tbuckley/cabot-search huggingface dataset:
Minimal cross-intolerance between nilotinib and imatinib in patients with imatinib-intolerant chronic myelogenous leukemia (CML) in chronic phase (CP) or accelerated phase (AP)
Authors: E. Jabbour, A. Hochhaus, P. le Coutre, G. Rosti, K. N. Bhalla, A. Haque, N. Gallagher, F. J. Giles, J. E. Cortes, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2008)

7063 Background: Nilotinib, a potent and highly selective BCR-ABL inhibitor, has been approved in both the US and Europe for the treatment of patients (pts) with Philadelphia chromosome-positive (Ph+) chronic phase chronic myelogenous leukemia (CML- CP) and accelerated phase (CML-AP) who are resistant or intolerant to prior therapy including imatinib. The current study examines cross- intolerance between nilotinib and imatinib among pts enrolled in the phase 2 registration study of nilotinib. Methods: Imatinib intolerance was defined as no prior major cytogenetic response (MCyR) and discontinuation of imatinib due to grade 3/4 adverse events (AEs) or persistent (> 1 month) or recurrent (recurred > 3 times) grade 2 AEs despite optimal supportive care. Nilotinib-imatinib cross-intolerance was defined as treatment with nilotinib and occurrence (regardless of causality) of grade 3/4, or persistence or recurrent Grade 2, of the same AE(s) that led to discontinuation of imatinib therapy. The planned starting dose of nilotinib was 400 mg twice daily (BID), which could be escalated to 600 mg BID for lack of response when safe. Results: Of 321 pts with CML-CP and 136 with CML-AP, 94 (29%) and 27 (20%), respectively, were enrolled following imatinib intolerance due to AEs. Only 1/72 pts (1%) with non-hematologic imatinib intolerance experienced a recurrence of similar grade 3/4 AEs during nilotinib therapy. Of 38 pts with hematologic intolerance to imatinib, only 7 (18%) discontinued nilotinib therapy due to a recurrence of similar grade 3/4 AEs; all occurred in CP pts due to thrombocytopenia. Nilotinib therapy also exhibited significant efficacy in 59 (63%) imatinib-intolerant CML-CP pts and 10 (40%) imatinib-intolerant CML-AP pts who experienced MCyR during nilotinib therapy. Conclusions: These results support earlier findings of minimal nilotinib cross-intolerance in imatinib-intolerant CML-CP and CML-AP pts. Thrombocytopenia emerged as the only imatinib-related laboratory abnormality leading to intolerance that may recur in some pts during nilotinib therapy. These results demonstrate that nilotinib is effective and well tolerated in patients with imatinib- intolerance. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Innovive Pharmaceuticals, Merck, Novartis, Wyeth
Association of gemcitabine (GEM) efficacy on unresectable invasive pancreatic carcinoma with intraductal papillary mucinous neoplasms.
Authors: Yusuke Hashimoto, Satoshi Shimizu, Kazuo Watanabe, Kumiko Umemoto, Hiroyuki Okuyama, Hideaki Takahashi, Izumi Ohno, Shuichi Mitsunaga, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2015)

478 Background: Invasive pancreatic carcinoma associated with intraductal papillary mucinous neoplasms (IC-IPMN) has showed more favorable prognosis than invasive pancreatic ductal carcinoma (IPDC) following surgical resection in some studies. IC-IPMN differs from IPDC in clinical manifestation and biology profile and is mostly surgically resectable in initial presentation. Chemotherapeutic effect on unresectable IC-IPMN is not described in the literature yet. Methods: Our pancreatic cancer database was reviewed to identify 43 patients with IC-IPMN between 2006-2013. IC-IPMN was determined with surgical pathology or with radiological diagnosis and biopsy evidence of adenocarcinoma. Of 43 patients, 14 unresectable IC-IPMN patients received GEM as first-line chemotherapy regimen. We investigated GEM efficacy, Overall Survival (OS), Progression Free Survival (PFS) and 1-year survival rate. Results: Characteristic baseline included gender (male: 9, female: 5), age (median: 73 years old), ECOG performance status (0-1, 92%), location (head 7, body/tail 6, diffuse 1), prior surgical resection (8), biliary intervention (5), metastasis (11), CRP (median: 0.15mg/dl, 0.1-1.0), CA19-9 (median: 29U/ml, 8-20820), CEA (median: 3.1ng/ml, 0.1-237). Median OS, PFS and 1-year survival rate were 24.0 months, 8.0 months and 86%. Gemcitabine therapy demonstrated 14% (2/14) response rate and 79% (11/14) disease control rate. Conclusions: UnresectableIC-IPMN indicates favorable survival and fair response to GEM in our study. Limitations are retrospective study at single center and small population due to its disease rarity.
NABTT 0306: A randomized phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM)
Authors: L. B. Nabors, T. Mikkelsen, T. Batchelor, G. Lesser, M. Rosenfeld, X. Ye, S. Piantadosi, J. Olson, S. Brem, S. Grossman
Journal: Journal of Clinical Oncology (2009)

