tbuckley/cabot-search huggingface dataset:
A phase II study of DJ-927 administered orally once every three weeks as second line therapy to subjects with locally advanced or metastatic non small cell lung cancer (NSCLC) after failure of platinum-based non-taxane regimen
Authors: A. Szczesna, E. Milanowski, E. Juhász, I. Albert, J. Von Pawel, Z. Sztancsik, R. Oyama, P. Baas
Journal: Journal of Clinical Oncology (2006)

17006 Background: For the treatment of NSCLC (1 st and 2 nd line) effective oral formulations of drugs are currently investigated. DJ-927 is a semi-synthetic novel taxane with in vitro activity against NSCLC cells lines. Phase I studies show active plasma concentrations after oral administration with hematologic dose-limiting toxicity (DLT). This multi-centre phase II study was conducted to evaluate the safety and efficacy of the DJ-927 in patients (pts) with recurrent NSCLC. Methods: Pts with locally advanced or metastatic NSCLC who have received one prior platinum (non-taxane) containing treatment regimen, performance status 0 -2, and adequate organ function were enrolled. Pts received an initial DJ-927 dose of 27 mg/m 2 on day 1 of cycle 1, orally, every 3-weeks. If &lt; 2 DLTs occurred at this dose, the next cohort of 6 pts would start at a dose of 35 mg/m 2 , every 3 weeks, and all subsequent pts would be treated at that dose level. The primary endpoint was to assess the response rate. Pts were also assessed for time to disease progression (TTP), survival and safety. Results: 36 pts were enrolled, male/female 27/9; median age of 57 years (range 33–75); ECOG 0/1/2 7/21/8; stage IIIB/IV 12/24. Histology included adenocarcinoma 5; squamous cell 16; large cell 3; undifferentiated 3; other 7; unknown 2. Thirty-four pts received DJ-927; the median number of cycles was 2 (range 1–8). The optimal dosing level was confirmed at 27 mg/m 2 as no dose escalation was performed based on toxicity data from parallel studies. Response in evaluable pts (completed Course 1) included CR 1, PR 1, SD 15, PD 8; for an overall response rate of 7 % and a disease control rate (CR, PR and SD) of 61%. Toxicity, ≥ grade 3, in evaluable pts (n = 32) included neutropenia (15), anaemia (6), thrombocytopenia (2), fatigue (2), nausea (2), anorexia (2), pneumonitis (1). Conclusions: In a 3-weekly setting, an oral dose 27 mg/m 2 of DJ-927 shows limited efficacy in 2 nd line therapy for NSCLC with neutropenia, gastrointestinal toxicity and fatigue as major side effects. [Table: see text]
A phase II randomized double blind multicenter trial of gemcitabine (Gem) plus imexon (IMX) versus Gem plus placebo (P) in patients with chemotherapy-naïve pancreatic adenocarcinoma (PC).
