tbuckley/cabot-search huggingface dataset:
Pharmacokinetic study of pegylated liposomal doxorubicin (PLD) in patients over 70: Association with increasing age and cutaneous toxicity.
Authors: A. Bononi, M. Gusella, I. Modena, C. Bolzonella, C. Barile, G. Crepaldi, D. Menon, L. Stievano, S. Toso, F. Pasini
Journal: Journal of Clinical Oncology (2010)

9155 Background: The use of chemotherapy in vulnerable and frail elderly pts still represents a challenge in geriatric oncology. PLD represents an appealing drug in elderly pts, because of reduced cardiac and haematological toxicity, while maintaining efficacy similar to that of the free drug. Aim of this study is the relation of PLD pharmacokinetics (PK) with clinical parameters in particular in the vulnerable and frail elderly subsets over 70. Methods: 20 patients aged between 70 and 86 years (median 78), 14 breast cancer, 3 ovarian cancer, 2 sarcomas and 1endometrial cancer all in stage III and IV, were enrolled. Comprehensive geriatric assessment (CGA) was performed before and at the end of the treatment. They received PLD 40 mg/m2 by intravenous infusion over 60 min every 4 weeks with standard pre-medication. Blood samples were taken at pre-infusion, 1 h, 7, 14 and 21 days after administration for the first 3 cycles. Plasma levels of doxorubicin were analyzed by HPLC. PK analysis was done by mono-compartmental model. Chi square and t test were used for statistical analysis. Results: CGA identified 4 (20%) fit, 9 (45%) intermediate and 7 (35%) frail pts. Median co- morbidity index was 2. Doxorubicin PK parameters varied widely among pts; mean values and coefficient of variation were as follows: Cmax = 22.6 mg/L, 19.4%; plasma half life (t1/2)= 82.1, 38%; AUC=115 mg × die/L, 45%. There was a significant linear correlation between increasing age and plasma t1/2 (p=0.007); pts aged > 78 had an AUC 58% higher than that of younger subjects (p=0.02). Pts with longer drug exposure (according to t1/2 median value= 89 h) had an increased risk of cutaneous toxicity (RR= 6.6, p=0.009). Responses rate (CR +PR) was 36%, SD 14% and PD 50%; pts achieving a response had a longer doxorubicin half life (108 h vs 66 h, p<0.01). Grade 4 toxicity and deterioration of the clinical status due to toxicity were not recorded. Conclusions: This study analyzed the PK of PLD in a subset of elderly pts over 70, mainly including frail and vulnerable subjects: drug exposure over time was statistically associated with increasing age and cutaneous toxicity, without affecting the general safety profile of the treatment. No significant financial relationships to disclose.
Docetaxel and oxaliplatin combination as second-line treatment in patients with advanced gastric cancer
Authors: G. Schinzari, E. D’Argento, M. Quirino, M. Basso, N. Trigila, G. Di Leonardo, A. Cassano, C. Pozzo, C. Barone
Journal: Journal of Clinical Oncology (2005)

4188 Background: Chemotherapy is the only treatment option for advanced gastric cancer (AGC) patients (pts). First line regimens are able to provide a slight but significant increase of survival rates. Pts with good performance status could receive a second line, even though there are no established indications. Several new drugs, like docetaxel, irinotecan and oxaliplatin have recently been shown to be active also for AGC, but no data are available on the efficacy and safety of a newer drugs combination regimen after progression to a platinum or a non platinum-based first line chemotherapy. Methods: Pts with histologically confirmed AGC and PS (ECOG) < 2, progressed after a first line were eligible. Based on a previous phase I study (Agelakis, ASCO 2000) pts were treated with docetaxel 75 mg/m2 day 1 and oxaliplatin 80 mg/m2 day 2, every 3 weeks, until progression or unacceptable toxicity. According to the Simon design, at least one response had to be achieved among the first 18 pts, followed by a second step with 22 more pts. Results: From September 2003 until now, twenty-three pts were enrolled. Male 75%, median age 62. Metastatic site was liver in 85% and lung in 35%; primary tumor not resected in 50%. First line treatment ECF 60%, cisplatin and infusional 5-FU 30%, irinotecan and infusional 5-FU 10%. Median number of cycles 4.8. The treatment was well tolerated with no toxic deaths. The incidence of NCI-CTC grade 3–4 toxicities was low: 8 pts (40%) had grade 3–4 neutropenia, febrile neutropenia was never observed. Three pts (15%) had grade 3 asthenia and 2 (10%) grade 3 neurotoxicity. Concerning efficacy, among 20 evaluable pts 3 (15%) had a confirmed PR, 8 (40%) a SD and 9 (45%) PD. An improvement of PS and a symptoms palliation have been seen in 7 pts (35%). Median time to progression was 4.8 months. Median overall survival has not been reached yet and the study is still ongoing. Conclusions: This regimen is safe and shows an interesting profile of efficacy. If data will be confirmed in larger phase II-III studies, it should be considered a suitable option as second line therapy for AGC in pts with good PS. No significant financial relationships to disclose.
Ethnicity and benefit of first-line chemotherapy in metastatic gastric adenocarcinoma (GC).
Authors: Mariam Vaezi, Jawaria Rahman, Dongyun Yang, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2015)

