Biomedical subjects

Judith S Kaur

Publications and source records attributed to Judith S Kaur.

15 recordsLinked to original sources

PubMed2006

Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma.

BACKGROUND: Patients with metastatic melanoma (MM) have very few therapy options. Based on reports of responses to paclitaxel and carboplatin (PC), 31 patients with MM were treated with PC. METHODS: Data regarding patients treated with PC were abstracted from medical records. Clinical outcomes as determined by the treating oncologist were used for this analysis. Response determination was retrospectively confirmed using Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Thirty-one patients with MM were treated with PC. Patients had a median of 2 previous therapies, with the majority (29; 94%) having failed prior temozolomide (TMZ) or dacarbazine (DTIC) therapy. The most commonly used regimen was weekly paclitaxel (at a dose of 100 mg/m(2)) and carboplatin (area under the curve 2) administered on Days 1, 8, and 15 of a 28-day cycle. An objective partial response was noted in 8 patients (26%) with an additional 6 patients (19%) having stable disease; therefore, a clinical benefit was noted in 45% of those patients treated. The median time to disease progression for the entire group was 3 months (range, 0-7 mos), with a median overall survival of 7.8 months (range, 1-14 mos). The clinical benefit derived by the 14 patients, which lasted for a median of 5.7 months (range, 2.5-7.3 mos), was considered to be clinically significant. At the time of last follow-up, eight patients continued to receive PC therapy. CONCLUSIONS: The PC combination appears to have definite and clinically meaningful activity when used as second-line therapy after TMZ or DTIC. Further evaluation of this regimen, alone or as a 'backbone' for other agents, needs to be considered.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

A phase I clinical and pharmacokinetic study of CS-682 administered orally in advanced malignant solid tumors.

CS-682 (1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl)-N4-palmitoylcytosine) is a novel orally administered 2'-deoxycytidine-type antimetabolite, which has a wide spectrum of antitumor activity in human tumor xenograft models. We conducted a phase I study to define the toxicity, pharmacokinetics and antitumor activity of CS-682 in patients with advanced solid tumors. Forty patients were enrolled to receive escalating doses of CS-682. CS-682 was given orally, once daily three times a week (Monday, Wednesday and Friday), for four weeks consecutively, followed by a two-week rest period. Twenty-two men and 18 women, median age 63.5 (range 31 to 82) were treated. The most common tumor type was colorectal cancer with 15 patients. Others tumors occurring in 3 or more patients included prostate, breast and lung carcinomas. Sixty percent of the patients had received greater than 2 prior chemotherapy programs. Patients have been treated at each of the following dose levels (mg/m2/day): 1.5, 12, 20, 25, 30, 50, 67, 90, 120, 160 and 220. Non hematologic toxicities grade 3 [NCI Common Toxicity Criteria (version 2.0)] related to treatment included nausea in 2, vomiting in 1, anorexia and asthenia in 2, and dehydration in 1. Severe hematologic toxicities (grade 3-4) were seen more frequently with 10 patients experiencing grade 3-4 neutropenia, 2 with grade 4 thrombocytopenia and 2 with grade 3 anemia. Neutropenia requiring hospitalization occurred in 3 patients. Dose-limiting neutropenia was observed at 220 mg/m2/day. The maximum tolerated dose was determined to be 160 mg/m2/day. No tumor responses were observed in this study. Six patients experienced stable disease, including one who has stable disease after having received 34 courses of CS-682. After oral administration, CS-682 is rapidly absorbed and metabolized to CNDAC, which is further metabolized by cytidine deaminase to the inactive product CNDAU. Peak plasma concentrations of CNDAC were achieved 2.2 +/- 0.9 h after drug administration and the terminal elimination half-life was 1.7 +/- 1.5 h. Measurable concentrations of CNDAU were first seen 0.60 +/- 0.31 h, peak plasma concentrations were achieved 3.1 +/- 0.9 h after the CS-682 dose, and the terminal elimination half-life was 2.3 +/- 1.7 h. The recommended phase 2 starting dose for the 3 days/week regimen of CS-682 is 160 mg/m2/day for 4 weeks repeated after a 2-week rest period.

Administration, Oral↗

PubMed2006

Peptide vaccination of patients with metastatic melanoma: improved clinical outcome in patients demonstrating effective immunization.

OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. METHODS: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

Adjuvants, Immunologic↗

PubMed2005

Small cell carcinoma of the urinary bladder. The Mayo Clinic experience.

