tbuckley/cabot-search huggingface dataset:
An open-label, dose-ranging study to assess the safety, efficacy, and pharmacokinetics of eltrombopag in treating thrombocytopenia in patients with advanced sarcomas receiving doxorubicin and ifosfamide.
Authors: S. P. Chawla, A. P. Staddon, C. Messam, A. M. Graham, Y. M. Mostafa Kamel
Journal: Journal of Clinical Oncology (2010)

TPS334 Background: Doxorubicin and ifosfamide are active in the treatment of sarcomas; however, this regimen is associated with grade 3/4 chemotherapy-induced thrombocytopenia (CIT), which may necessitate chemotherapy dose reductions and dose delays with the consequence of less disease control. Thrombocytopenia can also increase the risk of hemorrhage. CIT is primarily managed with dose reductions, dose delays, and platelet transfusions, each of which has significant limitations. Eltrombopag, an oral, small molecule thrombopoietin receptor agonist, increases platelet counts in patients with chronic immune thrombocytopenic purpura, chronic liver disease, and hepatitis C infection. This study will evaluate the safety and effectiveness of eltrombopag in patients with cancer. Methods: This open- label, nonrandomized, phase I, 2-part, sequential cohort, dose-escalation study will evaluate the safety and efficacy of eltrombopag when administered to patients receiving doxorubicin/ifosfamide. Eligible adult patients have locally advanced (with high risk for relapse) or metastatic soft tissue sarcoma, ECOG/Zubrod performance status of 0 or 1, have received ≤1 previous chemotherapy, and are candidates for doxorubicin/ifosfamide chemotherapy on a 21-day cycle. Patients will receive once-daily eltrombopag for 5 days prior to and 5 days after chemotherapy in cycles 2 to 6 to identify an optimal biologic dose (OBD). At least 3 patients will be enrolled into each of the following dose levels: 75, 100, 150, 200, 300 mg eltrombopag. An additional 3 patients will be enrolled if 1 patient experiences a ≥ grade 3 toxicity related to eltrombopag. Progression to the next dose level will be based on safety and pharmacokinetics data. Once the OBD is identified, that dose will be tested in additional patients on the aforementioned schedule and also on a schedule of eltrombopag daily on each of the 10 days following chemotherapy dosing in cycles 2 to 6. The primary endpoint is safety and tolerability as assessed by adverse events, changes from baseline in vital signs, and clinical laboratory parameters. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
The impact of an exercise intervention on body composition, fat distribution, and weight in breast cancer survivors
Authors: J. A. Ligibel, W. Chen, A. Keshaviah, K. Adloff, A. Partridge, T. Salinardi, E. P. Winer
Journal: Journal of Clinical Oncology (2006)

590 Background: Recent research has demonstrated that obesity increases a woman’s risk of breast cancer recurrence. Although the mechanism is not well understood, it is known that obese women have higher levels of insulin and other hormones related to energy balance. In this study, we sought to explore the impact of an exercise intervention on body composition, fat distribution, weight, and insulin levels in a population of breast cancer survivors. Methods: Inactive women with early stage breast cancer who had completed adjuvant chemotherapy and/or radiation were randomized to a 16-week exercise intervention or a normal care control group. The exercise intervention consisted of supervised strength training and unsupervised cardiovascular exercise, with a goal of 2 strength training sessions and 90 minutes of cardiovascular exercise each week. Measurement of weight, body composition, and circumference at the waist and hip, were collected at baseline and after 16 weeks in both groups. Fasting blood samples were also collected at these two time points for insulin and glucose levels, so that changes in these levels between the intervention and control groups could be compared. Results: Eighty-five women have been randomized; complete anthropometric data are presently available for 51. Women in the exercise group experienced a nonsignificant decrease in body weight, body fat, and circumference at the waist and hip, as compared to control patients. Participants completed a median of 84% of scheduled strength training sessions and 80% of recommended cardiovascular sessions. Strength increased by an average of 40% during the exercise intervention. Prior studies have demonstrated significant inter-assay variability in biomarker testing, thus insulin and glucose testing will be performed when all patients have completed the protocol. Conclusions: Compliance with the exercise intervention was good. Women in the exercise group experienced non-significant changes in anthropometric measures, and increased strength during the 16-week intervention. Final strength and anthropometric data from the entire cohort will be available for presentation. This project was supported by an ASCO Career Development Award and funding from the Lance Armstrong Foundation. No significant financial relationships to disclose.
Gene expression profile related to oxaliplatin resistance in a panel of sensitive human colorectal cancer cell lines with acquired resistance to the drug
Authors: A. Martinez-Cardus, E. Martinez-Balibrea, J. L. Manzano, E. Bandres, R. Malumbres, C. Marti, M. Taron, J. Garcia-Foncillas, A. Abad
Journal: Journal of Clinical Oncology (2006)

