tbuckley/cabot-search huggingface dataset:
Phase I/II trial of combination topotecan and vinorelbine in patients with refractory gynecologic cancer
Authors: A. Berchuck, A. A. Secord, L. J. Havrilesky, R. Wenham, J. T. Soper, D. L. Clarke-Pearson
Journal: Journal of Clinical Oncology (2004)

5152 Background: Topotecan (T) and vinorelbine (V) have shown efficacy in recurrent ovarian and cervical cancer. The purpose of this trial was to determine the recommended dose of combination T and V and to assess its efficacy in patients with refractory gynecologic cancer. Methods: Sixteen patients with measurable disease and advanced gynecologic malignancies were enrolled. The phase I study evaluated the toxicity of combining T (0.75–1.25 mg/m2) administered as a 30 minute infusion on days 1,2, and 3 and V (20–22.5 mg/m2) IVP on days 1 and 8 of a 21 day cycle. The phase II study evaluated 8 patients treated with T (0.75 mg/m2) on days 1,2, and 3 followed by V(20 mg/m2) IVP on days 1 and 8. Results: Five DLTs appeared during the first 8 cycles in levels 1 and 2. The MTD was reached and the recommended dose for this combination schedule was T: 0.75 mg/m2 on days #1, 2, and 3 combined with V: 22.5 mg/m2 on days # 1 and 8. Phase II: 8 patients have been enrolled at the recommended dose (median age 60 [35–74]; median PS 0) and have received 29 courses. The median number of prior chemotherapeutic regimens was 2 (range 1–5) and 1 patient had previously been treated with topotecan. All patients had platinum/paclitaxel resistant disease. There were 3 responses (1 CR, 2 PR) for a response rate of 37.5%. The median time to progression was 2.1 months (range, 1.3 to 7.4) and the median survival has not been reached. The predominant toxicity was hematologic and the toxicities were: grade 4 neutropenia (3/8; 37.5%), febrile neutropenia (3/8; 37.5%), and grade 2 anemia (4/8; 50%). Hematologic toxicity resulted in dose delays in 50% (4/8), dose modifications in 37.5% (3/8) and the use of granulocyte colony-stimulating factor in 25% (2/8) of patients. Conclusions: Therapy with combination topotecan and vinorelbine in patients with platinum/paclitaxel resistant ovarian cancer is active, but has significant hematologic toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Pharmacia Aventis; GlaxoSmithKline; Pharmacia
Compare the diagnostic value of FLT and FDG PET/CT in assessment of regional lymph nodes in thoracic esophageal squamous cell carcinoma
Authors: D. HanJ. Yu, X. Zhong, D. Mu, Z. Fu, B. Zhang, L. Zhang, W. Zhang
Journal: Journal of Clinical Oncology (2009)

e15620 Background: To determine whether FLT PET/CT can detect regional lymph nodes metastases in untreated thoracic esophageal squamous cell carcinoma. In view of the reported high sensitivity of FDG PET/CT for the evaluation of thoracic nodules of esophageal carcinoma, we additionally performed FDG PET/CT for direct comparison with that of FLT. Methods: From March 2008 to December 2008, 18 patients with thoracic esophageal squamous cell carcinoma underwent dual-tracer PET/CT examinations before surgery. The results of reviewing side-by-side FDG PET/CT and FLT PET/CT images for the diagnosis of locoregional lymph node metastases were compared prospectively in relation to pathologic findings. The PET images were visually inspected with the maximum standardized uptake value (SUVmax) determined from a circular region of interest (ROI) over the entire lesion. The differential threshold for malignancy was set as SUV FDG ≥2.5, and SUV FLT ≥1.4, respectively. Results: All patients underwent esophagectomy and lymphadenectomy, and pathologic examination confirmed nodes positive for metastasis in 14 patients and 42 of 344 excised nodes. The uptake of FDG (median SUVmax, 5.59; range, 2.5–10.6) in locoregional lymph nodes metastasis was significantly higher than that of FLT (median SUVmax, 2.93; range, 1.6–4.6). There were 14 false positive nodes in FDG PET and only 3 in FLT PET, 7 false negative nodes in FDG PET, while 11 false negative nodes in FLT PET. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FLT PET/CT were 73.81%, 99.01%, 95.93%, 91.18% and 96.45%, respectively, whereas those of FDG PET/CT were 83.33%, 95.36%, 93.90%, 71.43% and 95.36%, respectively. P values were 0.425, 0.014, 0.298, 0.055, and 0.541, respectively. Conclusions: FLT uptake in regional lymph node of esophageal carcinoma is significantly lower compared with FDG uptake.FLT PET has fewer false-positive findings compared with FDG PET. The specificity of FLT PET/CT is higher than that of FDG. We suggest that esophageal carcinoma N-staging need to combine FLT with FDG PET/CT images. No significant financial relationships to disclose.
Bronchial carcinoid tumours: Clinical features and management in a series of 45 patients
Authors: R. Srirajaskanthan, L. Marelli, A. Karpathakis, C. Toumpanakis, T. Meyer, J. Buscombe, M. Dusmet, M. Caplin
Journal: Journal of Clinical Oncology (2008)

