tbuckley/cabot-search huggingface dataset:
Grade 3/4 adverse events (AEs) of second generation tyrosine kinase inhibitors (TKIs) for imatinib resistant/intolerant patients in accelerated phase CML (AP-CML)
Authors: S. J. Snedecor, J. M. Stephens, K. T. Carpiuc, S. Y. Liou, M. F. Botteman
Journal: Journal of Clinical Oncology (2007)

17525 Background: Toxicity profiles of targeted therapies for resistant CML may impact the resources required to manage patients (pts). The objective of this study was to systematically compare the rates of Grade 3/4 AEs reported for nilotinib and dasatinib in imatinib resistant/intolerant AP-CML in preparation for development of an economic analysis. Methods: A systematic literature review was conducted using online databases to identify published articles, registration studies, or abstracts of trials for nilotinib 400 mg bid or dasatinib 70 mg bid in AP-CML. The base case incidence rates were based on accelerated phase pt data from the dasatinib product label and the nilotinib phase II pivotal trial which had similar median durations of drug exposure of ∼5 months. Grade 3/4 AEs were selected because of likely economic impact for medical treatment/monitoring. The ranges (if available) for incidence of AEs were summarized from other papers/abstracts to provide ranges for sensitivity analyses. Results: The incidence of Grade 3/4 AEs having likely economic impact and occurring in &gt;5% of pts are reported in the table . Rates of Grade 3/4 hematologic AEs for dasatinib were 1.8–2.6 times higher than those for nilotinib. Biochemistry abnormalities occurring in &gt;5% of pts included lipase increase for nilotinib in 6.7%, and hypophosphatemia (13%) and hypocalcemia (9%) for dasatinib. Grade 3/4 non-hematologic AEs such as pleural/pericardial effusions were also higher for dasatinib than nilotinib, though they occurred in &lt;5% of the population. Conclusions: The toxicity profiles of the second generation TKIs for imatinib resistant/intolerant AP-CML are different. Nilotinib’s lower rates of Grade 3/4 hematologic AEs and GI hemorrhage may result in reduced resource utilization. Further analysis is required to understand the economic impact of the differences in safety profiles. [Table: see text] No significant financial relationships to disclose.
Endostatin combined with chemotherapy as first-line therapy for stage IV melanoma patients: A phase II clinical study
Authors: C. Cui, Z. Chi, X. Yuan, L. Si, X. Sheng, L. Shen, J. Guo
Journal: Journal of Clinical Oncology (2009)

e20003 Background: To observe the efficacy and safety of rh-endostatin injection (Endostar) combined with chemotherapy as first line therapy for stage IV melanoma patients. Methods: From March 2007-March 2008, 20 metastatic melanoma patients were enrolled. Endostar (15 mg d1–14) combined with dacarbazine (250 mg/m 2 d1–5) or temozolomide (300 mg d 1–5) and fotemustine (100 mg/m 2 d6) were given every 28days. Response, toxicity and progression free survival(PFS) were analyzed. Results: Among 20 evaluable cases, with mean cycle 2.7±0.80, four achieved partial response, six stable disease, with response rate 20.0% (4/20) and clinical benefit rate 50.0% (10/20). The median PFS reached 4.5 months (95% CI: 3.85–6.9 months), overall survival 8.5 months (95% CI: 5.62–8.54 months), with 6 months PFS rate 35% (7/20), and 6 months survival rate 65% (13/20). The Grade 3/4 toxicity was mainly myelosuppression, 40% (8/20). One patient ceased the treatment because of sinus bradycardia. Conclusions: Endostar combined with chemotherapy show its efficacy on melanoma patients and may prolong PFS. No significant financial relationships to disclose.
Multiple bone and joint involvement in a boy with Staphylococcal sepsis.
Authors: H Caksen, K Uzüm, A Tutuş
Journal: Clinical Nuclear Medicine (2001)

