tbuckley/cabot-search huggingface dataset:
Interim analysis of a single-arm, phase II study of bevacizumab (BV) with modified OPTIMOX1 as first-line treatment of patients with metastatic colorectal cancer (mCRC): TCOG-GI0802.
Authors: M. Asano, S. Tanaka, A. Sato, N. Nakayama, K. Shimada, K. Konishi, K. Hibi, E. Sasaki, M. Kurihara
Journal: Journal of Clinical Oncology (2011)

578 Background: BV is widely used for treatment of metastatic colorectal cancer (mCRC) patients. Although BV was often administrated to mCRC patients in combination with oxaliplatin, optimal schedule remains unclear. Many mCRC patients cannot continue to use oxalipatin because of cumulative neurotoxity, which decreases patient's QOL and motivation.We postulated that modification of oxaliplatin schedule would improve TTF in intermittent oxaliplatin usage. Therefore, we planned to use BV with original OPTIMOX1 adiministration schedule; modified oxaliplatin dose (85 mg/m 3 ). Methods: Patients were enrolled with the criteria excluding neuropathy, PS ≥ 1, or no previous usage of oxaliplatin and BV, and then were received modified FOLFOX6 regimen (L-OHP 85 mg/m 2 , l-LV 200 mg/m 2 , 5-FU 400 mg/m 2 bolus, 5-FU 2,400 mg/m 2 46h continuous infusion) plus BV (5 mg/kg) q2wks x 6 cycles, followed sLV5FU2 (omit L-OHP) plus BV x 12 cycles regimen. After that, oxaliplatin reintroduction was done and mFOLFOX6 plus BV regimen was continued until PD. The evaluation of antitumor effect was done according to RECIST Criteria. Results: 40 patients accrued this trial. Median age was 65 years old. PS0: 89.5%, male: 75%, female: 25%, colon: 65.8%, rectal: 31.6%,colon + rectal: 2.6%. During initial 6 cycles of chemotherapy, 90% patients could continue chemotherapy. Response rate was 50%, and clinical benefit (including SD) was 92.1%. During Intial 6 cycles, G3 neuropathy occurred 2.6%, and G2 were 5%. Most frequent toxicity (≥G3) was neutropenia (30.8%) and anorexia (5.3%). One patient could complete the scheduled regimen. This patient continued mFOLFOX6+BV for 12 cycles after reintroduction keeping with PS 0, and was received FOLFIRI+BV regimen as second-line chemotherapy. Further information are under examination. Conclusions: This administration schedule was well tolerated and could continue chemotherapy longer than usual method. sLV5FU2+BV regimen was not affected reintroduction rate and progression free survival. BV with mOPTIMOX1 regimen can be expected to become a good treatment options for mCRC patients. No significant financial relationships to disclose.
Effect of body mass index (BMI) on outcomes after surgical resection and adjuvant therapy for pancreatic cancer patients.
Authors: M. R. Khawaja, N. Zyromski, M. Yu, H. R. Cardenes, C. M. Schmidt, G. Sandusky, T. J. Howard, E. G. Chiorean
Journal: Journal of Clinical Oncology (2011)

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m 2 vs. overweight/obese ≥ 25 kg/m 2 ). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p &lt; 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p &lt; 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.
Frequency of <i>Kras</i> mutation in colorectal cancer patients in a minority-based population at a community clinical oncology program (CCOP)–participating inner-city hospital.
Authors: M. Gaddh, H. V. Poola, K. K. Batra, M. R. Mullane, M. Sekosan, T. E. Lad
Journal: Journal of Clinical Oncology (2011)

