tbuckley/cabot-search huggingface dataset:
Investigation of hand-foot syndrome (HFS) observed in pazopanib (P)-treated patients (pts) with renal cell carcinoma (RCC).
Authors: H. A. Ball, Y. Lin, Z. Xue, B. Suttle, C. Xu, L. Huang, L. McCann, T. E. Hutson, C. N. Sternberg, L. N. Pandite
Journal: Journal of Clinical Oncology (2011)

3061 Background: HFS is an adverse-effect of several agents used to treat cancer, particularly the VEGF TKIs. HFS can be debilitating for patients, affecting their physical, mental, and social well-being. This study sought to explore demographic, pharmacokinetic (PK) and pharmacogenetic (PGx) factors which may contribute to pazopanib-related HFS in pts with RCC. Methods: Week (wk) 4 plasma P trough concentrations (Cmin) were determined for 204 out of 225 pts with advanced RCC from a phase II study (VEG102616). Logistic and ordinal regression analyses were used to evaluate the effect of demographic (gender, race, baseline weight and height) and wk 4 Cmin on occurrence and severity of HFS, respectively. For the PGx analyses, DNA samples were collected from consenting pts with advanced RCC from three P clinical studies; VEG102616 (phase II), VEG105192 (phase III), and VEG107769. Pts were defined as HFS cases (NCI-CTCv3 grade ≥ 1, n=33) or controls (grade = 0 with treatment duration >28 days, n=321). A total of 3012 SNPs in 89 candidate genes were evaluated. The penalized maximum likelihood logistic regression was used to evaluate the effect of genotypes on the HFS case-control status. Results: While the overall incidence was low (7.7%), a high proportion of east and south-east Asians exhibited HFS (21/71, 30%) compared to Caucasians (22/489, 4%). Wk4 Cmin (P = 0.0005) and race (P = 0.03) were significantly associated with occurrence of HFS by logistic regression. A similar correlation was observed between maximal HFS grades (CTC v3) and wk4 Cmin (P < 0.0001) and race (P = 0.0045). None of the genetic markers were significantly associated with HFS after correction for multiple comparisions. Five SNPs in ABCG2, PDGFRA, GZMB and TPCN2 genes showed suggestive association with HFS at a nominal significance level P<0.01 and with a plausible genetic model. Conclusions: Both race (Asian vs. Caucasian) and wk4 P Cmin concentrations are significant predictors of HFS. Candidate gene analyses revealed that some genetic markers may be associated with P- related HFS. However, as none of the markers passed the significance level of multiple testing corrections, further evaluation in independent data sets is required to confirm or refute these findings.
Safety and efficacy of single-agent adjuvant trastzumab in older women with breast cancer.
Authors: C. Owusu, H. D. Klepin, G. G. Kimmick, L. Sutton, A. Brufsky
Journal: Journal of Clinical Oncology (2011)

TPS109 Background: Trastuzumab is a humanized monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) protein. The addition of trastuzumab to adjuvant chemotherapy, either concomitant or sequential, leads to better outcomes for women with HER2-positive breast cancer and in the setting of metastatic disease, single agent trastuzumab is effective and extremely well tolerated. The main adverse effect of trastuzumab is cardiotoxicity, which necessitated discontinuation prior to the planned one year of therapy in 17% of women on adjuvant trials. Since age is a risk factor for the cardiotoxicity of trastuzumab, and women ≥ 65 years were under-represented in trastuzumab clinical trials, determination of the safety and efficacy of trastuzumab in this patient population is lacking. This study is designed to define the risk-benefit profile of adjuvant single-agent trastuzumab in older women. Methods: This open label, single arm, multi-center, phase II study will include 124 women with stage I-III, HER2+ (defined as either 3+ by immunohistochemistry or gene amplified by fluorescent in situ hybridization), breast cancer who undergo primary surgery (mastectomy or lumpectomy) with at least a sentinel lymph node dissection, and are unwilling to undergo or are unable to tolerate adjuvant chemotherapy. Trastuzumab will be given, at 8mg/kg IV loading dose followed by 6mg/kg IV every three weeks, for 52 weeks. Patients will be followed prospectively for five years or until death, whichever comes first. The primary objective of the study is to evaluate the three-year cumulative incidence of cardiac events. Secondary objectives include i) the three-year cumulative incidence of asymptomatic decline in Left Ventricular Ejection Fraction; ii) the five-year cumulative incidence of cardiac events; iii) three-year disease-free and overall survival; iv) identification of correlative biomarkers of cardiac events (troponin-I, N-terminal brain natriuretic protein, and pro-inflammatory cytokines); and v) the longitudinal changes in Health-related Quality of Life, functional, cognitive, and mental status. Ten patients have been enrolled thus far.
