tbuckley/cabot-search huggingface dataset:
A translational study of ixabepilone (BMS-247550) in renal cell cancer (RCC): Assessment of its activity and demonstration of target engagement in tumor cells
Authors: A. T. Fojo, M. E. Menefee, M. Poruchynsky, M. Edgerly, L. Mickley, E. Li Ning Tapia, M. Merino, F. Balis, S. Bates
Journal: Journal of Clinical Oncology (2005)

4541 Background: Agents targeting microtubules (MTs) are very effective anticancer drugs. Ixabepilone is a novel MT-stabilizing agent active in taxane-refractory models. Prior studies have shown that α-tubulin undergoes post-translational modification following assembly into MTs, including removal of the C-terminal tyrosine, exposing the penultimate glutamic acid (glu-tubulin) and acetylation of lysine 40. Methods: 67 patients with RCC were enrolled on study. 61 patients had a prior nephrectomy and 26 had received at least one prior systemic immune therapy. Treatment consisted of 6 mg/m2 ixabepilone on days 1–5 of a 21 day cycle. Response evaluations were performed every 2 cycles using RECIST. Patients with accessible tumor had biopsies prior to treatment and following the fifth dose of ixabepilone. Protein immunoblots were prepared and probed with antibodies to total and modified α-tubulins, and to β-actin. Results: 402 cycles have been administered. Grade 1, 2, or 3 neurotoxicity was recorded in 15, 17, and 2 patients, respectively. Partial responses have been observed in 8/57 patients with clear cell RCC after 2–9 cycles. MT stabilization was compared in pre- and post-treatment biopsies. Increased glu-tubulin, was observed in 11/12 patients with post-treatment levels 2–25 fold higher than pre-treatment. Similarly 2–100 fold higher acetylated tubulin levels were detected in 10/11 patients. Total α-tubulin levels were increased 2–12 fold (mean = 6.6 ± 3.7) in 8/12 patients, suggesting that tumor cells in some patients adapt to ixabepilone-induced polymerization with new tubulin synthesis. 24 hours after ixabepilone, PBMCs did not show any increase in acetylated or glu-tubulin over basal levels. Because VHL has been shown to stabilize MTs, sequencing is being performed to determine if a correlation exists between response to therapy and VHL status. Conclusions: Ixabepilone is an active agent in RCC, with major clinical responses observed. Assessing levels of glu-tubulin and/or acetylated α-tubulin provides a simple and reliable assay to demonstrate target engagement by MT-stabilizing agents and may help elucidate why these agents succeed or fail. No significant financial relationships to disclose.
Preliminary results of a randomized phase II trial of first-line treatment of gemcitabine (G) versus erlotinib (E) versus gemcitabine and erlotinib (GE) in patients 70 years or older with advanced non-small cell lung cancer (NSCLC).