13143 Background: Platinum drugs resistance acquisition is a complex process based in the alteration of genes that belong to several pathways related to drug metabolism. To clarify the multifactoriality of these mechanisms, we analyzed gene expression profile in the four CCR cell lines HT29, LoVo, DLD1 and LS513, and their sublines HTOXAR, LOVOXAR, DLDOXAR y LSOXAR that we induced oxaliplatin resistance in our laboratory. The aim of this work consisted on comparing gene expression profile between resistant cells group (cluster R) and sensitive cells group (cluster S) to determine genes and pathways that could play a role in oxaliplatin resistance acquisition process. Methods: Resistance level determination by MTT assay. Gene expression profile analysis through microarray technology (Human 19K oligo): labeled with Genisphere 3DNA Array350 (Dye Swap), and data analysis using Imagene 4.1, ArrayNorm1.7.2 y Genesis 1.5.0 (ANOVA). Results: According to ANOVA analysis of cluster R versus cluster S, we obtained 32 genes that showed significant changes in expression. 15 of these genes were up regulated and 17 were down regulated. We emphasize genes that belong to pathways previously related to oxaliplatin metabolism (AKT1, TRIP and NLK), family of genes that does not expressed in the same chromosome (KIAA0232 and KIAA0256, SLC39A9 and SLC30A9), and family of genes that had previously related to carcinogenesis processes (KRT19, KRT18 and KRT8). Conclusions: It is possible to develop oxaliplatin resistant CCR cell lines. In our oxaliplatin acquired resistance model, 32 genes showed gene expression changes between groups. These genes belong to signal transduction pathways and cellular integrity mechanisms and they could be a future oxaliplatin resistance prediction profile in colorectal cancer patients. No significant financial relationships to disclose.
Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic renal cell carcinoma
Authors: E. Jonasch, P. Corn, R. G. Ashe, K. Do, N. M. Tannir
Journal: Journal of Clinical Oncology (2007)

5104 Background: An 80 patient randomized open label phase II study is underway evaluating the safety and clinical benefit of sorafenib with or without low-dose interferon (LD IFN) in patients with untreated metastatic conventional (clear cell) renal cell carcinoma (mRCC). Prior studies combining sorafenib and conventional dose IFN demonstrated a response rate (RR) in the 20–30 percent range, higher than the 2–10 percent RR seen with sorafenib monotherapy, but with increased toxicity. Prior data suggest equivalent efficacy between LD and conventional dose IFN with fewer side effects. We postulated that low-dose IFN will add to the clinical benefit of sorafenib in patients with mRCC with minimal additional toxicity. Methods: Eligibility included conventional mRCC, measurable disease, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. Patients were treated with sorafenib 400mg PO BID or sorafenib at the same dose plus interferon alfa 0.5 million units SC BID. Primary endpoints included response rate and progression free survival (PFS). The probabilities of PFS and overall survival (OS) were estimated for each arm using Kaplan-Meier methods. Median PFS and OS were summarized, along with the 95% confidence intervals for each arm separately. Results: A total of 60 patients were enrolled as of January 8, 2007. Five patients were inevaluable, and 5 patients had not undergone first restaging. Treatment was well tolerated in both groups. Best response and PFS are summarized below. In the sorafenib arm, 13 out of 25 patients progressed or died. The median time to progression was 9.3 months (95% CI 5.8- not reached). In the sorafenib + IFN arm, 13 out of 25 patients progressed or died. Median time to progression was 9.3 months (95% CI 5.2- not reached). Median OS was not reached in either arm. Conclusions: These findings, although preliminary, suggest that adding low dose interferon therapy to sorafenib therapy does not provide superior cytoreduction of metastatic RCC, but provides equivalent PFS. [Table: see text] No significant financial relationships to disclose.
Frozen sock use in the prevention of docetaxel-induced nails and skin toxicities: Results of a case-control study
Authors: F. Scotte, E. Banu, J. Medioni, E. Levy, C. Ebenezer, S. Marsan, A. Banu, J. M. Andrieu, S. Oudard
Journal: Journal of Clinical Oncology (2007)