19076 Background: Bronchial neuroendocrine tumours account for 1–2% of all lung cancers; they are thought to arise from the neuroendocrine cells located in the bronchial mucosa. Management of bronchial carcinoids has evolved over recent years with the advent of new treatment modalities. To identify the optimal treatment pathway for patients with bronchial neuroendocrine tumours. Methods: We present a series of 45 patients referred to our institution from1998–2006. Histological diagnosis from our department was available for 39 patients, with the remainder having had histological assessment performed previously. Typical carcinoid was present in 25 cases, atypical in 9 cases, large cell nenuroendocrine carcinoma in 4 and one case of small cell lung carcinoma. All patients were staged at time of initial diagnosis with CT scan, in addition Octreoscans were performed when appropriate. Results: Initial therapy with surgical resection was performed in 19 patients, 2 of which underwent pre-operative chemotherapy. Recurrence occurred in 8 (42%), of which 4 were in patients with atypical carcinoids. Average duration of disease free survival post surgery was 61 months. Chemotherapy was first line therapy in 5 cases, four achieved disease stabilization and one case had progressive disease. Somatostatin analogues were used as first line therapy in 6 patients, for either symptom control and anti-tumour effect, the average time to disease progression was 10.5 months. Peptide receptor radiotargetted therapy, with Y-90 DOTA Octreotate, was given in 2 cases, both of whom achieved disease stabilization for 9 to 12 months respectively. There was no significant difference in survival based on histological classification between typical, atypical, large non-small neuroendocrine carcinoma. There was a significant difference between stage 4 and stage 1 disease at presentation and survival (p= 0.028). 5 year survival for bronchial carcinoids is better than that for most other lung cancers. Conclusions: In conclusion curative surgical resection is treatment of choice, however, chemotherapy, somastostatin analogues and peptide receptor radiotargetted therapy offers numerous palliative treatments for improving both symptoms and mortality. No significant financial relationships to disclose.
Mesenchymal Stromal Cells (MSC) Isolated from Human Osteosarcomas Show a High Progenitor Cell Frequency, Typical MSC Morphology, Surface Marker Profile, and Differentiation Capacity, and They Are Considerably Affected by Tyrosine Kinase Inhibitors in Vitro.
Authors: Jan Claas Brune, Ariane Tormin, Ulrike Bauer, Ulf Neumann, Pehr Rissler, Otte Brosjö, Richard Löfvenberg, Fredrik Vult von Steyern, Fredrik Mertens, Anders Rydholm, Stefan Scheding
Journal: Blood (2008)
Abstract 11933: Echoguided Lead Placement Benefits Patients with QRS Durations < 150 ms : Results from STARTER Randomized Controlled Trial
Authors: Josef Marek, Samir Saba, David Schwartzman, Sandeep K Jain, Evan C Adelstein, Olusegun A Oyenuga, Tetsuari Onishi, John Gorcsan
Journal: Circulation (2012)
A phase II study of 5-FU (CVI) and low-dose consecutive CDDP (LFP) therapy in advanced gallbladder carcinoma
Authors: K. Kobayashi, A. Tsuji, S. Morita, Y. Shima, T. Horimi, T. Shirasaka, T. Kanematsu
Journal: Journal of Clinical Oncology (2005)