Authors: T. Stinchcombe, D. S. Bradford, C. B. Lee, D. T. Moore, K. M. Bakri, M. A. Taylor, J. M. Crane, G. Schwartz, T. A. Hensing, M. A. Socinski
Journal: Journal of Clinical Oncology (2010)

7576 Background: Single-agent chemotherapy is the standard of care for elderly patients (pts) with advanced NSCLC. Methods: Pts were required to have stage IIIB or IV NSCLC, age ≥70 yrs, and performance status (PS) ≤2. Pts were randomized to arm A (G 1,200 mg/m2 on days 1 and 8 every 21 days), arm B (E 150 mg daily), or arm C (G 1,000 mg/m2 on days 1 and 8 every 21 days and E 100 mg daily). Pts could receive 4 cycles of G and E until disease progression or unacceptable toxicity. The primary objective was 6-month progression-free survival (6-PFS). This was a noncomparative phase II with a standard arm (A) and 2 investigational arms (B and C), and if the 6- PFS observed on arm B or C was ≥ 45% the arm would be consider worthy of further investigation. Planned enrollment was 49 pts per arm. Results: A total of 144 pts of the planned 147 have been enrolled; 10 pts did not receive treatment. Pts characteristics (n=132) and efficacy of arms A, B, and C are presented in the Table. The rate of grade 3/4 hematologic toxicities observed on arm A: neutropenia, anemia (both 9%) and thrombocytopenia (4%); arm B: none; arm C: anemia, thrombocytopenia (both 5%), and febrile neutropenia (2%). The common (≥5%) nonhematologic toxicities: observed on arm A: fatigue (13%); on arm B: diarrhea (7%), nausea, anorexia, dyspnea, and dehydration (all 5%); on arm C: dyspnea (27%), fatigue (14%), anorexia, nausea (both 7%), and diarrhea (5%). Conclusions: The 6-PFS of E alone and with G appears similar to single-agent G in an unselected patient population. Analysis of the CIRS-G, Qol, and correlative science investigations are ongoing. Characteristic Arm A:G Arm B:E Arm C: G+E Number 45 42 45 Median age (range) yrs 74 (70 to 86) 76 (69 to 86) 77 (70 to 90) Stage IIIB/IV (%) 22/78 12/88 20/80 Gender: male/female (%) 53/47 48/52 53/47 PS: 0/1/2 (%) 22/51/27 14/57/26 13/53/29 Never/light smoking hx (%) 16 11 17 Adeno/squamous/NOS (%) 67/16/13 63/10/26 62/13/22 Median PFS in months (95% CI) 3.5 (2.3-4.6) 3.0 (2.2-5.0) 4.4 (2.8-5.2) 6-PFS rate in % (95% CI) 21 (11-34) 26 (13-40) 24 (12-38) Median OS (95% CI) in months 6.8 (4.9-10.4) 6.5 (4.0-8.4) 6.0 (3.7-9.9) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Lilly, sanofi-aventis Abraxis BioScience, Celgene, Genentech, Lilly, Pfizer, sanofi-aventis
Imatinib mesylate experience of young patients with chronic myeloid leukemia in chronic phase—Care to cure
Authors: D. Biswajit, R. Rejiv, N. Manjunath, G. Prasad, S. Lakshmi, P. Devika, K. Geetha, T. G. Sagar
Journal: Journal of Clinical Oncology (2009)

7072 Background: Chronic myeloid leukemia (CML) with introduction of imatinib has been transformed into a chronic illness. The options of treatment in a patient less than 35 years include imatinib or allogenic stem cell transplantation. Hence we studied this unique subset to look at the response rates, adverse effects, progression free survival, and overall survival with imatinib mesylate. Methods: 477 patients with Philadelphia positive CML in chronic phase were retrospectively analyzed from January 2002 to December 2007 at Cancer Institute (WIA), Chennai, India. Standard criteria were used for response evaluation and adverse effects. Results: A total of 248 young CML patients with age less than 35 years (51.9%) were diagnosed in chronic phase. The median age of study population was 27 years (4–35). The male to female ratio was 1.9: 1. Risk stratification was done using Sokal index and were classified into low (32.3%), intermediate (50.4%), and high (17.3%). All patients received imatinib 400 mg as the initial dose. Complete hematological remission (CHR) was seen in 96.7%.Cytogenetic (FISH) and molecular (RTPCR) monitoring was possible in 53.2% and 17.3%, respectively. 72% of the patients had major cytogenetic response. Major molecular response was seen in 34.8% while complete molecular response occurred in 23.2% of the patients. Primary and secondary imatinib failure was seen in 3.1% and 16.9%, respectively. 6.7% had grade 3 and grade 4 hematological toxicities. The other common non hematological toxicities included pedal edema (13.7%), hypo or hyper pigmentation (60.0%), hyalgia (14.5%), diarrhea (1.6%), and liver dysfunction (1.6%). None of the patients discontinued imatinib due to toxicities. The 3-year DFS and OS was 86.2% and 89.5%, respectively. Patients with male sex (p = 0.04), spleen &gt; 8 cm (p = 0.02), high sokal index (p = 0.02), and loss of CHR (p &lt; 0.001) were associated with poor outcome. Conclusions: Imatinib in young patients have an excellent tolerance and response. A small subset does not respond to therapy or develop resistance during treatment. Hence it is essential to identify these poor responders and to offer stem cell transplantation at the earliest. No significant financial relationships to disclose.
