tbuckley/cabot-search huggingface dataset:
Risk factors for malignant spinal cord compression and leptomeningeal metastases in cancer patients presenting to an urgent care center
Authors: A. D. Klotz, A. B. Lassman, W. Shi, H. Thayler, J. Groeger
Journal: Journal of Clinical Oncology (2008)

9606 Background: Malignant spinal cord compression is an oncologic emergency that is associated with considerable morbidity including irreversible loss of neurologic function. As many of the presenting signs and symptoms of spinal cord compression are common to other less-threatening conditions, it would be helpful to identify early clinical predictors specific for spinal cord compression. Methods: The medical records of all patients who presented to the emergency department of a cancer center and required spine MRI imaging in 2003 were reviewed. MRI findings were correlated with neurologic presentation. Results: There were 176 MRIs performed on 164 patients (84 men, 80 women; median age 63, range 22–96) with breast (n=31, 19%), prostate (n=29, 18%), lung (n=26, 16%), colon (n=9, 5%), myeloma (n=9, 5%), or other malignancies (60, 37%). Fifty two (29.6%) MRIs demonstrated spinal cord compression (SCC, defined as thecal sac compression with associated T2 signal change in cord) and 13 (7.4%) demonstrated incidental leptomeningeal metastases (LM). Multivariate logistical regression analysis identified four independent predictors of SCC: male gender (OR=2.95, 95% CI= 1.27–6.85, p=0.01), prior history of vertebral fracture (OR=9.09, 95% CI= 3.90–21.17, p< 0.0001), severe back pain (OR=4.21, 95% CI= 1.76–10.06, p= 0.001), and abnormal sensory exam (OR=9.45, 95%CI= 3.29–27.20, P<0.0001). SCC was noted in 13% of patients with only one risk factor and 90% of patients with 3 or more risk factors. Of note, 21 (40%) of scans demonstrating SCC were performed in patients without clinical evidence of weakness. The three independent risk factors associated with the presence of LM include: age less than 55 (OR=5.52, 95% CI= 1.40–21.7, p=0.02), extensor plantar reflex (OR=10.96, 95% CI= 2.77–43.46, p<0.001), and absence of tenderness upon palpation of spine (OR=8.02, 95% CI= 2.06- 31.23, p=0.003). Conclusions: Some of these findings are consistent with prior retrospective studies and provide a useful framework for assessing cancer patients in whom the diagnosis of SCC or LM are considered. In particular, absence of leg weakness does not exclude SCC, and the high rate of incidental LM demonstrates the importance of performing contrast enhanced scans. No significant financial relationships to disclose.
CO2血管造影と血管内超音波(IVUS)を用いて総腸骨動脈ステント留置術を行った閉塞性動脈硬化症の1症例
Authors: 坂本佳子, 中村郁子, 松下哲也, 藤松大輔, 琴岡憲彦, 諸岡俊文, 吉田和代, 橋本重正, 挽地裕, 井上晃男, 野出孝一
Journal: Circulation (2007)
Vitamin E for oxaliplatin-induced peripheral neuropathy prophylaxis: A randomized phase II pilot study.