e14051 Background: Kras gene is a downstream target of epidermal growth factor receptor (EGFR) signaling. Activating mutations of this gene confer resistance to EGFR-targeted monoclonal antibodies and may also have prognostic significance. The prevalence of this mutation has been reported in 30-40% of colorectal cancers in United States. We present the frequency and associated clinico-social characteristics of this mutation in a cohort of predominantly minority-based population. Methods: We retrospectively reviewed records of patients with metastatic colorectal cancer at our institution over an 8-year period from 2003 to 2010. The objectives were to define the frequency of Kras mutation in this predominantly minority based population, and to study its relationship with various demographic and clinical parameters. Results: Between April 2003 and August 2010, 63 patients with metastatic colorectal cancer underwent Kras mutation testing. The majority were of African American (50%) or Hispanic (21%) descent. Caucasians represented only 27% of the study population. 42 (66.7%) tested positive for Kras mutation. A difference in mutation prevalence was seen with regards to gender (males vs. females; 32/45=71% vs. 10/18=55.5%), age (>/=50 vs. < 50; 32/47=68% vs. 10/16=62%) and primary tumor location (recto-sigmoid vs. colon; 19/25=76% vs. 23/37=62%). Conclusions: Our cohort of predominantly minority ethnicities shows a significantly higher prevalence of Kras mutations than previously reported national figures. This suggests that race is an important predictor of presence of this mutation, which in turn has therapeutic and potentially prognostic implications. Further studies are needed to better understand these racial differences and adopt a more personalized approach to colorectal cancers. Kras type Wild Mutant Total (%) Number (%) 21 (33.3%) 42 (66.7%) 63 (100%) Ethnicity African American 12 19 31 (50%) Hispanic 2 10 12 (21%) Caucasian 6 11 17 (27%) Asian 1 2 3 (1%) Gender Male 13 32 45 (71.4%) Female 8 10 18 (28.6%) Age at diagnosis <50 years 7 10 17 (27%) >/=50 years 14 32 46 (73%) Primary tumor location Colon 14 23 37 (59%) Rectosigmoid 7 19 26 (41%)
Experience with docetaxel in hormone-refractory prostate cancer (HRPC) at three Australian cancer centers: A retrospective study
Authors: E. J. Hovey, M. George, G. S. Gabriel, J. Shapiro, B. Chern, E. J. Moylan
Journal: Journal of Clinical Oncology (2005)

4786 Aim: To retrospectively review PSA response rate, and survival following the use of docetaxel (D) for metastatic HRPC. Background: HRPC is associated with poor prognosis and has historically been considered relatively chemo-resistant. Emerging data demonstrate clinical benefit with the use of D in HRPC, culminating in 2 recent published Phase III studies demonstrating survival benefit. Currently, D is not registered or reimbursed through Medicare (Pharmaceutical Benefits Scheme) for the treatment of HRPC in Australia. Methods: Retrospective audit (commenced September 2003) of the use of D for HRPC from January 2001- January 2004 in 3 Medical Oncology practices. Demographic data, baseline PSA, ECOG status, sites of disease, number of cycles received and PSA response rate were collected. Results: 35 patients (pts); median age 71yrs (50–88yrs). ECOG status: 0 (8pts), 1 (20pts), 2 (7pts). Mean duration from initial prostate cancer diagnosis to start of D 5.4yrs (0.2–13.5yrs). Mean baseline PSA doubling time, available for 18/35 pts, was 3.91 months (1–15). Median number of metastatic sites 1 (range 1–4): bone-34 pts, lymph nodes-10, liver-7 and lung-7. Twelve pts were chemo-naïve; 23 pts had received prior chemotherapy (21/23 received mitoxantrone). Twenty pts received D 3 weekly; 15 pts were on weekly schedules. Mean dose density was 23mg/m2/week. Pts received an average of 3.2 months of treatment (0.2–11.8). There were 170 recorded toxicities, of which 13 were grade 3–4, and two likely treatment-related deaths (sepsis). Twelve pts (34%) had >50% PSA response (4 chemo-naïve); of these 12 responders, 7 pts had a >75% PSA response (4 chemo-naïve). Median survival from start of D was 8 months with 37% alive at 12 months and 23% alive at 24 months. Conclusion: Docetaxel is active in HRPC (in both chemotherapy naïve and exposed pts) with a predictable toxicity profile.Our median survival of 8 months compared to a median survival of 18.9 months in the TAX-327 Phase III study is probably due to the fact that our patients on average were slightly older, more heavily pre-treated and more likely to have a poorer performance status. More research is warranted to identify predictors of response and toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
A phase I study of combination of panitumumab and bevacizumab in <i>KRAS </i>wild-type colorectal cancer patients who were previously treated with fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab.
Authors: Naoki Takahashi, Satoru Iwasa, Masanori Tachikawa, Masaru Fukahori, Kazuki Sudo, Yusuke Sasaki, Hirokazu Shoji, Yoshitaka Honma, Natsuko Okita, Atsuo Takashima, Tetsuya Hamaguchi, Narikazu Boku, Yasuhiro Shimada, Koki Yamagiwa, Yuka Ebata, Yasuo Uchida, Kazufumi Honda, Tetsuya Terasaki, Yasuhide Yamada
Journal: Journal of Clinical Oncology (2016)

