tbuckley/cabot-search huggingface dataset:
Association of intratumoral gene expression levels of thymidine phosphorylase (TP) and VEGF with clinical outcome in stage II/III rectal cancer patients treated with 5-fluorouracil and pelvic radiation in a phase III intergroup trial (SWOG 9304).
Authors: R. D. Ladner, C. M. Ulrich, C. J. Rankin, K. D. Danenberg, P. V. Danenberg, S. R. Smalley, K. W. Makar, J. K. Benedetti, C. D. Blanke, H. Lenz
Journal: Journal of Clinical Oncology (2010)

3640 Background: Stage II/III rectal cancer has an overall 5-year survival rate of approximately 50% despite neoadjuvant or adjuvant 5-FU and radiation therapy. The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity. We tested whether intratumoral gene expression levels of 12 genes involved in critical pathways of cancer progression (TS, TP, DPD, GSTP1,VEGF, IL-8, COX-2, EGFR, CyclinD1, P53, ERCC1, ERCC2) will predict the clinical outcome in rectal cancer patients. Methods: A total of 422 stage II/III rectal patients from a phase III trial (INT-0144, S9304) of three regimens of 5-FU and radiation were available for gene expression assays. mRNA was extracted from laser capture microdissected tumor tissue. cDNA was prepared by reverse transcription and quantitation of the candidate genes was performed using a fluorescence-based real-time detection method. The gene expression data were analyzed by splitting the expression data into three (tertiles) groups using thirty-third and sixty-sixth percentile. Results: In univariate analysis, the level of TP gene expression is significantly associated with disease-free survival (DFS) (p = 0.01). Patients with low or median TP expression showed better DFS compared to those with higher TP gene expression. (3 year DFS: low 65%; median 67%; high 79%). The level of VEGF gene expression is marginally significantly associated with DFS. Patients with low VEGF gene expression were associated with better DFS (p = 0.06) compared to median or high VEGF gene expression. (3 year DFS: low: 77%; median: 69%; high: 65%). All other genes tested did not show significant association with either overall survival or DFS. Conclusions: Our preliminary data suggest gene expression levels of TP and VEGF may help to identify patients with longer survival or DFS Future analyses will include regression trees to explore whether there are patient profiles based on combinations of these markers that better identify patient subsets with improved clinical outcome. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Response Genetics
SPIRITT: A multicenter, open-label, randomized, phase II clinical trial evaluating safety and efficacy of FOLFIRI with either panitumumab or bevacizumab as second-line treatment in patients with metastatic colorectal cancer (mCRC) with wild-type <i>KRAS</i> tumors.
Authors: A. L. Cohn, K. Krishnan, J. R. Hecht
Journal: Journal of Clinical Oncology (2010)

TPS195 Background: The optimal treatment of patients with mCRC who have progressed on a bevacizumab-containing regimen remains unclear. Many patients receive second-line chemotherapy with bevacizumab despite the lack of prospective, randomized data supporting this approach. A recent phase III study showed that combination of second-line FOLFIRI with panitumumab, a fully human monoclonal antibody directed against epidermal growth factor (EGFR) approved as monotherapy in patients with chemorefractory mCRC, improved progression-free survival (PFS) in patients with wild-type KRAS tumors when compared with chemotherapy alone. However, it is unclear how this regimen compares to second-line bevacizumab-containing regimens in patients with wild-type KRAS tumors. This study will evaluate the efficacy of panitumumab in combination with FOLFIRI compared to the same chemotherapy regimen plus bevacizumab in patients with wild-type KRAS mCRC who have progressed on standard first-line therapy (oxaliplatin-based regimen plus bevacizumab). Methods: This randomized, open-label study is being conducted in the United States. Patients with wild-type KRAS mCRC who have progressed after at least 4 doses of first-line oxaliplatin-based chemotherapy with bevacizumab are eligible. Patients will be randomized 1:1 to receive either FOLFIRI plus 6 mg/kg panitumumab or FOLFIRI plus bevacizumab (given at institutional standard dose) every 2 weeks. Treatment will be administered until disease progression, death, or withdrawal of the patient from the study. Currently, 213 of 277 planned patients have been enrolled. The primary endpoint of the study is PFS. Secondary endpoints include evaluation of the objective response rate, duration of response, time to progression, disease control rate, and overall survival. This study will also explore changes in patient-reported outcomes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Treatment of liver metastases with an intra-arterial chronomodulated schedule of irinotecan (I), 5FU, and oxaliplatin (O): A feasibility study.
Authors: M. S. Gonzalez, J. Rebollo, J. Farre, P. Bretcha, B. Valenzuela, V. Escudero-Ortiz, A. Crespo, A. Brugarolas
Journal: Journal of Clinical Oncology (2010)