2001 Background: EMD 121974 (cilengitide) is a selective integrin receptor inhibitor that is well tolerated and has demonstrated biological activity in patients with malignant glioma. The objectives of this phase II trial were to determine safety when combined with chemoradiation and estimate the overall survival for two different doses in newly diagnosed GBM. Methods: A total of 112 patients were accrued onto the trial through the NABTT CNS consortium. Cilengitide was administered by one-hour infusion twice a week with 18 patients treated in a safety run-in phase of 6 patients at the tested dose levels of 500 mg, 1000 mg, and 2000 mg. After safety completion, 94 patients were randomly assigned to either 500 mg or 2000 mg groups. To date, 55 out of 112 (49%) patients have died. Overall survival was estimated using all patients in this trial regardless of their treating dose. Results: The median age was 55 years old (range: 22–88) and the median KPS was 90 (range: 60–100). 86 out of the 112 (76.8%) had a craniotomy as their initial surgical procedure and 25 patients (22%) had a biopsy. There were no DLTs during the safety run-in phase. The estimated median survival time is 18.9 months (95% CI: 16.3 -30.0 months) for patients treated with RT+TMZ+EMD. The trial was closed to accrual on December 31, 2007. To date, 89 out of 112 patients were alive 12 months from their initial diagnosis. The overall survival at 12 months for all patients is 79.5% (95% CI: 71–87%). MGMT methylation status and survival based on dose levels received are not currently available. Conclusions: EMD 121974 (cilengitide) is well-tolerated when combined with standard chemoradiation (TMZ+RT) and may improve survival for patients newly diagnosed with GBM given the substantial differences between the estimated median survival and that seen in the EORTC study (Stupp, N Engl J Med, 2005). [Table: see text]
The role of EGFR MAbs C225 in breast cancer stem cells
Authors: Y. Shi, F. Zhang, M. Cao, Y. Zhang, Y. Xu, M. Huang, H. Wang, Y. Ma
Journal: Journal of Clinical Oncology (2009)

e22093 Background: The epithermal growth factor receptor(EGFR) signaling pathways has been implicated in self-renewal of breast cancer stem cells. It has been proved that the EGFR tyrosine kinase inhibitor-gefitinib significantly decreased the mammosphere- forming efficiency(MFE) in ductal carcinoma in situ (DCIS) derived cancer cells. We investigated the response of breast cancer stem cells in breast cancer cell line MCF-7 to EGFR MAbs C225(cetuximab). Methods: Cells were used for nonadherent (i.e.,mammosphere) culture and were divided into four groups according to the different culture medium whether or not including exogenous EGF and MAbs C225. MFE was calculated as the number of mammospheres (≥60um) and was expressed as a percentage. We Compared the percentage of CD44 + /CD24 - cells from the four groups, and measured the levels of the Wnt and Notch-3 gene expression of the four groups. Results: There was no significant difference of MFE between groups. In the presence of exogenous EGF, MAbs C225 significantly decreased the MFE and the percentage of CD44 + /CD24 - cells of mammospheres compared with exogenous EGF alone(0.7% versus 1.5%, P &lt; 0.001 and 4% versus 11%P &lt; 0.001;respectively). In the absence of exogenous EGF, MAbs C225 aslo statistically decreased the MFE and the percentage of CD44 + /CD24 - cells of mammospheres compared with that of lacking exogenous EGF and MAbs C225(0.53% versus 1.3%,P = 0.003 and 9% versus 3%, P &lt; 0.01;respectively). And we observed that the Notch-3 gene expression was compensativly increased in the two groups of addition of MAb C225. No significant differences of Wnt gene expression were observed between groups. Conclusions: EGFR MAbs C225 could disrupt mammoshpere formation and decrease the percentage of CD44 + /CD24 - cells of mammoshpere cells. The expression of Notch-3 is increased with the EGFR antagonistics in breast cancer stem cells. No significant financial relationships to disclose.
Effect of neoadjuvant chemotherapy on bone marrow micrometastases in women with locally advanced breast cance
Authors: R. Aft, L. Ylagan, S. Sadeghi, T. Eberlein, V. Herrmann, J. Dietz, P. Fracasso, M. Naughton, K. Weilbaecher
Journal: Journal of Clinical Oncology (2004)