9059 Background: Nails and skin toxicities (NST) of the hand occur in about 50% of patients (pts) treated with docetaxel (D). No clinical data exists on specific NST of the foot after D treatment. We prospectively investigated the efficacy and safety of an Elasto-Gel (Akromed, France) flexible frozen sock (FS) for the prevention of D-induced NST according to the results of a precedent study on the hand toxicities (JCO 2005). Methods: Cancer pts receiving D at 75 to 100 mg/m 2 (one hour infusion q3w) alone or in combination were eligible for this matched case-control study. Each patient wore a FS for a total of 90 minutes (min) on the right foot (15 min before to 15 min after D-infusion). The left foot acted as control was not protected by FS. NST were assessed at each cycle using NCI-CTC version 3 criteria and documented by digital photography. Comfort in socks wearing was assessed using an ad-hoc scale. Wilcoxon matched-pairs ranks test as a non-parametric method was used to determine the magnitude of the difference in terms of nails and skin toxicities between two matched groups. Results: Forty-nine pts were included: median age 64 years, M/F: 37/12, ECOG performance status 0/1/2 (%): 46/39/15, type of cancer (%): prostate: 53; breast: 20; lung: 18; others: 8. Nails toxicities were significantly lower in the FS-protected foot compared with the control foot (P=0.002, Wilcoxon test). Grade (G) of nails toxicities were (FS vs. control %): G 0 100 vs. 80, G 1–3 ; 0 vs. 20. Skin toxicity was not significantly different (P=0.18) with a low incidence of disorder (%) G 0 : 94 vs. 90, G 1 : 2 vs. 4, G 2 : 0 vs. 2 (missing data for 2 pts). Median time until nails toxicities occurrence was not significantly different between feet: 97 days with FS vs. 74 days in control foot. Skin toxicity occurred in both sides after a median of 96 days. FS comfort satisfied 74% of patients. Conclusions: Frozen sock significantly reduced nails toxicities of the foot associated with docetaxel treatment. No significant financial relationships to disclose.
Mortality and hospitalization in myelodysplastic syndromes (MDS) using the SEER-Medicare linked database
Authors: K. Lindquist, M. Danese, K. Knopf, J. Mikhael
Journal: Journal of Clinical Oncology (2009)

7091 Background: Mortality in patients with MDS is high, and most require transfusions, emergency department (ED) visits, and hospitalizations. The relationship between these outcomes with the key complications of MDS (anemia, neutropenia, thrombocytopenia) has not been well studied. Methods: Patients who were ≥ 66 years at MDS diagnosis in 2001 or 2002 were identified from SEER registries. Those with both Medicare Part A and B were followed until death or the end of 2005. Mortality, transfusions, ED visits, and hospitalizations were based on Medicare data. The presence of complications was based on diagnosis codes, transfusions, and medication use. Kaplan-Meier incidence was estimated for each outcome. Factors associated with each outcome were based on multivariable Cox models with baseline age, gender, race, co-morbidity level, socio-economic status indicators, and time-varying covariates for each complication. Results: In 1,863 MDS patients, the 3-month incidence of transfusion, ED and hospitalization was 45%, 41%, and 62%, and 3-year incidence was 75%, 87%, and 91% respectively. Median survival was 22 months. The 3-year incidence of anemia, thrombocytopenia and neutropenia was 89%, 37%, and 15% respectively. See table for multivariate results. Conclusions: Starting shortly after diagnosis, MDS patients have high rates of transfusions, ED visits, and hospitalizations. Diagnoses of anemia, neutropenia, and thrombocytopenia are strongly associated with this utilization. The presence of anemia and thrombocytopenia are important independent risk factors for death. [Table: see text] [Table: see text]
Conflicts of interest in economic analyses presented at the American Society of Clinical Oncology Annual Meeting.
Authors: S. Jang, Y. Chae, N. S. Majhail
Journal: Journal of Clinical Oncology (2010)