From the Department of Pediatrics,* Yüzüncü Yil University Faculty of Medicine, Van, Departments of Pediatrics† and Nuclear Medicine,‡ Erciyes University Faculty of Medicine, Kayseri, Turkey Received for publication February 17, 2000. Revision accepted June 27, 2000. Correspondence: Hüseyin Çaksen, Seymen sok. Gökdogan apt. No: 5/16, Demirlibahçe, Ankara, Turkey. E mail: [email protected]
Docetaxel and mitoxantrone, versus docetaxel mitoxantrone and letrozole as first-line therapy in advanced breast cancer: A randomized study
Authors: C. Gennatas, D. Mouratidou, N. Tsavaris, V. Michalaki, J. Psychogios, N. Poulakaki, C. Andreadis, N. Diamantopoulos, S. Gennatas
Journal: Journal of Clinical Oncology (2005)

722 Background: Doxetaxel (DCT) and mitoxantrone (MX) are highly active and potentially synergistic agents in the treatment of metastatic breast cancer (MBC). Letrozole, a nonsteroidal, third-generation aromatase inhibitor has shown efficacy in the treatment of postmenopausal women with advanced disease, producing objective tumor response rates of approximately 25% after failure of previous therapy. This study evaluates the combination of DCT and MX with or without letrozole in patients with MBC to determine the efficacy and toxicity of this therapy. Methods: One hundred and eleven (median age 62 yrs), postmenopausal previously untreated patients with MBC were studied. The patients were randomly assigned to receive the combination of Docetaxel 80 mg/m2, Mitoxantrone 12 mg/m2 every three weeks and Letrozole 2.5 mg daily (group A, n=56 pts), or Docetaxel 80 mg/m2 and Mitoxantrone 12 mg/m2, every three weeks (group B, n=55 pts). Response was assessed according to UICC criteria at 12 and 24 weeks. Results: The treatment with DCT and MX was well tolerated. Toxicity was low in both arms, without statistical difference: 24 grade I and 18 grade 2 cases were observed in Group A vs 22 grade I and 17 grade 2 cases in group B. At 24 weeks, complete remissions were seen in 9.8% of group B and 5.8% of group A, partial remissions were observed in 58.8% and 53 %, respectively; and stable disease was achieved in 9.8% and 13.7%, respectively. Disease progressed in 21.5% of group B patients and 27.4% of group A patients. None of these differences were significant Conclusions: Intensifying standard docetaxel and mitoxantrone first-line therapy in advanced breast cancer patients with letrozole hormone therapy may be of little benefit in terms of response rate. However, in the chemotherapy-hormonotherapy combination arm, there is a trend for more objective responses. No significant financial relationships to disclose.
Efficacy and safety of trastuzumab plus capecitabine in a German multicentre phase II study of pre-treated metastatic breast cancer
Authors: G. Schaller, N. Bangemann, J. Weber, A. Kleine-Tebbe, G. K. Beisler, B. Conrad, H.-J. Hindenburg, P. Klare, B. Ruhmland, A. Hinke
Journal: Journal of Clinical Oncology (2005)

