tbuckley/cabot-search huggingface dataset:
The case for proactive, collaborative data-updating in a statewide cancer clinical trial matching service
Authors: K. Moffitt, R. D. Marsh, C. Hudson
Journal: Journal of Clinical Oncology (2007)

6570 Background Florida has the second highest cancer incidence of any state in the United States. To address Florida's growing cancer burden and the need for increased clinical trial participation, Florida Cancer Trials (FCT) launched a web-based and phone-based Clinical Trial Matching Service for the State of Florida on November 1, 2004 (operated by EmergingMed). After 2 years of monthly outreach to 96 trial sites, the FCT wanted to assess the outcome and ongoing need for intensive, grass-roots data verification activities in light of other publicly available cancer clinical trial databases. Methods On 10/23/06, FCT staff extracted all trials containing at least one Florida trial site from the PDQ and ClinicalTrials.gov (CT.gov) database. The same extraction was produced from the TrialCheck database on 11/10/06. Each database was compared to the list of active cancer clinical trials in the FCT/EmergingMed database on the same day. Every trial-site listed in the PDQ/CT.gov database, but missing from the FCT/EmergingMed database, was contacted by FCT staff to confirm the accuracy of each trial/site combination. Results PDQ/CT.gov contained 547 trials listed with Florida trial sites on 10/23/06 (the FCT/EmergingMed database contained 526 trials on the same day). On 11/10/06, the TrialCheck database listed 528 trials with Florida trial sites (the FCT/EmergingMed database contained 513 verified trials on the same day). The PDQ/CT.gov database was missing 25% of Florida's open trials, while the TrialCheck database was missing 36% of Florida's open trials. Moreover, 19% of PDQ/CT.gov's trial listings and 25% of TrialCheck's listings for Florida were erroneous. Conclusions With 25%–36% of Florida's trials missing from public databases, and 19%–25% of their current listings being false listings for Florida, the FCT continues to conclude that a grass-roots, monthly data verification schedule is necessary to maintain a cancer clinical trial database that is suitable for use in referring patients and physicians to Florida's cancer clinical trial sites. No significant financial relationships to disclose.
Comorbidity and survival in cancer patients receiving palliative care
Authors: V. T. Chang, N. Sambamoorthi, B. Zhou, H. Yan, M. L. Gonzalez, P. Osenenko, Y. Alejandro, L. Duque, S. Srinivas, B. Kasimis
Journal: Journal of Clinical Oncology (2007)

9066 Background: Comorbidity has received increasing attention in the assessment of patients with early stage cancer, or at diagnosis. We studied whether three indices of comorbidity, the Charlson Comorbidity Index (CMI), the Cumulative Illness Rating Scale (CIRS), and the Kaplan Feinstein Index (KFI) add prognostic information for cancer patients receiving palliative care. Methods: In an IRB approved protocol, 103 patients with advanced cancer were seen at the time they were starting palliative care. They had a Karnofsky Performance Status (KPS) determination, and were followed longitudinally. Comorbidity scores were coded from the medical record. At this time, all patients had died and survival analyses were performed. Results: The median age was 69 years (range 41–87), median Karnofsky Performance Status (KPS) was 70% (range 20–90); primary sites were lung 41 pts (40%), prostate 23pts (22%), colorectal 10 pts (10%), other cancers 29 pts (28%). Median survival was 111 days (range 4–1,145 days). Median CMI was 10 (range 4–14), CIRS15 4 (2–5), CIRS16 9 (4–12), CIRS17 2.3 (1.5–3.33), CIRS18 1 (0–3), KFI 2 (0–3). In univariate survival analyses, when bisected by median values, the KPS, age, CMI, and subscales of the CIRS (CIRS 16, CIRS 17, CIRS18) were significantly related to survival, but not the KFI. In multivariate Cox regression analyses that included KPS (p&lt;0.0001) and age (p&lt;0.003) and a comorbidity index, the CMI (p&lt;0.0001), and certain subscales of the CIRS were independently predictive of survival, specifically the CIRS 15 (p&lt;0.0001), CIRS16 (p&lt;0.0001), CIRS 17 (p&lt;0.0001), and CIRS18 (p&lt;0.0001). The primary site was not an independent survival predictor. Conclusion: In patients with advanced cancer receiving palliative care, measures of comorbidity may contribute to refining estimates of prognosis and ultimately to health care resource utilization. The optimal comorbidity measure remains to be determined. These results will be confirmed in larger populations. Supported in part by the Soros Open Society Institute Project Death in America and VA HSRD IIR 02–103 No significant financial relationships to disclose.