6014 Background: Economic analyses of pharmaceutical agents are important determinants of health reimbursement decisions and are essential components of comparative effectiveness research. We conducted this study to determine the frequency of conflicts of interest (COI) in economic analyses presented at the ASCO annual meeting and to examine the association between the COI and study outcomes. Methods: ASCO annual meeting abstracts from 2004-2008 were searched for economic analyses using following search terms: cost, economic, dollar, cost-effective, cost-benefit. Abstracts in the Health Services Research category were also reviewed. Information was collected on the type of economic analysis, health technology assessed, author affiliations, the presence and the type of COI. Qualitative conclusions were rated according to following criteria: direct support (sponsored product is cost-effective or cost-saving), indirect support (no agent involved but results had the potential to promote sponsoring company's product, i.e., a study on costs of febrile neutropenia sponsored by a company which manufactures granulocyte colony-stimulating factor), or no support. Results: 232 original economic analyses were identified. 126 studies (54%) were conducted in the US. 117 studies (50%) evaluated a pharmaceutical product. First author affiliations included academic institutions (73%), consulting company employee (19%) and employee of sponsoring corporate (8%). 148 of 232 studies (64%) had at least one author with COI. Type of COI included research funding only (n = 5), employment only (n = 49), and personal financial interest such as consulting, honorarium, stock or other (n = 94). First authors of abstracts with a COI were less likely to be affiliated with an academic institution compared to abstracts without a COI (57% vs. 100%, p < 0.01). The conclusions of 125 of 148 economic analyses with COI directly (51%) or indirectly (34%) supported sponsor's product. Conclusions: COI are common in economic analyses presented at the ASCO Annual Meeting. Majority of economic analyses with COI support their sponsor's products. No significant financial relationships to disclose.
Osteopontin (OPN): A novel tumor marker of potential utility in metastatic breast cancer
Authors: V. Bramwell, G. Doig, A. Tuck, S. Wilson, K. Tonkin, T. Vandenberg, A. Chambers
Journal: Journal of Clinical Oncology (2004)

575 Background: OPN, a secreted integrin-binding malignancy-associated protein measurable in blood and tumor tissue, has potential clinical utility as a tumor marker in breast cancer. Methods: In metastatic breast cancer, a prospective study to determine if (a) OPN blood levels are prognostic for survival (b) changes in OPN levels beyond baseline provide additional information (c) OPN has advantages over other blood markers (CEA, CA 15.3, secreted HER2 (ECD/HER2)). Blood was collected before treatment, and every 3–12 weeks until death. OPN: measured in plasma, using our validated ELISA assay (Clin. Bioch. 29:231, 1996). Serum markers: measured by standard clinical (CEA, CA 15.3), and ELISA (ECD/HER2) assays. Results: Study entry - 158 women within 8 weeks of diagnosis of metastatic breast cancer; median age 61 (20–84) years; postmenopausal (138); time to first metastasis 36 (0–397) months. First systemic treatment: chemotherapy (43), hormone therapy (111), none (4). Analysis July 2003: 132 (84% dead, median follow-up 19 (0.2–62) months. All 4 markers measured in 1378 samples (median 9 (1–26) per patient). OPN levels (median 177, range 1–2648) were elevated relative to previously determined normal levels. We used survival analysis with time-dependent covariates to investigate changes in OPN levels and survival (alive/dead) at 3, 6 and 12 months from final OPN measurement. These analyses show (i) the higher the initial OPN, the lower a patient's chance of being alive at 3 months (p=0.0005); 6 months (p=0.0142); 12 months (p=0.02) and (ii) controlling for initial OPN level, any increase in OPN levels between readings confers an increased risk of death at 3 months (RR 1.73, p=0.04); 6 months (RR 1.55, p=0.04); 12 months (RR 1.58, p=0.03). We will present further analyses comparing OPN with the 3 other tumor markers. Conclusions: In metastatic breast cancer, we found that OPN levels, both at baseline and changes over time, are prognostic for outcome. No significant financial relationships to disclose.
A multinational phase III randomized trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small cell lung cancer (CCheIN): Interim analysis
Authors: K. Park, Y. Ahn, M. Chen, E. Cho, J. Kim, Y. Min, H. Kim, G. Zhu, D. S. Heo, Y. Wu
Journal: Journal of Clinical Oncology (2009)