697 Background: Approximately 30% of women newly diagnosed with breast cancer will have tumor cells present in their bone marrow. In this study, we have examined bone marrow for the presence of breast cancer cells in women with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Methods: Women with clinical stage II or III breast cancer were enrolled into a prospective randomized phase II trial. Women underwent bone marrow aspirations prior to and after 4 cycles of chemotherapy with epirubicin and docetaxel. Bone marrow mononucleated cells were isolated by Ficoll gradient, and 2–4x106 cells from each iliac crest were examined for the presence of cytokeratin positive cells after staining with AE1/AE3. Results: 34 patients have been enrolled since March 2003 (planned accrual 120). Bone marrow was analyzed from 29 patients. 58% of women were postmenopausal. The average tumor size was 4.5 cm and all tumors were grade II or III. 62% of tumors were estrogen receptor positive and 24% of tumor overexpressed Her-2. 55% of patients had detectable bone marrow micrometastases at the time of diagnosis. The number of cytokeratin positive cells detected ranged from 1–23. Patients with cytokeratin positive bone marrows tended to have estrogen receptor negative tumors (50% versus 23%) and clinically detectable axillary adenopathy (75% versus 46%). There was no difference in the average tumor size between the two groups. 16 women had bone marrow analysis after chemotherapy. None of the women who had negative bone marrows prior to chemotherapy had positive marrows after chemotherapy (7/7). Of the 9 women with positive bone marrows prior to chemotherapy, 6 had negative marrows after chemotherapy. Conclusions: Over 50% of women presenting with advanced breast cancer have tumor cells detectable in their bone marrow at the time of diagnosis. This subset of women tends to have estrogen receptor negative cancers and clinically positive axilla. Preliminarily, it appears that chemotherapy may result in the clearance of bone marrow micrometastases in a significant portion of women with detectable micrometastases prior to chemotherapy. Our study is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis; Pfizer
Recruitment and retention in the Wake Forest University CCOP Research Base.
Authors: L. D. Case, M. J. Naughton, G. J. Lesser, S. R. Rapp, M. Vitolins, V. R. Sheidler, G. L. Enevold, E. G. Shaw
Journal: Journal of Clinical Oncology (2010)

e19543 Background: Clinical trials can lead to important advances in treatment, prevention, and symptom management. Unfortunately, study participation is low, especially for minorities, the elderly, the poor, and those in rural areas. Participation is needed in all populations to ensure generalizable results. Retention in a clinical trial is also crucial. Dropout lowers study power and can result in biased estimates of treatment effect. We reviewed the accrual and retention of participants in clinical trials offered through the CCCWFU Research Base (CCCWFU-RB), which is comprised of CCOPS from a broad geographic base. Methods: The CCCWFU-RB is a Cancer Control Research Base which emphasizes symptom management trials. Accrual and retention estimates were pooled over all CCCWFU-RB cancer control studies. Actual minority accrual was compared to expected accrual based on incidence, prevalence, and population estimates in our recruitment area. Results: Between 2001 and 2009, 1388 patients were accrued to 12 cancer control protocols. Accrual rates ranged from < 1 per month to almost 5 per day; actual accrual typically lagged behind expected accrual. Participants were 19-91 years (median 57), with 31% 65+ years. The race/ethnic distribution was 87% white, 10% black, and 2% Hispanic. Based on our geographic recruitment area, 17% black and 4% Hispanic participation would have been expected. Retention on studies ranged from 50% to 92% with an average of 73% across our 6 largest trials. Drop-outs have resulted from unclear protocols and definitions, as well as patient refusal. Underrepresented participants were no more likely to dropout than any other participant groups. Conclusions: Recruitment of under-represented populations has been lower than expected, and retention of all study participants has been problematic. Steps have been taken to increase accrual of under-represented populations and improve retention, including education, clearer protocols and race-specific objectives. (Supported by NCI grant 3 U10CA081851.) No significant financial relationships to disclose.
Genomic profiling of early-onset and hereditary breast cancer.
Authors: Fahd Al-Mulla
Journal: Journal of Clinical Oncology (2014)

