PubMed Health⌕ Search

Biomedical subjects

D Spriggs

Publications and source records attributed to D Spriggs.

At least 19 recordsLinked to original sources
PubMed2001

Phase I trial of ifosfamide and 24-h infusional paclitaxel in pelvic malignancies: a Gynecologic Oncology Group study.

OBJECTIVE: The goal of this work was to develop a combination chemotherapy regimen consisting of ifosfamide and paclitaxel to be evaluated in the management of gynecologic malignancies. METHODS: The Gynecologic Oncology Group conducted a Phase I trial of the regimen, initially with paclitaxel (24-h infusion) delivered on Day 1 and ifosfamide (1 h) administered (with Mesna) over the subsequent 4 days. All patients received granulocyte colony-stimulating factor (G-CSF) starting 24 h after the Day 5 chemotherapy. Treatment was repeated on a 28-day schedule. A cohort of patients also received the alternate sequence of ifosfamide (4 days) followed by paclitaxel. RESULTS: Twenty-two patients were evaluated. Even at the lowest dose level tested (paclitaxel 135 mg/m(2) followed by ifosfamide 1 g/m(2)/day x 4 days) grade 4 neutropenia was almost universal, despite the routine use of G-CSF. The alternate drug administration sequence resulted in marrow suppression of similar severity. CONCLUSION: The combination of 24-h infusional paclitaxel with ifosfamide delivered over 4 days results in severe neutropenia, despite the administration of G-CSF, and is not recommended for further evaluation. In view of the known activity of the two agents in several malignancies, including cervix cancer, it would be reasonable to investigate the delivery of the agents employing alternative treatment schedules predicted to result in less severe marrow suppression (e.g., 3-h infusional paclitaxel).

Adult↗
PubMed2001

Identification of risk factors for requiring transfusion during front-line chemotherapy for ovarian cancer.

OBJECTIVE: Anemia requiring red blood cell (RBC) transfusion is common in ovarian cancer (OC) patients receiving post-debulking surgery chemotherapy. Erythropoietin use has been shown to decrease transfusion requirements in patients receiving chemotherapy. We sought to identify pretreatment risk factors that could identify patients at increased risk for requiring RBC transfusion during first-line treatment for ovarian cancer. METHODS: One hundred seventy-five consecutive patients who received chemotherapy with either carboplatin-paclitaxel or cisplatin-paclitaxel following debulking surgery for epithelial OC from 1993 to 1996 were identified. No patient received erythropoietin. Patient characteristics recorded included: age, stage, prechemotherapy hemoglobin, nadir hemoglobin, number of cycles and doses of chemotherapy received. The outcome was requiring RBC transfusion. Independent predictors of requiring RBC transfusion were identified using multivariate analyses. RESULTS: Median age of the cohort was 62 years (range, 28-86). Seventy-one and four-tenths percent had FIGO stage III/IV disease. Median prechemotherapy hemoglobin was 11 g/dL (range, 7.1-15.4); median nadir hemoglobin was 9.3 g/dL (range, 6.6-11.1). One hundred nineteen (66%) patients received cisplatin-paclitaxel, and 61 (34%) received carboplatin-paclitaxel. Of 175 patients, 31 (18%, 95% CI = 12-23%) required RBC transfusion. Independent risk factors for RBC transfusion were prechemotherapy hemoglobin <10 g/dL (P < 0.01, odds ratio = 3.78, 95% CI = 1.52-9.44) and carboplatin-paclitaxel versus cisplatin-paclitaxel treatment (P = 0.01, odds ratio = 3.14, 95% CI = 1.27-7.76). Of 175 patients, 40 (22.8%) had a prechemotherapy hemoglobin <10 g/dL. Fifty percent of patients with prechemotherapy hemoglobin <10 g/dL who received carboplatin-paclitaxel required RBC transfusion, compared with 7.7% of patients with hemoglobin >10 g/dL who received cisplatin-paclitaxel. CONCLUSION: Ovarian cancer patients frequently require RBC transfusion during postdebulking platinum-paclitaxel chemotherapy. Patients with prechemotherapy hemoglobin <10 g/dL and those receiving carboplatin-paclitaxel are at increased risk of requiring RBC transfusion. Early initiation of erythropoietin use in such patients may reduce transfusion needs.