Authors: S. J. Cohen, M. M. Zalupski, P. Conkling, F. W. Nugent, W. Ma, M. Modiano, R. A. Pascual, F. Lee, L. Wong, E. Hersh
Journal: Journal of Clinical Oncology (2010)

4076 Background: Imexon (Amplimexon) is a novel cyanoaziridine (MW: 111) which depletes thiols inducing oxidative stress and apoptosis. Like Gem, IMX inhibits ribonucleotide reductase and has synergistic cytotoxicity with Gem. In a phase I study of Gem plus IMX in PC, the combination was well tolerated at full doses of both drugs, with toxicity and overall survival comparable to historical controls with Gem alone. This phase II study assessed the efficacy of the combination compared to single agent Gem in a double blind, placebo controlled design. Methods: Patients were required to have metastatic (stage IV) PC, be chemotherapy naïve, have measurable disease and laboratory values within customary limits for a study in PC. A total of 142 PC patients were randomized at 34 US sites, to receive Gem at 1,000 mg/m2 on days 1, 8, 15 of a 28 day cycle and either IMX or IMX P at 875 mg/m2 on days 1, 8 and 15 of the cycle. IMX or IMX P was given over 60 minutes followed by Gem over 30 minutes. The primary endpoint of the study was overall survival with secondary endpoints being progression free survival, 6-month and one-year survival, response rate and toxicity. The study was blinded with Data Monitoring Committee oversight with the first efficacy analysis after 100 deaths. Accrual occurred from May 2008 to May 2009. Patient characteristics for the entire group were: median age 65 years (range 37-88), male/female ratio 56/44, ECOG PS 0/1 (%): 30/70 and metastatic (number):142. Anticipated toxicities based on our prior studies of the combination include fatigue, anemia, nausea, vomiting, leukopenia and abdominal pain. There were 32 serious adverse events which were considered possibly, probably or definitely related to the study regimens and included (by CTCAE category) gastrointestinal, infection, pain, blood bone marrow, constitutional symptoms pulmonary/respiratory, and one each in 7 other categories. As the study remains blinded, we cannot attribute the toxicity data to either arm of the study. The results of this study are anticipated between March and July of 2010 and if appropriate will form the basis of a phase III confirmatory study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AmpliMed Corporation AmpliMed Corporation AmpliMed Corporation
A phase II, single-arm clinical trial involving an alternative cancer treatment psorinum therapy in patients with advanced esophageal carcinoma.
Authors: Aradeep Chatterjee, Sudin Bhattacharya, Amitava Chakraborty, Radhe S. Bhakta, Ashim Kumar Chatterjee, Jaydip Biswas
Journal: Journal of Clinical Oncology (2012)

62 Background: We prospectively studied the clinical efficacy of an alternative cancer treatment “psorinum therapy” in treating advanced esophageal carcinoma (ECA). Methods: Our study was phase- II, open level, single arm and single stage. Participants’ eligibility criteria included (1) histopathology confirmation of ECA (2) inoperable tumor (3) no prior conventional cancer treatments (4) karnofsky performance status between 40 -70%. The primary outcome measures of the study were (1) to assess the radiological tumor response rate (using CT scanning procedure and following the RECIST criteria); (2) to assess how many participants survived at least 1 yr, 2 yrs, 3 yrs, 4 yrs and finally, after 5 yrs of the study. The secondary outcome measure was to assess the side effects of the investigational anti- cancer drug (psorinum) if any. Psorinum (an alcoholic extract of scabies slough and pus cells) was administered orally at a dose of 0.02ml / kg body weight / day as a single dose on an empty stomach for a complete course duration of 2 yrs to all the participants along with allopathic and homeopathic supportive cares. Results: 65 participants included in the final analysis at the end of the study. According to the RECIST criteria, complete response occurred in 11 (16.92%) case and partial response occurred in 20 (30.77%) cases. 44 (67.69%) of them survived at least 1 yr, 32 (49.23%) survived at least 2 yrs, 24 (36.92%) survived at least 3 yrs, 21 (32.31%) survived at least 4 yrs and 17 (26.15%) of them survived at least 5 yrs. These participants didn’t receive conventional or any other investigational cancer treatments. According to AJCC TNM staging system, 31 (47.69%) participants diagnosed at stage IV. Among them complete response observed in 4 (12.90%) cases, partial response observed in 8 (25.81%) cases and 5 (16.13%) of them survived at least 5 yrs. Conclusions: The results of the study show clinical efficacy of psorinum therapy in treating patients with advanced ECA. The investigational drug psorinum is non- toxic. Randomized controlled clinical trial should be conducted for further investigation of this alternative cancer treatment in treating esophageal cancer.