717 Background: Trastuzumab (Herceptin; H) in combination with a taxane has proven significant clinical benefits, including a survival advantage, compared with taxane alone in pts with HER2+ metastatic breast cancer (MBC). After pre-treatment with anthracyclines and/or taxanes it is necessary to offer pts an alternative regimen. Alternative agents to combine with H are therefore under investigation. Capecitabine (Xeloda; X) is an oral fluoropyrimidine carbamate with high activity in MBC and good tolerability. In-vivo data show that H+X have at least additive activity. Therefore, we investigated the combination of H+X in the clinical setting. Methods: 27 pts were enrolled in the study and received H 4mg/kg loading dose followed by 2mg/kg weekly and X 1,250mg/m2 twice daily days 1–14 of a 21-day cycle, given until disease progression. Eligible pts had IHC 3+ and/or IHC 2+/FISH+ disease. Results: Pre-treatment characteristics are based on 26 pts. 77% of pts had received radiotherapy. 88% had received prior (neo)adjuvant chemotherapy, including anthracyclines (73%) and taxanes (42%). 38% of pts had received a median of 2 previous lines of chemotherapy for MBC. 52% of pts were ER+ and 48% PgR+. Lesions involved visceral organs in 73%, with liver metastases present in 46%. Of 26 pts evaluable for HER2 status, 23 (88%) tested IHC 3+, 1 (4%) IHC 2+/FISH+, and 2 (8%) FISH+ only. 20 pts are currently evaluable for best response according to RECIST criteria and 24 for PFS. 17/26 pts have completed study treatment to date. The ORR was 60% (per protocol; 4 CR, 8 PR; n=20) and 48% (intent-to-treat; n=25). The median PFS was 28 weeks, and median OS 90 weeks. The combination was generally well tolerated. Grade 3/4 anaemia, leucopenia and thrombocytopenia were seen in 8%, 4% and 4% of patients, respectively. Grade 3/4 non-haematological toxicities included general aches (28%), motor dysfunction (20%), hand-foot syndrome (16%), vomiting (12%), and nausea (12%). Conclusions: These promising data highlight the efficacy and favourable tolerability of the combination of H with X in patients with HER2-overexpressing and intensively pre-treated MBC. Based on these data, further investigation of this combination is warranted. No significant financial relationships to disclose.
Phase II trial of erlotinib in elderly patients (age &gt; 70) with previously untreated advanced non-small cell lung cancer (NSCLC): An analysis of quality of life and symptom response
Authors: D. M. Jackman, B. Yeap, J. Lucca, P. A. Ostler, L. K. Morse, P. Fidias, T. J. Lynch, J. Temel, B. E. Johnson, P. A. Janne
Journal: Journal of Clinical Oncology (2006)

7168 Background: Elderly patients derive survival benefit but significant toxicity from chemotherapy for NSCLC. Erlotinib is associated with reasonable toxicity and has a survival benefit for relapsed patients previously treated with 1–2 chemotherapy regimens. This targeted agent may prove an effective and well-tolerated first-line therapy in elderly patients with advanced disease. Methods: 80 patients (chemo-naïve, age ≥ 70, PS 0–2, stage IIIB/IV NSCLC) were treated with erlotinib 150 mg/d as part of a phase II study. Primary endpoint was survival. QoL was a secondary endpoint, as assessed by LCSS at baseline and q4 weeks until progression. The primary endpoint of QoL analysis was to determine changes from baseline in LCSS score. Patients were eligible for QoL analysis if they completed an LCSS questionnaire at baseline and ≥ 1 other monthly follow-up visit. Each of 9 items was assessed on a 100mm visual analog scale from 0 (best) to 100 (worst); symptom improvement or worsening was based on a change of ≥ 10mm, with decreased scores implying improvement. Score differences between the baseline and best follow-up response of each subscale and total LCSS are assessed by the signed rank test. Results: 64 patients (80%) were eligible for QoL analysis. There was a trend towards improvement in QoL, based on the total LCSS score. Statistically significant improvements in dyspnea, cough, fatigue, and pain were seen, both in terms of median changes from baseline and the proportion of patients improved (Table). No patients were symptomatic for hemoptysis at baseline, so improvement could not be calculated. Conclusions: Erlotinib in elderly patients with advanced NSCLC was associated with encouraging survival (10.9 mo), a trend towards improved QoL, and statistically significant improvements in key symptoms of dyspnea, cough, fatigue, and pain. Mixed effects longitudinal modeling showing changes in LCSS over time will be presented at the conference. [Table: see text] [Table: see text]
A randomized phase II study of perifosine (P) plus imatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST)
Authors: A. P. Conley, D. Araujo, J. Ludwig, V. Ravi, B. L. Samuels, H. Choi, P. F. Thall, S. Patel, R. Benjamin, J. Trent
Journal: Journal of Clinical Oncology (2009)