Treatment of postmenopausal women with osteoporosis for 5 years with denosumab : two-year results from the FREEDOM trial extension
Authors: R. Chapurlat, H. G. Bone, Brandi M L, J. P. Brown, E. Czerwinski, n S Daizadeh, A. Grauer, M. A. Krieg, C. Libanati, Z. Man, D. Mellstrom, S. Radominski, Jean-Yves Reginster, H. Resch
Journal: Annals of the Rheumatic Diseases (2011)
Best supportive care in combination with polychemotherapy versus best supportive care alone as second-line therapy in stage IV metastatic melanoma (DeCOG MM-PAL 8)
Authors: J. Ulrich, U. Trefzer, W. Tilgen, D. Schadendorf, M. Kaatz, P. Mohr, C. Garbe, A. Hauschild
Journal: Journal of Clinical Oncology (2007)

8567 Background: To date, there is no evidence of survival benefit from randomized trials in stage IV metastatic melanoma (MM) after disease progression to first-line therapy. Therefore, we initiated a phase III trial to evaluate the impact on survival of polychemotherapy in patients (pts.) receiving best supportive care (BSC) as second-line therapy. Methods: This prospective multicenter controlled study was conducted by the Dermatologic Cooperative Oncology Group (DeCOG) with 13 participating centers. Pts. with stage IV MM disease between 18 and 75 yrs. and a Karnofsky performance status (KPS) &gt; 60 with progression after first-line chemotherapy or chemo-immunotherapy were offered to choose between polychemotherapy + BSC or BSC alone. Pts. were required to have adequate renal, liver and bone marrow function. The regimen consisted of cisplatin (50 mg/m 2 ), vindesine (3 mg/m 2 ) and dacarbacin (450 mg/m 2 ) given on day 1 and 8 every 28 days (CVD). Reevaluation according to WHO response criteria were performed every 2 cycles. Primary endpoint was the median overall survival (OS). Secondary endpoints were overall response rate (OR) (only CVD arm) and quality of life (QOL). Results: Between 1/02 and 8/06 120 pts. were recruited, a minority of 35 pts. (29%) chose the BSC arm (A) and 85 (71%) the CVD + BSC arm (B). Five pts. were ineligible, and thus 115 pts. treated per protocol. There was a significant lower KPS in arm A at study entry. At the time of data analysis, 85% of the pts. had died from melanoma. There was no siginificant difference (p=0.093) in median OS between the two arms, 9.0 [95% CI: 3,9–14,1] months in arm A and 8.0 [95% CI: 6,5–9,5] months in arm B. The OR in arm B was 7.5% (2 CR, 3 PR). Conclusions: Polychemotherapy (CVD) + BSC as second-line therapy in stage IV MM does not improve overall survival as compared to BSC alone. No significant financial relationships to disclose.