218 Background: There is a significant difference in the incidence and mortality of GC across the world. Our group presented data on the differences in the outcome of GC based on ethnicity in patients in California Cancer Registry. Data from global trials have highlighted differences in the benefit from antiangiogenic therapy in different ethnic populations. We conducted a retrospective analysis of patients (pt) with stage IV GC, who received first line platinum based chemotherapy (CT) at Los Angeles County Hospital between 2003 - 2010. We explored the interaction between demographics and benefit from CT. Methods: We searched the administrative records for pt with diagnosis of GC and identified 308 pt of which 198 had metastatic GC with first line CT at our center. Time to progression (TTP), defined as time from start of chemotherapy to radiographic or clinical progression, was the primary end point of the study. Results: Of the 198 patients, 118 (60%) were male. 134(68%) Hispanics (H), 44 (22%) Asian (A), 6 (3%) African American (AA), 5(3%) white (W), and 9 (4%) other ethnicities. Primary site of the tumor was body (B) in 71(43%), antrum and pylorus (P) in 67(34%), and cardia/fundus or GEJ (GEJ) in 26 (16%). In 34 (17%) the primary site was unknown. The median TTP in the entire population was 17.7 months (M) (95%CI: 12.7 -125). TTP in H, A, and AA was 16.7(95%CI, 12.2 -125), 17.8 (95%CI, 8.2 - 79.2), and 10.2M(95%CI: 6.0 -106) respectively [p=0.75]. There was no difference in TTP between males and females or based on the location of the disease. Conclusions: In our small dataset, there was no difference in benefit from platinum based CT by ethnicity, demographics, or disease site. This suggests that CT benefit is similar across different ethnic populations, and observed differences in trials with antiangiogenic therapy are related to angiogenesis in different ethnic groups.
Association of VEGF expression with poor prognosis among patients with low-grade neuroendocrine carcinoma
Authors: A. T. Phan, L. Wang, K. Xie, J. Zhang, A. Rashid, D. Evans, J. Vauthey, E. Abdalla, J. L. Abbruzzese, J. C. Yao
Journal: Journal of Clinical Oncology (2006)

4091 Background: Low-grade neuroendocrine carcinomas (LGNET) can arise from neuroendocrine cells throughout the body and have a wide range of aggressiveness. Reliable predictive and prognostic markers of outcome are lacking. Angiogenesis is critical for metastasis and tumor growth beyond a small tumor size and VEGF is a powerful mediator of tumor angiogenesis. Methods: LGNET tissue from 50 patients (24 with local-regional disease, 26 with metastasis) who underwent tumor resection at the University of Texas M.D. Anderson Cancer Center was evaluated for expression VEGF by immunohistochemistry. Chi-square and Fisher’s exact test were used to test the association between study parameters. Kaplan-Meier analysis was used to assess the affect of study parameters on progression free survival (PFS). Results: Strong, weak, and negative VEGF expression was observed in 32%, 54%, and 14% of cases respectively. Larger tumor size was observed among patients with strong VEGF expression. Mean tumor sizes in patients with strong, weak and negative VEGF were 4.8, 2.8, and 2.9 cm. Compared to the group with negative VEGF expression, VEGF (weak/strong) expression was associated with metastasis (14% v 58%; P = .045). The median PFS durations of patients with strong and weak VEGF expression were 29 months and 81 months respectively. With a median follow-up duration of 50 months, the median PFS duration for the group with negative VEGF expression has not been reached. Compared by log rank test VEGF expression was associated with poor PFS (P = .022). Conclusions: This study suggests that tissue VEGF expression is associated with aggressive tumor growth and metastasis among patients with LGNET. VEGF expression may serve as a useful prognostic marker following tumor resection. No significant financial relationships to disclose.
Combination motexafin gadolinium (MGd) and docetaxel is active in recurrent lung and other solid tumors: Results of a phase 1 trial
Authors: S. C. Phan, K. J. Pandya
Journal: Journal of Clinical Oncology (2005)