e13100 Background: Irinotecan, 5FU, and oxaliplatin are amongst the most active agents in the treatment of carcinomas with origin in digestive tract (DTC), given alone as single agents or in combination. Based in previous data from the literature describing the favorable results obtained with the intraarterial route in the treatment of hepatic metastases, we performed a feasibility study of the chronomodulated combination of I (40 mg/m2/d), 5FU (800 mg/m2/d ) and O (30 mg/m2/d) alternating along 3 days trough a radioguided catheter placed in the hepatic artery. Cycles were administered every 3 weeks to an intended maximum of 4 cycles per patient. Clorazepate and ketorolac for anxiety and back pain were used in addition to the common supportive medication. Methods: 17 patients (pts) (11f, 6 m) with histologically proven, heavily pretreated stage IV DTC metastatic to the liver were treated at our institution. Median age was 59 y (38-65). All pts were ECOG 0-2. Previous treatment included surgery (primary tumor ± liver; RFA, exeresis or both) and systemic chemotherapy with the aforementioned agents plus leucovorin. 11 pts had irresecable hepatic disease and in 6 the treatment was administered as adjuvant to hepatic surgery. 5 pts had also extrahepatic disease in response to a systemic schedule. Results: A total of 59 courses were administered (median 3, range 2-4). 2 pts were retreated after a relapse, 1 of them rendered free of disease by surgery. Toxic episodes grade III-V were: neutropenic fever (3/59; 5%), diarrhea (4/59; 6.8%), vomiting (5/59; 8.5%), and thrombosis of the hepatic artery (1/59; 1.7%). 3 pts died in the 4 weeks after the last cycle: 1 with severe diarrhea not controlled with ICU management, 1 aspirative pneumonia secondary to vomiting grade 3, and 1 bowel obstruction secondary to rapidly progressing peritoneal carcinomatosis. In 6/11 pts with macroscopic disease a partial response was observed. Conclusions: I, 5FU, and O at the initial referred doses and interval can be administered by intra-arterial route. Safety can be improved considering corrections in the basis of genotype of I metabolizing enzymes and pharmacokinetics of the three drugs. Further studies are warranted. No significant financial relationships to disclose.
Analysis of response to neoadjuvant chemotherapy (NCT) with doxorubicin plus cyclophosphamide followed by paclitaxel (AC- T) in triple negative locally advanced breast cancer (LABC) in Brazil
Authors: J. S. Nunes, A. T. Tsunoda, L. S. Viana, F. H. Souza, N. Castro, J. Hohmann, S. V. Serrano
Journal: Journal of Clinical Oncology (2008)

