tbuckley/cabot-search huggingface dataset:
Role of Metronomic Therapy in the Non-Surgical Management of Desmoid Tumors
Authors: G. Gupta, S. Banavali, A. Puri, A. Gulia, G. Chinnaswamy, B. Arora, S. Kulkarni, N. Shetty, S. Laskar, N.R. Khanna, N.M. Merchant, S.L. Juvekar, B. Rekhi
Journal: Annals of Oncology (2014)

ABSTRACT   Aim: Desmoid tumors (Fibromatosis) are slow growing, locally invasive tumors with a propensity to recur despite wide excision. Data on the use of systemic therapy are sparse. Metronomic Therapy (MT) is a multi-targeted therapy with anti-angiogenic, immunomodulatory and tumor dormancy effects. This retrospective audit aims to study the efficacy, safety and need for further surgical intervention in patients of desmoid tumors treated with MT.  Methods: Patients who received MT for fibromatosis between January 2002 and December 2012 were included in the study. MT protocol consisted of Methotrexate 30 mg/m2 i.v weekly and Vinblastine 6 mg/m2 i.v. weekly for 1 year along with Tamoxifen 20 mg/m2 PO BD for 2 years. Response was evaluated using Magnetic Resonance Imaging or Computed Tomography scans every 6 monthly using the Response Evaluation Criteria in Solid Tumors version 1.1. Toxicities were recorded using the National Cancer Institute Common Toxicity Criteria version 3.0.  Results: 42 patients received MT for ≥6 months, median age was 30 years (range 2 - 58 years) with M:F ratio of 1:1.33. 27 (64.3%) patients had tumors arising in extremities, 8 trunk, 5 intra-abdominal and 2 in head & neck region. 26 patients had recurrent fibromatosis. The median follow up was 29 months. The mean duration for which patients received Methotrexate, Vinblastine and Tamoxifen were 9.85 months, 9.4 months and 16.92 months respectively. 4 (9.5%) cases had grade 3/4 neutropenia. Non-hematological toxicity was documented in 24 patients. Grade 3/4 toxicity consisted of nausea, peripheral neuropathy, and transaminitis in 1 each and vomiting in 2 patients. 4 patients discontinued MT due to toxicity. Response was evaluable in 38 patients- 21% had Partial Response and 79% had Stable Disease as the best response. 15 patients (35.7%) required second line therapy due to disease progression. Only 6 patients (14.28%) eventually required surgery for disease control. The median progression free survival (PFS) was 74 months (95%CI 42.45 - 105.54). The 3 year-PFS for patients with primary disease was 68.6±13.8% and for those with recurrent tumors was 87.4±6.8% (p=0.58).  Conclusions: MT has reasonable efficacy and is well tolerated. The upfront use of MT in advanced desmoid tumors, with surgery being reserved for non-responders or those with progression can be a reasonable approach.  Disclosure: All authors have declared no conflicts of interest.
Safety and efficacy of the combination carboplatin and paclitaxel in patients (pts) with recurrent head and neck squamous cell carcinoma (HNSCC)
Authors: D. Ferrari, A. Rocca, S. Oldani, F. Zannier, T. Tartaro, C. Carbone, C. Codecà, L. Calabrese, F. Chiesa, P. Foa
Journal: Journal of Clinical Oncology (2006)