30 Background: Worldwide, breast cancer is the most common cancer in women. Susceptibility is thought to be polygenic and the risk tends to increase in women with positive family history of breast cancer. Methods: We proposed an ambitious Middle Eastern-based study that entailed exome sequencing of approximately 50 women from the Middle East (M.E) with moderate family history of any cancer. DNA from tumor samples with matching lymphocytes from the same subjects and 50 normal Middle Eastern women without history of familial or sporadic cancers in the family, were subjected to whole-exome sequencing on the HiSeq 1000/2000 Illumina platforms to map major breast cancer–activating genetic defects. Results: Several unique to the M.E region and novel germline mutations in non-BRCA1/2 genes were identified in this cohort. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. More importantly, the breast cancers showed interesting copy number and mutations variants that may aid our understanding of breast cancer initiations. Conclusions: The M.E. breat cancer may be caused by a unique set of germline variants and that the M.E breast cancers may represent an entity that may aid in our understanding of this common disease.
Association between HU177 serum level and prognosis in patients with primary melanoma
Authors: H. Hamilton, D. Krich, P. J. Christos, R. L. Shapiro, R. S. Berman, A. C. Pavlick, D. Polsky, L. Liebes, P. C. Brooks, I. Osman
Journal: Journal of Clinical Oncology (2009)

9044 Background: Cleavage of type IV collagen during extracellular matrix (ECM) remodeling leads to exposure of cryptic regulatory sites within the ECM shown to be involved in tumor angiogenesis. Increased levels of a soluble form of the cryptic epitope HU177 in sera of melanoma patients have been shown to be associated with greater tumor thickness and nodular histological subtype. In this study, we investigate the association between HU177 serum levels and melanoma patients' clinical outcomes. Methods: Sera from 209 patients with primary melanoma prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the New York University Langone Medical Center (85 females, 124 males, mean age=58, mean thickness=2.09 mm, Stage I n=140, Stage II n=40, Stage III n=29) were analyzed for HU177 level. HU177 serum levels at the time of diagnosis were then correlated with disease-free survival (DFS) and overall survival (OS). Results: Median follow-up time for survivors was 54.9 months (range 2–81 months). Thirty-eight of the 209 (18%) patients developed recurrences, and 34 of the 209 (16%) patients died during follow-up. HU177 sera levels ranged from 0–139.9 ng/ml (mean=6.2 ng/ml; median=3.7 ng/ml). Because the distribution of HU177 levels was positively skewed, we analyzed the data using the median in addition to the mean. HU177 level &gt; 3.7 ng/ml (the median) was associated with a higher rate of melanoma recurrence (p=0.04) and increasing mortality (p=0.01) in a Kaplan Meier analysis. HU177 remained an independent prognostic factor for DFS and OS when controlling for tumor thickness and histological subtype in multivariate Cox proportional hazards regression models. In the DFS hazard model controlling for tumor thickness and histology, the hazard ratio for HU177 &gt;3.7 ng/ml (the median) was 2.01 (95% CI= 1.002, 4.04; p=0.049). In the OS hazard model controlling for tumor thickness and histology, the hazard ratio for HU177 &gt;3.7 ng/ml (the median) was 2.23 (95% CI=1.06, 4.70; p=0.03). Conclusions: Increased serum level of HU177 identifies a subset of primary melanoma patients with worse prognosis and suggests that anti-angiogenic therapy in the adjuvant setting may be a rational approach. [Table: see text]
Does the perceived risk of breast cancer recurrence and death affect the use of complementary medicines by cancer patients?
Authors: S. Verma, E. Rakovitch, D. George, A. Giotis, F. Charbonneau, T. Petrella, J.-P. Pignol, M. Trudeau, M. Clemons
Journal: Journal of Clinical Oncology (2004)

