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J T Thigpen

Publications and source records attributed to J T Thigpen.

At least 19 recordsLinked to original sources
PubMed2001

Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men.

BACKGROUND: The protein c-erb B-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsy specimens from women diagnosed with malignant tumors. Current studies suggest that soluble fragments of the c-erb B-2 oncogene may be released from the cell surface and become detectable in patients with a carcinoma of the breast. Consequently, the purpose of this study is to assay soluble c-erb B-2 protein in the saliva of healthy men and women to determine the reliability of the assay. METHODS: To determine the diagnostic utility of this oncogene, we assayed the soluble form of the c-erb B-2 protein in the saliva with an enzyme-linked immunosorbent assay. The study population consisted of 10 healthy women and 9 healthy men who were serially sampled for saliva 3 times a day for a 5-day period. Saliva was collected from each subject at 9 AM, 4 PM, and 9 PM during the 5-day period. RESULTS: We found the presence of c-erb B-2 protein in the saliva of both groups of subjects. The salivary levels of c-erb B-2 were not significantly different when compared for gender differences. Likewise, the results suggest that sampling during various times of the day for salivary c-erb B-2 levels has no effect on marker concentration. Reliability analyses showed that supervised salivary collections were more reliable than unsupervised collections. CONCLUSIONS: The results of this pilot study suggest that the assay for salivary c-erb B-2 protein is reliable and might have potential use in the initial detection and follow-up screening for the recurrence of breast cancer in both men and women.

Adult↗
PubMed2000

A preliminary study of CA15-3, c-erbB-2, epidermal growth factor receptor, cathepsin-D, and p53 in saliva among women with breast carcinoma.

A panel of markers used to aid in the diagnosis and treatment of breast cancer was examined in the saliva of a cohort of healthy women, women with benign lesions of the breast, and women with diagnosed breast cancer. We found recognized tumor markers c-erbB-2 (erb), cancer antigen 15-3 (CA15-3), and tumor suppressor oncogene protein 53 (p53) in the saliva of all three groups of women. The levels of erb and CA15-3 in the cancer patients evaluated, however, were significantly higher than the salivary levels of healthy control subjects and benign tumor patients. Conversely, pantropic p53 levels were higher in control subjects compared with those women with breast cancer and those with benign tumors. Although cathepsin-D and epidermal growth factor receptor were detected, they did not demonstrate any clear correlation with disease status. The results of the pilot suggest that these markers have potential use in initial detection and/or follow-up screening for the detection of breast cancer in women.

Adult↗
PubMed2000

The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study.

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.

Adult↗
PubMed2000

Chemotherapy for advanced ovarian cancer: overview of randomized trials.

Until the mid-1970s, standard therapy for ovarian carcinoma was a single alkylating agent. Subsequently, combination chemotherapy was shown to be superior to such therapy. During the 1980s, cisplatin-based combination chemotherapy became the standard chemotherapy regimen for advanced ovarian cancer; however, other classes of agents with documented activity against ovarian tumors appeared to be cross-resistant with platinum. The introduction of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the early 1990s, with its apparent lack of cross-resistance with platinum compounds, was a notable advance in ovarian cancer management that dramatically altered the standard of care. During the 1990s, the combination of platinum (cisplatin or carboplatin) plus paclitaxel rapidly evolved into front-line chemotherapy for advanced ovarian cancer. The series of randomized phase III studies that have compared the activity of platinum/paclitaxel with alternative regimens, including the previous standard combination of cisplatin/cyclophosphamide, support the combination of platinum/paclitaxel as the current standard chemotherapy for advanced ovarian cancer. Outstanding issues that stem from this phase III experience include the impact of nonprotocol salvage regimens on survival and the potential benefits of sequential single-agent regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.

BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3). RESULTS: The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively. CONCLUSIONS: Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.

Adult↗
PubMed1999

CA 15-3 and c-erbB-2 presence in the saliva of women.

Two markers used to aid in the diagnosis and treatment of breast cancer were examined in the saliva of a cohort of 135 healthy women. The investigators detected the presence of cancer antigen 15-3 (CA 15-3) and c-erbB-2 in the saliva sampled from the 135 women. The marker concentrations for CA 15-3 and c-erbB-2 were also evaluated and compared in terms of tobacco usage, menopausal status, estrogen usage, systemic diseases, prescription medications, race, and age. The results of the study showed no association between the aforementioned variables and salivary marker concentrations. The results of this study establish a baseline for measuring the biomarkers in the saliva of women with no evidence of malignant disease and add further support to the notion that salivary concentrations of CA 15-3 and c-erbB-2 may be useful in the detection of breast cancer and/or the post operative follow-up of patients being treated for carcinoma of the breast.