759 Background: Clinical benefit of combination of panitumumab and bevacizumab (PB) based on the BBP strategy in third-line chemotherapy is unclear. There was no prospective data about the pharmacokinetic interaction between bevacizumab and panitumumab. Methods: This study composed two parts; 1) PB part: phase I study of PB to estimate its recommended dose, 2) CPB part: feasibility study to investigate the safety in combination of bevacizumab and panitumumab at the recommended dose in the phase I part with irinotecan (CPT-11) at the dose used in the prior chemotherapy. Inclusion criteria was as follows; 1) Age: ≥ 20 and &lt; 76 years old, 2) performance status ≤ 1, 3) histologically colorectal adenocarcinoma with KRASwild-type, 4) patients who previously received fluoropyrimidine, oxaliplatin, CPT-11 and bevacizumab for unresectable metastatic disease. Three dose levels of panitumumab (Level 1: 6mg/kg, Level 0: 5mg/kg, Level -1: 4mg/kg) was set in PB part and starting dose level was Level 0. Bevacizumab was administered at fixed-dose of 5mg/kg regardless of dose levels of panitumumab. All drugs were administered on day1 and repeated every 2 weeks. Definition of dose limiting toxicity (DLT) was grade 4 hematological adverse events or ≥ grade3 non-hematological adverse events despite the supportive care observed in 28 days from day1 of cycle 1. Results: There were no cases showing DLT at level 0 (n = 3) and level 1 (n = 3) in the PB part and recommend dose was determined as panitumumab 6mg/kg and bevacizumab 5mg/kg. In the whole treatment course at level 1, grade 3 rash acneiform was observed in 2 patients and 2 patients achieved partial response. In six patients (CPT-11 150mg/m 2 , biweekly n = 3, 120mg/m 2 n = 3) enrolled in the CBP part, grade 3 toxicities were leukopenia/neutropenia (n = 1), mucositis (n = 1), diarrhea (n = 1), rash acneiform (n = 1), thromboembolic event (n = 1). Two out of 6 patients achieved partial response in CPB regimen. Conclusions: The recommended dose of PB regimen were panitumumab 6mg/kg and bevacizumab 5mg/kg. Combination of panitumumab and bevacizumab showed manageable toxicity. Clinical trial information: UMIN000009362.
Capecitabine (X) plus gemcitabine (G) as first-line treatment in patients (pts) with locally advanced/metastatic pancreatic cancer: an open-label, multicenter phase II study
Authors: H.-S. Song, Y.-R. Do, H.-M. Chang, K.-H. Lee, Y.-H. Kim, D.-S. Hong, J.-Y. Cho, K.-E. Lee, S.-Y. Kim, M.-H. Ryu
Journal: Journal of Clinical Oncology (2005)

