-CTx and NT-CTx (28/49; 57.2% vs. 8/13; 61.5%). T-CTx was associated with an almost complete suppression of enhancement not only of breast cancers, but also of BEL and of BPE in the same patients, with average reduction of enhancement by -89.9% ±9.3%, by -90.2%±11.8%, and by -91.2%±7.5 %, respectively. After T-CTx, cancers with partial (n = 21) or pCR (n = 28) exhibited a similar reduction of enhancement (-81.8% ± 17.5 % vs. -93.9% ± 2.3 %; p = 0.22). After NT-CTx, the reduction of enhancement of cancers was significantly less pronounced compared to T-CTx (-41.1%±22.8% versus 88.1± 13.9%; p &lt; 0.0001), and effects on enhancement of BEL and BPE were significantly less pronounced compared to that of cancers in the same women (p &lt; 0.0001). MRI overestimated response, i.e. was false-negative for residual disease, in 66.7% (14/21) patients after T-CTx, versus 20% (1/5) after NT-CTx. Conclusions: The reduction of enhancement observed in breast-cancers after T-CTx is, in part, unrelated to their oncological response. MRI-detectable effects of taxanes represent a combination of specific anti-mitotic, and non-specific, probably anti-angiogenic effects. This impacts the accuracy with which DCE-MRI predicts pCR to neoadjuvant T-Ctx.
Results of a study of the oral inhibitor PTC299 on tumor VEGF synthesis.
Authors: J. J. Luke, L. A. Callahan, C. H. Darby, E. Moss, J. Winkelman, J. Barth, G. L. Elfring, A. Ogden, G. K. Schwartz, M. M. Gounder
Journal: Journal of Clinical Oncology (2011)

3069 Background: Antiangiogenic drugs interfere with the VEGF signaling pathway. PTC299, an oral investigational drug, is designed to inhibit the synthesis of VEGF and other angiogenic cytokines in tumors. In models of human cancer xenografts in mice, single‐agent PTC299 decreases intratumoral and circulating VEGF levels and results in regression, eradication, or delay of tumor growth. This report analyzes the effect of single-agent PTC299 on human serum VEGF (sVEGF) in patients (pts) with advanced solid tumors. Methods: In stage 1 of this phase Ib study, monotherapy was given 4 weeks on and 2 weeks off at escalating weight-based doses 0.3, 0.6, and 1.2 mg/kg BID. In stage 2, monotherapy was given continuously with escalating unit dosing of 100 mg BID followed by cohorts at 100, 120, 160, and 200 mg TID. Treatment continued to disease progression. Safety, PK, and clinical activity were assessed; sVEGF levels were obtained Day 1 (D1) and Day 42 (D42). Results: Stages 1 and 2 enrolled 29 pts; (M13:F16); median age 61 years (range 30-80); ECOG PS 0 (n=17) or 1 (n=12); median prior therapies for metastatic disease 2.5 (range 0 to 8). No MTD was observed through 200 mg TID. Adverse events were infrequent, usually Grade 1. There was no hypertension. Median time on treatment was 10 weeks (range 0.3 to 84) including 3 H&N pts (12, 12, 63+ wks), 4 thyroid carcinoma pts (6, 10, 12, 84 wks) and 3 chondrosarcoma pts (30, 31+, 36 wks). 21 had pre/post sVEGF samples. D1 sVEGF levels were elevated (normal ≤300 pg/mL) in 10/21 pts. Pts with elevated D1 sVEGF have statistically significant D42 sVEGF decrease as compared to those with normal D1 sVEGF, with median reduction of 165.3 pg/mL (37.7%) and 20.8 pg/mL (18.3%) respectively (p=0.001). PTC299-induced sVEGF reductions were correlated with stable disease ≥12 wks (p=0.049) and were dose-dependent. Conclusions: Single-agent PTC299 significantly reduces circulating sVEGF in pts with elevated D1 levels. The drug has been generally well tolerated and shows clinical benefit, especially in pts where sVEGF reductions were observed. These data give preliminary support for the proposed mechanism of action that PTC299 inhibits tumor VEGF with unchanged physiological sVEGF production.
Safety, pharmacokinetics, and pharmacodynamics results from a phase I trial of BAY 86-9766 (RDEA119), a MEK inhibitor, in patients with advanced cancer.
Authors: L. Gore, K. Lewis, D. D. Von Hoff, G. J. Weiss, R. K. Ramanathan, A. A. Adjei, G. K. Dy, W. W. Ma, N. J. Clendeninn, D. P. Leffingwell, B. Sheedy, C. Iverson, J. N. Miner, Z. Shen, L. Yeh, R. L. Dubowy, M. Jeffers, P. Rajagopalan, C. D. Weekes
Journal: Journal of Clinical Oncology (2011)