15534 Background: Pts with recurrent HNSCC have a dismal prognosis; treatment options are poorly effective and burdened with toxicity. In this clinical setting, cisplatin and paclitaxel have demonstrated activity despite relevant side effects. The purpose of this phase II trial was to investigate whether a combination of carboplatin and paclitaxel could offer a better toxicity profile without affecting efficacy. Methods: Pts with bi-dimensionally measurable disease, previously treated with induction chemotherapy (Cisplatin and 5-FU) followed by concomitant chemo-radiotherapy, were studied. Treatment consisted of Carboplatin AUC 5 and Paclitaxel 175 mg/m 2 intravenously every 3 weeks. G-CSF and darbepoetin alpha were allowed in case of neutropenia (N &lt; 1000/mm 3 ) or anemia (Hb &lt; 11 g/dL). Pts were evaluated for toxicity and response. Results: So far, 15 pts were enrolled. Median age was 53 yrs; ECOG P.S. was 0–1. Site of disease at relapse was head and neck excluding lips and sinus; 12 out of 15 pts had stage IV disease. All pts were evaluated for response and toxicity. After three cycles of chemotherapy, we observed 1 complete response (6.6%) and 7 partial responses (46.6%), with a 53.2 % overall response rate (95% CI 26.6–78.7%). Stable disease was seen in 2 patients (13.3%) and progressive disease was observed in 5 pts (33.3%). Toxicity was mild: we recorded 1 case of G3 toxicity (neutropenia) and no G4 side effects. Three pts experienced G1–2 neuropathy and 4 pts G1–2 hematologic toxicity (neutropenia and thrombocytopenia). Conclusions: The current regimen was feasible and effective. The combination of Carboplatin and Paclitaxel was well tolerated and could be safely administered to pts with recurrent HNSCC as second line treatment. Enrollment and data collection are still ongoing. No significant financial relationships to disclose.
Outcome of treatment with 2nd and 3rd generation platinum-based chemotherapy in advanced non-small cell carcinoma (NSCLC): A single institute experience
Authors: K. Khodadad, M. R. Malekzadegan, N. Hashemi, A. Azadi, A. H. Abdollah Shamshirsaz, M. Padyab, H. Emami
Journal: Journal of Clinical Oncology (2007)

18169 Background: The cornerstone of treatment in patients with advanced NSCLC is chemotherapy. During past years 3rd generation cytotoxic drugs have replaced 2nd generation drugs in combination with platinum. Although some trials suggest that newer agents are less toxic and with better response rates compared to older ones, but overall survival outcomes are similar. Methods: Between 1999- 2005, 275 patients with advanced NSCLC (unresectable IIIA, IIIB and IV) have been treated in our center with either frontline 2nd (204 pts.) or 3rd (71 pts.) generation, platinum-based regimens. Retrospectively we analyzed the outcome of treatment (i.e. response rate and overall survival) in these patients according to the generation of chemotherapy regimen. Results: Male/female ratio was 3.6/1 and mean age 58.9. Pathology subtypes includes: adenocarcinoma (49.8%), squamous cell carcinoma (28%), undiff. NSCLC (21.8%) and large cell carcinoma (0.4%). The RR was higher with 3rd generation protocols compared to 2nd generations (47.9% vs 26.5%, P = 0.001) but the median OS in both groups was statistically non-significant (12.07 vs 10.57 m). Analyzing RR and OS in different pathology subtypes shows that in adenocarcinoma and squamous cell ca. the RR is higher with 3rd generation compared to 2nd generation (40.5% vs 20%, P=0.01 &amp; 72.8% vs 27.3%, P=0.005 respectively), but the OS between these two generations was not statistically significant in both pathology subtypes. In undiff. NSCLC the outcome between 2nd and 3rd generation is non-significant in terms of OS and RR. The distribution of different stages in both study groups was statistically similar. Conclusions: Based on this study the 3rd generation protocols in the treatment of advanced NSCLC is superior to 2nd generation protocols in term of RR, although the median OS is statistically non-significant. No significant financial relationships to disclose.
Clinical prognostic factors for distant metastases and survival in patients with primary uveal melanoma: A 10-year follow-up of a single center cohort study
Authors: A. H. Schmittel, N. E. Bechrakis, P. Martus, G. Gudacker, D. Mutlu, C. Scheibenbogen, N. Bornfeld, M. H. Foerster, E. Thiel, U. Keilholz
Journal: Journal of Clinical Oncology (2007)