Escalated Focal Liver Radiation and Concurrent Hepatic Artery Fluorodeoxyuridine for Unresectable Intrahepatic Malignancies
Authors: Laura A. Dawson, Cornelius J. McGinn, Daniel Normolle, Randall K. Ten Haken, Suzette Walker, William Ensminger, Theodore S. Lawrence
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the response, time to progression, survival, and impact of radiation (RT) dose on survival in patients with intrahepatic malignancies treated on a phase I trial of escalated focal liver RT. PATIENTS AND METHODS: From April 1996 to January 1998, 43 patients with unresectable intrahepatic hepatobiliary cancer (HB; 27 patients) and colorectal liver metastases (LM; 16 patients) were treated with high-dose conformal RT. The median tumor size was 10 × 10 × 8 cm. The median RT dose was 58.5 Gy (range, 28.5 to 90 Gy), 1.5 Gy twice daily, with concurrent continuous-infusion hepatic arterial fluorodeoxyuridine (0.2 mg/kg/d) during the first 4 weeks of RT. RESULTS: The response rate in 25 assessable patients was 68% (16 partial and one complete response). With a median potential follow-up period of 26.5 months, the median times to progression for all tumors, LM, and HB were 6, 8, and 3 months, respectively. The median survival times of all patients, patients with LM, and patients with HB were 16, 18, and 11 months, respectively. On multivariate analyses, escalated RT dose was independently associated with improved progression-free and overall survival. The median survival of patients treated with 70 Gy or more has not yet been reached (16.4+ months), compared with 11.6 months in patients treated with lower RT doses (P = .0003). CONCLUSION: The excellent response rate, prolonged intrahepatic control, and improved survival in patients treated with RT doses of 70 Gy or more motivate continuation of dose-escalation studies for patients with intrahepatic malignancies.
Histone deacetylase inhibitor ITF2357 is effective on the P39 cells. A gene expression study
Authors: M. Petrini, S. Galimberti, M. Canestraro, H. Savli, G. A. Palumbo, B. Nagy
Journal: Journal of Clinical Oncology (2008)

18024 Background: ITF2357 is a histone deacetylase inhibitor that has been reported to induce apoptosis in myeloma and acute leukemia. We assessed if ITF2357 would exert an anti-proliferative and pro-apoptotic effect on a myelo-monocytic cell line (the P39). Methods: Samples were hybridized on Whole Human Genome Microarray (Agilent). The genes identified as de-regulated by bortezomib were then analyzed for network and gene ontology by Ingenuity Pathway Analysis software. Results have been confirmed by using the TaqMan Low Density Array Human Apoptosis Panel. Results: With an IC50 of 0.8 mcM, ITF2357 was able to inhibit proliferation and induce apoptosis of P39 cells. ITF2357 blocked cell cycle in the G1 phase at low dose (0.5 mcM) and in the G2 phase at higher dose (0.8 mcM). The production of reactive oxygen species (ROS) was significantly increased after exposure to this histone deacetylase inhibitor. In the untreated P39, 84 of the 93 genes involved in the apoptotic pathway and represented in the Taqman Low-Density Arrays were expressed. After 12h-treatment, ITF2357 down-regulated 9 genes and up-regulated 11 genes. After 24 hours, ITF2357 down-regulated 48 genes and up-regulated 3 genes only. Among down-regulated genes, BAD, BCLXL, BCL2, BCL2L10, whereas APAF1 was significantly up-regulated. IL6, IL10, inflammation, NF-kB, PDGF, TGFbeta and apoptosis were the pathways more significantly modified. Among the down-regulated genes, JUN, NF-kB, TNFalpha, IL1beta could be clinically relevant. Indeed, IL1beta has been reported to induce activation of NF-kB, with consequent cell proliferation in acute leukemia; consequently, a down-regulation of IL1beta expression, in addition to the direct down-regulation of NF-kB, could suggest an anti-proliferative effect in MDS. Moreover, TNFalpha plays a well-known pathogenetic role in MDS: it induces apoptosis in the maturing cells causing pancytopenia, but also stimulates the proliferation of the primitive progenitors, accounting for the hypercellular bone marrow frequently observed in MDS. The ability of ITF2357 of down-regulating TNFalpha expression would be also relevant. Conclusions: In summary, biological results and gene expression assays suggest the possible use of histone deacetylase inhibitors in treatment of high-risk MDS. No significant financial relationships to disclose.