Clinical experience with ferric carboxymaltose as treatment of cancer-associated anemia.
Authors: T. Steinmetz, B. Tschechne, G. Virgin, M. Felder, J. Wamhoff, H. Tesch, R. Rohrberg, N. Marschner
Journal: Journal of Clinical Oncology (2011)

e19561 Background: Controlled studies showed that intravenous iron can improve hemoglobin (Hb) levels and decrease the need for erythropoiesis-stimulating agents (ESAs) and blood transfusions in anemic cancer patients. This observational study provides data on effectiveness and safety of ferric carboxymaltose (FCM) in routine treatment of anemia in cancer patients. Methods: 642 cancer patients (≥18 years) with iron deficiency anemia were registered from Dec 2008 to Jul 2010 at 73 German hematology/oncology practices. FCM was administered without restriction on dose and concomitant ESA or blood transfusion use. This interim analysis assessed safety in 581 patients receiving at least one FCM dose, and evaluable Hb difference (effectiveness) in those also completing the study by August 2010 (n=401). Results: Patients (mean age 64 years; male 49%) mainly presented with solid tumors (90%) and received cytotoxic chemotherapy (72%); 20.9% were previously treated for anemia. Mean total iron dose per patient was 1,333 mg; 15.7% received also an ESA and 25.6% a blood transfusion. Mean Hb increased within 5 weeks and remained between 11–12 g/dL until the end of the 12-week study period (Table). Benefit was comparable in patients with mild and moderate-severe anemia. Hb also improved comparably in patients treated with FCM alone or with concomitant ESAs. FCM treatment was well tolerated. Possibly or probably drug-related adverse events (AEs), mainly nausea and diarrhea, were reported for 2.4% of patients. Two fatal cases occurred: one of unknown cause and unrelated to FCM and one after a possibly related respiratory insufficiency. Two serious AEs (tachycardia, dyspnea) were unlikely related to FCM. Conclusions: Hb of FCM-treated anemic cancer patients effectively stabilized at 11–12 g/dL independent of baseline Hb levels and concomitant erythropoietic therapy. This observational study suggests FCM is beneficial as anemia treatment in cancer patients. Hb at baseline (BL) and increase to Wk 5 and Wk 12 (g/dL). Patients (n) BL* DHb to Wk 5+ DHb to Wk 12+ All (401) 10.0 ± 1.4 1.0 1.4 BL Hb <10 g/dL (206) 9.0 ± 0.9 1.7 2.2 BL Hb 10-11 g/dL (116) 10.4 ± 0.3 0.7 1.1 FCM only (345) 10.1 ± 1.4 1.0 1.4 FCM + ESA (56) 9.4 ± 1.2 1.4 1.5 * Mean ± SD. + Difference of means vs BL.
Efficacy and Safety of Gemtuzumab-Based Regimens in Patients with CD33-Positive Refractory Leukemia.
Authors: Suijing Wu, Xin Du, Wei Lin, Jianyu Weng, Jianjun Zhang, Maohua Zhou, Zhixin Huang, Jianhua Su, Zilun Huang, Zesheng Lu
Journal: Blood (2007)
A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer.
