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[Assessment of the efficacy, safety and pharmacokinetics of SKG-02 (recombinant human TSH) in postoperative diagnosis of well-differentiated thyroid cancer--a Japanese prospective, controlled, multicenter open-label study].
Konishi, J, Tamaki, N, Nakada, K, Kusakabe, K, Maki, M, Kanbe, M, Higashi, T, Endo, K, Ikekubo, K, Yokoyama, K, et al
Kaku igaku. The Japanese journal of nuclear medicine. 2010;(4):479-96
Abstract
OBJECTIVE This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC). METHODS Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated. RESULTS In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics. CONCLUSIONS SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.
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A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: a trial of the Chicago, PMH, and California Phase II Consortia.
Nimeiri, HS, Oza, AM, Morgan, RJ, Huo, D, Elit, L, Knost, JA, Wade, JL, Agamah, E, Vokes, EE, Fleming, GF
Gynecologic oncology. 2010;(1):37-40
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Abstract
OBJECTIVES To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. METHODS This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0-1 prior chemotherapy regimens, and ECOG performance status RESULTS Fifty-six patients (40 with carcinoma, 16 with carcinosarcoma) were enrolled between March 2005 and August 2007. Two (5%) patients with uterine carcinoma had a partial response (PR) and 17 (42.5%) achieved stable disease (SD). Five had SD lasting at least 4 months. The 6-month progression-free survival rate for patients with carcinoma was 29%, and the median overall survival was 11.4 months. No patients with carcinosarcoma had an objective response. Four (25%) had SD, and one had SD lasting 18 months. The 6-month progression-free survival rate was 13%, and the median overall survival was 5.0 months. Grade 3/4 drug related toxicities included: hypertension (13%), hand-foot syndrome (13%), hypophosphatemia (7%), anemia (5%), rash (5%), diarrhea (5%), thrombosis (5%), fatigue (5%) and bleeding (5%). CONCLUSION Sorafenib had minimal activity in patients with uterine carcinoma. Predictive factors for potential benefit are needed.
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Evaluation of vinorelbine in persistent or recurrent nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group Study.
Muggia, FM, Blessing, JA, Waggoner, S, Berek, JS, Monk, BJ, Sorosky, J, Pearl, ML
Gynecologic oncology. 2005;(1):108-11
Abstract
OBJECTIVE The Gynecologic Oncology Group (GOG) has studied a number of drugs to determine their activity in patients with previously treated squamous and nonsquamous cancer arising in the uterine cervix. A Phase II study with intravenous vinorelbine was initiated for this purpose in patients with Stage IVB, recurrent, or persistent nonsquamous carcinomas who had received one prior chemotherapy or were not eligible for other studies. METHODS Eligible patients had to have measurable disease, GOG performance status of 0-2 and adequate bone marrow, liver, and renal function. The treatment consisted of vinorelbine 30 mg/m(2) on days 1 and 8, repeated every 21 days. Tumor measurements and toxicities were recorded every treatment cycle. RESULTS Thirty patients were enrolled with 28 patients deemed eligible and evaluable. Only two confirmed partial responses (7.1%) were noted. Neutropenia was the most common toxicity with 9 of 28 (32%) experiencing either grade 3 or 4 changes. Anemia was severe in seven. Neuropathy was more than mild in three patients. Severe events, such as fatigue, hypertension, or pulmonary changes attributed to drug administration, occurred only in one or two instances. CONCLUSION With the dose schedule and assessment criteria employed, vinorelbine had only minimal activity in nonsquamous cancer of the cervix.
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A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma.
Jatoi, A, Ellison, N, Burch, PA, Sloan, JA, Dakhil, SR, Novotny, P, Tan, W, Fitch, TR, Rowland, KM, Young, CY, et al
Cancer. 2003;(6):1442-6
Abstract
BACKGROUND Recent laboratory and epidemiologic studies have suggested that green tea has antitumor effects in patients with prostate carcinoma. This Phase II trial explored green tea's antineoplastic effects in patients with androgen independent prostate carcinoma. METHODS This study, which was conducted by the North Central Cancer Treatment Group, evaluated 42 patients who were asymptomatic and had manifested, progressive prostate specific antigen (PSA) elevation with hormone therapy. Continued use of luteinizing hormone-releasing hormone agonist was permitted; however, patients were ineligible if they had received other treatments for their disease in the preceding 4 weeks or if they had received a long-acting antiandrogen therapy in the preceding 6 weeks. Patients were instructed to take 6 grams of green tea per day orally in 6 divided doses. Each dose contained 100 calories and 46 mg of caffeine. Patients were monitored monthly for response and toxicity. RESULTS Tumor response, defined as a decline ≥ 50% in the baseline PSA value, occurred in a single patient, or 2% of the cohort (95% confidence interval, 1-14%). This one response was not sustained beyond 2 months. At the end of the first month, the median change in the PSA value from baseline for the cohort increased by 43%. Green tea toxicity, usually Grade 1 or 2, occurred in 69% of patients and included nausea, emesis, insomnia, fatigue, diarrhea, abdominal pain, and confusion. However, six episodes of Grade 3 toxicity and one episode of Grade 4 toxicity also occurred, with the latter manifesting as severe confusion. CONCLUSIONS Green tea carries limited antineoplastic activity, as defined by a decline in PSA levels, among patients with androgen independent prostate carcinoma.