7538 Background: Currently, the recommended treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). The efficacy of consolidation chemotherapy after CCRT needs to be confirmed. The aim of this phase III randomized trial is to determine the efficacy of consolidation chemotherapy with docetaxel (D) and cisplatin (P) following definitive CCRT with the same agents in stage III inoperable NSCLC. Herein we report the pre-planned interim analysis. Methods: Patients with inoperable stage III NSCLC were randomized to either CCRT alone (observation arm) or CCRT followed by consolidation chemotherapy (consolidation arm). N2 or N3 disease was confirmed by PET and/or pathology. CCRT with D (20 mg/m 2 ) and P (20 mg/m 2 ) was administered every week for 6 weeks with a total dose of 66 Gy of thoracic RT as 33 fractions. In the consolidation arm, patients were further treated with 3 cycles of D and P (35 mg/m 2 each on day 1 and 8, every 3 weeks). The primary endpoint is time to progression (TTP). Total target number of patients is 458. Results: From Oct 2005 to Mar 2008, 233 patients were enrolled and 226 were randomized (observation 112; consolidation 114). Patients’ characteristics were similar in both arms. In the consolidation arm, 83 patients (73%) received consolidation chemotherapy, of whom 52 (45%) completed 3 planned cycles. Grade 3–4 neutropenia occurred in 5.4% of 203 consolidation cycles. Common non-hematologic toxicities of all grades during consolidation were anorexia (47%), nausea (37%), vomiting (16%), fatigue (35%) and esophagitis (31%). At the time of this analysis, there were 40 and 41 deaths in the observation and consolidation arms, respectively. Treatment-related mortality rates were similar. With a median follow-up of 28.2 months, the median TTP was 9.0 months in the observation arm and 13.9 months in the consolidation arm (P=0.19). Median overall survival was 20.7 and 21.2 months, respectively (P=0.49). Conclusions: This interim analysis suggests that consolidation chemotherapy with DP after CCRT with weekly DP is feasible and relatively well tolerated. Patient enrollment is ongoing. No significant financial relationships to disclose.
Radiochemotherapy versus chemotherapy in locally advanced cervix cancer: A pilot study.
Authors: M. Arena
Journal: Journal of Clinical Oncology (2010)

e15561 Background: Many reports have correlated 1) hypoxia with attenuated responses to radiotherapy and 2) a good oxygenation as function of high HGB level in the peripheral blood. There is agreement to increase to the response to the radiotherapy of head and neck with the use of erythropoietin to increase the hemoglobin level. Methods: From January 2002 until January 2009 we treated 88 patients with cervix locally advanced, 26 patients in stage IIB, 28 in stage IIIA 20 in stage III B and 14 patients in IV stage. 44 patients previously treated with chemotherapy (cisplatin, ifosfamide, paclitaxel), the response of chemotherapy was 12 PR,7NC,3 PD. All patients had an HGB between 9 and 12 gr/dL and from 2 weeks before radiotherapy we daily treated with erythropoietin 10,000 UI to increase HGB between 13 and 14 gr/dL, then we gave erythropoietin every day with radiotherapy. In the second group 44 patients were treated with radiotherapy plus 5FU 1g/sm/day, days 1-5, continuous iv infusion + carboplatino 80 mg and erythropoietin. Results: We have analyzed the patients one month after radiotherapy we valued the result of the treatment. Only in 28 /44 patients we used to increase the HGB to 13-14 gr, in the other 8 patients (37% ) the value of HGB was between 9-11 gr. The response to radiotherapy was 26 PR, 16 NC and 2 PD. The response of the second treatment was 15 CR,7 PR. In 8/44 we used to interrupt treatment for III grade of leuko-thrombocytopenia. Conclusions: In patients, previously treated with chemotherapy, the residual disease is probably hypoxic and therefore is radio-resistant for this reason does not increase the efficacy of radiotherapy nonstante the value of HGB between 13-14 gr, after chemotherapy we had a compromised bone marrow hence we coclude that it is difficult to increase the value of hgb after chemotherapy for bone marrow failure. We are continuing the radiotherapy in concomitant with 5FU plus carboplatin and erytropoeitin in the first choice of treatment of cervix cancer locally advanced seeing the good response 30/44 patients with complete response and 14 /44 partial response No significant financial relationships to disclose.