Authors: Rui-hua Xu, Lin Shen, Keming Wang, Gang Wu, Chunmei Shi, Kefeng Ding, Lizhu Lin, Jinwan Wang, Jianping Xiong, Changping Wu, Jin Li, Yunpeng Liu, Dong Wang, Yi Ba, Jueping Feng, Yuxian Bai, JingWang Bi, Liwen MA, Jian Lei, Hao Yu
Journal: Journal of Clinical Oncology (2015)

513 Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and is the fifth leading cause of cancer death in China. No standard care is available for patients with advanced CRC who failed the second-line treatment. Famitinib is a small-molecular, multi-target receptor tyrosine kinase inhibitor which primarily acts against angiogenesis. This phase II study was designed to evaluate the efficacy and safety of famitinib in the treatment of advanced colorectal cancer. Methods: This is a multi-center, randomized, double-blind, placebo-controlled, phase II clinical study (ClinicalTrials.gov Registration No.: NCT01762293). Totally 154 patients with advanced colorectal cancer who failed second or later-line treatments were randomized in a 2:1 ratio to receive either famitinib or placebo at 25 mg each day in each treatment cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and safety. The statistical analyses of endpoints were using intent-to-treat population. Results: Of 154 patients randomized, the mPFS was 2.8 and 1.5 months in the treatment group and control group, respectively (p=0.0034; HR=0.58). The ORR was 2.02% and 0.00% (p=0.54) and the DCR was 57.58% and 30.91% (p=0.0023) in the treatment group and control group, respectively. Analysis of OS data is ongoing. The frequently reported adverse events (AEs) include neutropenia, thrombocytopenia, hypertension, proteinuria, and hand-foot syndrome and were most grade 1/2. The incidences of serious adverse events (SAEs) for the famitinib and placebo groups were 11.11% and 9.09%, respectively (p=0.7884). Overall, famitinib was well tolerated and toxicities were manageable. Conclusions: Famitinib improved the PFS in patients with advanced metastatic colorectal cancer resulting in higher ORR and DCR in the treatment group with good safety and tolerability. Clinical trial information: NCT01762293.
Rates of inclusion of teenagers and young adults (TYA) with cancer into UK National Cancer Research Institute (NCRI) clinical trials, 2005–2007
Authors: J. Whelan, L. A. Fern
Journal: Journal of Clinical Oncology (2008)

6586 Background: The specific needs of TYA with cancer are being increasingly recognised. Poorer inclusion rates into clinical trials for TYA have been assumed but not systematically investigated in the UK. We set out to determine accrual rates (AR) of TYA in the UK. Methods: We analysed accrual by age to Phase III trials recruiting newly diagnosed patients (pts) with leukaemia, lymphoma, central nervous system, bone and male germ cell tumours, under the auspices of the NCRI. AR were expressed as the ratio of patients entered onto trial compared to the number of new cases diagnosed in 2004. No data were available for Northern Ireland. Results: AR fell significantly for pts aged more than 15 yrs. AR dropped from 49.8% for pts 10–14 yrs, to 25.1% for pts 15–19 yrs and further still to 16.5% for pts 20–24 yrs during 2005/06. AR for 2006/07 demonstrated slight increases in inclusion rates for pts aged 10–14 and 15–19 but fell for those aged 20–24 compared to 2005/06, 51.4%, 28.3% and 13.2% respectively. National trends were similar. We looked at accrual by paediatric, 5–14 yrs, versus adult oncology, 15–24 yrs. AR for pts 5–14 yrs was 56.3% compared to 20.2% of pts 15–24yrs, with similar trends across the UK (table). AR varied considerably between cancer types and between years related to opening and closing of trials. Conclusions: There is a decline in inclusion of TYA in clinical trials beyond 15 yrs. This reflects trial availability and design during 2005/07 as well as trial access. Trial age eligibility criteria often fail to reflect tumour biology, and are frequently set by organisational considerations. Reversing this trend will require collaboration between adult and paediatric groups to increase trial availability, access and participation UK accrual rates to NCRI trials by age, 2005- 07 UK England Wales Scotland 5–14 yrs 56.6 50.0 40.3 38.9 15–24 yrs 20.2 19.0 11.4 12.1 No significant financial relationships to disclose.
Development and initial validation of a metabolite profile for the early detection of breast cancer recurrence.