Phase III trial of capecitabine + oxaliplatin (XELOX) vs. 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (FOLFOX4) as 2<sup>nd</sup>-line treatment for patients with metastatic colorectal cancer (MCRC)
Authors: M. L. Rothenberg, M. Navarro, C. Butts, Y. Bang, J. V. Cox, R. Goel, S. Gollins, L. L. Siu, D. Cunningham
Journal: Journal of Clinical Oncology (2007)

4031 Background: Capecitabine is an oral fluoropyrimidine that has demonstrated similar efficacy to 5-FU/LV in the 1 st -line treatment of MCRC. Most patients now receive multi-agent chemotherapy and FOLFOX4 has become a popular regimen in this setting. We conducted a phase III study comparing XELOX with FOLFOX4 in patients who had received prior treatment with irinotecan in combination with bolus and/or infusional 5-FU/LV for MCRC. The primary endpoint of the study was time-to-tumor progression (TTP). With 610 patients, this study had 80% power to detect non-inferiority of the XELOX vs. FOLFOX, defined by a progression hazard ratio (HR) of &lt;1.3. Methods: Patients were treated with XELOX (oxaliplatin 130mg/m 2 i.v., capecitabine 1,000mg/m 2 bid oral x 14 days, q3w) or FOLFOX4 (as described previously). Results: The study recruited 627 patients (the intent-to-treat - ITT - group). Baseline characteristics were well balanced. The primary objective of the study was met with a progression HR of 0.97 for the XELOX group (95% CI, 0.83–1.14). Median TTP was 4.8 months for XELOX- and 4.7 months for FOLFOX4-treated patients. Overall survival was also similar between the groups with a death HR of 1.03 for the XELOX group (95% CI, 0.87–1.23). Median survival was 11.9 months for XELOX- and 12.6 months for FOLFOX4-treated patients. Grade 3/4 toxicities occurred in 60.1% of XELOX- and 72.4% of FOLFOX4-treated patients. The most common treatment-related grade 3/4 adverse events (XELOX vs. FOLFOX4) were: diarrhea (20 vs. 5%), neutropenia (5 vs. 35%), fatigue (5 vs. 8%), paresthesia (9 vs. 8%), nausea/vomiting (6 vs. 5%). The rate of grade 3 hand-foot syndrome was 3.5% with XELOX and 0.6% with FOLFOX4. The 60-day all cause mortality was 3.9% in XELOX- and 4.2% in FOLFOX4-treated patients. Conclusions: These results demonstrate that second-line treatment with XELOX is non-inferior to FOLFOX4 in terms of PFS. Results for overall survival and response rates were also similar between the two groups. The safety profile was similar to previous studies, with no unexpected toxicities. Study supported by Hoffmann-La Roche. No significant financial relationships to disclose.
Phase II study of gemcitabine in combination with docetaxel in patients with advanced pancreatic carcinoma. Preliminary results
Authors: L. Chauvenet, G. Des Guetz, T. Aparicio, C. Boiron, L. Ecochard, E. Chirat, D. Mayeur, R. Vanica, C. Bouleuc, D. Paraiso, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2005)

4208 Background: Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. New approaches, alone and in combination with gemcitabine, are being developed. So we assess the efficacy and toxicity of combination therapy with gemcitabine and docetaxel in patients with unresectable pancreatic carcinoma. Methods: Thirty-one patients (pts) with unresectable, biopsy proven, pancreatic carcinoma were eligible for this study. Patients received docetaxel either 50 mg/m(2) or 35 mg/m(2) regarding hepatic enzyme levels, followed by gemcitabine 1,200 mg/m(2) biweekly until progression or intolerable toxicity. The primary study endpoint was objective response rate. Results: The median age of pts was 60 years (range, 42–81). Male/female ratio was 22/9. Out of the 31 eligible patients, 20 patients were evaluable for response rate. After 2 cycles (2 months), 4 patients had a partial response (20%) and 7 patients had a stable disease (35%). Hematologic toxicity was NCI grade (gr) 1–4 anemia (45% of 220 cycles), neutropenia gr 4 (4%) and thrombocytopenia gr3–4 (2%). Febrile neutropenia occurred in 8% of patients. Non-hematological toxicities were few, including grade 1–2 nausea/vomiting (16%), alopecia (80%), grade 3 fatigue (5%), grade 2–3 mucositis (4%). High cumulative doses of docetaxel have been shown to produce fluid retention (13% of lower limb edema). Conclusions: The response and tolerance data reported here for combination therapy with gemcitabine and docetaxel are encouraging given the poor prognosis associated with unresectable pancreatic cancer. Final results will be presented for the meeting No significant financial relationships to disclose.