8152 Background: Complementary and alternative medicines (CAM) are frequently used by patients with breast cancer. However, the reasons and the perceived benefits of CAM usage by these patients remain unclear. The objective of this study is to assess CAM usage among women with breast cancer and to evaluate the presence of psychological morbidity and perceptions of risk among women who do and do not take CAM. Methods: Breast cancer patients attending outpatient clinics at a single Canadian cancer centre were approached by their oncologist. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer, and of dying of breast cancer. The presence of anxiety and depression was scored using the Hospital Anxiety and Depression Scale. Patient demographics were also collected. Responses were scored and compared between CAM users and non-users. Results: A total of 251 patients completed the survey. CAM usage was reported by 43.4% of patients. Individuals who used CAM were younger 53.1 yr. vs. 63.0 yr. (p<0.001), better educated (p<0.001), and in full time employment 25.7% vs. 16.3 % (p<0.001) compared to non-users. There were no differences related to ethnicity, marital status, household income or tumor stage among users and non-users of CAM. CAM users perceived their risk of recurrence (p=0.011) and death from breast cancer (p=0.0001) as being significantly greater compared to non-CAM users. There were no significant differences in anxiety or depression scores between CAM and non-CAM users. Conclusions: Women with breast cancer who use CAM are younger, better educated and in full time employment compared to those not reporting CAM usage. CAM usage is associated with increased perception of breast cancer recurrence and of breast cancer-related death. This perceived risk may have contributed to increased CAM usage. It is important for physicians to know what the patients are taking and to identify the reasons these treatments were chosen. No significant financial relationships to disclose.
Phase II study of docetaxel, cisplatin and 5-FU induction chemotherapy followed by concurrent chemoradiotherapy for advanced nasopharyngeal cancer
Authors: S. Cho, W. Bae, J. Hwang, H. Shim, J. Lee, S. Lim, W. Chung, I. Chung
Journal: Journal of Clinical Oncology (2008)

17010 Background: This study was performed to determine the feasibility and safety of the induction chemotherapy with docetaxel, cisplatin and 5-FU (DCF) followed by concurrent cisplatin/radiotherapy for advanced nasopharyngeal cancer. Methods: Patients with histologically confirmed nasophryngeal cancer without prior treatment, ECOG PS ≤ 2, at least one measurable lesion and adequate organ functions were eligible. Docetaxel (70 mg/m2) and cisplatin (75 mg/m2) were given as an 1-h intravenous infusion on day 1, followed by 5-FU (1,000 mg/m2) as a 24-h continuous infusion for 4 days repeated every 3 weeks and subsequently received cisplatin at a dose of 100 mg/m2 every 3 weeks with radiotherapy up to 7000 cGy. Results: Nineteen patients were enrolled and their median age was 47 years. One patient was lost of follow up after 1 cycle of chemotherapy. Four patients refused radiotherapy, fourteen patients were completed treatment. Complete response was shown in 11 patients (76.8%; 95% CI, 0.49–0.95), partial response was shown in 2 (14.3%; 95% CI, 0.02–0.42) and one patient had progressive disease (7.1%; 95% CI, 0.01–0.33). Therefore, ORR was seen in 13 (92.9%). The median time to progression was 39.4 ± 14.1 months (95% CI, 11.7–67.0), and the median overall survival was not reached. The main hematological toxicity was neutropenia and leucopenia. Greater than grade 3 neutropenia were observed in 27 cycles (50%) and 14 patients (73.7%). Febrile neutropenia developed in one patient (5.3%). The major non-hematological toxicities were asthenia and nausea, but grade 3 or 4 toxicity was not seen. Conclusions: The DCF induction chemotherapy followed by cisplatin/radiotherapy for advanced nasopharyngeal cancer is effective with manageable toxicities. No significant financial relationships to disclose.