tbuckley/cabot-search huggingface dataset:
Adjuvant breast cancer treatment in Argentina: Disparities between prescriptions and funding requirements—A survey
Authors: M. V. Costanzo, A. Nervo, C. Lopez, R. Chacon
Journal: Journal of Clinical Oncology (2008)

17571 Background: Early breast cancer is a highly frequent disease in Argentina. Adjuvant treatment is a very important tool to cure patients. In Argentina cancer treatment is provided by the government in the public sector and by social securities in the private sector. In the public sector, medicines are often provided free of charge but some drugs may be unavailable. In the private sector, medicines are more available but not more affordable. There are approximately 400 medical oncologists in Argentina. To understand how medical oncologists treat early breast cancer in our country we developped a survey eliciting their indications and the difficulties they have. Methods: We sent a survey by email to all actively practicing 2007 Argentinian Society of Clinical Oncology members. Survey items consider both: the “ideal indication” (what the medical oncologists think is the best treatment for the patient) and the “real indication” (what the medical oncologist could indicate due to circumstance). The questionnaire posed multiple therapeutic options in negative axilla (with no risk factors, one or more risk factors and HER 2 positive or negative), positive axilla and chemo, hormonotherapy and trastuzumab use. Results: Of 300 emailed surveys, 95 were returned for an overall response rate of 31%. There was substantial variation between “ideal indication” and “real indication” (see Table). The degree of satisfaction with the indication was 40% for hormonotherapy and 86.4% with chemotherapy but medical oncologists noted their difficulties to obtain drugs to begin treatment and to continue it. Conclusions There is important heterogeneity in what medical oncologists think is the best indication and what they could indicate to their patients due to diverse circumstances. Ideal indication Real indication Trastuzumab in high risk negative axilla (NA) 71 44 Trastuzumab in positive axilla (PA) 95 81 Aromatase inhibitors in NA premenopausal (ovarian ablation, OA) 29 14 Aromatase inhibitors in NA postmenopausal 73 50 Aromatase inhibitors in PA premenopausal (OA) 56 34 Aromatase inhibitors in PA postmenopausal 93 74 No significant financial relationships to disclose.
A phase I study of GW572016 in patients with solid tumors
Authors: H. Minami, K. Nakagawa, K. Kawada, H. Mukai, M. Tahara, T. Kurata, H. Uejima, T. Nogami, Y. Sasaki, M. Fukuoka
Journal: Journal of Clinical Oncology (2004)

3048 Background: GW572016 is a small molecule tyrosine kinase inhibitor that interrupts both EGFR and ErbB2 signal transduction pathways. To evaluate safety, pharmacokinetics and antitumor activity, and to determine the recommended dose of GW572016, a phase I study was conducted in patients (pts) with advanced solid tumors in Japan. Methods: GW572016 was administered orally once daily until pts had disease progression or unacceptable toxicities. A cohort of 6 pts was treated at 900, 1200, 1600, and 1800 mg/day. Grade 3 toxicities were considered dose limiting, and the maximum tolerated dose (MTD) was a dose at which 2 of 6 pts had grade 3 toxicities. Pharmacokinetics was evaluated on days 1 and 21. Results: Grade 1–2 rash, diarrhea, anorexia, fatigue, stomatitis, nausea and vomiting were the most frequent adverse events. Because 2 patients at 1800 mg/day experienced grade 3 diarrhea (one of them also had grade 3 elevation of GGT), the MTD was 1800 mg/day. The steady state concentration of GW572016 in serum increased with dose; 820±448 and 1899±1356 ng/mL at 1200 and 1600 mg, respectively. These concentrations exceeded the IC50 values for in vitro tumor cell growth. The pharmacokinetic profiles in Japanese pts were similar to those of Western pts. Two pts had partial responses (PRs) by RECIST; a pt with trastuzumab-resistant breast cancer (Her2, 3+; ER/PgR, negative) at 1600 mg/day, and a male pt with squamous cell carcinoma of the lung at 900 mg/day. Twelve pts (6 non-small cell lung cancers, 3 colorectal cancers, breast cancer, cervical cancer, and ovarian cancer) had stable disease (SD). In PR and SD pts, 8 pts continued treatment for more than 3 months. Standardized uptake values (SUV) measured by PET decreased significantly in two patients; one with breast cancer in which SUV was reduced by 60% had PR, and another with colorectal cancer in which SUV was reduced by 42% had SD for more than 8 months. Conclusions: GW572016 was well tolerated when administered orally in doses from 900 mg/day to 1600 mg/day once daily, with preliminary evidence of anti-tumor activity in heavily pretreated patients. Phase II studies are warranted, and 1600 mg/day or less is recommended based on the results of this study. No significant financial relationships to disclose.