Pulmonary toxicity in patients with myeloma and lymphoma undergoing high dose chemotherapy and autologous stem cell rescue
Authors: C. D. Ford, R. Dent, J. E. Pearl, F. B. Petersen
Journal: Journal of Clinical Oncology (2005)

6677 Background: Eligibility determination for high dose chemotherapy and autologous stem cell rescue often includes pulmonary function testing (PFT). However, there is little current published information on the effects of commonly used high dose regimens on PFTs. Methods: We retrospectively reviewed the charts of 100 patients who received either high dose melphalan for myeloma (n= 47) or the BCNU containing regimens BCV/BEAM for lymphoma (n= 53) and who had undergone pre-treatment and at least one post-treatment PFTs. Paired and independent T tests were used to ascertain statistical significance. Results: Patients receiving melphalan (200 mg/m2) showed no significant change in their mean FVC, FEV1, and corrected DLCO [100% (range 76–133), 100% (76–142), 99% (68–166) of baseline, respectively] at 3 months post-transplant and a trend to improvement from baseline at 1 year that was significant in the case of FVC (p=0.02). Contrarily, patients receiving BCNU regimens showed significant decreases in mean FVC, FEV1, and DLCO at 3 mos. [92% (range 66–114; p<0.001), 95% (77–115; p<0.001), and 82% (47–113; p<0.001) of baseline, respectively]. By one year, FVC and FEV1 in lymphoma patients had recovered but DLCO, although improved to a mean of 89% (range 62–116) of baseline, remained significantly lower (p=0.003). Patients with lymphoma who had received prior mediastinal irradiation and/or bleomycin had greater decreases in the 3-month DLCO but these differences did not reach statistical significance. No detrimental effects on 3-month decreases were discernable for age, smoking history, the use of high dose cyclophosphamide in the mobilization regimen, amount of prior chemotherapy, or prior history of pulmonary disease such as pulmonary embolus and pneumonia. Conclusions: On average, high dose melphalan produces little pulmonary toxicity. BCNU containing regimens should be used more cautiously. The relative contributions of measurement error and patient variability to the wide ranges are currently under study. More work should be directed at identifying the factors, other than the preparative regimens, that contribute to pulmonary function compromise following high dose regim ens. No significant financial relationships to disclose.
424. Successful Immunotherapy of Cancer Stem Cells Requires Memory and the Adaptive Immune System of the Host
Authors: Patrick Schmidt, Nicolas Desbaillets, Pierre Dessen, Nancy Thompson, Joerg Huelsken
Journal: Molecular Therapy (2015)

The Cancer Stem Cell (CSC) hypothesis puts a, not necessarily rare, subpopulation of cells on the top of a tumor forming hierarchy, pointing to the importance of their destruction when aiming on a final cure. However, current studies targeting CSCs rather focus on the tumor initiating capacities of these cells than on their maintaining capacity in an established lesion. In this presentation we describe an immunotherapeutic approach of targeting the minor CSC subfraction by exploiting the stem cell related wnt-pathway. We found that a memory effect, provided by engineered T cells, is essential to keep the re-formation of CSCs from bulk tumor cells under control. Furthermore, our treatment setting is able to re-activate the host's non engineered T cells against the majority of tumor cells, which leads to a long lasting tumor-free survival in our mouse model system. These findings implicate a leading role for immunotherapy when targeting the tumor stem cell fraction.
Open versus robot-assisted radical prostatectomy: A contemporary analysis of an all-payer discharge database.