Authors: Daniel Raftery, Haiwei Gu, Vincent Asiago, Leiddy Alvarado, Danijel Djukovic, Robert Ballas
Journal: Journal of Clinical Oncology (2012)

5 Background: The detection of recurrent breast cancer is limited by poorly performing CA markers that are both insensitive and late markers. Because of their sensitivity to biological status, metabolite markers may provide better diagnostic performance and earlier detection. Detectable perturbations in the metabolic profiles of patients often result from altered metabolism in cancer. We report on the discovery and initial validation of a metabolite profile for the early detection of recurrent breast cancer. Methods: We applied a combination of nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) to analyze the metabolite profiles of 116 serial serum samples from 20 recurring patients and 141 serial samples from 36 breast cancer survivors with no evidence of disease (NED). Multivariate analysis was used to identify 11 metabolite markers that were used to build a model with high accuracy (AUROC &gt;0.88 using 10 fold cross validation) with a sensitivity of 68% and specificity of 94%. Strikingly, over 55% of the patients could be correctly predicted to have recurrence on average 13 months before clinical diagnosis, representing a large improvement over the current diagnostic assays CA 27.29 and CA 15-3 (Cancer Res. 2010; 70, 8309-18). The metabolites were then ported to an LC-MS/MS platform and a method was developed to quantify these metabolites using stable isotope labeled compounds. Due to difficulty in obtaining some labeled compounds the profile was reduced to 9 metabolites. The multivariate algorithm was recalculating using five-fold cross validation and using 211 patient samples. During this work we found that the performance of the assay could be improved by adding CA27-29 values to the assay, which mainly ensured excellent specificity. Results: The profile was tested using a separate validation set of 96 patient samples run identically. The performance was similar to the training set with a sensitivity of 65% and specificity of 93%. Recurrence detection was approximately 11 months ahead of clinical diagnosis (based on imaging for symptomatic patients) and about 2 years ahead of CA 27-29 alone. Conclusions: This metabolite profile has promise for early recurrence detection.
A survey of current practices in the management of chronic myeloid leukemia (CML).
Authors: M. J. Mauro, J. E. Cortes, R. A. Larson, P. M. Herout, V. K. Bollu, A. Niyazov, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6513 Background: A previous survey of the management of CML conducted in 2005 reported on physician self-reported practice patterns (Cancer 2007;109:1365-75). Methods: We conducted a US-based survey via an online questionnaire consisting of items updated to reflect changes in clinical practice, tyrosine kinase inhibitor (TKI) therapy and current guidelines. Results: 507 board certified medical oncologists/hematologists responded to the survey; most (72%) were in the private practice setting. For initial choice of therapy in chronic phase CML, nearly 60% chose varying doses of imatinib (IM); 40% chose nilotinib or dasatinib (NI/DA). Achievement of complete cytogenetic response (CCyR) at 6 or 12 months (32.5%) or both CCyR and major molecular response (MMR) at 12 months (23.3%) was felt to be indicative of effective initial TKI therapy. Complete molecular response (CMR, 44%) and MMR (27%) were reported as primary treatment goals. Marrow based studies were used in <50% of respondents for initial monitoring and nearly 50% cited uncertainty or unfamiliarity with international scale (IS) reporting of qPCR. Regarding suboptimal response, only 26% reported that they would maintain a dose of 400 mg IM daily for a patient achieving CCyR but not MMR after 2 years of therapy; 34% reported that they would change the treatment to NI/DA and 52% would increase the IM dose. Scenarios more likely to result in a change from IM to NI/DA included failure to achieve MMR after IM for 2 years, or perceived treatment failure while on IM. In a patient not in CCyR, 74% of respondents monitor response by cytogenetic studies every 3-6 months. In a patient in CCyR, 85% of respondents monitor response by molecular studies every 3-6 months. A slight majority (54%) of respondents would assess for BCR-ABL mutations if MMR is not achieved 2 years after initiation of TKI; of note up to 30% of respondents cite use of mutation analysis with initial diagnostic studies. Conclusions: From the surveyed physicians, achievement of at least MMR is the predominant treatment goal in chronic phase CML, and most would adjust the imatinib dose or change therapy to a NI/DA in order to achieve MMR even after CCyR. These approaches will be discussed in relation to the European Leukemia Net (ELN) guidelines.
Relationship of quality of life at presentation to resected pancreas cancer pathologic features.