4141 Background: X is highly active and well tolerated in both gastrointestinal and breast cancers. G is active in advanced pancreatic cancer and has shown synergistic activity with X in phase I/II trials. We conducted a multicenter phase II study to evaluate the efficacy and safety of X + G as first-line treatment in pts with locally advanced/metastatic pancreatic cancer. Methods: Eligible pts had measurable pancreatic cancer (RECIST criteria), KPS ≥70%, and adequate bone marrow, renal and hepatic function. Prior chemotherapy for pancreatic cancer and prior radiotherapy to the target lesion being measured in the study were not allowed. Pts received X 825mg/m2 orally twice daily on days 1–21 + G 1000mg/m2 by 30-minute infusion on days 1, 8, and 15, every 4 weeks for up to 6 cycles. Results: Baseline characteristics of the 63 pts enrolled between March 2003 and May 2004: male/female (60%/40%); median age 62 years (range 39–75); liver metastases (56%). Pts received a total of 233 cycles (median 3.7 cycles, range 1–6). 60 pts are currently evaluable for safety and 58 for efficacy. The overall response rate, disease control rate and 1-year survival were 24%, 74% (14 PR + 29 SD), and 27%, respectively. The median progression-free survival and overall survival were 5.4 months (95% CI, 3.3–7.6 months) and 7.5 months (95% CI, 5.0–10.0 months), respectively. X + G was well tolerated. Non-hematological adverse events (grade 2/3/4) were: vomiting (8/3/0%), nausea (8/2/0%), anorexia (3/2/0%), hand-foot syndrome (7/0/0%), constipation (5/2/0%), general weakness (3/0/0%), insomnia (2/0/0%) and diarrhea (2/0/0%). Grade 3/4 neutropenia and grade 3 thrombocytopenia occurred in 29% and 27% of pts, respectively. Updated clinical data will be presented at the meeting. Conclusions: The combination of X + G appears to be active and well tolerated as first-line treatment in pts with advanced/metastatic pancreatic cancer. No significant financial relationships to disclose.
Lymphatic metastasis in well-differentiated appendiceal cancer: Prognostic factors and associations with outcome.
Authors: Joshua S. Hill, Safia Rafeeq, Matthew H.G. Katz, Michael J. Overman, Laura A. Lambert, Richard E. Royal, Paul F. Mansfield, Keith F. Fournier
Journal: Journal of Clinical Oncology (2012)

406 Background: Well-differentiated appendiceal adenocarcinomas (WDAA) are rare tumors characterized by peritoneal spread. Lymph node metastasis can occur, yet the association between nodal spread and recurrence is poorly understood. Methods: A single institution retrospective review of patients seen between August 1993 and January 2010 with a pathologic diagnosis of WDAA who underwent colectomy was conducted. Patients with zero lymph nodes found during pathologic review were excluded. Parameters evaluated included demographics, presence of lymph node metastasis, completeness of cytoreduction and time to recurrence. Results: Of 688 patients with appendiceal neoplasms, 160 (23.3%) had WDAA. The mean age at diagnosis was 50.7 years and 81 (50.6%) were male. Median follow-up after diagnosis was 58.5 months. One hundred patients (62.5%) had regional or distant metastasis present at the time of colectomy. Seventy-eight (48.8%) colectomies were performed at outside institutions. The median number of nodes examined was 12. Twelve patients (7.5%) were found to have nodal metastasis. The rate of peritoneal metastasis did not correlate with the presence of nodal metastasis (node positive 9/12, 75% versus node negative 91/148, 61.5%; p=0.35). No difference in the ability to perform complete cytoreduction existed for those with and without nodal metastasis (66% versus 51% p=0.19). Examining patients with complete cytoreduction and ≥ 12 months of follow-up, there was an increased risk of recurrence among patients with lymphatic metastasis compared to those without (5/8, 62.5% versus 15/61, 24.6%; p=0.03). In this subset, median disease-free-survival in lymph node positive patients was 53 months compared to 109.1 months in patients without nodal metastasis (p=0.08). Conclusions: Patients with WDAA tumors have an overall favorable prognosis; however, patients with lymph node metastasis appear to have an increased risk of recurrence and apparent shortened disease free survival. Right colectomy may be warranted in this patient population.
Factors influencing patient preferences for outpatient treatment of febrile neutropenia.
Authors: N. Lathia, P. K. Isogai, C. De Angelis, S. Walker, M. C. Cheung, N. Mittmann
Journal: Journal of Clinical Oncology (2011)