BACKGROUND: Small cell carcinoma (SCC) of the urinary bladder accounts for 0.35-0.70% of all bladder tumors. There is no standard approach to the management of SCC of the urinary bladder. METHODS: The authors performed a retrospective study at Mayo Clinic (Rochester, MN) to characterize the clinical and pathologic features of patients with SCC of the urinary bladder diagnosed between 1975 and 2003 with emphasis on management. RESULTS: Forty-four patients were identified who had primary bladder SCC, 61.4% of whom had pure SCC. The male:female ratio was 3:1, the mean age was 66.9 years, and the mean follow-up was 3.2 years. Twelve patients (27.3%) had Stage II disease, 13 patients (29.6%) had Stage III disease, and 19 patients (43.2%) had Stage IV disease. The overall median survival was 1.7 years. The 5-year survival rates for patients with Stage II, III, and IV disease were 63.6%, 15.4%, and 10.5%, respectively. Six of eight patients with Stage II bladder SCC achieved a cure with radical cystectomy. Five patients with Stage IV disease had obvious metastases and received chemotherapy. Fourteen patients underwent radical cystectomy and were diagnosed later with locally advanced disease (T4b) or lymph node metastasis (N1-N3; Stage IV disease). Only 2 of 19 patients with Stage IV disease who received adjuvant chemotherapy were alive at 5 years. CONCLUSIONS: Patients with bladder SCC should undergo radical cystectomy except when metastatic disease is present (M1), in which case, systemic chemotherapy is indicated. Adjuvant treatment is not indicated for patients with Stage II disease after radical cystectomy but should be considered for patients with Stage III and IV disease. Chemotherapy should be a platinum-based regimen.

Age Distribution↗

PubMed2005

Sample genetic policy language for research conducted with native communities.

BACKGROUND: [corrected] We have been repeatedly asked to clarify genetic issues that have cultural ramifications for Native communities. METHOD: In the following commentary, we explain selected genetic issues that may vary among tribal nations; nonetheless, scientists should allocate sufficient time to meet with the tribal leaders and/or members of the tribal institutional review board prior to designing a genetic study to learn how selected issues are perceived by that specific tribal nation. RESULTS: Tribal nations generally encourage and mandate community-based participatory research methodology. CONCLUSIONS: We have included in this commentary draft language for study protocols to support researchers and tribal nations when developing studies pertaining to genetic issues.

Communication↗

PubMed2005

A survey of attendees at Native American health care conferences: knowledge, attitudes, and practices about cigarette smoking.

BACKGROUND: Cigarette smoking rates and related health consequences among Native Americans are the highest of any US ethnic group. METHODS: A sample of the attendees at American Indian and Alaska Native health care conferences participated in a survey about cigarette smoking. RESULTS: Of 162 respondents, 11.1% were current smokers, 7.5% of physicians were current smokers, and 80% were lifelong nonsmokers. The majority would ask a smoker to put out cigarettes and would not display ashtrays at home. Nearly all Native American physicians asked their patients about smoking and advised smokers to quit. Respondents were more likely to agree that smoking causes lung cancer (98.7%) as compared to knowing of the associations of smoking with cervical cancer (70.2%), depression (54.5%), and that it is more serious in women (55.2%; P < .01). CONCLUSIONS: Current smoking rates were low, and the physicians advised smokers to quit. However, there was less awareness about women's health problems that relate to cigarette smoking as compared to other health consequences of smoking.

Adult↗

PubMed2004

Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma.

BACKGROUND: Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS: Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity. RESULTS: Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS: Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.

Adult↗

PubMed2004

Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer: a Phase 2 trial.

BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy in American men, yet treatment of its metastatic androgen-independent form remains inadequate. This mandates development of new therapies such as immunotherapy. In this Phase 2 trial, we determined the efficacy of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein containing prostatic acid phosphatase (PAP) and GM-CSF. METHODS: We enrolled 21 patients with histologically documented androgen-independent prostate carcinoma that could be evaluated by radionuclide bone scan or computed tomography scan. APC8015 was prepared from a leukapheresis product; it contained autologous CD54-positive PA2024-loaded APCs with admixtures of monocytes, macrophages, B and T cells. APC8015 was infused intravenously twice, 2 weeks apart. Two weeks after the second infusion, patients received three subcutaneous injections of 1.0 mg of PA2024 1 month apart. We monitored patients' physical condition, immune response, and laboratory parameters. RESULTS: Nineteen patients could be evaluated for response to treatment. The median time to progression was 118 days. Treatment was tolerated reasonably well; most adverse effects were secondary to APC8015 and were NCI Common Toxicity Criteria Grade 1-2. Four of the 21 patients reported Grade 3-4 adverse events. Two patients exhibited a transient 25-50% decrease in prostate-specific antigen (PSA). For a third patient, PSA dropped from 221 ng/ml at baseline to undetectable levels by week 24 and has remained so for more than 4 years. In addition, this patient's metastatic retroperitoneal and pelvic adenopathy has resolved. PBMC collected from patients for at least 16 weeks proliferated upon in vitro stimulation by PA2024. For the patient with responsive disease, PBMC could be stimulated for 96 weeks. CONCLUSIONS: This study demonstrates a definite clinical response of androgen-independent prostate cancer to APC immunotherapy. Currently we are studying this mode of therapy in Phase 3 trials.