Adult↗
PubMed2001

Assessing the status of research on violence-related problems among youth.

Presents results of a systematic review of abstracts on studies related to violence and youth in an effort to identify areas that have received little attention in the psychological literature and to present recommendations for future research. A total of 1,168 empirical articles on violence-related problems in youth were identified by a PsycINFO (American Psychological Association, 1980-1999) search. These articles were then classified in a multidimensional grid, allowing for comparisons among different types of articles. A review of abstracts from these articles indicated that most of the research activity has been descriptive (e.g., reviewing correlates or predictors of violence involvement) or assessment related (e.g., evaluating specific measures). Fewer articles examined the treatment or prevention of violence-related problems among youth. Further, the majority of studies pertained to direct exposure to violence (as a victim or perpetrator), with very few studies looking at the effects of witnessing violence, knowing individuals exposed to violence, or being exposed to violence through the media. Comparing treatment and prevention articles, we found that the least empirical attention was paid to the prevention of violence-related problems in youth, and not a single study was identified through this search that sought to examine the prevention of youth witnessing violence. Implications for future research agendas are discussed.

Adolescent↗
PubMed2000

Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial.

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 microg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers.

Adjuvants, Immunologic↗
PubMed2000

Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging.

The location and possible lateralization of structures mediating autonomic processing are not well-described in the human. Functional magnetic resonance imaging procedures were used to demonstrate signal changes in multiple brain sites during blood pressure challenges. Magnetic resonance signals in brain tissue were visualized with a 1.5 Tesla scanner in 11 healthy volunteers (22-37 years), by using echo-planar procedures. Images were collected during baseline states and three pressor challenges: cold application to the hand or forehead, and a Valsalva maneuver. Image values from experimental conditions were compared with corresponding baseline values on a voxel-by-voxel basis to identify brain regions responsive to physiologic activation. Probability maps (P < 0.01) of voxel changes, with Bonferroni corrections for multiple comparisons, were determined, and amplitude of signal changes associated with significance maps were pseudocolored and overlaid on anatomic images. The time courses and extent of signal alterations in defined unilateral regions were followed and compared with changes in corresponding regions on the contralateral side. Pressor challenges elicited significant regional signal intensity changes within the orbitomedial prefrontal cortex, temporal cortex, amygdala, hippocampal formation, thalamus, and hypothalamus. Cerebellar, midbrain, and pontine areas were also recruited. Signal changes, especially at forebrain sites, were often highly lateralized. The findings indicate that (1) transient, behaviorally-coupled cardiovascular challenges elicit discrete activity changes over multiple brain sites, and (2) these activity changes, especially in specific prefrontal and temporal forebrain regions and cerebellum, are often expressed unilaterally, even to a bilateral challenge.

Adult↗
PubMed1999

Acquisition of electrophysiologic signals during magnetic resonance imaging.

We describe a low cost system for acquiring electrophysiological signals during magnetic resonance imaging. The system consists of high common-mode-rejection and low noise operational amplifiers, coupled by fiber optic cables to a receiver located at the periphery of the magnetic field. The system minimizes noise introduction which would contaminate image signals.

Electrophysiology↗
PubMed1999

Phase II trial of intraperitoneal cisplatin and mitoxantrone in patients with persistent ovarian cancer.