11551 Background: Breast cancer is the commonest and most lethal female cancer in Brazil. Barretos Cancer Hospital is a reference center for cancer prevention and treatment. In 2006, stage III represented 31% of our patients (pts). Combination of highly effective drugs as anthracyclines and taxanes can improve complete response rates, a known marker for better survival. As triple negative LABC is a poor prognosis subtype, this combination could improve treatment benefits. Methods: We reviewed all charts of pts with stage III breast carcinoma, confirmed by biopsy with ER/PR negative and c-erbB2 IHC-score 0 or +/3+, who performed NCT with ACx4 (doxorubicin 60mg/m2 + cyclophosphamide 600mg/m2 q3w) followed by Tx4 (paclitaxel 175mg/m2 q3w) between Jan/2006 and Jan/2007. Primary endpoint: complete pathologic response rate (pCR), defined by absence of invasive carcinoma in both surgical specimen and axillary lymph nodes. Secondary endpoints: complete clinical response (cCR) and partial response (PR) rates, conservative surgery rate, compliance and toxicity. This study was approved by our institutional ethics committee. Results: 24 pts were included, median age: 53y [35–67], median follow-up: 15m [8,9–22,5]. Stages were IIIA-14pts (58,3%), IIIB-9pts (37,5%), and IIIC-1pt (4,2%). Median tumor size (MTS): 60mm [25–130], 20 pts (83,3%) had tumor >50mm. Response rates were pCR-5pts (20%), cCR-8pts (33%), PR-12pts (50%). Stable disease and progression of disease during NCT occurred in 2pts (8,5%) each. MTS reduced to 13mm (3–95). 5 pts (20%) were submitted to conservative surgery. There was no death or grade 4 toxicity. All pts received at least 8 cycles of NCT, but 7pts (30%) had reducing dose, due to toxicity. Grade 3 adverse events included: thrombocytopenia-3pts, neutropenia-1pt, peripheral neuropathy-2pts, anemia-1pt. Conclusions: AC-T is a good option to NCT in this specific poor prognosis subgroup with large tumors and triple negative LABC, with acceptable toxicity, and pCR comparable to the literature. Considering its lower costs it could be a reasonable choice for developing nations. Prospective studies and longer follow-up are needed to confirm this preliminary data. No significant financial relationships to disclose.
Multi-center phase II/III randomized controlled clinical trial using TNFerade combined with chemoradiation in patients with locally advanced pancreatic cancer (LAPC)
Authors: M. Posner, K. J. Chang, A. Rosemurgy, J. Stephenson, M. Khan, T. Reid, W. E. Fisher, I. Waxman, D. Von Hoff, R. Hecht
Journal: Journal of Clinical Oncology (2007)

4518 Background: TNFerade is a replication-deficient adenoviral vector carrying the transgene for human TNF-a protein, regulated by the radiation-inducible promoter Egr-1. A 50 patient (pt) phase II dose-escalation study in LAPC showed a possible dose-dependent improvement in survival. To confirm these findings, the randomized Pancreatic Cancer Clinical Trial with TNFerade (PACT) study was developed. PACT is a 330 pt study, powered to detect a 20% absolute increase in the primary efficacy endpoint (overall survival at 1 year) compared to standard of care (SOC) chemoradiation. An interim analysis of safety and efficacy was planned after the first 51 pts were randomized. Survival data to 11/15/06 has been evaluated and are reported here. Methods: The TNFerade arm pts received a five- wk treatment of weekly injections of 4 x 10 11 pu TNFerade, continuous infusion 5-FU (200 mg/m 2 /day x 5 days/wk) and 50.4 Gy radiation. TNFerade was administered by percutaneous CT-guided transabdominal injection. The SOC arm received the same regimen, without TNFerade injections. Patients were randomized 2:1 to the TNFerade and SOC arms. The first 51 randomized pts were assessed for evidence of objective response (OR) and overall survival Results: Assessment of response data is still ongoing. TNFerade + SOC was well tolerated. One year survival, the primary endpoint of the study, was 70.5% in the TNFerade + SOC arm versus 28.0% in the SOC arm, an absolute increase of 42.5%. The median survival for TNFerade + SOC pts was 515 days compared to 335 days for the SOC pts. The logrank statistic for comparison between the two arms is X 2 = 2.014 (p=0.16). Conclusions: The interim survival data is preliminary. The magnitude of the difference in survival in favor of the TNFerade + SOC arm, however, is encouraging. The data appears to corroborate previous findings from the dose-escalation study, which showed an apparent survival advantage in the 4×10 11 pu dose group compared to 4 x 10 9 pu group. A second interim analysis is planned with larger patient numbers to determine whether this early positive trend is confirmed. No significant financial relationships to disclose.
Relationships among quality of life and survival in anemic patients with advanced cancer undergoing chemotherapy
Authors: J. A. Sloan, P. L. Schaefer, T. E. Witzig, P. J. Novotny, P. T. Silberstein, J. D. Beardon, J. B. Allred, J. A. Mailliard, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2005)