10563 Background: P inhibits activation of the Akt pathway which results in apoptosis and block cancer cell proliferation. Since AKT is a molecule downstream of Kit, its inhibition may overcome Kit-dependent imatinib resistance. We performed a phase II trial to assess antitumor activity of perifosine in patients with advanced GIST who were refractory to imatinib mesylate. Methods: Pts with Kit(+) advanced GIST who have PD on IM were eligible. Pts continued their current dose of IM and were randomized to one of two dosing schedules of P (Arm A: 100 mg p.o. qd x 28 + IM or Arm B: 900 mg [300 mg p.o tid] qweekly + qd IM). A Bayesian approach was utilized to assess a target response rate or 20% with an unacceptable toxicity rate of 15% or less. Response was measured at q8 wk intervals by RECIST and Choi criteria. The primary endpoint was to determine the efficacy of P with IM in pts with advanced GIST with PD while receiving IM. Results: From 8/2005 to 7/2008, 41 pts were accrued. After 1 pt exclusion and 2 cross-overs, 22 pts were in Arm A and 18 pts in Arm B. Median age was 58 (range, 32–82), 51% were male, and median ECOG PS was 1. The most common primary site of disease and metastasis was the stomach (29%) and liver (66%), respectively. KIT genotype was available for 22 pts(54%); 5(12%) WT, 13(32%) exon 11 mutations, and 4(10%) exon 9 mutations. The median number of cycles was 2 (range, 1–24). By Choi and RECIST, 30 pts(73%) and 36 pts(87%) were available for response, respectively. No CR was identified but the PR rate was 4/36 (11%) by Choi (4 PR, 9 SD) and 0/36 (0%) by RECIST (16 SD). 4/5 (80%) of pts with WT KIT appeared to benefit (Choi: 1 PR, 3 SD; RECIST: 4 SD). Median PFS and OS for 40 pts were 2.2 months and 18.3 months. No difference in PFS was noted for the 2 schedules. Toxicity was assessed in 39 pts; 46 grade 3 events and 4 grade 4 events (ALT elevation, blurred vision, fatigue, and mood alteration) were noted. The most common grade 3 event was fatigue (20%). Three pts (7%) were removed from the study for toxicity (Arm A:1 pt, Arm B:2 pts). Conclusions: The addition of P to IM has minimal activity in IM-refractory GIST although its activity in GIST with WT KIT may be further investigated. No significant financial relationships to disclose.
Phase I-II trial of prolonged gemcitabine (G) infusion in combination with paclitaxel (P) in heavily-pretreated advanced breast cancer (ABC) patients (pts)
Authors: P. Vici, A. Fabi, D. Sergi, S. Carpano, L. Di Lauro, P. Foggi, P. Papaldo, D. Giannarelli, F. Cognetti, M. Lopez
Journal: Journal of Clinical Oncology (2008)