8546 Background: Metastases from uveal melanoma have an extremely poor prognosis. Factors predicting development of metastases and survival are of critical importance for future adjuvant trials investigating innovative immunotherapeutic approaches in patients with uveal melanoma. Methods: We reanalyzed all patients with uveal melanoma, who received primary treatment in 1994 and 1995 in our hospital, from whom we previously had reported 5-year follow-up data. Data on primary tumor, local therapy and follow-up were collected. Results: Of 271 patients 78.2% of patients were available for 10 years follow up. Median follow-up was 123 months. A total of 68 patients (25.1%) developed metastases. Kaplan-Meier analysis revealed a 10-year progression free survival (PFS) of 65% for the whole patient cohort. 10-year PFS was 25% in patients with extraocular tumor growth (EOG). Patients with ciliary body involvement (CBI) or a largest tumor diameter (LTD) &gt; 14 mm had a 10-year PFS of 56.3% and 52%, respectively, which was significantly lower than in patients without ciliary body involvement or LTD &lt; 14 mm. 10-year overall survival was 57.5% for the whole patient cohort. 10-year survival was 20% in patients with EOG and 42.3% in patients with CBI and 43.2% in patients with LTD &gt; 14 mm. Univariate analysis revealed EOG, CBI and LTD &gt; 14 mm to be predictive for overall survival (p &lt; 0.02, log-rank test for all variables). Conclusions: This study confirmed our previous 5-year follow-up data and determined determined ciliary body involvement and a largest tumor diameter &gt; 14 mm to be the most important clinical risk factor for metastases and survival. Therefore patients with ciliary body involvement and LTD &gt; 14 mm are candidates for adjuvant therapeutic interventions within future trials. No significant financial relationships to disclose.
Vaccination of renal cell cancer (RCC) patients with modified vaccinia ankara delivering the tumor antigen 5T4 (TroVax [T]) administered + low dose interleukin-2 (IL-2): A phase II trial
Authors: J. Hernandez-McClain, R. J. Amato, W. H. Shingler, S. Naylor, J. Jac, J. P. Willis, S. Saxena, R. Harrop
Journal: Journal of Clinical Oncology (2008)

5101 Background: The attenuated vaccinia virus MVA has been engineered to deliver the tumor antigen 5T4 (TroVax[T]). More than 90% of RCC overexpress 5T4. TroVax has been evaluated in an open-label phase II trial in metastatic RCC patients in which the vaccine was administered in combination with low dose IL-2. The safety and immunological potency of T in combination with IL-2 was determined. Methods: Eligibility: pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiologic parameters, Karnofsky performance status ≥80%, no active CNS involvement. IL-2 was administered in 8 week cycles as a subcutaneous injection at a dose of 250,000 u/kg in week 1 (days 1–5), 125,000 u/kg in weeks 2–6 (days 1–5) followed by 2 weeks off. Up to 6 cycles of IL-2 were administered over a 48 week period. T was administered by intra-musclular injection every 3–4 weeks for the first 4 injections and every 8 to 12 weeks thereafter. Twenty-five patients with metastatic RCC were treated with T plus IL-2. 5T4-specific cellular and humoral responses were monitored and clinical responses assessed according to RECIST criteria. Results: T was well tolerated with no serious adverse events attributed to vaccination. Of 25 intent to treat patients, 21 mounted 5T4-specific antibody responses. Three patients showed a complete response (2 for 24+ and 1 for 12+ months), 6 patients had disease stabilization (6 to 21+ months) and the remainder had progressive disease. Median progression free survival (PFS) and overall survival (OS) was 3.4+ months (1.5–24.8+) and 12.9+ months (1.9–24.8+) respectively. A statistically significant correlation was detected between the magnitude of 5T4-specific antibody responses and PFS and OS (both P<0.05). Conclusions: T was safe and well tolerated in all patients in combination with IL-2. The high frequency of 5T4-specific immune responses, number of complete responses and correlation with clinical benefit are encouraging and warrant further investigation. A phase III study with T is ongoing in this indication. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oxford Biomedica (UK), Ltd. Oxford Biomedica (UK), Ltd. Oxford Biomedica
Validation of Elevated Blood Soluble PD-L1 As an Independent Prognostic Marker in Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Thierry Fest, James R Cerhan, Maher K Gandhi, Imane Azzaoui, Pauline Crooks, Matthew J Maurer, Noel Milpied, Mark S Hertzberg, Thierry Lamy, Stephen M. Ansell, Susan L Slager, Andrew L. Feldman, Mikael Roussel, Thomas M Habermann, Herve Ghesquieres, Thomas E. Witzig, Brian K Link, Delphine Rossille
Journal: Blood (2014)
Hyperplastic Lesions in the Mammary Glands of Sprague-Dawley Rats After 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene Treatment&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: L J Beuving, L J Faulkin, K B DeOme, V V Bergs
Journal: JNCI Journal of the National Cancer Institute (1967)
Thymidylate synthase and thymidine phosphorylase expression in resected colorectal liver metastases do not predict overall survival nor response to chemotherapy
Authors: M. Blitz, L. J. Carroll, C. A. Butts, T. Moyana, N. M. Kneteman, L. D. Jewell, H. C. Birnboim, D. J. Jonker, J. A. Maroun, D. L. Bigam
Journal: Journal of Clinical Oncology (2004)