Adolescent↗
PubMed1999

Randomised trials in ovarian cancer: trial design considerations.

Randomised clinical trials are considered the definitive source of evidence for guiding decisions in clinical practice. The concept of a clinical trial is based on sound scientific, ethical, and practical principles. The strength of evidence that an individual trial provides is assessed on the manner in which these principles are incorporated into the design and execution of the trial. Since the way these principles are incorporated into a trial is judgmental, the strength of evidence from an individual trial is a matter of degree. The purpose of this paper is to present some of the scientific, ethical and practical considerations surrounding the selection of endpoints and determination of sample size for trials in ovarian cancer.

Female↗
PubMed1999

First line chemotherapy with carboplatin plus paclitaxel in advanced ovarian cancer--a new standard of care?

Cisplatin 75 mg/m2 plus paclitaxel 135 mg/m2 administered over 24 hours have been established as the standard treatment for advanced ovarian cancer. This schedule can not be administered in an outpatient setting. A European-Canadian trial confirmed the superiority of cisplatin-paclitaxel, but failed to improve the therapeutic index of this combination by reducing infusion length of paclitaxel from 24 to 3 hours. The reduction of infusion duration combined with a dose escalation of paclitaxel from 135 mg/m2 to 175 mg/m2 induced a high rate of neurotoxicity. A further attempt to improve the therapeutic index of platinum-taxane combinations was started with the substitution of cisplatin by carboplatin. At least 7 phase I/II trials evaluated this combination. The promising results of these studies led to the initiation of 5 randomised phase III trials with carboplatin plus paclitaxel administered in 3-hours. Two of these trials have completed accrual and preliminary data were available for this review. Although long-term survival data are not available, the current results warrant the conclusion that the combination of carboplatin AUC 5-6 plus paclitaxel 175 mg/m2 in a 3-hours infusion can be regarded as an alternative for the first-line treatment in patients with advanced ovarian cancer. Final analysis of the above mentioned phase III trials with longer follow-up is awaited and will define the ultimate role of this combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Basal cell carcinoma with lung metastasis diagnosed by fine-needle aspiration biopsy.

Basal cell carcinoma of the skin is one of the most common types of cancer. Its natural history is one of local recurrence rather than metastatic spread. Certain histologic features and primary tumor size seem to be risk factors for metastases. The diagnosis of metastatic disease imparts a poor prognosis with a short median survival. Treatment is usually in the form of systemic chemotherapy with cisplatin-based combination described as most active agent.

Aged↗
PubMed1999

American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants.

PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Adult↗
PubMed1999

Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.

PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

Administration, Oral↗
PubMed1999

High-dose chemotherapy in ovarian carcinoma.

High-dose chemotherapy supported by bone marrow transplantation is being seriously investigated as a way to increase response and prolong survival in women with ovarian carcinoma. This report is a broad review of attempts over the past several years to demonstrate advantages of the high-dose approach. The existing data for dose escalation, short of doses requiring hematopoietic stem-cell transplant, demonstrate increased response rates, but no survival advantage. When even higher doses of chemotherapy are used in concert with autologous transplant to combat hematologic toxicities, even higher response rates have been reported. Despite this, all survival data from these later studies are limited. There is some hint of survival benefit in certain populations, such as those women with limited disease or perhaps in more advanced disease that has not been previously treated. All of the studies taken as a whole effectively demonstrate the need for randomized trials to address the issue of whether this approach provides any advantage over standard-dose chemotherapy. Future efforts at studying high-dose chemotherapy and autologous transplantation for ovarian carcinoma should be focused in this area; until results are available from such trials, high-dose chemotherapy with transplant will remain an experimental procedure.

Antineoplastic Agents↗
PubMed1999

Limited-stage ovarian carcinoma.