1110 Background: Among the innovative combinations in ABC pts, P and G showed synergistic action and activity. After a previous experience with biweekly schedule (Vici P et al, 2006), we carried out a phase I-II trial to test the biweekly combination with G administered as a dose-rate of 10 mg/m2/minute, which produce higher levels of active metabolites compared to shorter administration. Methods: 54 ABC receiving almost one prior line of chemotherapy for advanced disease including anthracyclines were treated in phase I study with P 150 mg/m2 and G 1,000 to 1,200 mg/m2 (10 mg/m2/minute), days 1, 14, every 28, without G-CSF support. Recommended G dose for phase II trial was 1,200 mg/m2. Overall response rate (ORr) and time to progression (TTP) with overall survival (OS), were primary and secondary endpoints, respectively for phase II trial. Results: 36 heavily pretreated pts entered in the second part of study. To date all pts were evaluable for toxicity and 32 pts for activity. Main characteristics were as follows: median (m) age 58 ys (22–78), m ECOG PS 1 (0–3), pre/postmenopausal 3/33, prior anthracycline/docetaxel treatment in 36/22 pts, m number of previous chemotherapy lines for advanced disease 2 (1- 5). The dominant metastatic site was: soft tissues 11%, bone 22%, viscera 67%. As activity we observed: 2 (6.2%) CR, 10 (31.2%) PR (ORr: 37.5% [95%CI, 20.6%-54.4%]) and 14 (43.7%) SD. As an intent- to treat analysis, response rate was 33.3%. Responses by number of metastatic sites were 41.6%, 30% and 25%, in one, two and three sites, respectively. Median time to response was 4 months (mo), m TTP 10 mo, m OS was not reached yet. Severe myelosuppression was uncommon with no cases of treatment delayes/dose reduction due to haematological toxicity. Moderate grade of peripheral neurotoxicity was encountered in 5.5% of pts. Myalgias and asthenia were frequently observed. Grade 2 transient and reversible hepatotoxicity was recorded in 5.5% of the pts. Conclusions: G 1,200 mg/m2 prolonged dose rate infusion combined with P as a biweekly schedule is an effective regimen in heavily pretreated ABC pts, with a favourable safety profile. Prolonged G infusion does not seem to improve shorter G administration activity. No significant financial relationships to disclose.
Factors associated with publication of plenary presentations at the Annual Meeting of the Society of Gynecologic Oncology
Authors: J. Cohen, J. Y. Shin, D. Teoh, C. A. Hamilton, D. S. Kapp, J. K. Chan
Journal: Journal of Clinical Oncology (2008)

17566 Background: To determine the factors associated with the publication of plenary presentations at the annual meeting of the Society of Gynecologic Oncology (SGO). Methods: Between 2000 and 2005, all plenary presentations from SGO were reviewed. A Pubmed search was performed to identify subsequent publication of the presentation. Chi-squared test and logistic regression analyses were employed to analyze factors associated with publication. Results: Of 378 main, focused or express plenary presentations, 282 (74.6%) were clinical and 96 (25.4%) translational/basic science studies. 173 (45.8%) involved multiple and 205 (54.2%) were from single institutions. The types of study included, chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trials (6.9%). 90.7% of these studies had positive results. 292 (77.2%) of presentations were published. The median time from presentation to publication was 13 months (1–76). The majority of the studies were published in Gynecologic Oncology (36.5%), Journal of Clinical Oncology (5.6%), and Clinical Cancer Research (5.0%). In univariate analyses, main plenaries were more likely to be published as compared to focused and express plenaries (80.5% vs. 78.8% vs. 62.0%; p=0.021). Studies from multiple institutions were more likely to be published compared to single institutions (83.2% vs. 72.2%; p=0.011). Clinical studies were more likely to be published compared to translational/basic science studies (81.2% vs. 65.6%; p=0.002). In addition, randomized clinical trials were more likely to be published compared to cohort, chart review and translation research (92.3% vs. 71.7%, 82.9%, and 64.0%; p<0.001). The median time to publication from multiple rather than single institutions was significantly longer (17 vs. 11.5 months; p<0.001). Logistics regression analysis showed that single vs. multiple institutions (OR=1.94, 95% CI=1.16–3.26; p=0.012) and type of study (OR=1.72, 95% CI=1.36–2.18; p<0.001) were important independent factors associated with publication. Conclusions: A high percentage (77.2%) of plenary sessions at SGO resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published. No significant financial relationships to disclose.
Talactoferrin alfa may prolong progression-free survival in advanced renal carcinoma patients
Authors: S. Srinivas, W. M. Stadler, R. Bukowski, R. Figlin, T. Hayes, E. W. Yankee, E. Jonasch
Journal: Journal of Clinical Oncology (2006)