6027 Background: There are many tools available for measuring cancer patient quality of life (QOL). Baseline QOL data, derived from multiple measurement tools have been identified as prognostic variables for patients with advanced cancer. The purpose of this study was to compare four different ways of assessing QOL in patients with advanced cancer and to describe the relationship between QOL changes and survival in this population. Methods: A double-blind study involved 344 patients with advanced cancer randomized to receive epoetin alfa (40,000 units subcutaneously weekly with escalation to 60,000 units) versus placebo (Witzig, JCO, December, 2004). QOL was assessed monthly by a single-item Uniscale, the Symptom Distress Scale (SDS), the FACT-Anemia scale, and FACT-Fatigue scale. QOL data were translated to a 0–100 point scale. There were no significant differences between treatments in any of the four QOL variables so we undertook a comparative analysis of the four QOL measures across the entire study group. Results: Mean (SD) QOL scores among the 4 QOL tools were significantly different at baseline (p=0.0001) with values of 66 (24) for Uniscale, 74 (13) for SDS, 64 (14) for FACT-An and 51 (22) for FACT-Fatigue. Correlations among the four QOL scales at baseline indicated moderately strong relationships to pseudo-redundancy with correlation coefficients ranging from 0.46 to 0.89. Bland-Altman analysis indicated that there were significant differences between pairs of scales except the Uniscale and the FACT-Fatigue scale (p=0.21). Patients who reported a 10-point improvement in any of the QOL scores survived longer than those who did not (Uniscale: 13 months versus 10 months, p=0.08; SDS 17 months versus 10 months, p=0.0001; FACT-An 16 versus 10 months, p=0.028; and FACT-Fatigue, 15 months versus 9 months, p=0.0001). The variability of the single-item Uniscale was greater than that of the other three scales. Conclusions: Each of the assessments focused on different aspects of patient QOL, resulting in moderate correlation, but not redundancy. While measuring different aspects of patient QOL, changes in scores for the scales indicated an ability to predict survival in this advanced cancer population. No significant financial relationships to disclose.
Relationship between compliance, costs, hospitalizations for CML and GIST patients using imatinib mesylate
Authors: R. Halpern, V. Barghout, N. Mody-Patel, D. Williams
Journal: Journal of Clinical Oncology (2008)

6598 Background: Imatinib mesylate is an oral tyrosine kinase inhibitor dosed daily for treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). The relationships between imatinib compliance and costs and inpatient hospitalizations (IP hosp) for CML and GIST patients (pts) were analyzed with multivariate regression. Methods: Claims data from a large national US health plan were used. Pts had ≥2 imatinib claims from 6/1/01–3/31/05; ≥1-year follow-up (F-U) after 1st imatinib claim; and diagnosis of CML (ICD9 205.1x) or GIST (ICD9 159.0, 159.8, 159.9 or evaluation of claims history and attribution of GIST by independent hematologist/oncologist). Compliance measure was medication possession ratio ((days of imatinib during F- U/days of F-U)*100). Compliance categories were: good, ≥90%; medium, 70–89.9%; poor, <70%. Comorbidity measure was Charlson Comorbidity Index (CCI). Total F-U medical and healthcare (medical + pharmacy) costs, IP hosp and length of stay (LOS) were measured. Costs were modeled with Lin's regression; IP hosp and LOS were modeled with negative binomial regression. Varying F-U time was controlled. Covariates were compliance; controls were cohort, demographic and CCI. Results: 374 CML and 91 GIST pts were identified with mean age 51 and 58 years, respectively. Unadjusted mean medical costs were 87% lower for CML pts, and 57–62% lower for GIST pts, with good compliance versus (vs) poor during each F-U Years 1 and 2. Multivariate analysis showed pts with good compliance had $121,247 lower medical costs, $57,266 lower healthcare costs, 31.3 times fewer IP hosp, and 9.1 times shorter LOS, on average, vs poor compliance. Good compliance pts, vs medium, had 3.8 times fewer IP hosp and 2.1 times shorter LOS, on average. Pts with GIST (vs CML) and higher CCI (sicker) had significantly higher medical and healthcare costs. Conclusions: Good imatinib compliance was associated with substantially lower F-U medical and health care costs vs poor compliance, controlling for condition, demographic and health factors. Compliance with imatinib may lead to lower medical and overall healthcare costs, and fewer and shorter IP hosp. This analysis shows the critical importance of compliance as a clinical and cost-efficiency issue. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Medroxyprogesterone acetate (MPA) versus venlafaxine for hot flashes: A North Central Cancer Treatment Group trial
Authors: C. L. Loprinzi, R. Levitt, J. A. Sloan, S. R. Dakhil, D. L. Barton, R. Dalton, J. D. Bearden, J. A. Mailliard, L. K. Tschetter, P. J. Novotny
Journal: Journal of Clinical Oncology (2005)