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High dietary fiber consumption is not associated with gastrointestinal discomfort in a diet intervention trial.
McEligot, AJ, Gilpin, EA, Rock, CL, Newman, V, Hollenbach, KA, Thomson, CA, Pierce, JP
Journal of the American Dietetic Association. 2002;(4):549-51
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Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum.
Rosenberg, P, Andersson, H, Boman, K, Ridderheim, M, Sorbe, B, Puistola, U, Parö, G
Acta oncologica (Stockholm, Sweden). 2002;(5):418-24
Abstract
The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly (arm A) or every 3 weeks (arm B). and to assess the safety of intravenous steroids versus standard peroral premedication. Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were randomized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks. The median delivered dose intensity was 77.6 mg/m2/week in the weekly arm, and 72.7 mg/m2/week in the every 3 weeks arm. WHO grade 3-4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity, response rate, time to progression or survival between arms was observed. Weekly paclitaxel at a dose of 67 mg/m2/week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks. Intravenous steroids are a safe alternative to oral steroids.
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I-125 versus Pd-103 for low-risk prostate cancer: morbidity outcomes from a prospective randomized multicenter trial.
Wallner, K, Merrick, G, True, L, Cavanagh, W, Simpson, C, Butler, W
Cancer journal (Sudbury, Mass.). 2002;(1):67-73
Abstract
PURPOSE The purpose of this study was to test the hypothesis that the shorter half-life of Pd-103 versus I-125 results in a shorter duration of radiation-related symptoms after prostate brachytherapy. METHODS As of February 2000, 110 of a planned total of 380 patients with 1997 American Joint Commission clinical stage T1c-T2a prostatic carcinoma (Gleason grade 2-6, prostate-specific antigen, 4-10 ng/mL) had been randomly assigned to implantation with I-125 (144 Gy, TG-43) or Pd-103 (125 Gy, NIST-99). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urologic Association (AUA) and Radiation Therapy Oncology Group criteria at 1, 3, 6, 12, and 24 months. Use of alpha-blockers to relieve obstructive symptoms was not controlled for but was noted at each follow-up point. All patients reported here have a minimum 1-year follow-up. Randomization was carried out at a central enrollment office where eligibility criteria were confirmed and the patient assigned by computerized random number generator to one of the two treatment arms. Patients were assigned to 95 blocks of four. Most statistical comparisons shown here are by Student's unpaired t-test at specific follow-up times, as indicated in the figure legends. Additionally, considering the patients' scores change overtime, repeated measures were incorporated in a mixed model assuming an unstructured covariance matrix. RESULTS Patients in each arm were well matched by preimplant prostate volume, AUA score, and age. The AUA scores peaked at the 1-month point for both isotopes and then gradually declined. The difference was greatest at 6 months, when I-125 patients had a mean AUA score of 16 (+/- 8), compared with 11 (+/- 10) for the Pd-103 patients. By 12 months, mean AUA scores for the Pd-103 patients had decreased to 12 (+/- 9), compared with 13 (+/- 8) for the I-125 patients. At 6 months after implantation, 41% of Pd-103 patients were still taking alpha-blockers, versus 44% of I-125 patients. The differences between isotopes were more marked in patients with a low pretreatment AUA score or smaller preimplant transrectal ultrasonography volume. Results of the mixed model, incorporating repeated measures for each patient, showed that the effect of isotope choice on AUA score depended on time. This effect was further dependent on baseline AUA score, but not on transrectal ultrasonography volume or on age. Urinary and rectal morbidity was generally low, typically grade 1 or 2. There was a trend to greater morbidity with I-125 than with Pd-103, most markedly at the 6-month time point. DISCUSSION Patients treated with Pd-103 recovered from their radiation-induced prostatitis sooner than I-125 patients. It appears that patients with minimal pretreatment urinary obstructive symptoms are the most likely to experience implant-related exacerbations of their symptoms and are the most likely to benefit from the more rapid half-life of Pd-103 rather than I-125.