5-fluorouracil, leucovorin, and oxaliplatin with or without docetaxel in elderly (65 years or older) patients with esophagogastric cancer: FLOT65+ trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
Authors: S. Al-Batran, N. Ho-mann, J. T. Hartmann, M. H. Moehler, C. Pauligk, S. Probst, V. Rethwisch, N. Prasnikar, J. Stoehlmacher, E. Jaeger
Journal: Journal of Clinical Oncology (2010)

4013 Background: Elderly patients (pts) with esophagogastric cancer often do not receive effective 3-drug combination therapies due to tolerability concerns. This study evaluates a 2- versus a 3-drug combination in older adult pts with esophagogastric cancer. Methods: Pts ≥ 65 yrs of age with metastatic or locally advanced disease were stratified by ECOG PS, liver metastases, potential resectability, and pharmacogenetic risk (experimental) and were randomized to receive infusional 5-FU 2,600 mg/m2, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) or the same regimen plus docetaxel 50 mg/m2 (FLOT), every 2 weeks. The primary endpoint was response rate (RR), having an 80% power to detect an improvement of RR from 30% to 50% using a p-level 0.1. Secondary endpoints included Toxicity, progression-free (PFS) and overall survival (OS), and time to treatment failure (TTF). Results: 143 pts (FLOT/FLO, 72/71) were randomized between Aug 2007 and Oct 2008 of whom 140 pts were eligible. Median age was 70 yrs and median ECOG was 1. 31% of pts had locally advanced potentially resectable disease (FLOT, 30%; FLO, 32%). Pts received a median of 8 cycles in both arms. FLOT was significantly superior to FLO regarding RR (49.3% vs. 27.5%, p = 0.018), TTF (4.4 vs. 3.8 months, p = 0.012) and PFS (9.1 vs. 6.7 months, p = 0.048). Median OS was 17.3 months with FLOT and 14.4 months with FLO (p = 0.275). FLOT was associated with significantly more NCI-CTC grade 1-4 alopecia (p < 0.001), neutropenia (p < 0.001), diarrhea (p = 0.009), and nausea (p = 0.041), but there were no differences between arms for complicated neutropenia, serious adverse events (SAEs), treatment durations, withdrawals/discontinuations for toxicity, or toxic deaths. Conclusions: FLOT improved efficacy in elderly pts with esophagogastric cancer. The increased toxicity did not result in intolerability in this specific population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
Single-center experiences of neoadjuvant systemic therapy in breast cancer: Individualization of the treatment
Authors: M. Gumus, B. O. Ustaalioglu, M. Seker, A. Bilici, T. Salman, B. Sönmez, M. Aliustaoglu, M. Eser, T. Salepci, M. Yaylaci
Journal: Journal of Clinical Oncology (2009)

e11628 Background: Neoadjuvant chemotherapy is one of the standard treatment options for patients with locally advanced breast cancer for twenty five years. In this study, we evaluate results of neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively analyzed 68 patients with locally advanced breast cancer. Anthracycline/taxane-based chemotherapy regimens were prescribed mostly for neoadjuvant chemotherapy. Before chemotherapy was given, patients were examined for distant metastasis by radiologic methods thereafter if patient had distant metastasis, they were excluded. Patients with breast cancer received neoadjuvant chemotherapy were analyzed according to age, menopausal status, type of surgery, response to the treatment, histopathological properties and survival. After 3 to 6 cycle of chemotherapy patients were reevaluated by clinically and radiologically for response. Surgery was performed for appropriate patient thereafter adjuvant locoregional and systemic chemotherapy were continued. Results: Median age was 47 (29–43) years. 