3007 Background: BAY 86-9766 is a highly selective, allosteric inhibitor of MEK1/2. A phase I dose-escalation trial was conducted to determine the maximum tolerated dose (MTD), pharmacokinetics (PK) and pharmacodynamics (PD) in patients with advanced metastatic or locally recurrent solid tumors. Methods: Sixty-nine patients received doses from 2-160 mg once daily (QD) or 50-80 mg twice daily (BID). Tumor types included 22 colorectal (CRC), 8 melanoma, 5 prostate, 5 NSCLC, 5 pancreatic, 3 adrenal, 3 cholangiocarcinoma, 2 breast and 16 other. Patients were given a single oral dose on Day 1, were off drug for 7 days, and then began a 28-day course of daily continuous dosing. If benefiting, dosing continued in 28-day courses with tumor response and PD assessed every 2 courses. Safety was assessed by adverse events (AEs), clinical laboratory tests, vital signs, ECGs, ECHO/MUGA scans and physical exams. PK was collected each course. PD assessments included circulating tumor cells, leukocyte phosphorylated ERK (pERK) and leukocyte released tumor necrosis factor alpha (TNFα). Biopsies from 12 of 20 MTD patients were genotyped, of which 8 were assessed for changes in Ki67, pERK, and phosphorylated AKT. Results: The MTD was 100 mg/day. At this dose, the most common treatment-related AEs were rash, diarrhea, nausea, vomiting, fatigue, and peripheral edema. Central nervous system AEs occurred predominantly at doses of 100-160 mg/day. Group mean Cmax and AUC0-24 values increased linearly with dose. At doses of 60 mg QD, 100 mg QD and 50 mg BID, a significant suppression of leukocyte pERK and TNFα was seen through 24 hours post dose. Tumor pERK showed significant reduction from baseline in 75% of the samples. Initial mutational analysis revealed 0% NRAS, 0% PTEN, 8% PIK3CA, 17% KRAS, 17% BRAF, and 17% KRAS/PIK3CA. Stable disease (≥ 4 courses) was achieved in 10 patients and 1 patient with CRC who was KRAS-wild type had a confirmed partial response. Conclusions: BAY 86-9766 was generally well tolerated at doses ≤ 100 mg daily with rash being the most common treatment-related AE. At the MTD, significant inhibition of tumor pERK was observed in a variety of disease types and genetic backgrounds.
Outpatient palliative care needs of metastatic cancer patients treated with radiation therapy.
Authors: Shayna Eliana Rich, Jacqueline Castagno, Rebecca Beaulieu, Anamaria R Yeung
Journal: Journal of Clinical Oncology (2015)

73 Background: It is unclear how frequently patients with metastatic cancer treated with radiation therapy have unmet physical, psychological, spiritual, and practical needs of patients. This study aims to determine the level of support needed to meet this burden. Methods: We performed a telephone survey to evaluate the unmet needs of living patients with stage IV metastatic cancer treated with radiation therapy at a single institution in the priot six months. Data were collected using the Palliative care Outcome Scale, a validated 12-question survey about unmet patient needs, and its associated symptom scale. We examined patient treatment history by reviewing medical records. Among 87 eligible patients treated, 45 had died, 19 could not be reached, and two declined participation. Thus, 21 patients were included in the analysis. Results: Most frequent diagnoses were lung (24%; 5/21) or colorectal cancer (19%; 4/21). Most patients’ recent radiation course had palliative intent (62%; 13/21), but eight had received ablative radiation. No patients were undergoing radiation treatment when the survey was administered, and 57% (12/21) were receiving chemotherapy. Despite most patients seeing a physician within 2 weeks of the survey (median 1.7 weeks; range 0-11.4 weeks), most patients reported pain (67%) and anxiety (57%), and about 50% reported these issues as moderate or worse. At least one-third of patients reported having each need unmet. Patients complained of a median of five symptoms, with 57% of patients reporting any symptom severe. Patients on chemotherapy (n = 12) reported more symptoms and increased symptom severity, but 44% of patients reported moderate pain even among those not undergoing any therapy. Conclusions: Patients with metastatic cancer recently treated with radiation therapy continue to have substantial needs that are often not being met by standard oncologic care, despite recent visits with physicians. Although many of these patients are receiving chemotherapy and may be identified for palliative care programs through the medical oncology service, radiation oncology clinics should also routinely integrate quality palliative care for patients with metastatic cancer.
Assessment of the near-Infrared Fluorescent Protein FP635 for Dynamic In Vivo Imaging in Models of Adaptive Immune Responses.
Authors: Simone S Riedel, Marco Herold, Markus Hirschberg, Christian Brede, Carina A Baeuerlein, Ana-Laura Jordáan-Garrote, Carolin Kiesel, Miriam Ritz, Jeanette Baker, Robert S Negrin, Hermann Einsele, Andreas Beilhack
Journal: Blood (2009)
Recurrence rates of resected appendix carcinoid tumors: A 20-year experience at Memorial Sloan Kettering Cancer Center.
Authors: Jennifer Murphy, Andrew Rosowicz, Leonard Saltz, Philip Paty, Michael P. La Quaglia, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2016)