Authors: Jeffrey J. Leow, Quoc-Dien Trinh, Benjamin I. Chung, Steven L. Chang
Journal: Journal of Clinical Oncology (2015)

33 Background: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted in the US despite the lack of Level 1 evidence. There is no conclusive evidence regarding its morbidity profile compared to open RP (ORP). Our aim was to compare perioperative outcomes of RARP vs. ORP on a contemporary cohort of patients. Methods: Using the Premier Hospital Database, an all-payer discharge database representing over 600 hospitals in the US, we captured men diagnosed with prostate cancer (ICD-9 code 185) who underwent a radical prostatectomy (60.5) from 2003 to 2013.We classified procedures as RARP through a review of the charge description master by identifying supplies unique to robotic procedures. We evaluated 90-day postoperative complications (using Clavien classification), transfusion of blood products, operating room time, length of stay and direct hospital costs. We performed regression analyses, adjusting for potential confounders, accounting for clustering by hospitals and survey weighting to ensure nationally representative estimates. Results: Over the 11-year study period, there was a total of 345,313 ORP and 328,731 RARP. The use of RARP grew rapidly from 2% in 2003 to 85% in 2013 (p&lt;0.001). On adjusted analyses, compared to ORP, RARP patients were less likely to suffer major complications (odds ratio [OR] 0.77, p=0.03), readmissions (OR 0.81, p=0.02), or receive blood products (OR 0.28, p&lt;0.001). RARP patients had shorter LOS (-0.88 days, p&lt;0.001). Mean operating room time for RARP was longer by 71 min (p&lt;0.001); higher surgeon and hospital volume were significant predictors of shorter operating time. 90-day direct hospital costs were higher for RARP (+$4085, p&lt;0.001), primarily attributed to operating room and supplies costs. Conclusions: Our contemporary analysis of men who underwent RP found that the robotic approach appears to confer a perioperative morbidity advantage at a higher cost. The widespread adoption of RARP in the management of localized prostate cancer implies a randomized trial will unlikely be conducted; therefore this large retrospective study may represent the best available evidence for the morbidity and cost profile of ORP vs. RARP.
Effect of primary polychemotherapy after sentinel lymph node biopsy on the necessity for lymphadenectomy in stage II breast cancer patients
Authors: U. Bohn, M. Pavcovich, P. Jimenez, M. Hernandez, M. Lloret, M. Cazorla, I. Reyes, T. Baratta, C. Bustos
Journal: Journal of Clinical Oncology (2009)

e11589 Background: Sentinel lymph node (SLN) biopsy is the standard procedure for assessing axillary status in stage I-II breast cancer patients. Realizing this procedure before the administration of primary polichemotherapy would reduce the number of unnecesary lymphadenectomy in patients with negative sentinel lymph node. Methods: From January 2006 to May 2008, twenty-one patients with breast cancer on stage II-IIIA were included in the study. The median age was of 49 years (range 22–74y). The median palpable tumour size was of 3.5cm (range 1.8–6.0) and by ultrasonography 2.0cm (range 1.8–5.0cm.). Stage II:19 and Stage III:2 (cT:6.0cm.). Breast biopsy was performed in all cases with: IDC:20. G1:9 (42,8%), G:2:11(52%) and G3:1(4,76%). ER+:18 (85,7%), PR+:13 (61,9%), HER2 (+):6 (28,5) and triple negative:3 (14,2%).The scheme of treatment was: 4Epi: 90mg/M2 and Cyclophosphamide 600mg/M2 day 1/3w/4cycles, followed by paclitaxel (P) 100mg/M2 day 1/wekly/8. Trastuzumab was given during one year 4/2mg/Kg and started with (P). Tumorectomy and limphadenectomy was planned, followed by radiotherapy ± Hormonotherapy ± trastuzumab. Results: The 21 patients were evaluable for the analysis. The median sentinel lymph nodes resected was of 2 (range 2–6). The SLN biopsy was positive in 12 (57,1%) cases and negative in 9 (42,8%). Followed the primary chemotherapy, tumorectomy and axillary lymphadenectomy (AL) were performed in all 21 cases. The 12 positive SLN showed in the AL 9/12 (75%) pN0 and the 9 negative SLN showed in the AL 0/9 (0%) pN1. There were 4/20 (20%) completely pathological tumour response and 4/20 (20%) cases with only isolated malignant cells. The treatment was well tolerated with not a case of grade 3–4 toxicity. Conclusions: The primary chemotherapy given after the biopsy of sentinel lymph node was very effective showing in the lymphadenectomy a high percentage of pathologic negative lymph nodes (9/12) and an overall tumour response of 40% (8/20) with 4/20 (20%) completely pathological response and 4/20 (20%) cases with only isolated malignant cells. No significant financial relationships to disclose.