4261 Background: Unresectable and recurrent gallbladder carcinoma (GBca) are known to be poor prognosis. In Japan 5-FU alone or modified FAM therapy was once tried to these malignancies, but no objective response was aquired. By the way, 5-FU and CDDP combination chemotherapy (FP) has been widely used as standard chemotherapy for gastrointestinal cancer, and in Japan FP therapy was modified into 5-FU (CVI) and low-dose consecutive CDDP (LFP) Therapy from 1990. Because of low toxicity and relatively high response rate, LFP therapy has been widely used for the treatment of gastrointestinal cancers in Japan. We are conducted a single arm phase II study of LFP therapy in patients with advanced GBca. Methods: Patients with advanced or recurrent bile duct carcinoma received LFP therapy. 5-FU (160mg/m2/day) was continuously infused over 24 hours using an implantable port and CDDP (3mg/ m2/day) was infused for half an hour. The administration schedule consisted of 5-FU for 7 consecutive days and drip infusion of CDDP twice a week for each four weeks according to response and tolerance. RESIST criteria was used to assess tumor response. The toxicity was estimated by NCI-CTC (ver.3). Median survival time (MST) and median time to treatment failure (TTF) was calculated by the Kaplan-Meier method. Results: Between May 1996 and September 2003, 13 patients were entered into this trial. Information is available for all patients. Characteristics were: mean age 69.4±5.0: male 6: locally advanced 10, postoperative recurrence 3. Overall, most common toxicity was appetite loss occurring 38.5% of patients. Hematological toxicity (up to grade 2) was occurring in 23.1% of patients. No grade 4 toxicity occurred. All the patients are evaluable for effects with an over all response rates of 46.2% (6 PR, 2 NC, 5 PD). Estimated MST is 150 days. 1-year and 2-year survival rate were 16.8% and 0.0%, respectively. Estimated median TTF is 85 days. Conclusions: This study resulted in high response rate and tolerable adverse effect. This outpatient-basis LFP therapy promises to advance the quality of life of the cancer patients and to be useful in the clinical management of advanced or recurrent GBca tract malignancy for first line chemotherapy. No significant financial relationships to disclose.
A phase III randomized placebo controlled NCCTG trial of carboxyaminoimidazole (CAI) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: E. A. Johnson, R. S. Marks, S. Mandrekar, S. Hillman, J. Mailliard, T. Dentchev, N. Reuter, J. Jett, E. A. Perez
Journal: Journal of Clinical Oncology (2005)

7054 Background: Benefit from chemotherapy (ctx) for NSCLC has plateaued. Agents with novel mechanisms may provide further gain. CAI has in-vitro effects including inhibition of tumor cell motility, adhesion, and growth. Methods: CAI/placebo at 250 mg/day was given orally as maintenance therapy in stage 3 or 4 NSCLC patients within 6 weeks of completion of first line ctx (Stage 3 patients may have received thoracic radiotherapy). Eligible patients had stable or responding disease to one ctx regimen of 3–6 months (mo) duration; ECOG performance status of 0,1,2; absence of untreated brain metastases and adequate hematologic, hepatic and renal function. The study closed early due to slow accrual (targeted 360, observed 186). 360 patients followed for a minimum of 1 year would have provide 80% power to detect a 40% increase in the primary endpoint of median survival with a two-sided 5% type I error rate. The 154 observed deaths in the 186 patients accrued provide 80% power to detect a 60% increase in median survival. Results: Between 4/99 and 8/04, 186 patients (94 CAI, 92 placebo) were randomized with balance in median age, performance status, gender, histology, stage and response status to initial ctx. Incidence of severe (grade 3+) adverse events (AE) was not significantly different for CAI compared to placebo (42% vs. 34%, p=0.24). AE (primarily grade 1,2) observed more often in the CAI group included fatigue (55.6% vs 29.4%, p=0.0003), anorexia (31.1% vs 13.0%, p=0.003), nausea (61.1% vs 30.4%, p<0.0001), and vomiting (32.2% vs 14.1%, p=0.004); and grade 3+ AE included neurosensory (8.5% vs. 0.0%, p=0.004) and ataxia (11.1% vs. 3.3%, p=0.05). Patients discontinued treatment for AE/refusal more often in the CAI group (34.5% vs 6.8%, p<0.0001). Median follow-up is 20.0 mo. Both median survival and time to progression are not significantly different between the two groups (11.8 mo vs 10.5 mo, p= 0.93; 3.2 mo vs 2.5 mo, p=0.88). Conclusion: The addition of CAI following chemotherapy does not provide clinical benefit over placebo in advanced NSCLC. No significant financial relationships to disclose.
Effect of body mass index (BMI) on autologous peripheral blood stem cell transplant (APBSCT) outcomes for multiple myeloma (MM)
Authors: R. F. Connor, Y. Keung, S. Arrington, J. Lovato, J. Cruz, I. Molnar, D. D. Hurd
Journal: Journal of Clinical Oncology (2005)