Authors: S. O. Afonseca, D. d. I. G. Cubero, A. Del Giglio
Journal: Journal of Clinical Oncology (2011)

e19505 Background: Oxaliplatin (Ox) is platinum based and frequently used medication that is a part of many chemotherapy regimens for several gastrointestinal malignancies. One of the most important limitations to its use is the induction of both acute and chronic peripheral neuropathy (PN) that affects most of the treated patients, requiring at times even treatment interruption. Previous studies showed that vitamin E could reduce by 50% PN induced by cisplatin. We aimed at evaluating if Vitamin E could also prevent Ox induced acute PN. Methods: This is a prospective, phase II, randomized pilot study. Patients were randomized 5 days before Ox to receive either vitamin E 400 mg daily or placebo, continuously, until after the end of Ox based chemotherapy. We evaluated PN intensity by the CTCAE version 3 and specific Ox PN gradation scales, as well as the speed of conduction and the amplitude of the electric potentials of the right ulnar and sural nerves before and at the end of Ox based treatment. We included patients with colorectal and gastric cancer scheduled to receive Ox based regimens (FLOX, FOLFOX, EOX, XELOX). We excluded patients with a previous history of PN or of having received other chemotherapy regimens (except isolated 5-fluouracil) and those currently receiving gabapentin, carbamazepine, amytriptiline, amifostine or multivitamins. Both groups received calcium and magnesium supplements before and after oxaliplatin infusions. This study was designed to detect a 50% decrease in the incidence of PN with a power of 0.8 and a type I error of 0.05. Results: 18 patients were randomized to Vitamin E and 16 to Placebo. We observed throughout the study 83% of grades I/II PN in Vitamin E versus 68% in the placebo group (p = 0.45). No statistically significant differences were observed in the nerve conduction studies between groups. We observed a trend of more diarrhea in patients who received vitamin E (55.6 vs 18.8%, p = 0.06) without other significant differences in the toxicities between groups. Conclusions: We could not demonstrate in this study a significant decrease in the incidence of acute Ox induced PN with vitamin E.
Survival without quality of life decrease in old women with metastatic breast cancer treated by chemotherapy
Authors: E. Carola
Journal: Journal of Clinical Oncology (2005)

904 Background: Today more than 50% of women suffering from breast cancer are 65 years old and over. Besides, a specific screening is recommended to estimate these patients’ overall health conditions. So we carried out a study regarding older patients with metastatic breast cancer treated by LFM (Leucovorine, 5Fu, Mitoxantrone). The main purpose being to evaluate their survival without quality of life decrease. We chose the following specific validated scales that are easy to use for older people: • Katz Scale for Daily Activities Living • Goldberg Scale for Anxiety • Iris Scale for quality of life • Minimental test of Folstein for cognitive function Results: fourteen patients participated. Average age was 78 (73–86). Performance status (OMS) is 0 for 21.4%, 1 for 35.7%, 2 for 28.6%, unknown for 14.3%. Main metastatics locations are bone, liver and lung. 76 courses were studied. Thirteen patients were evaluated for toxicities. 53% had a neutropenia grade 3–4, but only one patient had a febrile neutropenia (7.7%); 30.8% had an athenia grade 2; 7.7% had an anemia grade 2 (without using erythropoëtine); main non-hematological toxicities were one mucositis grade 3, one nausea grade 2, 3 alopecia grade 1 and one headache grade 2. The global response rate is 14.3% (all partial response); Stabilization rate is 64.3% and progress rate is 7.1%; one patient was non evaluable and another one non measurable.With a three-years follow-up the global survival is 20% and the desease free survival is 13%. Every responders had no change or improvement in score of quality of life. Conclusion: these results reveal the following issues: First that specific screening for older patients are very hard to get from oncologists. Second that if chemotherapy is probably possible for older people, many questions still remain specially regarding benefits/ toxicity risks. Meaning that more studies will be necessary to give older population affected by cancer desease the most appropriate treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Fentanyl as pre-emptive treatment of pain associated with turning mechanically ventilated patients: a randomized controlled feasibility study