6041 Background: Febrile neutropenia (FN) is a serious hematologic toxicity of cancer chemotherapy. Studies show that patients at low risk for FN complications can be treated safely and effectively at home instead of in hospital. The objective of this study was to evaluate factors affecting patient preferences for outpatient treatment of FN using a discrete choice experiment (DCE). Methods: We asked patients with non-Hodgkin lymphoma undergoing chemotherapy to complete a self-administered DCE questionnaire based on the following attributes: out-of-pocket costs (levels: $10, $25, $50, $100); unpaid caregiver time required daily (levels: 1 hour, 2 hours, 4 hours, 8 hours); and probability of return to hospital (levels: 5%, 10%, 20%, 50%). Using these attributes, we generated sets of paired scenarios based on an orthogonal main effects plan. Ten paired scenarios were included in the final questionnaire. For each pair, we asked participants to select the scenario they preferred, to assess how they traded off between attributes. We analyzed results using logistic regression. Results: Seventy-eight patients completed the questionnaire. The mean age of participants was 59.6 years (range: 23.7 - 87.2 years) and 46 (59%) were male. Eleven patients (14%) had been previously hospitalized for treatment of FN. Six hundred and ten paired scenarios were included in the analysis. The regression coefficients for all three attributes were statistically significant (p<0.01), indicating that they all influence the willingness of patients to accept outpatient FN therapy. For every $20 increase in out-of-pocket costs the adjusted odds ratio (OR) of accepting outpatient care was 0.84 (95% CI: 0.77, 0.91); for every 1 hour increase in unpaid caregiver time required daily the adjusted OR was 0.92 (95% CI: 0.87, 0.97); and for every 10% increase in probability of return to hospital the adjusted OR was 0.49 (95% CI: 0.45, 0.53). Conclusions: Out-of-pocket costs, unpaid caregiver time required, and probability of return to hospital all significantly influence patients’ willingness to accept outpatient treatment of FN. Healthcare decision makers could use this information to design and implement programs for delivery of outpatient care for FN.
VDAC1 and prognosis in surgically resected non-small cell lung cancer.
Authors: C. M. Grills, K. J. O'Byrne, K. Gately, D. A. Fennell
Journal: Journal of Clinical Oncology (2010)

7029 Background: The likelihood of relapse following surgery for non-small cell lung cancer (NSCLC) is determined by clinical and genetic factors. Metabolic status of tumors may influence outcome. The voltage dependent anion channel type 1 (VDAC1), regulates mitochondrial ATP/ADP exchange and was explored in relation to survival following surgical resection. Methods: A NSCLC gene expression library curated from publically available data (NCBI GEO), comprised ten independent datasets (N=618 samples). The VDAC1 expression distribution was stratified into tertiles, prior to logrank univariate and Cox multivariate survival analyses. Analysis was performed using R and TMev. Across all the datasets, p values were corrected for multiple comparisons by calculating q values based on the method of false discovery rates. Genes that were determined as significant in at least 50% of the datasets were retained to generate a meta-signature comprising consistently differentially expressed genes correlated with VDAC1. Results: In a combined univariate analysis, VDAC1 overexpression conferred worse overall survival (OS) 52 vs. 101.6 months (m), p=0.0323. Cox regression analysis showed VDAC1 expression to be an independent prognostic factor (p<0.0001), as was stage (p<0.0001) but not age nor gender. Stage I patients had much better survival with low VDAC1, H R 0.52 (C.I. 0.31 – 0.82). A subset of 41 genes were significantly and consistently differentially regulated in VDAC1 overexpressing samples in >20% of the datasets; 6 genes > 50%. CSNK1A1, G3BP1, HNRNPC, HSPA4, HSPA9 and UBE2D2, all of which are upregulated. HNRNPC, HSPA4, HSPA9 and UBE2D2 are involved in protein ubiquitination pathways and CSNK1A1 regulates EIF2 function. HSPA9 is also involved in anti-apoptosis pathways while G3BP1 is linked to Ras protein signal transduction. Conclusions: VDAC1 overexpression is associated with shorter survival following surgical resection of NSCLC, especially for stage I patients. Further, the association between VDAC1 and genes regulating protein ubiquitination, apoptosis and EIF2 function protein suggests a role for these processes in more aggressive NSCLCs and may reflect potential molecular pathways for therapeutic development. No significant financial relationships to disclose.