Metastases outside the abdomen (MOA) are associated with initial high tumor burden (TB) in gastrointestinal stromal tumors (GIST)
Authors: S. Aliberti, G. Grignani, P. Allione, D. Rota-Scalabrini, F. Carnevale-Schianca, A. Bucci, D. Caravelli, A. Galla, R. Ferraris, M. Aglietta
Journal: Journal of Clinical Oncology (2006)

9546 Background: In GIST MOA are rare events (8–10%) with a prognostic and predictive impact (JCO 2005;23:5795). To stage GIST, NCCN recommends either CT or abdominal MRI + chest imaging, suggesting PET scan only if early response assessment is needed. Therefore, MOA may be missed by standard work up. We evaluated if TB (largest tumor diameter &gt; 12 centimetres) at diagnosis was associated to a higher incidence of MOA. Methods: From 01/02 to 12/05, 66 pts affected by GIST were either treated or followed-up at our hospital. Routine initial work up consisted in: chest CT + CT or MRI abdominal scan. Pet scan was performed if: uncertainties after standard imaging, to monitor “neoadjuvant” therapy or within clinical trials. Identified MOA if unique, would be considered for fine needle biopsy whilst multiple MOA would be monitored by most appropriate imaging technique. Results: Twenty-three pts (34%) had TB between 13 and 31 centimetres. At diagnosis 10 pts (15%) had MOA located in: lung (7 pts), bone (2 pts) subcutaneous tissue (1 pts). In this unfavourable group 9 pts (14%) were affected by tumors larger than 12 cm. Pts without MOA were 56 (85%) of whom 14 (21%) had TB. The association between initial TB and MOA was statistically significant (p&lt;0.001). Conclusions: In this small series, high tumor burden is positively correlated to MOA. If these data should be confirmed, initial diagnostic work up could usefully include both chest CT and PET scan in abdominal mass beyond 12 centimetres wide. A precocious recognition of MOA would allow to better control therapeutic response and to better identify high-risk patients. No significant financial relationships to disclose.
Electrical spinal cord stimulation during radiotherapy and temozolomide in high grade gliomas. A phase II report
Authors: B. Clavo, F. Robaina, A. Cabezon, I. J. Jorge, P. Ponce, B. Pinar, A. Ruiz, E. Otermin, M. A. Hernandez, J. L. Carreras
Journal: Journal of Clinical Oncology (2006)

11510 Background: Ischemia-hypoxia in high grade gliomas (HGG) turns tumor cells more aggressive and more resistant to radiotherapy (RT) and temozolomide (TMZ). Higher glucose metabolism pre-treatment has been correlated with better response to TMZ using 18-FDG-PET. In preliminary works, we have reported that electrical spinal cord stimulation (SCS) can modify loco-regional oxygenation, blood flow and metabolism in HGG. The aim of this study was to evaluate tumor response and toxicity in HGG using SCS during RT plus TMZ. Methods: 10 patients (males/females: 8/2; median age: 51 years (30–68)) were enrolled in this trial. Tumors were 6 glioblastomas and 4 relapsed anaplastic gliomas. Diagnosis was after complete resection (1), subtotal resection (6), biopsy (1) or MRI + PET (2 relapsed HGG). Tetrapolar electrode for SCS was percutaneously inserted on the posterior surface of the cervical spinal cord at C2-C4 level. RT was at 2 Gy/fraction, 5 fractions/week, total dose 60 Gy (40 Gy in previously irradiated tumors). TMZ was administered at 75 mg/m 2 daily during RT, followed by at least 6 cycles of adjuvant TMZ at 200 mg/m 2 . Tumor response was evaluated by CT and PET. Results: After concurrent RT+TMZ, CT showed: 5 partial response (PR), 3 complete response (CR), 2 