Authors: Gemma Robleda, Ferran Roche-Campo, Maria-Àngels Sendra, Marta Navarro, Ana Castillo, Ainhoa Rodríguez-Arias, Elena Juanes-Borrego, Ignasi Gich, Gerard Urrutia, José M. Nicolás-Arfelis, Kathleen Puntillo, Jordi Mancebo, Josep E. Baños
Journal: Intensive Care Medicine (2015)
Bosutinib (SKI-606) exhibits clinical activity in patients with Philadelphia chromosome positive CML or ALL who failed imatinib
Authors: C. Gambacorti-Passerini, T. Brummendorf, H. Kantarjian, G. Martinelli, D. Liu, T. Fisher, B. Hewes, A. Volkert, R. Abbas, J. Cortes
Journal: Journal of Clinical Oncology (2007)

7006 Background: Bosutinib (SKI-606) is an orally available, dual Src/Abl kinase inhibitor. To assess safety and preliminary clinical activity of bosutinib, we conducted a phase 1/2 study in patients (pts) with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) who were imatinib resistant/intolerant. Methods: In part 1, 18 pts with imatinib- relapsed/refractory chronic phase (CP) CML received bosutinib 400 mg/day (3 pts), 500 mg/day (3 pts), or 600 mg/day (12 pts). Part 2 was an expanded cohort of 51 pts with all phases of Ph+ CML and ALL dosed at 500 mg daily. Timed blood samples were collected on days 1–3, 15 for PK analysis. Results: Of 69 pts, median age was 59 yrs; 48 were CP; 90% imatinib resistant. Drug-related grade 1/2 adverse events (AEs) occurring in =10% of CP pts: diarrhea (69%), nausea (44%), vomiting (19%), abdominal pain (13%), rash (13%). Grade 3/4 AEs occurring in =5% of CP pts: rash (6%), thrombocytopenia (6%). 17 pts required dose reductions. In evaluable imatinib-resistant CP-CML pts with no prior exposure to other Abl inhibitors, 16/19 (84%) had complete hematologic response (CHR); 4/21 had partial and 7/21 had complete cytogenetic responses for major cytogenetic response (MCyR) rate of 52%. Of 58 pts evaluable for mutations, 13 different imatinib-resistant mutations were found in 32 pts. 12/14 CP pts with non-P-loop mutations and 3/3 with P-loop mutations achieved CHR. 5/11 CP pts with non-P- loop mutations and 1/1 with P-loop mutation achieved MCyR. 4/9 evaluable advanced leukemia pts had CHR, 2 had MCyR. After oral administration, steady state exposure of bosutinib was nearly 2-fold higher than single-dose exposure. Mean elimination half-life was approximately 22–27 hours, supporting a once-daily dosing regimen. Conclusions: Bosutinib was well tolerated in pts with CML, with primarily low-grade gastrointestinal and dermatologic AEs. Bosutinib showed clinical activity in imatinib-resistant pts with cytogenetic responses and CHR across a range of mutations. Durability of response continues to be assessed. [Table: see text]
Population characteristics and prognostic factors in metastatic non-small cell lung cancer (NSCLC): The Fox Chase Cancer Center (FCCC) experience
Authors: V. Paralkar, T. Li, C. J. Langer
Journal: Journal of Clinical Oncology (2007)

7644 Background: With increasing use of MRI and PET to stage NSCLC, the demographics, performance status and distribution of metastases at diagnosis in this patient (pt) population are changing; it is important to reassess the prognostic roles played by baseline clinical variables in the modern therapeutic era. Methods: We retrospectively evaluated the charts of 189 consecutive, unselected pts with stage IV NSCLC seen and followed at the Fox Chase Cancer Center between Oct 2000 and Aug 2003. Data on a variety of pt variables including demographics, histology, metastases, key laboratory tests and treatment were compiled. We intended to identify those that played statistically significant prognostic roles. Results: Median age at diagnosis was 62 years; 77% of pts had PS 0–1 at first presentation. 