Acid Phosphatase↗

PubMed2004

Evaluation of a training program to prepare community health representatives to promote breast and cervix cancer screening among native american women.

BACKGROUND: Native American women have very poor 5-year breast and cervix cancer survival rates compared to other US population groups. We evaluated a training program that prepares community health representatives (CHRs) to promote prevention and early detection of these diseases. Two questions guided the evaluation: (1) Are CHRs an appropriate focus of training? and (2) Does training empower CHRs and, indirectly, their facilities to educate about breast and cervix cancer, promote screening, and teach breast self-exam skills to American Indian and Alaska Native women? METHODS: Twenty CHRs (3 Indian Health Service regions, 9 separate employers) responded to a telephone survey consisting of Likert scale and multiple option and short-answer questions. Analysis relied on descriptive statistics and measures of central tendency. RESULTS: By tenure, cultural and community membership, and ability to adapt to audience needs and setting demands, CHRs make appropriate training recipients. Training improves skills and their use and appears to increase employers' reliance on CHRs for screening promotion and education about cancer. Posttraining, more women hear and heed the screening message. CONCLUSIONS: CHRs are an appropriate focus of training. Training leads to increased screening-related activities and should be continued and expanded.

Breast Neoplasms↗

PubMed2003

The hospice patient's primary caregiver. What is their quality of life?

OBJECTIVE: The purpose of this study was to (1) assess the quality of life (QOL) of the primary caregivers of hospice patients and (2) to analyze the ability of the hospice staff to accurately judge caregiver QOL. METHODS: A longitudinal pilot study of QOL of caregivers of patients entering hospice was undertaken. Caregivers and hospice personnel completed numerous questionnaires every 2 weeks until patient death. Global QOL and component constructs, as well as the demands of illness on the caregiver and profile of moods, were assessed. Simple descriptive statistics at each time point and summary measures (area under the curve) were calculated to describe the QOL profile of caregivers and staff perceptions of the caregivers. Cronbach's alpha coefficient was applied to verify tool internal consistency in a hospice population. Correlation coefficients were supplemented by Bland-Altman procedures for comparing scales measuring the same construct to compare the scores given by caregivers about themselves and staff ratings of the caregivers. The study had 80% power to detect an intracase difference between caregiver and staff ratings of the caregiver of 0.4 times the standard deviation using a two-sided paired t test with a 5% type I error rate. RESULTS: Caregiver QOL was relatively high and stable over time. Caregiver's QOL was correlated with the patient's overall QOL/hospice staff accurately evaluated caregiver QOL. CONCLUSIONS: By drawing attention to issues that affect the caregiver, we can improve delivery of hospice care and positively impact QOL for both caregiver and patient. Linear analog self-assessment scales are valuable tools for hospice staff to assess caregivers.

Caregivers↗

PubMed2003

Metastatic melanoma presenting as cardiac mass and hemobilia.

We present a rare case of malignant melanoma of unknown primary origin presenting as cardiac and cholecystic masses. In this 72-year-old man, a cardiac lesion caused right ventricular outlet obstruction, and gallbladder lesions led to hemobilia. Right atrial and gallbladder metastases were resected. After 2 years of disease-free survival, the patient had recurrent skin lesions, which were treated with local resection and dacarbazine. The patient has survived for more than 5 years after initial diagnosis, with continued complete clinical remission. This case illustrates the importance of aggressive surgical resection and chemotherapy in the treatment of metastatic malignant melanoma.

Aged↗

PubMed2002

Evaluation of a program to train nurses to screen for breast and cervical cancer among Native American women.