6717 Background: The percent of overweight Americans (BMI>25) increased to 31% in ’99-’02. Increased BMI has been associated with increased mortality in patients (pts) with MM. Decreased overall survival (OS) and disease free survival (DFS) in obese patients undergoing autologous transplant for newly diagnosed AML has been reported. We examined the effect of obesity in pts undergoing APBSCT for MM. Methods: This was a retrospective study of 46 consecutive pts with MM undergoing APBSCT 2001–4. Preparative regimen was Melphalan 200 mg/m2. Adjusted weight (average of ideal and actual body wt) was used to determine dose for pts with body weight >125% of ideal. Pts were grouped by BMI [wt (kg)/ht (m)2] according to NIH guidelines: <24.9 normal/low; 25–29.9 overweight; >30 obese. Log-rank tests were used to compare event times. Results: Mean age was 56 (range 40–74); 56% were male, 74% White, and 26% Black; 96% received VAD and 4% Thalidomide. 40% of our pts were obese and 26% were overweight. 52% received Melphalan dose adjustment. 3-year OS was 89% (95% CI 79 - 100) and median DFS was 2.4 yrs (95% CI 1.4 - NA). Three obese deaths were related to disease progression while one normal weight pt died from transplant complications. While the median DFS was 2.6 years, 1.5 years, and 1.1 years for the normal, overweight, and obese groups respectively, the difference was not statistically significant (p = 0.3). Complete response or near complete response rates after transplant were 92%, 88%, and 72% for the normal, overweight, and obese groups respectively (p=0.4). There were no statistically significant differences between the groups regarding hospital stay, time to engraftment, incidence of bacteremia, antibiotic use, or complication rates of mucositis, diarrhea, engraftment syndrome, or intubation. Conclusions: There was no statistically significant difference in transplant outcomes among BMI groups. Our small sample size and melphalan dose adjustment may have contributed to minimize the difference in the outcomes between BMI groups. Currently, our data suggests that the use of autologous PBSCT in obese pts with MM is feasible with dose adjustment. A large prospective study is required to confirm our findings. No significant financial relationships to disclose.
Abstract 4467: Targeting of chemokine receptor CXCR4 inhibits invasion and sensitizes melanoma cells to chemotherapeutic agents
Authors: Manoj K. Pandey, Deepkamal Karelia, Vijay P. Kale, Krishne Gowda, Arun K. Sharma, Rogerio I. Neves, Shantu G. Amin
Journal: Cancer Research (2015)

Abstract Malignant melanoma is highly metastatic and resistant to conventional therapies. Although numerous clinical approaches for treating melanoma have been adopted, none led to a remarkable therapeutic effect. Recently new drugs have been developed for treatment of metastatic melanoma, and hold great promise; however complete effects are still distant dream because of resistance. We have learnt that the most aggressive melanomas are generally resistant to strategies which target one signaling pathway. Thus an agent targeting multiple signaling pathways would maximize therapeutic outcome. We have identified one such agent named as gambogic acid (GA) that is natural and derived from medicinal plant Garcinia hanburyi (also called mangosteen or kokum). Moreover this agent has a potential to target several pathways responsible for survival and chemoresistance of several cancers including melanoma. Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been associated with inferior survival, poor prognosis, chemoresistance and metastasis of malignant melanoma. We, therefore, investigated whether GA could inhibit CXCR4 signaling and suppress invasion of malignant melanoma cells. Through docking studies we predicted that GA directly interacts with CXCR4. This xanthone down-regulates the expression of CXCR4 on melanoma cells in a dose- and time-dependent manner. Suppression of CXCR4 expression by GA correlated with both inhibition of SDF-1α-induced invasion of melanoma cells. GA also inhibited expression of MMP-9, VEGF, c-Myc and phosphorylation of Erk1/2 in melanoma cells. Importantly, GA markedly enhances the efficacy of PLX-4032 and dacarbazine against melanoma cells. Citation Format: Manoj K. Pandey, Deepkamal Karelia, Vijay P. Kale, Krishne Gowda, Arun K. Sharma, Rogerio I. Neves, Shantu G. Amin. Targeting of chemokine receptor CXCR4 inhibits invasion and sensitizes melanoma cells to chemotherapeutic agents. [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 4467. doi:10.1158/1538-7445.AM2015-4467
Is age an independent predictor of clincially significant prostate cancer in a referral population? A case for needle biopsy in the elderly
Authors: G. Hanson, J. Wright, J. Kim, L. S. Borden, C. R. Porter
Journal: Journal of Clinical Oncology (2007)