58% had single organ metastasis; 35% had metastases to the brain (half of these had brain only and a third had solitary brain metastasis). 51% of all pts received palliative radiation to the brain at some point after dx. Overall median survival was 10.8 months. The 1-yr, 2-yr, 3-yr and 4-yr overall survival rates were 44.2%, 21.9%, 11.6% and 7.8% respectively. On multivariate analysis, statistically significant negative prognostic factors included PS ≥ 2 (HR: 1.9, 95% CI: 1.1–3.3), serum albumin ≤ 3 (HR: 1.7, 95% CI: 1.1–2.8) and metastases to &gt; 1 organ (HR: 1.6, 95% CI: 1.03–2.3). Bone and liver metastases, though associated with worse survival in univariate analysis, were not found to be independent predictors of survival. Gender had no bearing on outcome. Conclusions: Survival rates in this advanced NSCLC cohort equal or exceed contemporaneous ECOG figures. PS, serum albumin and number of organs with metastases are independent prognostic factors in NSCLC. The increasing detection of brain metastases at 1st presentation of metastatic NSCLC suggests that the role of prophylactic cranial irradiation in the management of early NSCLC should be explored. No significant financial relationships to disclose. [Table: see text]
Combined analysis of P53 Arg72Pro, GSTM1 and GSTT1 gene polymorphisms as predisposing factors for non-small cell lung cancer (NSCLC) development
Authors: R. Dziadziuszko, A. Szymanowska, E. Jassem, A. Borg, K. Holm, M. Perkowska, W. Rzyman, G. Kobierska-Gulida, J. Limon, J. Jassem
Journal: Journal of Clinical Oncology (2005)

9581 Background: Gluthatione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphisms are involved in biotransformation and detoxification of potential carcinogens. Arg72Pro P53 gene polymorphism is suspected to be a predisposing factor for NSCLC development as polymorphic variants of this gene have markedly different apoptotic potential. The aim of this study was to establish the frequencies of the polymorphic Arg72Pro, GSTM1 and GSTT1 genotypes in Polish population and to assess the associated risk of NSCLC development. Methods: Study group included 240 NSCLC patients (52 females and 188 males) who underwent pulmonary resection between the year 1996 and 2000. Control group included 590 healthy subjects. DNA was extracted from frozen blood samples. Genotyping of GSTM1 and GSTT1 genes was performed by PCR-based techniques with co-amplification of human beta globin gene as a positive internal control. Arg72Pro was evaluated by RFLP and DHPLC methods. Results: The proportion of Arg72Pro (pro72 variant), GSTM1null and GSTT1null polymorphisms in NSCLC patients was respectively 54%, 58% and 22% compared to 46% (odds ratio [OR] 1.38; 95%CI 1.01–1.87), 49% (OR 1.43; 95%CI 1.06–1.94) and 21% (OR 1.06; 95%CI 0.74–1.53), respectively in healthy subjects. The proportion of GSTM1 null genotype combined with pro72 variant of the P53 gene in NSCLC patients and in healthy subjects was 33% and 21%, respectively (OR 1.93; 95% CI: 1.37–2.72). Conclusions: These results indicate that P53 (pro72 variant) and GSTM1 (null genotype) polymorphisms carry increased risk of NSCLC development. This effect is particularly high in carriers of both polymorphic genotypes. GSTT1 polymorphism does not carry increased risk of NSCLC development. No significant financial relationships to disclose.
Phase II study of hydroxyurea and gemcitabine in recurrent or persistent squamous cell cancer of the head and neck
Authors: S. Shibata, D. Lim, Y. Yen, M. Koczywas, R. Morgan, L. Leong, G. Somlo, K. Margolin, C. Ruel, J. Doroshow
Journal: Journal of Clinical Oncology (2006)