Conflicts Of Interest In Pharmaceutical Sponsored Research On Erythropoietin Receptors In Cancer: An Updated Analysis
Authors: Alyssa Trenery, Samuel Kessler, Van Slooten Eleasa, Akida Lebby, Charles L. Bennett, Paul Yarnold, Paul Ray, Dennis W. Raisch, Gowtham Rao, Peter Georgantopoulos, LeAnne Norris, Simone Boyle, Ashlyn Byrne, Matthew Bialkowski, Oliver Sartor
Journal: Blood (2013)
Second cancers after uterine cervical cancer treated with radiation therapy
Authors: T. Ohno, S. Kato, H. Tsujii, S. Sato, K. Fukuhisa, M. Wakatsuki, T. Nakano, T. Arai
Journal: Journal of Clinical Oncology (2005)

5028 Background: Characterization of second cancer risk after radiation therapy is important in terms of patient management and enabling clinicians to choose the optimal treatment. Methods: We analyzed 2167 patients who had been treated with radiation therapy for uterine cervical cancer between 1961 and 1986. Relative risks (RRs) of second cancer were calculated by using the disease expectancy table provided by the Center for Adult Disease in Osaka. Results: The total number of person-years follow-up was 25771 and 60 patients were lost to follow-up. Two hundred and three patients developed second cancer after radiation therapy, which represents a significant increase in risk compared with a comparable normal population (RR=1.19, 95%CI=1.03–1.37). The estimated cumulative probability for development of a second cancer was 10.9% at 15 yeas and 19.8% at 25 years. The risk was significantly elevated for uterine corpus (RR=6.6, 95%CI=3.10–13.53), lung (RR=1.65, 95%CI=1.07–2.47), and leukemia (RR=3.11, 95%CI=1.35–6.88). Of the 1364 patients who survived longer than or equal to 5 years, 40 developed second cancer in the irradiated field. The estimated cumulative probability for development of a second cancer was 2.38% at 15 yeas and 4.77% at 25 years. In patients who developed second cancer in the irradiated field, the 5-year overall survival rate was 11.2% and the median survival time was 6 months, indicating the poor prognosis. Conclusions: Significantly increased risk of second cancers after radiation therapy for cervical cancer was observed and the cumulative probability of developing second cancers has increased with longer follow-up. No significant financial relationships to disclose.
A phase II study of tasisulam sodium (LY573636) as second-line treatment for patients with unresectable or metastatic melanoma.
Authors: J. M. Kirkwood, R. Gonzalez, D. S. Reintgen, P. R. Clingan, R. R. McWilliams, R. L. Ilaria, D. P. de Alwis, A. Zimmermann, M. P. Brown, M. Millward
Journal: Journal of Clinical Oncology (2010)

8541 Background: Tasisulam is a novel anticancer agent that induces apoptosis through the intrinsic pathway and has antiangiogenic properties in vitro. The mechanism of action is being further evaluated. Tasisulam has demonstrated activity across a broad range of tumors, including melanoma. The primary objective of this phase II study was to determine the overall response rate (ORR) in pts who received tasisulam as second-line chemotherapy for unresectable or metastatic melanoma. Secondary objectives aimed to characterize the clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), duration of response, and the pharmacokinetics and safety of tasisulam. Methods: Tasisulam was administered IV over 2 hours on day 1 of 21-day cycles using a lean body weight-based dosing algorithm targeting a Cmax of 420 μ g/mL as a loading dose in cycle 1 and a chronic dose (65% of the loading dose) in subsequent cycles. Tumor response (investigator assessed) was evaluated according to RECIST and toxicity according to NCI-CTC (v3). Results: Of the 68 pts enrolled, 26 (38%) were females and 42 (62%) were males with a median age of 59 years (range, 26-83). Most pts had an ECOG PS of 1 (54%) and stage IV disease (88%). No pts had CR; 8 (12%) pts had PR, for an ORR (CR+PR) of 12% (90% CI, 5-18%). 