Authors: L. Pujol, B. I. Carr
Journal: Journal of Clinical Oncology (2011)

e19631 Background: Relationship of pain or depression to pancreas tumor invasiveness is unclear. Methods: Patients with resected pancreas adenocarcinoma (n=126) filled out measures of quality of life (FACT-HEP), depression (Center for Epidemiologic Studies – Depression; CES-D) and pain (Brief Pain Inventory – Short Form, BPI) at their one-month post-operative clinic visit. This study correlated baseline pre-operative baseline labs and pain with post-operative pathological parameters and scores on the psychological questionnaires. Results: Bivarate correlations were performed and further analyses completed when pathological variables and psychological variables were significant at the p<0.05 level. Seventy-five percent (75%) of patients endorsed moderate to severe depressive symptomatology. Depression was predicted by the size of tumor (p<0.02), but none of the other pathological variables. One third of the patients (33%) reported no pain. We found that patients with high and low depression, as measured by the CES-D, did not differ in tumor size, neural or vascular involvement, positive margin, local invasion or pancreatitis. However, higher depression levels correlated with increased lymph node invasion (p<0.029). Lower emotional well-being was associated with positive margins (p<0.03). Pain severity, measured by BPI was not predicted by any of the pathological variables. However, interference in life activities due to pain was associated with tumor size (p<0.01). Patients with metastases noted lower functional well-being (p<0.02) and higher pain interference in life activities (p<0.05) than patients without metastases and also had higher CA 19-9 levels (p<0.027). Patients with neural invasion reported lower emotional well-being than those with without invasion (p<0.05) and patients with lymph node involvement reported lower social/family well-being (p<0.05). Elevated CA19-9 levels positively correlated with neural, vascular and lymph node invasion (p<0.05), pancreatitis and lower physical well-being (p<0.05). Conclusions: Baseline pain and depression correlated poorly with pathological features, but elevated CA 19-9 levels correlated well.
Risk factors for severe weight loss after gastrectomy for gastric cancer.
Authors: Kenki Segami, Toru Aoyama, Taiichi Kawabe, Shigeya Hayashi, Yousuke Makuuchi, Tsutomu Sato, Takanobu Yamada, Tsutomu Hayashi, Hirohito Fujikawa, Yasushi Rino, Munetaka Masuda, Takashi Ogata, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2015)

38 Background: Body weight loss (BWL) is frequently observed in gastric cancer patients who underwent gastrectomy for gastric cancer. Recently, we reported that severe BWL after gastrectomy was a significant risk factor for continuation of S-1 adjuvant chemotherapy. However, risk factors of BWL after surgery remain unclear. Methods: The present study retrospectively examined the patients who electively underwent curative gastrectomy for gastric cancer between January of 2012 and June of 2014. All patients received peri-operative care of ERAS protocol. %BWL was calculated by percentile of body weight at one month after surgery to preoperative body weight. Severe BWL was defined as %BWL over 10%. Risk factors for severe BWL were determined by both univariate and multivariate logistic regression analyses. Results: Two-hundred seventy eight patients were examined. Median age (range) was 68 years (27-86). Median body mass index (range) was 22 (13.4-33.5). Thirty patients had received neoadjuvant chemotherapy. Operative procedure was total gastrectomy (TG) in 97 patients (Open in 61 and laparoscopic in 36) and distal gastrectomy (DG) in 181 patients (Open in 94 and laparoscopic in 87). Median operation time (range) was 268.5 minutes (95-554). Median blood loss (range) was 115 mL (0-1600). Morbidity of grade 2 or more defined by Clavien-Dindo classification was observed in 37 patients including pancreatic fistula in 8, anastomotic leakage in 5, and abdominal abscess in 3. No mortality was found. Completion of ERAS protocol without any variance was 95.3%. Median %BWL was 6% (-4.3% to 19.5%). Both univariate and multivariate logistic analyses demonstrated that morbidity (odds rate 3.56, p=0.001), blood loss over 300ml (odds rate 2.04, p=0.0356), and total gastrectomy (odds rate 2.1, p=0.0258) were significant risk factors for severe BWL. Conclusions: Nutritional intervention trial to inhibit BWL after gastrectomy should be focused on the patients who developed morbidity, showed blood loss over 300ml, or received total gastrectomy.
Nelarabine Can Be Safely Incorporated into an Intensive, Multiagent Chemotherapy Regimen for the Treatment of T-Cell Acute Lymphocytic Leukemia (ALL) in Children: A Report of the Children’s Oncology Group (COG) AALL00P2 Protocol for T-Cell Leukemia.
Authors: Kimberly Dunsmore, Meenakshi Devidas, Michael J. Borowitz, Naomi Winick, Stephen Hunger, William L. Carroll, Bruce Camitta
Journal: Blood (2006)