3138 Background: MGd is a novel anti-neoplastic agent that targets tumors and generates reactive oxygen species (ROS) by redox cycling. Pre-clinical models show that MGd enhances the cytotoxic activity of several chemotherapy drugs including taxanes in lung cancer. This phase I trial evaluated safety and response rate of MGd in combination with docetaxel in patients (pts) with recurrent solid tumors. Methods: Pts with progressive recurrent solid tumors, adequate bone marrow, hepatic and renal function and performance status (PS 0,1)were eligible. Cohorts of 3 pts were treated with increasing doses of MGd, starting at 2.5 mg/kg IV followed by docetaxel 75 mg/m2 30 minutes later. Treatments were repeated q3wks. Results: Ten pts were treated with MGd (2.5–10 mg/kg) and docetaxel. There were 4 males/6 females with a median age of 62 yrs (range 45 -75). Diagnoses included non-small cell lung (6, NSCLC); ovarian (2); breast (1); prostate (1). Pts had a median of 3 prior chemotherapy regimens (range 0–13), 5 pts had previously received a taxane. In pts with NSCLC, 2 had failed >=2 therapies, 2 pts had failed taxanes. Reported toxicities in more than one patient include asthenia, leukopenia, diarrhea, skin discoloration, urine discoloration, injection site reaction, nausea, and stomatitis, without reaching dose limiting toxicity. Partial responses (PR) were observed in 5 of the first 9 evaluable pts. Three pts with NSCLC (3/5) had a PR including two that failed prior taxanes. PRs also were seen in prostate (1/1) and in breast previously treated with paclitaxel (1/1). Pts received a median of 2 cycles (range 1–11) and responses had a median duration of 12 weeks (range 6–33). Conclusions: MGd in combination with docetaxel was well-tolerated and did not increase expected docetaxel toxicity. Responses in heavily pre-treated pts including those having failed taxanes were seen. This combination should be studied further, especially in NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacyclics Pharmacyclics Pharmacyclics
Once-weekly epoetin beta treatment in anemic patients with breast cancer receiving chemotherapy: Interim analysis of a multicenter, single arm study
Authors: L. Del Mastro, M. Clavarezza, D. Amadori, O. Garrone, R. Mattioli, L. Ponchio, L. Latini, S. Saracchini, A. Fabi, T. Gamucci
Journal: Journal of Clinical Oncology (2007)

19605 Background: Epoetin beta administered three times weekly is effective in the treatment of anemia in patients with malignancy. This study investigated the efficacy and safety of a more convenient and reduced frequency administration of epoetin beta 30,000 IU sc once weekly in anemic patients with early or metastatic breast cancer receiving chemotherapy (CT). Methods: Patients &gt;18 years with early or metastatic breast cancer receiving CT with hemoglobin (Hb) &lt;11 g/dL were enrolled in this open-label, single-arm, multicenter study. Patients received epoetin beta until Hb was = 12 g/dL. The primary endpoint was the proportion of patients with an Hb increase =2 g/dL from baseline or achievement of Hb =12 g/dL after 12 weeks of treatment in the absence of transfusion. Other endpoints included: median time to response, median change in Hb level after 12 weeks of treatment from baseline and proportion of patients with a Hb increase =1 g/dL at week 4. Adverse events (AEs), vital signs, and laboratory safety were recorded. Results: Interim data are presented for 101 patients (out of 200 patients enrolled) who had completed treatment to date. Patients’ characteristics were: median age 58 years (33–81), PS 0–1 88%, metastatic disease 49%, median baseline Hb 10.1 g/dL (7.8–11.7). Overall, 46% (95% CI: 35.5–57.6) of patients responded according to the primary end point, the median time to response was 42 days (95%CI: 15–103). Secondary objectives: median Hb increase after 12 weeks was 1.7 g/dL (CI95%: -1.6 to +5.4), at week 4 an Hb rise =1 g/dL was observed in 44% of patients (CI95%: 33.0–57.4). Overall, 13/101 (13%) patients required red blood transfusions, the median number of transfusion was 2. The incidence of treatment-related AEs (6.9%) was consistent with the current label for epoetin beta. Conclusions: These preliminary results indicate that Epoetin beta 30,000 IU once weekly is effective and well tolerated in patients with early or advanced breast cancer receiving CT. [Table: see text]
Effect of hyperacute immunotherapy in addition to standard adjuvant therapy for resected pancreatic cancer on disease-free and overall survival: Preliminary analysis of phase II data.
Authors: J. M. Hardacre, M. F. Mulcahy, M. Talamonti, J. C. Obel, C. S. Rocha Lima, H. Safran, G. R. Rossi, L. Tennant, N. N. Vahanian, C. J. Link
Journal: Journal of Clinical Oncology (2010)