221 Background: NETs of the appendix are rare neoplasms most often discovered during incidental appendectomy. Risk of nodal metastases based on single institution series has suggested that appendix carcinoid tumors &gt; 2 cm should undergo a right colectomy. Unlike other tumors, lymph node involvement does not change management given the lack of adjuvant therapies. We sought to evaluate our experience of patients with resected appendix carcinoid, the risk of recurrence, and the benefit of surveillance following resection. Methods: A single institution database of all patients with diagnosis of neuroendocrine tumors was queried for all resected appendix carcinoid tumors. Excluded were patients with large and small cell neuroendocrine tumors, goblet carcinoid, and patients with inaccessible patient records. Results: 88 patients were included from August, 1994 through December, 2013. The mean age at diagnosis was 37.1(9.9-75.8). There were 19 (22%) children (less than 18 years of age) and 69 (78%) adults. Females represented 72% of all patients. All patients had well differentiated tumors. Median follow-up was 2.5 years (1-16.5 years, 45% of which had longer than 3-year follow-up). 43/88 (49%) patients underwent right hemicolectomy (average size 2 cm) and 45/88 (51%) simple appendectomy (average size 0.9 cm). Most patients were followed with CT scans and laboratory evaluations and frequency of surveillance was inconsistent. There were no recurrences (0/88). Ten-year survival was 100%. Conclusions: This is one of the largest series of resected appendix carcinoid reported and no patients recurred. Prognosis was excellent and in the absence of metastatic disease, excessive imaging and/or laboratory testing should be avoided. We question the use of routine right hemocolectomy in these patients.
Open partial nephrectomy with modified technique: Comparison to results from contemporary laparoscopic series.
Authors: Thomas Alexander Voegeli, Richard Demming
Journal: Journal of Clinical Oncology (2015)

473 Background: To evaluate the surgical and oncological outcome of patients undergoing a modified procedure of open partial nephrectomy which was done with a new technique leaving out selective suturation of renal calices and vessels. Methods: We analyzed 120 consecutive open partial nephrectomies (2005-2010) which were performed with a modified technique at a mid-volume center. This technique included the use of an absorbable non-woven textile consisting of polyglycolic acid, extra-large needles and argon plasma coagulation. The surgical and oncological outcome was evaluated by statistical analysis of the medical records. Results: The mean patient age was 62.8 years (52.6% male). Mean pathological tumor size was 3.0 cm (± 1.4 cm), 53.3% of the tumors were renal cell carcinoma. The mean operative time was 101.7 minutes (±33.6 min) and the mean blood loss was 283.9 ml (±368.5 ml). Ischemia was performed in 23.1% with a mean warm ischemia time of 13.3 minutes ( ± 6.4 min). The operative complication rate was 1.7 %. Topical hemostatic agents were used in 20.2 %. The most frequent postoperative complications were bleeding (5%), pleural effusion (4.2%), urinoma (2.5%), pneumonia (2.5%), wound infection (2.5%) and acute renal failure (2.5%). Five-year cancer specific survival rate was 94.1%. Conclusions: The modified technique of open partial nephrectomy can be performed with high surgical and oncologic safety. Duration of the procedure and ischemia time are short. Due to the rare use of hemostatic agents, the costs can be reduced. Open partial nephrectomy with this technique achieve better results than reported from contemporary reported laparoscopic series, especially regarding warm ischemia and time needed for surgery.
Disparities in access to palliative care services among cancer patients in south Texas.
Authors: Sherri L. Rauenzahn, Susanne Schmidt, Ifeoma Aduba, Jessica Jones, Laura LaNiel Tenner
Journal: Journal of Clinical Oncology (2016)