Celecoxib in combination with irinotecan (CPT-11), 5-fluorouracil and leucovorin in patients with advanced cancer: A phase I, pharmacokinetic study
Authors: P. J. Creaven, M. M. Javle, L. Pendyala, P. Smith, D. C. Noel, R. V. Iyer, D. D. Lawrence, Y. M. Rustum
Journal: Journal of Clinical Oncology (2005)

2092 Background: We demonstrated in preclinical model that CPT-11 induced diarrhea can be prevented by celecoxib. Higher doses of CPT-11 could be administered with celecoxib in vivo resulting in improved therapeutic efficacy. Methods: In this phase I study, we escalated CPT-11 dose in FOLFIRI regimen with a fixed dose of celecoxib. We also investigated potential pharmacokinetic (PK) modulation of CPT-11 by celecoxib. CPT-11 dose escalation was planned in 4 dose levels (DL): 180, 200, 220 and 260 mg/m2 along with standard doses of 5-fluorouracil and leucovorin in FOLFIRI schedule administered 2-weekly. Celecoxib was administered in dose of 400 mg p.o. bid, starting day 2 of cycle 1. PK of CPT-11, SN-38 and SN-38G were obtained on day 1 (pre-celecoxib) and day 14 (with celecoxib) in 3 patients (pts) with complete sampling. Standard 3+3 dose escalation schema was used. Plasma concentrations of CPT-11, SN-38, and SN-38G were analyzed with validated HPLC method with fluorescence detection. PK parameters assessed included Cmax, and AUC for CPT-11, SN-38 and SN-38G. Institutional Review Board approval was obtained for this study. All patients signed informed consent. Results: Fourteen pts with advanced cancers were enrolled. Pt characteristics were: 8 males, 6 females, median age 52 yrs, ECOG 0/1/2: 1/12/1 pts; all had prior chemotherapy (median 1 regimen). Diagnosis: 7 colorectal, 6 esophageal, 1 unknown primary. One pt (1/6) had a DLT at DL2 (febrile neutropenia). Two pts had a DLT at DL3 (G3 emesis and myocardial infarct); trial was halted at DL3. Diarrhea was limited and cause for discontinuation in none. Grade 2 and 3 diarrhea occurred in 2 pts each. Celecoxib had no influence on the PK of CPT-11 and its metabolites. SD was best response noted in 6/8 and PR in 1/8 evaluable pts. Three pts with esophageal cancer received 12 cycles (maximum for protocol) and continue treatment off study. Conclusions: MTD of CPT-11 in FOLFIRI schedule with celecoxib is 200 mg/m2. Diarrhea at this dose is self-limited. No PK interactions between CPT-11 and celecoxib were apparent. The activity of this combination in esophageal cancer appears promising. (Supported by grant from NCCN) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Eli Lilly, Genentech, Roche
Randomized phase III trial comparing infused 5-fluorouracil/folinic acid (LV5FU) versus LV5FU+irinotecan (LV5FU+IRI) as adjuvant treatment after complete resection of liver metastases from colorectal cancer (LMCRC). (CPT-GMA-301)
Authors: M. Ychou, W. Hohenberger, S. Thezenas, M. Navarro, P. Gascon, C. Bokemeyer, E. Shacham-Shmueli, F. Rivera, C. Kwok-Keung Choi, A. Santoro
Journal: Journal of Clinical Oncology (2008)

LBA4013 Background: 5FU regimens have been suggested to be effective in the adjuvant setting after LMCRC. Irinotecan (IRI) combined with infused 5FU regimens showed improvement in outcome of advanced colorectal cancer. The aim of this international, randomized trial was to compare the adjunction of IRI to FUFA in this setting. Methods: Main inclusion criteria: complete surgical resection (R0) of exclusively liver metastases with no prior treatment for metastatic disease. Patients were randomized to either: arm A, FA 400mg/m2/2h iv, 5FU 400mg/m2/2h bolus, followed by 2400 mg/m2/46h continuous infusion q2w for 12 cycles, or arm B, FUFA+IRI 180mg/m2/d1. The primary endpoint is disease-free survival (DFS). The analysis was planned after at least 147 events were observed and a minimum of 1 year of follow up in order to detect a hazard ratio of 0.64 (alpha=5%, power=85%). Secondary endpoints include safety and overall survival. Results: Between 12/2001 and 7/2006, 321 pts from 15 countries were randomized. The 2 arms were well balanced (Arms A/B): number treated 153/153, median age 61/63 years, male 65%/59%, and for the stratification factors, only 1 liver metastasis 64%/64%, prior adjuvant chemotherapy 35%/40%, and diagnosis of liver metastasis more than 1 year after resection of primary tumor 37%/39%. Median follow-up was 42 months for both groups. The overall HR for DFS adjusted for the stratification factors was 0.89 (95%CI: 0.66–1.19, log-rank p=0.47). Median DFS was 21.6 for FUFA vs 24.7 months for FOLFIRI. No significant treatment effect was observed for any level of the stratification factors. However, there was a tendency for improved DFS for patients treated with FOLFIRI within 42 days after surgery. Grade 3/4 toxicities (%) in Arms A/B were respectively: any toxicity 34/51, neutropenia 7/23, diarrhea 8/14, vomiting 3/5, nausea 3/3. Conclusions: These results indicate that there was no overall advantage in terms of DFS for the addition of IRI to FUFA. However, we cannot exclude a benefit for patients starting chemotherapy before 6 weeks after surgery. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer
Do patients with apparently resectable pancreatic adenocarcinoma receive guideline-directed care?
Authors: J. K. Shim, M. Piperdi, T. P. McDade, G. L. Whalen, M. E. Sullivan, B. Piperdi, J. F. Tseng
Journal: Journal of Clinical Oncology (2008)

15579 Background: Meaningful survival for patients with pancreatic cancer requires surgical resection; adjuvant therapy has been demonstrated to improve survival. However, actual rates of resection and adjuvant therapy for patients referred for surgical resection remain unknown. Methods: This study examined 104 consecutive patients with pancreatic adenocarcinoma evaluated at a single surgical center from January 1, 2002- June 30, 2007. Patients were identified from a prospective pancreatic database; medical records were retrospectively reviewed. Results: Of 104 referred patients, 32 were found on further preoperative workup to have locally advanced or metastatic disease; 9 patients who had apparently resectable tumors did not undergo operation because of poor performance status (6) or patient preference (3). 63 patients were taken to the operating room with curative intent, of whom 8 were found to have metastasis and 3 were found to have locally advanced disease upon surgical exploration. 52 patients underwent resection with curative intent, of whom 30 completed adjuvant therapy, defined as radiation and systemic chemotherapy (23) or neoadjuvant therapy followed by resection (7). Reasons for not completing adjuvant therapy included surgical (6) or medical (2) complications; disease progression (3); and patient preference (2); 9 patients had adjuvant therapy planned but not completed at the time of these analyses. Conclusions: Of the 104 patients referred for possible resection of pancreatic cancer, 60.6% (63/104) underwent attempted curative operation, and 50.0% (52/104) had successful pancreatic resection. Of those undergoing resection, 57.7% (30/52) completed adjuvant/neoadjuvant chemoradiation. Our results suggest that a substantial proportion of patients with apparently resectable pancreatic cancer do not complete the recommended surgery and adjuvant therapy in a timely fashion. Given the lack of recent progress demonstrated in clinical trials of novel pancreatic cancer therapies, increasing the proportion of patients who receive all indicated components of treatment, including surgical resection and adjuvant therapy, may currently be among the best methods of improving overall survival for patients with pancreatic adenocarcinoma. No significant financial relationships to disclose.