4059 Background: Pancreatic cancer portends a poor prognosis, with long-term survival less than 5%. Even for the fortunate ∼ 20% of patients with resectable disease who also receive adjuvant therapy, one/three/five-year survival rates only approximate 70%/30%/18%. Better chemotherapies and/or other treatment modalities are needed to improve survival for pancreatic cancer patients. Methods: Two open-label nonrandomized phase II studies evaluate live, allogeneic, cellular immunotherapy (HyperAcute-Pancreas, HAPa) plus standard adjuvant gemcitabine-based chemotherapy/5-FU-based chemoradiotherapy for patients with resected pancreatic adenocarcinoma. Disease-free (DF) and overall (OS) survival are the primary and secondary endpoints, respectively. Results: To date, 62 patients have enrolled to receive standard adjuvant therapy plus biweekly injections of HAPa (average 9.2 injections, range 1-14, 44 patients with 37 injections). The median patient age is 61 years, with 52% (32/62) female. Prognostic data include median tumor size of 3.1 cm, lymph node-positivity rate of 81%, R1 resection rate of 26%, and CA 19-9 > 180 in 19% of patients. Median DFS has not been reached, with a 13.2-month lower 95% bound on the median DFS from Kaplan-Meier analysis, based on 22 patients with ∼ 11 months of follow-up. Compared to historical median DFS rates of ∼ 11 months, the data suggest a pending significant increase in median DFS. For patients with ∼ 1 year of follow-up, the OS rate is 90% (18/20). Common side effects of HAPa are erythema and induration at the injection site, with no significant grade 3 or 4 toxicities reported. Conclusions: Our data suggest that the addition of HAPa to standard adjuvant therapy for resected pancreatic cancer may improve survival. A phase III study is under way. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NewLink Genetics NewLink Genetics
Abstract 18676: Early Changes of Pulmonary Vascular Remodelling After Pulmonary Thrombendarterectomy Measured by Cardiac MRI
Authors: Andreas Rolf, Johannes Rixe, Won Kim, Christoph Liebetrau, Sebastian Szardien, Nils Koerlings, Thorsten Kramm, Stefan Guth, Christian Hamm, Eckhard Mayer
Journal: Circulation (2012)

Purpose: Chronic Thrombembolic Hypertension (CTEPH) occurs in about 3.8% of patients with acute pulmonary embolism. The longterm prognosis is poor, however pulmonary thrombendarterectomy (PEA) offers a potential cure with excellent outcome. Several surrogate markers of pulmonary vascular remodelling have been defined. The max. PA velocity and acceleration time (AT) or its equivalent normalised over ejection times (AT/ET) reflect pulmonary pressure, the relative area change of the PA (RAC) and PA-flow-contour analysis derived dicrotic notch are indicative of changes of pulmonary vascular resistance (PVR). All these parameters can be measured excellently by cardiac magnetic resonance (CMR). In the present study we sought to quantitate surrogate markers of pulmonary vascular remodelling and reverse remodelling before and after PEA by CMR. Methods: patients underwent CMR 2 ± 1 day before and 10 ± 2 days after PEA. Flow/Time curves, PA area and PA max. velocity were derived from Phase-Contrast velocity encoded gradient echo sequences. The temporal resolution was adjusted to 11 ms, sequences were acquired with three signal averages in free breathing to allow for longer acquisition times needed for increased temporal resolution. All numerical data are presented as means ± SD, differences were tested with t-test for paired data, differences in frequencies were tested with McNemar's test. Results: 65 patients were included, mean age 56 ± 16, 28 females. PA peak velocity improved from 61 ± 17 cm/s to 74 ± 19, p = 0.001, AT/ET improved from 0.32 ± 0.06 to 0.36 ± 0.09, p = 0.002, RAC showed a trend to lower values and decreased from 29 ± 1.9% to 25 ± 1.2%, p = 0.1, a diastolic notch was found in 51 of 65 patients before PEA and only in 12 of 65 patients post surgery, p = 0.0001. In those patients in which the notch persisted, there was a trend to smaller notch ratios post PEA 1.37 ± 0.17 vs. 1.12 ± 0.24, p = 0.06. Conclusion: CMR is an excellent tool to monitor pulmonary vascular remodelling after PEA for CTEPH. We were able to demonstrate improved surrogate markers of PA pressure and resistance as early as 10 days after PEA in a large series of 65 patients.
Statin use and inflammation in prostate biopsy tissue
Authors: J. Shannon, L. Collins, G. Adams, G. Luhr, M. Garzotto
Journal: Journal of Clinical Oncology (2007)