24 (35%) pts had SD (no progression after 2 cycles), and the CBR (CR+PR+SD) was 47% (90% CI, 37-57%); 25 (37%) pts had PD, and 11 (16%) pts did not have complete lesion measurements. Median PFS was 2.6 months (90% CI, 1.5-2.9) and median OS was 9.6 months (90% CI, 7.1-11.9). Most common (> 5 pts) grade 3 and 4 drug-related hematologic toxicities were thrombocytopenia in 3 (4%) and 11 (16%) pts, neutropenia in 5 (7%) and 6 (9%) pts, respectively, and anemia in 5 (7%) pts (grade 3 only). Most common drug-related nonhematologic toxicities were fatigue in 5 (7%) and mucositis/stomatitis in 3 (4%) pts (grade 3 only). Conclusions: Tasisulam administered at a targeted Cmax of 420 μ g/mL on day 1 of 21-day cycles demonstrated activity and tolerable toxicity as second-line treatment in pts with malignant melanoma. A registration trial is ongoing in metastatic melanoma. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Eli Lilly Australia, Lilly Lilly Eli Lilly Australia Eli Lilly Australia, Lilly Eli Lilly Australia
Effects of zoledronic acid in prostate cancer cell lines: A pharmacogenomic approach
Authors: A. G. Pinillos, J. M. Alfaro, G. Gomez, E. Fernandez, C. Paino, A. Moyano, F. J. M. Alonso, M. I. Arenas, A. Molares, E. Caso, M. V. T. Lobo
Journal: Journal of Clinical Oncology (2005)

4782 Background: The LNCaP and the PC3 cells are widely used as models for prostate cancer. Aminobisphosphonates inhibit proliferation and induce apoptosis in these cells by interfering the mevalonate pathway. We tested the hypothesis that some of its effects over cell growth could be amelorated by the uptake of cholesterol from serum lipoproteins. Methods: The response of androgen-dependent, low-passage (LP) LNCaP and androgen-independent, high-passage (HP) LNCaP and PC3 cells to zoledronic acid was studied. Cells were grown in RPMI with 5% foetal calf serum and treated with zoledronate at different concentrations. Cells cultured with lipoprotein depleted serum (LPDS) were also included. We have analysed the genetic profile of untreated vs. zoledronic-acid treated cells by the use of cDNA microarrays (HG-Focus array, 8,500 genes, from Affymetrix). We studied the changes in genes involved in cholesterol metabolism. Results: PC3 were more sensitive to zoledronate-induced cell growth inhibition and the effects were not be significantly amelorated by serum lipoproteins. The apparent resistance of LP-LNCaP cells could be partially reversed by removing the lipoproteins from serum. It suggests the existence of compensatory mechanisms for the inhibition of the mevalonate pathway in these cells, and that an increased use of cholesterol from lipoproteins may play an important role. We also studied the effects of LPDS in HP-LNCaP cells, where the effects were similar to that observed in PC3. When data from microarrays were analysed, an increased expression in LP-LNCaP cells and a reduced expression in PC3 cells observed in the genes of enzymes of mevalonate pathway, lipases and lipoprotein transporters. Mevalonate decarboxylase, farnesyl transferase, 7-dehydrocholesterol reductase and lipase A, cholesterol transporters, the low density lipoprotein receptor and the scavenger receptor class B isotype II (not previously described in prostate cells) were the most affected. Conclusions: These changes might also reflect different adaptative responses to zoledronate and therefore, different mechanisms for chemoresistance. This study was supported by Novartis Spain and the Instituto de Salud Carlos III (project Fis02/3003). No significant financial relationships to disclose.