No effective screening test for ovarian carcinoma exists. Consequently, only 25% of patients have limited (FIGO stage I-II) disease, and most of these will be at high risk for recurrence. Management requires categorization of the primary neoplasm as low or high risk. Those at low risk have all the following characteristics: grade I disease limited to the ovary, no tumor on the surface of the ovary, negative peritoneal cytology, and no ascites. The 5-year disease-free survival rate exceeds 90%; hence, surgical resection (total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and careful surgical exploration) followed by observation is the treatment of choice. Patients at high risk have one or more of the following features: grade 2 or 3 disease, disease outside of the ovary, tumor on the surface of the ovary, positive peritoneal cytology, or ascites. Recurrence rates approximate 40%. Platinum-based adjuvant chemotherapy yields a recurrence rate approximately half that obtained with no adjuvant therapy.

Female↗
PubMed1995

Chemotherapy as a palliative treatment in carcinoma of the uterine cervix.

The vast majority of patients with cervix carcinoma present with either preinvasive or minimally invasive (stage IA) disease and are cured with surgery alone. The remaining patients can be classified into two groups: those with disseminated (extrapelvic) disease at the time of presentation or recurrence after initial treatment and those with advanced pelvic disease. In the first group, the goal of therapy is palliative and the principal modality is chemotherapy. A number of single agents have significant activity (> or = 15% response rate): the platinum compounds, certain alkylating agents, the anthracyclines, bleomycin, the vinca alkaloids, certain antifols, 5-fluorouracil, 5'-floxuridine, ICRF-159, hexamethylmelamine, and CPT-11. Although uncontrolled trials report high response rates with combination regimens, no such regimen has been shown to be superior to single-agent therapy. The current standard of care for initial treatment is single-agent cisplatin 50 to 100 mg/m2 every 3 weeks, with an expected 23% response rate. In the second group, palliation takes the form of prevention of recurrence. Patients who have stage IIIB or IVA disease benefit from the addition of concomitant chemotherapy to radiation. The current standard of care is hydroxyurea 80 mg/kg orally twice weekly during radiotherapy. For patients with stage IB or II disease, surgery and/or radiotherapy remains the standard of care. Although concomitant or neoadjuvant chemotherapy followed by either surgery or radiotherapy has been evaluated, no conclusive evidence proves the value of the addition of chemotherapy to the management of these patients. Ongoing phase III trials are evaluating both approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study.

PURPOSE: From 1979 to 1984, 356 eligible patients with advanced or recurrent endometrial carcinoma no longer amenable to therapy with surgery, radiotherapy, or progestins were treated with doxorubicin alone or doxorubicin in combination with cyclophosphamide. PATIENTS AND METHODS: Patients were randomized to receive doxorubicin 60 mg/m2 intravenously (i.v.) with or without cyclophosphamide 500 mg/m2 i.v. every 3 weeks for eight drug courses. All patients had received prior therapy with progestins with subsequent progression of disease. No patients had received prior therapy with cytotoxic drugs. Of 356 patients, 300 had measurable disease. RESULTS: Among 132 patients treated with doxorubicin alone, there were seven complete responses (5%), 22 partial responses (17%), 73 with stable disease (55%), and 30 with increasing disease within 2 months of study entry (23%). For the 144 patients who received the combination, there were 18 complete responses (13%), 25 partial responses (17%), 75 with stable disease (52%), and 26 with increasing disease (18%). The median progression-free interval for those patients who received doxorubicin alone was 3.2 months, while it was 3.9 months for those who received the combination. The median survival duration for doxorubicin patients was 6.7 months, while it was 7.3 months for the combination patients. None of the unadjusted estimates of treatment differences are statistically significant. Prognostic features that had an impact on outcome included one factor associated with an increased likelihood of response (presence of measurable lung metastases) and four features associated with a poorer survival (poor performance status [PS] of 2 or 3, high pathologic grade, and presence of liver metastases or other intraabdominal disease). If these features are taken into account in multivariate analyses, there is no statistically significant evidence for differences in response rates (relative odds of response, 1.58; P = .06, one-tailed test), and survival duration is slightly longer in the combination regimen (17% reduction in death rate; P = .048). CONCLUSION: The combination of doxorubicin plus cyclophosphamide thus appears to offer a small advantage over doxorubicin alone in the management of endometrial carcinoma at the expense of more frequent and severe myelosuppression and gastrointestinal toxicity.

Adenocarcinoma↗
PubMed1994

Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.

PURPOSE: This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS: Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS: Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION: Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.

Adult↗