4600 Background: Talactoferrin alfa (formerly known as recombinant human lactoferrin, rhLF) is a novel immunomodulatory 80 kD protein with demonstrated oral anti-tumor properties in animal models, and promising early results in patients with advanced renal cell carcinoma (RCC) in Phase 1/2 trials. Methods: An open label Phase 2 study of Talactoferrin Oral Solution at 1.5 g talactoferrin alfa b.i.d. given up to a maximum of 4 cycles of 12 weeks on, 2 weeks off was conducted at 6 sites. Eligibility included predominantly clear cell histology, failure of at least one prior systemic therapy, tumor progression within the prior 9 months, a performance status of &lt;2 (ECOG) and adequate organ function. The primary endpoints were the incidence of 14-week progression-free survival (PFS) and overall tumor response (by RECIST). The statistical plan specified an objective of 12.5% response rate or a progression-free survival rate of ≥40% at 14 weeks. Secondary endpoints included median PFS and median overall survival (OS). Results: Forty-four patients were enrolled. Eighteen patients (41%) were considered low risk and twenty-six (59%) considered intermediate risk based on the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. There were no talactoferrin-related Grade 3 or 4 adverse events or laboratory abnormalities. The most common related grade 1 or 2 adverse events were gastrointestinal symptoms. There was one unconfirmed tumor response and the 14-week PFS was 55%. The median PFS was 21 weeks (46 weeks and 9.4 weeks in the patients with low and intermediate risk prognostic factors, respectively). The median OS has not yet been reached. Conclusions: Talactoferrin alfa is well tolerated. The 14-week PFS met the pre-specified criteria for success (&gt;40%). Due to the heterogeneity of tumor biology of RCC, any further evaluation of talactoferrin in this population should be in a larger randomized trial. [Table: see text]
Phase II trial of irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) given weekly on alternating weeks with granulocyte colony-stimulating factor support in the treatment of extensive-stage small cell lung cancer
Authors: J. Uyeki, F. M. Johnson, L. Feng, B. O. Peeples, G. J. Blumenschein, F. V. Fossella, D. D. Karp, K. M. Pisters, D. J. Stewart, B. S. Glisson
Journal: Journal of Clinical Oncology (2007)

18119 Background: Irinotecan has significant activity in small-cell lung cancer. Randomized trials comparing IP to EP have yielded conflicting results. Our phase I study of alternating weekly therapy with IP and EP with granulocyte colony-stimulating factor (G-CSF) support found this regimen to be tolerated and active in untreated small cell lung cancer.(Johnson et al Clin Lung Cancer 2003) Methods: Based on these findings we conducted a phase II study to estimate the efficacy of weekly combination therapy in previously untreated patients with extensive disease small-cell lung cancer (ED-SCLC). Patients received 12 weeks of therapy with cisplatin (20 mg/m 2 ) on day 1 and irinotecan (100 mg/m 2 ) on day 1 and G-CSF days 2–5 (IP) alternating with cisplatin (20 mg/m 2 ) on day 1 and etoposide 60 mg/m 2 on days 1–3 with G-CSF on days 4–7 (EP). Patients with asymptomatic brain metastases were included. The primary end point was overall survival. Results: 38 patients were enrolled from 7/2001 to 7/2006. The median age was 60 years (range 37–73) and 55% were female. ECOG performance was 0 in 11 patients, 1 in 25 patients and 2 in 2 patients. 87% of patients completed 12 weekly cycles of chemotherapy (range 1–12) with 90% of the planned dose intensity of irinotecan delivered. The objective response rate in 33 evaluable patients was 87% (0 CR, 30 PR). Median follow-up time was 43.7 months. Median progression free survival was 6.4 months (95% CI 5.16–7.59 months). The median survival was 10.9 months (95% CI 8.61–13.5 months). The 2 year survival rate was 19% (95% CI 5–31%). Grade 3–4 non-hematologic toxicities included diarrhea (8%), hyponatremia (5%), dehydration (3%), and neutropenic fever (5%).Grade 3–4 hematologic toxicities included anemia (13%), neutropenia (5%), and thrombocytopenia (3%). There was 1 therapy related death due to sepsis. Conclusions: Weekly therapy with IP alternating with EP with growth factor support was well tolerated in patients with untreated ED- SCLC, but did not show improved progression-free or overall survival when compared with historical controls at our institution. No significant financial relationships to disclose.