OBJECTIVE: The aim of this study was to determine the feasibility and efficacy of intraperitoneal cisplatin and mitoxantrone in patients with very small-volume residual disease at second-look surgery after completion of primary platinum-based intravenous chemotherapy. PATIENTS AND METHODS: Between February 1992 and February 1994, 42 patients were treated with up to five cycles of intraperitoneal cisplatin (100 mg/m2)/mitoxantrone (10 mg/m2). Patients were evaluated for surgically defined response rate and followed for progression-free (PFS) and overall survival (OS) using an intention-to-treat analysis, and grouped according to disease volume at initiation of treatment. RESULTS: The mean age of all patients was 48.5 years. Thirty patients (71%) were Stage III at diagnosis; 18 patients (43%) had microscopic disease at the initiation of IP therapy, and 24 patients (57%) had macroscopic disease. Twenty-eight patients completed three or more cycles of protocol therapy, and 14 patients were changed to standard intravenous therapy after receiving fewer than three cycles of treatment secondary to catheter-related problems (12 patients), cisplatin ototoxicity (1 patient), or withdrawal from study (1 patient). Using an intention-to-treat analysis, the median PFS was 22.5 months, and the median OS of all patients (N = 42) was 47 months (6-72 months) with a median follow-up of 62.7 months. When grouped according to size of disease at initiation of treatment, the OS has not been reached at 62.7 months of follow-up in patients (N = 18) with microscopic disease. CONCLUSIONS: (1) The combination of IP mitoxantrone and cisplatin has an unacceptable catheter failure rate due to mitoxantrone toxicity; (2) PFS and OS is longer in patients with microscopic rather than macroscopic residual disease; and (3) intraperitoneal platinum-based chemotherapy in patients with very small-volume residual disease may result in improved survival.

Adult↗
PubMed1999

Letter

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

A pilot study of melphalan, tumor necrosis factor-alpha and 41.8 degrees C whole-body hyperthermia.

PURPOSE: To evaluate the feasibilitv of sequencing (based on preclinical modeling) tumor necrosis factor-a (TNF) at two dose levels with melphalan (L-PAM) and 41.8 C whole-body hyperthermia (WBH) for 60 min. PATIENTS AND METHODS: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 microg/m2) and six patients were treated at TNF dose level II (100 microg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/ m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. RESULTS: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with <25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). CONCLUSION: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

Adult↗
PubMed1999

Whole body hyperthermia cytokine induction: a review, and unifying hypothesis for myeloprotection in the setting of cytotoxic therapy.

Whole Body Hyperthermia (WBH) enhancement of chemotherapy and/or radiation without a concomitant increase in myelosuppression has been documented in clinical trials. We propose that the biological basis for this phenomena relates in part to the previously reported induction of peripheral cytokines by WBH, that is, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and the regulatory cytokine IL-10. To further explain this myeloprotection and the additional clinical observation that WBH promotes early engraftment of bone marrow (when used as part of an allogenic bone marrow transplant preconditioning regimen) we developed a hypothesis: WBH increases peripheral IL-1 beta, IL-6, and TNF-alpha resulting in a secondary induction of IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF) in the bone marrow, for which supportive data also exists. Taken collectively, these data provide an increased understanding of the biological sequelae of fever, as well as a testable unifying hypothesis, for future antineoplastic treatment strategies.

Bone Marrow↗
PubMed1999

Implementation of disease management guidelines in patients with advanced ovarian cancer.

Individual variability in care practices traditionally has been a strong force in oncology practice in the United States. Such variability has necessarily led to inconsistencies in resource utilization and quality of care. The concept of outcomes management has grown from a recognition of this variability and from a desire to both optimize the quality of care and control costs. Disease management guidelines are based on the current best evidence and expert opinion. Designed to outline appropriate frameworks for care, guidelines reduce variability, minimize underutilization and overutilization of resources, provide compliance information, and ultimately lead to improved quality of care. Guidelines also can form a critical framework for cost estimation. The development of guidelines for salvage therapy of ovarian cancer at our institution has led to an excellent ability to estimate costs. Institution of these guidelines has led to several findings, including the realization that the use of more expensive drugs does not necessarily lead to an increase in the overall costs of care. The use of oral agents was found to be far less expensive than the use of intravenous agents, however. Efficacy analyses are ongoing. The goals for the management of advanced ovarian cancer in traditional care and managed care settings are the same: high-quality care with attention to costs. Such an approach can increase the number of patients with this challenging disease who have access to high-quality care.

Decision Making↗
PubMed1998

Prognosis of patients treated with whole-brain radiation therapy for metastatic gestational trophoblastic disease.