8014 Background: Hot flashes are a prominent symptom in breast cancer survivors. Available data demonstrate that both venlafaxine and progestational agents substantially decrease hot flashes. This trial was developed to compare these two agents. Methods: 227 women, reporting at least 14 hot flashes/wk were randomized to venlafaxine (37.5 mg/day for a wk, then 75 mg/d, 109 pts) versus MPA (400 mg IM, 109 pts) versus MPA (500 mg IM q 2 w for 3 doses, 9 pts, arm closed early due to slow initial study accrual), after being stratified for age, tamoxifen use, raloxifene use, and the duration and frequency of hot flash symptoms. Assuming 109 pts per each of the 2 main study arms, this study had 90% power to detect a difference between the two treatments of 1 hot flash per day, or a drop of 16% from baseline, with a 5% Type I error. Results: At this time, data are reported for 185 evaluable pts (81%). All examined pretreatment factors were equally balanced between the two major treatment groups. 90% of participants reported ≥ 4 hot flashes/d while 35% reported ≥ 10 hot flashes/d. At wk 7 (compared to the baseline wk) pts on 400 mg/d MPA, vs those on venlafaxine, had greater reductions in median hot flash frequencies (85% vs 52% reduction, p<0.0001) and reductions in median hot flash scores (88% vs 57% reduction, p<0.0001). 24% of MPA (400 mg/d) pts reported no hot flashes at wk 7, compared to 1% of venlafaxine pts (p<0.0001). Pts on 400 mg/d MPA had less trouble sleeping (p=0.04), less sleepiness (p=0.01), less constipation (p<0.0001), less abnormal sweating (p=0.0001), and less hot flash distress (p<0.0001). Pts on venlafaxine had trends for less trouble with “controlling their feelings” (p=0.06), less “feeling tense” (p=0.07), and less “stress” (p=0.08). Conclusion: A single dose of MPA is well tolerated and relieves hot flashes better than does venlafaxine. No significant financial relationships to disclose.
Epstein Barr viral DNA in the serum of children and adolescents with Hodgkin disease and early response to chemotherapy
Authors: M. A. Higman, C. L. Schwartz, L. Chen, A. R. Chen, D. Friedman, R. Hutchison, S. B. Kawash, C. Orr, R. F. Ambinder
Journal: Journal of Clinical Oncology (2008)

10017 Background: The presence of Epstein-Barr virus (EBV) in tumor cells in a subset of Hodgkin Disease (HD) is well recognized, but the prognostic significance of the association remains unclear in the pediatric population. We sought to determine whether viral copy number in serum might serve as a surrogate for detection of EBV in tumor cells and whether detection of EBV in tumor cells might have prognostic significance. Methods: The Children’s Oncology Group (COG) collected serum and tissue samples from patients enrolled on AHOD0031, a study for newly diagnosed, intermediate risk HD. Pediatric patients with newly diagnosed intermediate risk HD (all stages except I A/II A without bulk or III B/IV B) were enrolled on a dose-dense, response-based treatment protocol. Patients were classified as Rapid Early Responders (RER) if they achieved a 60% reduction in 2 dimensional tumor area after two cycles of therapy). Patients had the option to provide blood and tissue to a biologic bank. The EBV tumor status [(+) or (−)] was determined by in situ hybridization. Serum EBV DNA copy number was quantified using real-time quantitative PCR. Sera were obtained prior to chemotherapy, at one week after the start of chemotherapy and after two cycles of chemotherapy. Patients with Lymphocyte Predominant HD were excluded from this analysis. Results: EBV tumor status and pretreatment viral copy number were available for 139 patients. Detection of EBV in serum was associated with EBV(+) tumor status (Fisher exact test p < 0.0001). Ninety-one percent of patients with EBV (+) tumors had RER as compared to 71% of patients with EBV(−) tumors (p = 0.022). Patients with pretreatment copy number of >10^2 copies were predominantly RER (27/28 patients), compared to 88 RER among 123 patients with copies <100 (p=0.003). Conclusions: We conclude that EBV copy number in pretreatment sera from children and adolescents with HD is associated with the detection of EBV in tumor cells by in situ hybridization. Rapid tumor responses occur more frequently in pediatric patients with EBV(+)tumors. Viral copy number pre treatment and during therapy may be useful as a marker. No significant financial relationships to disclose.