17,6 % of them were younger than 35 years and 42,6 % were premenopausal. Median follow-up time was 19 month. After 3 to 6 cycle of neoadjuvant chemotherapy 64 of patients responded to therapy (94,1 %). Breast conserving surgery was performed for 15,6 % patients. In histopathologic analysis most of patients were invasive ductal carcinoma and there was lymph node invasion for 84,9 %. Estrogen and progesterone receptor status were negative for 18,6 % of patients and cerbB2 was positive for 14,8 % of patients. Median disease free survival time was 44 month (SE: 9; 95% CI: 25–62) but median overall survival time could not be reached. Three years disease free survival rate and overall survival rate were 55,3% and 90,1% respectively. According to Cox regression analyses; we did not find any demographic and pathologic characteristic of breast cancer that is related to prognosis. Conclusions: In recent years neoadjuvant chemotherapy in breast cancer is increasingly being used for early stage disease. Further study will be facilitated establishment of guidelines for preselecting patients for neoadjuvant chemotherapy and will provide beneficial effect on treatment option and survival. No significant financial relationships to disclose.
Age-Stratified Analysis Of The Prognostic Role Of Minimal Residual Disease Detection By Flow Cytometry, In Adult Patients With Acute Myeloid Leukemia
Authors: Francesco Buccisano, Luca Maurillo, Alfonso Piciocchi, Maria Ilaria Del Principe, Chiara Sarlo, Mariagiovanna Cefalo, Concetta Ditto, Ambra Di Veroli, Daniela Nasso, Marco Refrigeri, Maria Antonietta Irno Consalvo, Daniela Fraboni, Consuelo Conti, Giovanni Del Poeta, Francesco Lo Coco, Sergio Amadori, Adriano Venditti
Journal: Blood (2013)
Down-Regulation of CEBPA Expression Has a Stronger Impact on Myeloid Differentiation in Human Versus Mouse Cells: Mechanistic Implications for CEBPA Mutations in AML.
Authors: Gabriela Bernadeta Iwanski, Birte Niebuhr, Maike Täger, Susanne Roscher, Carol Stocking, Jorg Cammenga
Journal: Blood (2008)
CAPIRI plus bevacizumab (CAPIRI-B) versus FOLFIRI plus bevacizumab (FOLFIRI-B) for the treatment of patients with metastatic colorectal cancer (mCRC).
Authors: N. Ziras, A. Polyzos, N. Xenidis, A. Kalykaki, N. E. Androulakis, P. Papakotoulas, N. K. Kentepozidis, P. Makrantonakis, S. Xynogalos, I. Sougklakos
Journal: Journal of Clinical Oncology (2010)

3542 Background: To evaluate the efficacy and safety of CAPIRI-B in comparison with those of FOLFIRI-B as first-line treatment for patients with mCRC. Methods: Patients were randomized to receive either CPT-11 (180 mg/m2, d1), LV (200 mg/m2, d1+2) and 5-FU (400 mg/m2/d bolus and 600 mg/m2/d, 22h infusion, d1+2) plus bevacizumab 5 mg/kg every 2 weeks (FOLFIRI-B: arm A; n = 160 pts) or CPT-11 (250 mg/m2, d1) and capecitabine (2,000 mg/m2, d1-14) plus bevacizumab 7.5 mg/kg every 3 weeks (CAPIRI-B: arm B; n = 159 pts). Results: All patients were evaluable for toxicity and 303 for efficacy. There was no difference in terms of median PFS (FOLFIRI-B: 10.5 and CAPIRI-B: 10.1 months; p = 0.9), median overall survival (FOLFIRI-B: 27.9 months and CAPIRI-B: 29.9 months; p = 0.9) or response rates (RR) (FOLFIRI-B: 40.4% and CAPIRI-B: 40.7%; p = 0.9). Patients treated with CAPIRI-B had a significantly higher incidence of diarrhea (p = 0.018) than those treated with FOLFIRI-B. Treatment delays were observed in 4% and 3% in Arm A and B patients, respectively (p = 0.3). Dose reduction was required in 4% and 9% Arm A and B patients, respectively (p < 0.001). Treatment discontinuation due to treatment-related toxicity occurred in 4% and 11% Arm A and B patients, respectively (p = 0.01). Two treatment related deaths were recorded in each arm and the three of them were related to bevacizumab (one bowel perforation and two thromboembolic events). Conclusions: The outpatient CAPIRI-B regimen could be considered as a reasonable option of first- line treatment for patients with mCRC since it showed comparable efficacy with the FOLFIRI-B despite its higher incidence of diarrhea. No significant financial relationships to disclose.