5142 Background: Approximately 232,090 new cases of prostate cancer were diagnosed in the U.S. in 2005. As the population ages and life expectancy increases, physicians will increasingly be faced with patients in their 70’s who can be expected to live for greater than 10 years. Many of these patients are screened for prostate cancer and may ultimately be evaluated by a urologist. Clinically significant prostate cancer is still diagnosed in men in this age group. To address this issue, we evaluated a large prostate biopsy database to assess the nature of prostate cancer diagnosed in elderly men in a referral population. Methods: A prospective database of 790 men who had undergone biopsy by a single urologist (CRP) was reviewed. Demographic data was recorded. Patients with Gleason score 7–10 were defined as having clinically significant disease. Multivariate regression analysis was performed to determine the relationship of increasing age with higher Gleason scores (7–10) on biopsy. We divided our patients into clinically applicable age groups of greater than or equal to 70 and less than 70 years. Results: The mean age of patients was 63.1 years. Men over 70 years old were more likely to have increased mean prostatic volume (P &lt; 0.001), abnormal DRE (P &lt; 0.001) and presence of prostate cancer (P &lt; 0.001). Patients aged 70 or older had more than a three-fold increased risk of Gleason 7 or greater cancer (OR 3.32, p &lt;0.001). An abnormal DRE (OR 3.65, p&lt;0.001) and PSA &gt;10 (OR 4.05, p &lt;0.001) were also independently associated with a statistically significant chance of detecting Gleason 7 or greater cancer. Conclusions: Age is an independent predictor of clinically significant prostate cancer in a referral population. Patients who are 70 years or older with a 10-year life expectancy should be counseled that they are at higher risk of harboring clinically significant prostate cancer and should therefore be considered for prostate needle biopsy. [Table: see text] No significant financial relationships to disclose.
Medical oncologists and quality of life of women treated for breast cancer.
Authors: C. R. Friese, T. M. Pini, P. Abrahamse, S. T. Hawley, S. J. Katz
Journal: Journal of Clinical Oncology (2010)

6051 Background: Quality of life (QOL) of breast cancer patients receiving chemotherapy varies widely. More information is needed as to how the organization of care influences the experience of breast cancer patients. We examined the extent to which medical oncologists (oncs) influence breast cancer patient QOL near the time of chemotherapy. Methods: 3133 women with nonmetastatic breast cancer diagnosed from 6/05-2/07 in Detroit and Los Angeles were identified through SEER registries and surveyed after diagnosis (n = 2268, response rate 72.4%). For women who received systemic chemotherapy (n = 1,116), treating oncs were identified and surveyed (n = 207, RR 65%). Patient survey, SEER and onc data were then merged (480 patients and 145 oncs). The 5 subscales of the FACT-B – social well being (SWB), functional (FWB), physical (PWB), emotional (EWB), and breast cancer specific (BCS) - were dependent variables. Independent variables included patients factors (demographics, stage, surgery type, chemotherapy status (completed vs. ongoing), comorbidities) and onc factors (practice size, use of support personnel, university affiliation, weekly patient care hours, breast cancer case volume, frequency of visits during chemotherapy, and education/support resources). We compared the mean FACT-B scores across oncs. For each FACT-B subscale, we used random effects models to evaluate the variation at the onc level, sequentially controlling for patient and onc factors. Results: The mean (SD) FACT-B score for the sample was 95.1 (1.0) (best possible score = 144), with a range across 145 oncs between 44 and 135. The variation in FACT-B scores explained by onc characteristics was modest (7.9%). Similar effects were found for SWB (9.3%), FWB (8.2%), and BCS (7.2%). The variation explained by oncs for EWB (6.6%) and PWB (3.2%) was weaker. No specific onc variables were significantly associated with the FACT-B or subscales. Conclusions: There is modest variation in QOL among breast cancer patients receiving chemotherapy that is attributable to oncs. Oncs contribute most to SWB and FWB. Further understanding of the mechanisms by which oncology practices improve patient QOL is warranted. No significant financial relationships to disclose.