3605 Background: Enzyme expression has been reported to be of both predictive and prognostic significance in patients with colorectal liver metastases (CLM). We determined whether thymidylate synthase (TS) and/or thymidine phosphorylase (TP) can be used to determine the prognosis of patients with CLM who have undergone potentially curative hepatic resection and whether TS and/or TP status can be used to predict which patients would be likely to benefit from (neo)adjuvant chemotherapy. Methods: Paraffin tumor blocks from 99 patients who received potentially curative liver resections for CLM were evaluated. TS and TP expression were assessed by immunohistochemistry (IHC) assays. Overall survival (OS) and disease-free survival (DFS) were compared between high and low expressors of TS and TP singly and in combination. The predictive value for response to (neo)adjuvant chemotherapy of TS alone as well as the TS / TP combination were evaluated. Results: Median OS for the TS+ group (n=47) was 4.51 years and DFS was 2.37 years, which were not significantly different from those of the TS- group (n=52): 4.05 years and 1.14 years (p=0.44 and p=0.10). Similarly, TS status did not predict the differential effects of (neo)adjuvant chemotherapy on OS (TS- p = 0.72, TS+ p = 0.49) or DFS (TS- p = 0.91, TS+ p = 0.28). Median OS for the TP+ group (n=10) was 4.35 years and DFS was 0.50 years, which were not significantly different from those of the TP- group (n=89): 4.05 years and 1.52 years (p=0.66 and p=0.24). TS/TP- tumors did not demonstrate improved OS (4.04 vs 4.51 years; p = 0.47) or DFS (1.20 years vs 1.96 years; p = 0.17). Similarly, TS/TP status did not predict the differential effects of (neo)adjuvant chemotherapy on OS (TS/TP- p = 0.73, TS/TP+ p = 0.67) or DFS (TS/TP- p = 0.95, TS/TP+ p = 0.40) Conclusions: TS and TP individually or in combination as measured using IHC appear not to be important prognostic indicators of OS or DFS in patients who underwent potentially curative liver resections for CLM. In addition these classifications can not be used to predict the differential effects of (neo)adjuvant chemotherapy in these patients. No significant financial relationships to disclose.
Combination therapy of chemokine receptor inhibition plus PDL-1 blockade potentiates anti-tumor effects in a murine model of breast cancer
Authors: Heiyoun Jung, Ashley Bischof, Karen Ebsworth, Linda Ertl, Thomas Schall, Israel Charo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Trafficking and expansion of myeloid derived suppressor cells (MDSCs) plays a major role in immune suppression of tumor. MDSCs express chemokine receptors which likely mediate their recruitment to the tumor microenvironment. Suppression of T cells is also mediated by the
Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of a morphological iron index: a study of 192 cases
Authors: Y.M. Deugnier, J.W. Halliday, K.M. Summers, R. Moirand, L. Fletcher, O. Loreal, P. Brissot, L.W. Powell
Journal: Hepatology (1992)
Imatinib mesylate plus hydroxyurea for adults with recurrent/progressive low-grade glioma: Final phase II study results.
Authors: K. Peters, A. Desjardins, J. J. Vredenburgh, B. Dryman, S. Gururangan, H. S. Friedman, D. A. Reardon
Journal: Journal of Clinical Oncology (2010)