stable disease (SD). After 6 adjuvant cycles of TMZ, CT (median 10 months after surgery) showed: 4 PR, 3 CR, 3 progression disease (PD). PET showed post-surgical residual tumor in the 9 evaluated patients. After 6 cycles of TMZ, PET showed: 4 CR, 2 PR (they obtained delayed CR after 12 and 18 cycles of TMZ), PD n = 2, and two patients without PET assessment (1 with PR in CT, and 1 without tumor in CT). For the study group median overall survival (OS) was 22 months (95% CI = 14–30) and for glioblastomas 16 months (95% CI = 6–26). For relapsed anaplastic gliomas mean OS was 37 months (95% CI = 22–52). One patient did not finish scheduled adjuvant TMZ and only one patient experienced hematological toxicity with neutropenia G-I and thrombopenia G-III. Conclusions: Electrical SCS during RT+TMZ did not increase toxicity. Preliminary data about tumor response and OS seem to be encouraging and they support further research. Supported by Grants: FUNCIS 03/09 and ISCiii, RTICCC C03/10. No significant financial relationships to disclose.
Phase II study of neoadjuvant treatment with docetaxel, doxorubicin and capecitabine (ATX) in locally advanced or inflammatory breast cancer
Authors: P. Khosravi-Shahi, M. Mendez, R. Quiben, I. Palomero, Y. Izarzugaza, J. Belon, P. Garcia-Alfonso, G. Perez-Manga
Journal: Journal of Clinical Oncology (2008)

11544 Background: Studies suggest that the combination of chemotherapy, surgery and radiotherapy improves survival rate in patients with LABC. The primary objective of the present study was to evaluate response rate of neoadjuvant treatment with docetaxel (T), doxorubicin (A) and capecitabine (X) in locally advanced or inflammatory breast cancer patients (LABC). Secondary endpoints included time to progression, overall survival and toxicity profile. Methods: Patients with histologically confirmed LABC, ECOG PS ≤2, age ≤75 years, LVEF >50%, and adequate bone marrow, renal and hepatic function were eligible. Prior systemic therapy, surgery or radiotherapy for breast cancer was not allowed. Patients with invasive bilateral breast cancer were not included. Treatment: T (30 mg/m2 i.v.) days 1, 8 and 15; A (50 mg/m2 i.v.) day 1 and X (1,500 mg/m2 p.o.) days 1–14, in a 4-week course repeated for up to four cycles, followed by surgery. Patients received a maximum of six cycles, according to investigator criteria. Radiotherapy and hormone therapy were allowed after surgery. Expression of markers was determined by immunohistochemistry before chemotherapy. Results: A total of 60 patients were included in the analysis: median age 48 years (range: 25–73); hormonal receptor status: ER+ 46.6%, PR+ 42.6% and Her-2+ 25%. Median cycles of neoadjuvant treatment was 4 (95% CI: 3–5). Median tumor size at diagnosis was 5 cm (95% CI: 2–8 cm). Of 60 patients evaluable for efficacy, 5 achieved cPR in both breast and nodes and 16.7% reached cPR only in nodes. Only 18% of the patients underwent conservative surgery. A total of 98.3% of the patients received postsurgical chemotherapy treatment. 62% and 38.7% of the patients received adjuvant radiotherapy and hormone treatment, respectively. Median follow-up time was 20 months. Three-year DFS and OS were 76% and 90%, respectively. Grade III/IV toxicity included neutropenia (74%), febrile neutropenia (9%), thrombocytopenia (5%), mucositis (12%), diarrhea (12%), nausea/vomiting (5%) and asthenia (2%). Conclusions: Neoadjuvant ATX every 28 days for four cycles is an active regimen in LABC with a manageable toxicity profile before surgery. No significant financial relationships to disclose.