BACKGROUND: Routine screening for breast and cervical cancers lowers mortality from these diseases, but the benefit has not permeated to Native American women, for whom the five-year survival rate is the lowest of any population group in the United States. To help address this problem, an educational/training program was designed to enhance the skills of nurses and other health service providers and develop clinic support systems to better recruit, screen, and follow clients for breast and cervical cancer screening services. METHODS: A total of 131 nurses participated in the training program at 33 different sites between 1995 and 2000. Prior to and following training, each participant was given a questionnaire to determine knowledge of breast and cervical cancer screening techniques and recommendations, cancer survival and risk factors, and situational scenarios. RESULTS: The average score for the pretest was 54% correct. The posttest average was 89% correct. The percent correct increased 35% from pre- to posttest (p < 0.001). CONCLUSION: The knowledge to implement a successful screening program can be acquired through the current curriculum.

Breast Neoplasms↗

PubMed2002

Phase II trial of KW2189 in patients with advanced malignant melanoma.

KW-2189, a semisynthetic duocarmycine antibiotic has been shown to exert antiproliferative effects against human tumor cell lines in vitro and animal tumor models in vivo. Phase I studies identified myelosuppression as the most noteworthy adverse effect. Presented are two concurrent phase II studies assessing the antitumor and toxicity profile of KW-2189 in metastatic melanoma patients. One of the studies accrued patients with a history of prior melanoma therapy and the other accrued patients without a history of prior melanoma therapy. KW-2189 was administered at 0.4 mg/m2 to previously treated patients and 0.5 mg/m2 to the previously untreated. Treatment was administered intravenously on day 1 of a 6-week cycle. Thirty previously untreated and 15 previously treated patients were accrued. The toxicity profiles of the both groups of patients were similar. Of the 15 previously treated patients, 8 completed once cycle of treatment, 2 completed 2 cycles, and 5 completed 3 cycles. Dose modification for neutropenia/ thrombocytopenia was necessary in six patients. Among the previously untreated cohort (30 patients), 16 completed 1 cycle, 5 completed 2 cycles, 4 completed 3 cycles, 3 completed 4 cycles, and 2 completed 6 cycles. Doses were modified (neutropenia or thrombocytopenia) in 11 patients. None of the 15 previously treated patients responded to therapy. Four patients remained stable during two cycles. Five of the previously untreated patients achieved a partial remission/regression. Response duration ranged from 2.8 to 16.6 months. Overall objective response rate was 17%. Regarding survival, one previously treated patient is still alive 2.9 years after study entry, and three previously untreated patients are still alive 1.6, 2.3, and 2.9 years after study entry. The 1-year survival rate for previously treated patients is 27% and for the untreated patients is 23%. In summary, the lack of significant antitumor activity of KW-2189 and its associated toxicity suggest that further testing of this regimen in patients with stage IV melanoma is not warranted.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Evaluating the WEB training program for cancer screening in Native American women.

The Native Women Enjoying the Benefit (WEB) program trains nurses to perform breast and cervical cancer screening examinations for Native American women. Several evaluations have shown that the program improves nurses' knowledge and skills, and nurses value its positive impact on clinic, nurse, and patient behaviors. Beyond effectiveness, program longevity often rests upon equilibrium that results from alignment between a program's values and principles with those of its sponsoring organization and pertinent surrounding environments. We examined how Native WEB values align with those of its 2 most relevant environments-the medical institution (immediate environment) that sponsors it and the broader health care context (distal environment). We found that social justice views articulated in Catholic social teaching served as a convenient synthesis of the 2 environments' values and principles. We used this conception of social justice to determine whether the Native WEB program reflected the perspectives of its immediate and distal environments.

Breast Neoplasms↗

PubMedDate not supplied

Lessons learned while developing "Clinical Trials Education for Native Americans" curriculum.

This paper highlights lessons learned while developing the Clinical Trials Education for Native Americans (CTENA) curriculum. The CTENA is a culturally specific clinical trials education curriculum that evolved from another ongoing NCI-supported project, Clinical Trials Education for Colorado Providers. The multicultural team learned many lessons while developing, pretesting, and revising this curriculum. These include allocating sufficient time and resources to tailor presentations for diverse tribal settings and workshop participants, addressing barriers to participation in clinical trials through culturally appropriate strategies, providing information to foster informed decision making related to participation, and writing as a team to increase cultural breadth of examples and interactive experiences. There are multiple challenges to developing and implementing a culturally acceptable curriculum on clinical trials within medically underserved communities. Both the multicultural team and the curriculum benefited from the collaborative process, resulting in a culturally relevant clinical trials curriculum that will assist Native Americans to make informed choices about clinical trials participation. The lessons shared here, which may need to be modified to be culturally relevant to other underrepresented communities, may be beneficial to others developing similar curricula for other medically underserved populations.

Clinical Trials as Topic↗