2060 Background: Imatinib mesylate (IM) and hydroxyurea (H) have shown activity when administered independently to patients with low-grade glioma (LGG). We therefore evaluated the combination of these two agents among adults with recurrent/progressive LGG. Methods: Key eligibility criteria: age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky 60% and adequate organ function. IM and H were given on a continuous oral daily schedule for 28 day cycles; IM was administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. All patients received 500 mg twice a day of H. Patients were evaluated every other month with physical and MRI examinations. Results: Sixty-four patients with recurrent or progressive LGG enrolled including 32 with astrocytoma and 32 with oligodendroglioma. Median age was 44.3 years (range 22.6-83.3 years) and 34 (61%) were male. Twenty-two (34%) were on EIAED. Prior therapy included radiation in 11 (17%) and chemotherapy in 19 (30%). Grade 3 or 4 toxicity (> 1 patient) was limited to neutropenia (n = 4, 6%), thrombocytopenia (n = 2, 3%) and nausea (n = 2, 3%). The most common grade 2 toxicities were fatigue (n = 25, 39%), nausea (n = 12, 19%) and rash (n = 7, 11%). Median follow-up for all patients is 141.1 weeks (95% CI: 29.1, 151). Median PFS for astrocytoma and oligodendroglioma patients were 43.5 weeks (95% CI: 31.7, 63.7) and 43.3 weeks (95% CI: 24.9, 53.6), respectively. Four patients remain on study therapy in cycles 28, 35, 37 and 55. Conclusions: Continuous daily treatment of imatinib plus hydroxyurea is well tolerated and associated with encouraging activity among adults with recurrent/progressive LGG. No significant financial relationships to disclose.
Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.
Authors: G L Clayman, A K el-Naggar, S M Lippman, Y C Henderson, M Frederick, J A Merritt, L A Zumstein, T M Timmons, T J Liu, L Ginsberg, J A Roth, W K Hong, P Bruso, H Goepfert
Journal: Journal of Clinical Oncology (1998)

PURPOSE Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.
Phase I trial of vandetanib and oral etoposide (VP-16) for recurrent malignant gliomas (MG).
Authors: A. Brickhouse, J. J. Vredenburgh, S. Gururangan, D. A. Reardon, A. Desjardins, K. Peters, J. E. Herndon, J. Norfleet, J. Marcello, H. S. Friedman
Journal: Journal of Clinical Oncology (2010)

2038 Background: Recurrent MGs have a poor prognosis. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are critically important in glioma biology. Vandetanib is a multikinase inhibitor, predominantly of VEGF and EGF. Methods: Patients had recurrent grade 3 or grade 4 MG. The patients were not on enzyme inducing anti-epileptic drugs (non-EIAED). Patients were treated with daily oral vandetanib and VP-16. The trial design was a modified 3 + 3 phase I design, with the dose levels outlined below (Table). Each cycle was 28 days. Results: 35 patients have been accrued. There was more hematologic toxicity than expected in cohort A, with 3/6 of the patients enrolled at dose level 1 developing grade 4 neutropenia. The protocol was amended. Six patients had no dose-limiting toxicity at the new dose level 1B. One patient had grade 4 neutropenia at dose 2B. One patient had grade 3 mucositis at dose 3B. There were two DLTs at dose 4B, diarrhea, melena and dyspnea on exertion, and the other had increased liver function tests. There has been clinical activity, with patients remaining stable on study for multiple cycles, up to 12 cycles. Conclusions: Vandetanib and VP-16 appear to interact to produce more marrow toxicity than expected, but is well tolerated at reduced dose VP-16. The MTD was vendetanib 300 mg daily and VP-16 50 mg/d days 1–21. In addition, the phase I trial continues with patients on EIAEDs. A phase II trial is planned. Dose level Vandetanib VP-16 (days 1-21) -1A 100 mq qod 50 mg/m2/d 1A 100 mg qd 50 mg/m2/d 1B 100 mg qd 50 mg/d 2B 100 mg qd 50 mg/d 3B 100 mg qd 50 mg/d 4B 100 mg qd 50 mg/d No significant financial relationships to disclose.