Modified-dose capecitabine + bevacizumab for the treatment of advanced/metastatic hepatocellular carcinoma (HCC): A phase II, single-arm study
Authors: C. Hsu, T. Yang, C. Hsu, H. Toh, R. J. Epstein, L. Hsiao, A. Cheng
Journal: Journal of Clinical Oncology (2007)

15190 Background: The oral fluoropyrimidine capecitabine (X; Xeloda®) has anti-tumor activity in metastatic colorectal, breast, gastric cancers and HCC. The humanized monoclonal antibody bevacizumab (A; Avastin®) targets VEGF and limits tumor angiogenesis. The combination of X+A is active in breast cancer xenografts and increases the objective response rate (ORR) in patients (pts) with anthracycline- and taxane-resistant breast cancer. X+A also appears to be highly active when administered with irinotecan as first-line treatment for metastatic colorectal cancer. We report data from a multicenter, Ensign’s 3-stage design, open-label phase II trial of X+A as first- line treatment for HCC. Methods: Pts with untreated, histologically confirmed advanced HCC received X 800mg/m 2 orally bid d1–14 and A 7.5mg/kg i.v. infusion d1. Treatment was repeated q3w x6 cycles in the absence of disease progression or unacceptable toxicity. Pts without progressive disease after 6 cycles of X+A could continue on the same doses of X+A. Primary endpoint was ORR (RECIST); secondary endpoints were disease control rate, progression-free survival (PFS), overall survival, and safety. Results: 45 patients were enrolled. By Dec 2006 the 25 patients (male, 88%; median age 52 years; Child-Pugh A) enrolled in Stages 1 and 2 of the study had completed at least 6 months’ follow-up and were assessed for efficacy and safety. ORR (CR+PR) was 16% (95% CI 4.5–36.1%) and disease control rate (CR+PR+SD) was 60% (95% CI 38.7–78.9%). Median overall survival was 10.7 months (95% CI, 5.3–14.7) and median PFS was 4.1 months (95% CI, 1.6–6.2); the PFS rate (i.e. the event (PD or death) free rate) at 3 and 6 months was 64% (95% CI 45.2–82.8%) and 34% (95% CI 15.1- 53.2%), respectively. Median number of cycles per patient was 5 (range 1–6). The most common treatment-related grade 3 toxicities included hand-foot syndrome (n=2), nail changes (n=1), diarrhea (n=1), nausea/vomiting/hiccups (n=1), gastric ulcer hemorrhage (n=1). Conclusions: X+A appears to be both effective and well tolerated as first-line treatment for HCC, providing support for further evaluation of this combination in this difficult-to-treat cancer. No significant financial relationships to disclose.
Association of vascular endothelial growth factor (VEGF) with outcome in metastatic solid tumor treated with antiangiogenic therapy.