The ideal screening age for breast cancer in developing countries.
Authors: H. Al Ratroot, H. Wadaani, M. S. A. AbdelHadi
Journal: Journal of Clinical Oncology (2011)

79 Background: Due to the lack of structured breast cancer screening programs in developing countries early detection is generally based on international western criteria. This principle is not valid in many instances since women withdraw from voluntary involvement in such activities. In addition breast cancer in developing countries is characterized by younger age and advanced disease at the initial presentation. This review aims to identify the suitable screening age for women in developing countries in order to develop a reliable national structured screening programs. Methods: This retrospective study was undertaken at King Fahd Hospital of the University, eastern province of Saudi Arabia between 1984-2010. Medical records of patients diagnosed with from the outpatient department and hospital admission records was reviewed. It mainly focused on demographic data and the time of presentation. Radiological and histo-pathological records were also reviewed. Results: The total number of patients reviewed was 483. The majority of patients were within the reproductive age group. Considering the standard screening age is 40 years, patients are divided into two groups, group I included those below the age of 40 years accounting for 193 patients (40%), while group II above the age of 40 years accounting for 290 patients (60%). Patients in group I were mostly reassured and were mainly diagnosed initially using ultrasonography, while in group II mammography aided in diagnosis. Conclusions: Despite the undisputable concept that breast cancer has higher predilection for women above the age of 40 years, yet in developing countries, a substantial subset of affected younger women contradicts this concept. The need for breast cancer screening cannot be overemphasized, yet, international screening guidelines for breast cancer cannot be fully implemented in developing countries. Therefore, it is mandatory that screening programs should be tailored according to individual communities. Dropping the screening age by a decade may possibly increase the capture of early breast cancer and improve the outcome.
Correlation between hemoglobin and quality of life in women undergoing adjuvant chemotherapy for breast cancer
Authors: J. Mortimer, W. Bardwell, S. Blair, Y. Podbelewicz-Schuller
Journal: Journal of Clinical Oncology (2005)

590 Background: Fatigue is a recognized complication of adjuvant chemotherapy and compromises quality of life. We sought to determine the impact of Hemoglobin (Hg) level on physical and mental function using the SF36 in women undergoing adjuvant chemotherapy for localized breast cancer, none received erythropoietic growth factors. Methods: 75 women with early stage breast cancer were enrolled in a study addressing psychosocial support for women undergoing adjuvant therapy. Within 30 days of initiating adjuvant therapy, and 2, 6, and 12 mos. afterwards, pts. completed a battery of questionnaires and interviews addressing quality of life and psychosocial adjustment to cancer. The SF36 consists of 8 subscales that are consolidated into separate Physical (physical functioning, role limitations due to physical problems, general health, bodily pain) & Mental (energy/fatigue, social functioning, role limitations due to emotional problems, emotional well-being) Health summary scores. Serial Hg levels were captured retrospectively on 40/46 women treated with chemotherapy. No patient received erythropoietin or red cell transfusions during the course of adjuvant chemotherapy. Simple