130 Background: Palliative medicine is dedicated to improving quality of life for patients throughout their disease course. The integration of palliative medicine in oncology practice has increased due to growing evidence of benefits for patient. While the collaboration of palliative and oncology care is beneficial, access to palliative services remains an issue for cancer patients. The aim of this project is to evaluate how insurance status impacts palliative care access for cancer patients in South Texas. Methods: During a 5-month study period, 607 patients from medical oncology clinics were evaluated based on their Edmonton Symptom Assessment System (ESAS) scores collected during their clinic visit to determine symptom burden and palliative care need. If providers saw a need, palliative care referrals were made. 27 unique patients received a total of 32 referrals over the study period. We examine time to initial palliative care appointment after the first referral was made. We compare time to consult based on where patients were able to receive palliative services. Location of care was based on type of insurance coverage. Results: During our study period, 13 patients were eligible to receive care through the University of Texas (UT) Medicine System (Group A) and 14 patients qualified for care at University System, which provides services to under-insured and safety net patients (Group B). Of the 27 referred patients, 85% made efforts to seek palliative care (n = 23), of which 78% had a palliative care visit (n = 18). On average, patients seeking care at the safety net facility (Group B) had 29.8 days longer wait times until their first potential visit (p &lt; 0.01) compared to patients eligible for UT Medicine (Group A). Time to actual visit was on average 39.2 days longer for patients in Group B compared to patients in Group A (p = 0.02), averaging at 55.7 days for patients seeking care at the safety net facility. Conclusions: This investigation revealed a 4-fold increase in time to scheduled visit depending on insurance coverage. While this study is limited by a small sample, data suggests that under-insured oncology patients may have significantly different access to palliative care services which may impact the quality of cancer care.
Role of inflammatory monocyte mobilization in growth of liver metastasis in a murine model of metastatic pancreatic cancer.
Authors: Roheena Z. Panni, Timothy M. Nywening, Brian Belt, Dominic E. Sanford, Peter S. Goedegebuure, David Linehan
Journal: Journal of Clinical Oncology (2015)

299 Background: Pancreatic cancer (PC) is currently the fourth leading cause of death and the mortality rate approaches 100% due to early metastatic spread. Liver is the most common site of metastasis in PC. Our group and others have shown that PC induces cellular changes in the liver which include increase in inflammatory monocyte and macrophage population, long before development of metastasis. Based on our preliminary data, we developed a murine model of metastatic PC to study the role of chemotherapy in addition to novel IM blocking agents in established PC metastasis. Methods: We implanted spontaneously derived murine PC cell line (KCKO) orthotopically in the tail of pancreas of WT mice. 10 days after tumor implantation, there was an increase in infiltrating IM and macrophages in the liver by flow-cytometry and IHC. There was also an upregulation of genes associated with development of metastasis and recruitment of myeloid cells i.e. CCL2, CSF1, s100a4, s100a8, CXCL12, LOX, VEGF-A (P&lt;0.01) by RT-PCR. However, there was no evidence of tumor metastasis at this stage in the liver. We removed the primary tumor on day 10. At this time, mice were injected with βluc-KCKO in the inferior pole of the spleen which was removed. Liver metastases were detectable by bioluminescence in 100% mice after 15 days of splenic injection. Results: Mice with established liver metastasis were randomized to treatment with CCR2i, FOLFIRINOX, CCR2i and CCR2i+FOLFIRINOX or vehicle. Mice were treated for 4 weeks and were imaged biweekly in-order to quantify tumor burden in the liver. Mice were sacrificed after 4 weeks and flow-cytometry studies were performed on peripheral blood, bone marrow and liver. The peripheral blood IM were significantly increased in mice bearing liver metastasis. However, CCR2i efficiently blocked the recruitment of IM and macrophages in liver (p&lt;0.01). The burden of liver metastasis was significantly decreased after four weeks of treatment. Interestingly, the lowest tumor burden was found in livers of mice treated with combination of CCR2i and FOLFIRINOX. Conclusions: We demonstrate that CCR2i in combination with FOLFIRINOX decreases macrophages in the liver and impairs growth of liver metastasis.