15524 Background: Preclinical studies demonstrate increased activity when hydroxyurea (HU) is given prior to gemcitabine (G). Clinical feasibility was demonstrated in a phase I trial (Yen, et. al. Cancer Chemother Pharmacol. 2002 ). We performed a phase II trial treating patients (pts) with squamous cell head and neck cancers (SCCHN). Methods: Pts had metastatic or incurable locally recurrent SCCHN. Prior chemotherapy was allowed, but not required. Serum creatinine ≤2.0 mg/dl, bilirubin &lt;3.0 gm/dl, AST/ALT &lt;5× ULN and KPS ≥60% were required. HU 500 mg orally every 6 hours for 4 doses was given on day 1 of a 21-day cycle. On day 2, 6 hours after HU, G 750 mg/m 2 was given over 30 minutes. This sequence was repeated on day 8 and 9. After 8 pts, G was given at 500 mg/m 2 . G-CSF was given on day 10 and until the WBC count was &gt;10k/μl. The primary endpoint was response rate (RR), with an early stopping rule for &lt;3 objective responders among the first 18 pts. Results: 22 pts (17 M) were accrued, 16 with prior chemotherapy and 19 with prior radiation. The first 8 pts received G 750 mg/m 2 . Two pts died of neutropenic fever (NF) during course 1. Subsequently 14 pts received G 500 mg/m 2 . 18 pts were evaluable for response, with 1 still in follow-up. Partial response was seen in 1 pt, stable disease in 9, and progressive disease in 8. The overall median survival of the 22 pts was 6 months and the median progression free survival (PFS) was 2 months. The primary toxicity was hematologic. Grade 4 neutropenia was seen in 7/22 pts during the 1 st cycle (5 at G 750 mg/m 2 ) with 5 cases of NF. Grade 4 thrombocytopenia occurred in 1 pt at G 750 mg/m 2 . Conclusions: The RR and PFS of treated pts treated were not promising and further accrual is not planned. Analysis of biopsy materials is planned to see if responsive pts can be selected. (Supported by NCI Grant CA33572). No significant financial relationships to disclose.
An international phase II study of cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with metastatic colorectal cancer (CRC) expressing Epidermal Growth Factor Receptor (EGFR). Preliminary results
Authors: J. M. Tabernero, E. Van Cutsem, J. Sastre, A. Cervantes, J.-L. Van Laethem, Y. Humblet, P. Soulié, S. Corretgé, M. Mueser, A. De Gramont
Journal: Journal of Clinical Oncology (2004)

3512 Background: Cetuximab (Erbitux) is an IgG1 monoclonal antibody targeting the EGFR, shown to be effective in patients (pts) with EGFR-expressing metastatic CRC refractory to prior irinotecan-based chemotherapy (Cunningham ASCO 2003). Cetuximab has demonstrated high efficacy with an acceptable safety profile in combination with different regimens of irinotecan/FA/5-FU as 1st-line treatment (Rosenberg ASCO 2002; Van Laethem and Folprecht ASCO 2003). This trial was designed to evaluate the efficacy and safety of cetuximab with the FOLFOX-4 regimen as 1st-line treatment. Methods: Pts received cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) plus FOLFOX-4 (every 2 weeks: oxaliplatin 85 mg/m2, day 1; FA 200 mg/m2 IV 2h and 5-FU 400 mg/m2 IV bolus followed by 600 mg/m2 IV for 22h, days 1 and 2) until PD or unacceptable toxicity. Main inclusion criteria included pts with non-resectable metastatic CRC, EGFR expression on tumor, no previous chemotherapy for metastatic CRC, and ECOG PS = 2. Results: Of the 61 pts screened 50 (82%) showed EGFR expression on the tumor. 43 pts have finally been enrolled. Currently, baseline data from 25 enrolled pts are available: M/F 16/9, median age 65 years (range 43–75), colon/rectum 17/8, ECOG PS=0/1 16/9, number of organs affected=1/2/3: 13/9/3. The observed best overall response was based on 20 evaluable pts: 14 (70%) partial response (of these, 7 responses have been confirmed so far), 5 (25%) stable disease, 1 not evaluable who withdrew his consent after 1st infusion. Two pts underwent curative resection of their hepatic metastasis after confirmed response. So far, 8 serious adverse events were observed (4 5-FU related diarrhea, 1 pulmonary embolism, 1 pneumonia, 1 PD with obstructive jaundice, 1 gout) none of them related to cetuximab. Conclusion: These preliminary data suggest that cetuximab may be safe and effective when combined with FOLFOX-4 in first-line treatment of patients with metastatic CRC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Farma y Quimica, S.A; Merck KGaA Merck KGaA Merck KGaA
Neoadjuvant, adjuvant, and palliative treatment with imatinib in patients with gastrointestinal stromal tumors.