Authors: J. M. Jurado-García, J. Trigo Perez, I. Sevilla, B. Pajares, L. Alonso-Carrión, M. Pérez, J. L. García-Puche, E. Alba
Journal: Journal of Clinical Oncology (2010)

e21106 Background: Vascular endothelial growth factor (VEGF) have important roles in angiogenesis, predicting risk and prognosis in several solids tumor. VEGF-2578 AA and VEGF-1154 AA genotypes were associated with a superior median overall survival when using bevacizumab in metastatic breast cancer. We investigated the association of VEGF polymorphisms to efficacy and toxicity in metastatic renal, ovarian, lung and breast cancer treated with antiangiogenic therapy. Methods: We performed genotype for selected VEGF polymorphisms in promoter regions (2578 C/A, 1498 C/T, 7351 G/A, 1154 C/T), 5′UTR (634 G/C), 3′UTR (G/A) rs3025053, in exons 1 (6624 A/G), exon 6 (R32 Ter C/C), exon 8 (786 C/T,1301 C/T, 1462 A/G, 1497 C/T, 1575 A/G, 1691 C/T, 2038 A/G, 2145 C). DNA was extracted from venous blood of patients with non-curable solid tumors who have received treatment with bevacizumab N=23 (46%) or raf kinase inhibitors 54%; vatalanib (PTK-787) N=3, sunitinib (SU011248) N=8, sorafenib (BAY 43-9006) N= 13, ZD6474 N=1 and AMG706 N= 1. Kaplan-Meier survival analysis was used to assess the association between VEGF staining and either progression-free survival (PFS) or overall survival (OS). Results: 49 patients have received a median of 6 (1-19) cycles of treatment, 70% was used simultaneously with QT. According to the criteria of NCI-CTC the severe toxicity G3-4 occurred in 47%, 9% with a definite suspension of the drug. The toxicity was not associated with VEGF genotypes. Efficacy; 5/49 patients (10%) had complete response and 12/ 49 (24%) partial responses by RECIST criteria. With a median follow up of 12 months, the ILP was 8.1 months dt (5.1). The analysis of VEGF polymorphisms identifies the variant GG/AG of the 3′UTR promoter region rs3025053 with a significant difference in OS regarding their variant AA. Conclusions: Our data suggest that VEGF polymorphism can be a predictor of clinical outcomes in antiangiogenic therapy and warrants further investigation. No significant financial relationships to disclose.
A Comment From a Radiotherapeutic Point of View Regarding the ASCO Guidelines on the Role of Bisphosphonates in Breast Cancer
Authors: V.E. Kouloulias, C. Dardoufas, J. Kouvaris, C. Gennatas, L. Vlahos
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.7.2106 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11283148 A Comment From a Radiotherapeutic Point of View Regarding the ASCO Guidelines on the Role of Bisphosphonates in Breast Cancer V.E. KoulouliasxV.E. KoulouliasSearch for articles by this author , C. DardoufasxC. DardoufasSearch for articles by this author , J. KouvarisxJ. KouvarisSearch for articles by this author , C. GennatasxC. GennatasSearch for articles by this author , L. VlahosxL. VlahosSearch for articles by this author Show More Medical School, University of Athens, Radiotherapy Department, Areteion Hospital, Athens, Greece https://doi.org/10.1200/JCO.2001.19.7.2106 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Tumor-derived alpha-fetoprotein (tAFP) causes immune and metabolic dysfunction in monocyte-derived dendritic cells
Authors: Patricia M Santos, Angela Pardee, Greg M Delgoffe, Lisa H Butterfield
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Alpha-fetoprotein (AFP) is an oncofetal antigen expressed by over 50% of hepatocellular carcinoma (HCC) tumors. AFP-L3 is the major isoform present in the serum of HCC patients and is associated with poor patient prognosis. While HCC tumor-derived AFP (tAFP) contains >80% of AFP-
Preclinical evaluation of the dual specific Src/Abl kinase inhibitor AZD0530 in lung cancer
Authors: O. Gautschi, P. Purnell, C. P. Evans, J. C. Yang, W. S. Holland, R. J. Bold, S. Virudachalam, P. N. Lara, D. R. Gandara, P. H. Gumerlock
Journal: Journal of Clinical Oncology (2006)