15624 Background: The statin class of drugs has been shown to affect tumors through a number of mechanisms including inhibiting tissue inflammation. Inflammation is a common finding in men undergoing a prostate biopsy and may play a role in prostatic tumorigenesis. We set out to determine whether the use of statin drugs was associated with altered tissue inflammation on prostate biopsy. Methods: Data were collected on all men with a PSA &lt;/= 10 ng/ml that underwent a prostate biopsy. A urinalysis to rule out the presence of infection was carried out in all men. The presence or absence of cancer and/or inflammation was determined by pathology report review. Statin data were recorded from the VA electronic pharmacy database. Statin duration and intensity variables were calculated for each subject based on total days used for each statin at each prescribed dose. Only men with a negative biopsy were considered in our analyses. Odds ratios (OR) as estimates of the relative risk for prostate inflammation associated with each level of statin use and 95 percent confidence intervals (CI) were obtained using pooled conditional logistic regression stratified on year of biopsy. Results: Out of 1,482 men with data available on inflammation, family history of prostate cancer, age and race; 436 were found to have prostatic inflammation. In final adjusted models stratified on year of biopsy (prior to 1997, 1997–2001, 2001 -2006) we found no association between any statin use (OR=0.88, 95% CI (0.70–1.11)), intensity of use (OR=0.93, 95% CI (0.86–1.01)), or duration of use (OR=0.932, 95% CI (0.86–1.01). These results did not change when individual statin types were analyzed. Conclusions: Statin use was not associated with a reduction in tissue inflammation in men undergoing a prostate biopsy. If statin use affects prostatic carcinogenesis, it is unlikely to do so by affecting tissue inflammatory networks. No significant financial relationships to disclose.
Effect of chemotherapy on exercise capacity in patients with advanced non-small cell lung cancer (NSCLC)
Authors: G. Kasymjanova, H. Kreisman, C. Pepe, L. Lajeunesse, S. Gagne, E. Dajczman, D. St. Pierre, J. Agulnik, D. Small
Journal: Journal of Clinical Oncology (2007)

9115 Background: The 6 minute walking distance (6MW) is commonly used to evaluate cardiopulmonary exercise capacity in a variety of patient (pt) populations. Although the 6MW test improved in advanced breast cancer pts who responded to 2 cycles of chemotherapy, (Nieman et al 1995), little is known about exercise capacity of pts with inoperable lung cancer. We prospectively evaluated 6MW in advanced NSCLC pts at diagnosis and following 2 cycles of chemotherapy (CT). Methods: 6MW was performed twice pre (one practice test) and once post 2 cycles of CT. Intent to treat (ITT) analysis was performed in pts who did not complete the last walk. A score of 0 was assigned to those who died and the last observation was carried forward for those with missing data. Results: 59 pts were enrolled though 6 pts withdrew following the practice test due to clinical deterioration (2 pts), pulmonary embolism (1pt), leg pain following the practice walk (1 pt) and withdrawal of consent (2 pts). The mean age of the remaining 53 pts was 61 ±11, PS was 0–1 in 46 (87%) and 2 in 7 (13%) of pts. 8 pts (15%) were stage 3A/3B and 45 (85%) were stage 3B /4 NSCLC. 45 (85%) pts received platinum-based doublets, whereas 8 (15%) had monotherapy. 39 pts completed the study and 14 pts did not complete the second evaluation (4 died, 8 withdrew due to worsening symptoms and 2 were lost for follow-up). The practice 6MW of the 20 pts who dropped out was 361±99 m compared to 448± 93m for the 39 who completed the study (p=0.002). The 6MW decreased from 461±108 m (range 247–748) to 431±98 (range 431–630) in the 39 pts who completed the study (p=0.02) and from 444±106 to 395±107 in the 53 pts using the ITT analysis (p&lt;0.003). There was a clinically significant (&gt;54 m) decrease in 6MW in 11 pts (28%), an increase in 6MW in 2 pts (5%), and no change in 26 (67%) others. The 6MW was higher in men and in pts in stages 3A/B (p&lt;0.05). Conclusions: Exercise capacity, measured by 6MW, declines significantly after two cycles of chemotherapy. This decline may have been underestimated as pts with lower 6MW were more likely to drop out of the study. No significant financial relationships to disclose.