Authors: B. E. Nilsson, K. Sjolund, E. P. Nilsson, B. Wangberg, O. Nilsson, H. Ahlman
Journal: Journal of Clinical Oncology (2010)

10087 Background: The tyrosine kinase inhibitor (TKI) imatinib is the first-line palliative treatment inhibiting mutated KIT. Our aim was to compare the survival of patients only surgically treated in the preimatinib era with that after introduction of the drug in a defined population. Methods: During 2002-2008, 107 GIST patients were treated. Neoadjuvant imatinib (n=10) was used for organ-preservation, patients with R0-resection received imatinib adjuvantly (n=45), and those with R2-resection had life-long palliative imatinib (n=28) Patients with low/intermediate risk GISTs (n=23) underwent surgery only. These groups were compared with historic controls from our population-based series (n= 259) matched for sex, age, tumor size, and mitotic rate. Mutational analysis of KIT and PDGFRA was performed in all cases. Results: In the high-risk group 10 patients had neoadjuvant imatinib with 100% 5-year estimated progression-free survival (vs. 30% in 89 matched historic controls, p<0.001). The mean size of these tumors decreased in diameter from 20.3 cm to 10.1 cm and the surgical procedures were thus limited (gastric resection, wedge liver resections, and salvage of cardia, pancreas and rectum). 45 patients with high risk GIST had adjuvant imatinib after radical (R0) surgery, with 85% 5-year estimated recurrence-free survival (p<0.001) vs. 35% in historic controls; 28 patients were treated with palliative imatinib after tumor reduction (R2) with 55% 5-year estimated over all survival vs. 5% in 29 historic controls (p<0.001). In the low/intermediate-risk (NIH consensus) group there were no recurrences after surgery only vs. 3 in the historic control group. Conclusions: Neoadjuvant treatment with imatinib is recommended for patients with bulky tumors to facilitate organ preserving surgery, and adjuvant imatinib only for high (not intermediate) risk patients after with R0 resection. Palliative imatinib improves survival in R2 resected patients. No significant financial relationships to disclose.
Phase I clinical and pharmacokinetic study of a 14-day infusion of etoposide in patients with lung cancer.
Authors: H Minami, K Shimokata, H Saka, H Saito, Y Ando, K Senda, F Nomura, S Sakai
Journal: Journal of Clinical Oncology (1993)

PURPOSE A phase I study was conducted to determine the maximum-tolerated dose (MTD) of a 14-day continuous infusion of etoposide, and to evaluate the pharmacokinetics in patients with lung cancer. PATIENTS AND METHODS Etoposide was administered continuously through a central venous catheter using a pump. The starting dose level was 300 mg/m2 over 14 days, with dose escalations of 100 mg/m2 over 14 days until unacceptable toxicities occurred. Pharmacokinetic studies were performed in all patients. RESULTS Twenty-one patients, 20 with non-small-cell lung cancer and one with refractory small-cell lung cancer, received 37 courses. No World Health Organization (WHO) grade III or greater toxicity occurred at doses up to 400 mg/m2 over 14 days. At 700 mg/m2 over 14 days, all four patients experienced grade III or IV leukocytopenia, and two developed grade III stomatitis. No cumulative toxicity was observed. A steady concentration of etoposide was achieved 24 hours after the start of chemotherapy, and it was significantly correlated with surviving fractions of leukocytes (r = -.64, P = .001) and platelets (r = -.68, P &lt; .001). The leukocyte count at the termination of chemotherapy predicted the nadir count (r = .93, P &lt; .001). CONCLUSION Steady blood levels of etoposide were maintained for prolonged periods, during 14-day continuous infusions. Leukocytopenia and stomatitis were dose-limiting. Nadir counts and surviving fractions of leukocytes were predicted by the leukocyte count at the end of chemotherapy and the concentration of etoposide, respectively. The recommended dose for phase II trials is 600 mg/m2 over 14 days.