13108 Background: AZD0530 is a highly selective, orally available, dual specific Src/Abl kinase inhibitor in clinical development. We tested this agent in multiple lung cancer cell lines in vitro. We hypothesized that activity of AZD0530 may depend on the level of activated (pY416-)Src, and that Src inhibition may decrease Bcl-xL protein levels and lower the barrier to apoptosis. Methods: NSCLC (A549, Calu-1, Calu-6) and SCLC (H69, H526) cells were incubated with 0.001–100 μM AZD0530 for 1–72hrs. Proliferation (MTT), DNA-content (flow cytometry), and protein levels of Src, pY416-Src, PARP, and Bcl-xL (Western blotting) were assessed. Results: Basal pY416-Src was detectable in most cell lines except H526. AZD0530 decreased pY416-Src levels at submicromolar concentrations in pY416-Src positive cells. In A549, Calu-1 and Calu-6, AZD0530 blocked cell growth in a time- and dose-dependent way (IC50 = 7–25 μM) by arrest in G1, retaining a cytostatic effect at submicromolar concentrations in A549 and Calu-1. AZD0530 induced apoptosis in 10–22% of these cells at micromolar concentrations, accompanied by a decrease of Bcl-xL protein in A549 and Calu-1. In H69 and H526, growth inhibition by AZD0530 was limited (IC50 &gt;100 μM). Conclusions: 1) AZD0530 induced apoptosis at micromolar concentrations, and inhibited cell growth at micromolar to submicromolar concentrations in some cell lines. 2) pY416-Src is a potential marker for drug responsiveness, but other factors should also be tested. 3) Decrease of Bcl-xL by AZD0530 may render cancer cells more sensitive to chemotherapy. These data suggest that Src kinase inhibitors merit further testing in lung cancer, both alone and in combination with other agents. (Support: Swiss National Science Foundation, Swiss Cancer League, AstraZeneca). [Table: see text]
A phase I/II study of topotecan and sorafenib in recurrent, platinum-resistant ovarian cancer: HOG GYN-111.
Authors: D. Matei, R. Ramasubbaiah, J. Schilder, S. M. Perkins, C. Whalen, T. Breen, C. S. Johnson, M. Callahan, T. Jones, G. Sutton
Journal: Journal of Clinical Oncology (2010)

5108 Background: Recent data showed that the multikinase inhibitor sorafenib (S) is active in ovarian cancer (OC). The scope of this trial was to determine efficacy and tolerability of S in combination with topotecan (T), an FDA-approved agent for platinum resistant OC. Methods: This multi-institutional phase I/II study was designed to determine the maximum-tolerated dose (phase I) and the response rate (phase II) to the regimen S+T in platinum resistant OC. Secondary endpoints were to measure PFS, toxicities, and rate of clinical benefit. Eligible patients had measurable or detectable recurrent OC, up to three prior cytotoxic treatments, ECOG PS of 0-1 and normal end-organ function. S was administered orally daily and T was given IV weekly at a fixed dose of 4 mg/m2, 3 weeks on and 1 week off during a 28 day cycle. For the phase I trial a 3 + 3 dose escalation design was used, testing two S dose levels: 400 mg daily (level 1) and 800 mg daily (level 2). The T dose was reduced to 3.5 mg/m2 weekly. The regimen tested during phase II was S at 400 mg daily and T at 3.5 mg/m2 weekly. Results: 16 pts were enrolled in phase I and 14 pts in phase II; all 30 were evaluable. Median age was 52.5 years (range 35-79), 27 pts had OC, and 3 pts had PPC. Nine pts were platinum refractory, 18 platinum-resistant, and 3 had platinum allergy. Median number of cycles administered was 2.5 (0-15). There were 5 PRs (16.7%), and 12 pts (40%) with stable disease (SD). Four PRs were recorded during phase I and 1 PR during phase II. Of these, 2 PRs occurred in pts receiving T at 4 mg/m2 and 1 PR in a pt receiving S at 800 mg/day. Median SD duration was 4.2 months (95% CI, 3.7-4.9). The most common treatment related all grade toxicities were nausea (53%), anemia (53%), thrombocytopenia (40%), neutropenia (50%), fatigue (37%), vomiting (23%), hand-foot syndrome (HFSR), and anorexia (20% each). Grade 3/4 toxicities included neutropenia (23%), thrombocytopenia (17%), anemia (10%), and fatigue, nausea, vomiting (6.7% each). One case of grade 3 HFSR was recorded. Conclusions: S can be safely combined with T in OC patients, but requires reduction of T to 3.5 mg/m2 weekly. The combination has clinical activity, however most responses were registered in pts receiving the higher doses of S or T. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer Bayer