correlations were conducted between SF36 variables & Hg levels. Results: The median age was 47.3 yrs. (Range 28 –78 yrs.); 38 (45.5%) were stage I;22 (55.5%) stage II. For this exploratory study, significance level was set at p<.10. At 2 mos. 8 (23.4%) had Hg < 11 mg/dl compared with 4 (12.9%) at 12 mos. We identified no relationship between the level of Hg and the Physical Health or Mental Health summary scores. In the subscale analysis we found a relationship between the Hg at 2 mos. and energy and fatigue at 12 mos. (r=0.71, p=0.002); Hg at 6 mos. and role limitations due to physical problems at 6 mos. (r=0.44, p=0.035); Hg at 12 mos. and role limitations due to emotional problems at 12 mos. (r=0.54; p=0.040). Conclusions: Low Hg after initiation of chemotherapy predicted for fatigue at 12 mos. despite marrow recovery. This raises the possibility that low Hg levels in response to chemotherapy are a marker of lowered physiologic reserve. This study was conducted at Washington University and supported by NIH CA72554–02 No significant financial relationships to disclose.
A phase I study of oxaliplatin and etoposide in pediatric patients with refractory solid tumors
Authors: L. M. McGregor, S. L. Spunt, V. M. Santana, C. F. Stewart, D. A. Ward, J. Wu, A. Watkins, S. P. Ivy, W. L. Furman, M. Fouladi
Journal: Journal of Clinical Oncology (2008)

10024 Background: The combination of a platinating agent with etoposide is effective in many pediatric solid tumors. In preclinical models, oxaliplatin is as potent as cisplatin or carboplatin. Clinically, oxaliplatin is effective against tumors considered cisplatin-resistant with less toxicity. This study evaluated the safety and estimated the maximum tolerated dose (MTD) of oxaliplatin in combination with etoposide in children with refractory solid tumors. Methods: Oxaliplatin was given intravenously (IV) over 2 hours on day 1 with IV etoposide on days 1–3 of a 21-day course. Cohorts of 3–6 patients were enrolled at 3 dosage levels. Two levels of etoposide [75 (level 1) then 100 (level 2) mg/m2/day] were explored with oxaliplatin 130 mg/m2. At dose level 3, oxaliplatin was increased to 145 mg/m2 with etoposide 100 mg/m2/day and calcium and magnesium infusions. Results: The 16 patients (median age 8 years, 11 male) received a total of 63 courses (median 3, range 1–13). At dose level 1, dose-limiting epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose-limiting toxicity (DLT) occurred at level 2 (n=6). At dose level 3, 2 of 4 patients experienced dose-limiting neutropenia. One patient (level 1) experienced life-threatening anaphylaxis during the oxaliplatin infusion of course 3 and a patient (level 2) with a previous allogeneic bone marrow transplant experienced pneumatosis intestinalis during course 2. Six patients required prolongation of the oxaliplatin infusion due to acute sensory neuropathy. No patients treated at dose level 3 with electrolyte infusions experienced grade 3/4 acute neuropathy. Responses were observed in medulloblastoma (1 CR) and pineoblastoma (1 PR); 3 others had disease stabilization for at least 5 courses [atypical teratoid rhabdoid tumor, ependymoma, high-grade sarcoma (n=1 each)]. Conclusions: The MTD is oxaliplatin 130 mg/m2 on day 1 with etoposide 100 mg/m2 /day on days 1–3. The DLT is grade 4 neutropenia lasting >7 days. Calcium and magnesium infusions did not allow further escalation of the oxaliplatin dose. The combination was tolerable with promising antitumor activity seen in patients with embryonal brain tumors. Future studies will include the addition of ifosfamide to create a potentially less toxic regimen similar to ICE. No significant financial relationships to disclose.