We evaluated the effect of multiple treatment- and disease-related variables on the outcome of patients receiving whole-brain radiation therapy (WBRT) for metastatic gestational trophoblastic disease (GTD). Between November 1967 and December 1994, 21 patients were treated at our institution for GTD metastatic to the brain. All received WBRT, of median 2200 cGy (range 200-3600 cGy). Median follow-up, from date of diagnosis of brain metastases, was 77 months (range 11-170 months). The 5-year actuarial local control of initial brain metastases with > or = 2200 cGy was 91%, compared to 24% with < 2200 cGy (P = 0.05). The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100 and 83%, respectively, compared to 8 and 0%, respectively, for the 12 whose extracranial disease was not controlled (P = 0.0002). Four (33%) of the patients with persistent or progressive extracranial disease later developed new sites of brain metastases, compared to 0% of the patients whose extracranial disease was controlled (P = 0.05). Eleven patients progressed at their initial site(s) of brain metastasis or developed new intracranial lesions; 6 of them died of brain metastases. Survival of patients with GTD metastatic to the brain is excellent if extracranial disease can be controlled. The total dose of radiation is critical in achieving control of initial brain metastases. Patients with uncontrolled extracranial disease are more likely to develop new brain metastases. Salvage of intracranial failures after WBRT is rare.

Actuarial Analysis↗
PubMed1998

Palliative benefit of external-beam radiation in the management of platinum refractory epithelial ovarian carcinoma.

In vitro studies and clinical experience have suggested that patients with platinum-refractory epithelial ovarian carcinoma exhibit cross-resistance to radiation. Salvage with radiation in these patients is rare. However, radiation is often utilized to palliate symptoms caused by these chemotherapy-resistant tumors. Forty-seven patients with platinum-refractory epithelial ovarian carcinoma were referred for palliative radiation and 33 (70%) were evaluable for response. One to four regimens of platinum-based chemotherapy (median 2.7) were given to each patient prior to radiation therapy. Of the 33 evaluable patients, 23 (69.7%) had a complete resolution of symptoms after radiation, 8 (24%) had a partial resolution, and 2 were unassessable because of unrelated medical complications. The median duration of response was 11 months (range 1-86) and closely approximated their survival. Thirteen of 33 patients (39%) obtained relief of symptoms for greater than 12 months, with 10 of 33 (30%) having symptoms controlled for 6 to 12 months. In only 10 patients (30%) was the duration of palliation less than or equal to 6 months. Four patients required reirradiation to the same area for recurrence of their symptom. External-beam radiation therapy can provide effective and durable palliation of symptoms in platinum-refractory epithelial ovarian carcinoma patients.

Adult↗
PubMed1998

A phase II trial of intraperitoneal cisplatin and etoposide as consolidation therapy in patients with Stage II-IV epithelial ovarian cancer following negative surgical assessment.

PURPOSE: To determine the efficacy of three courses of intraperitoneal (i.p.) cisplatin (CDDP) and etoposide (VP-16) as consolidation therapy following pathologically negative second-look surgical reassessment for Stage IIC-IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Between September 1988 and April 1996, 40 patients were treated with three cycles of i.p. CDDP (100 mg/m2)/VP-16 (200 mg/m2) as consolidation therapy. Survival was compared to that of a group of 46 contemporaneous patients undergoing observation only. RESULTS: Median age of the 36 eligible patients was 52 years (range 30-70 years). Stage distribution was II (3), III (31), and IV (2); histologic grade was 1 (2), 2 (7), 3 (25), and not recorded (2); and residual disease at completion of initial surgery was none/microscopic in 13/36 (36%) patients. Median age of the 46 patients who did not receive consolidation was 52 years (range, 27-80 years); stage distribution was II (18), III (26), and IV (2); histologic grade was 1 (5), 2 (12), 3 (28), and not recorded (1). With a median follow-up of 36 months in both groups, 14/36 (39%) of the protocol group have recurred compared with 25/46 (54%) of those undergoing observation alone. Median disease-free survival (DFS) for the observed patients is 28.5 months and has not been reached in the consolidation group. Disease-free survival distribution between the two groups was compared using the log-rank test and was found to be significant (P = 0.03). Multivariate analysis revealed that the only significant predictor of improved DFS was protocol treatment (P < 0.01). CONCLUSION: Intraperitoneal consolidation with CDDP/VP-16 following negative second-look reassessment in patients with advanced EOC resulted in a significant increase in DFS compared to nonprotocol patients treated concurrently who underwent observation alone.

Adult↗
PubMed1998

Chemotherapy in gynecologic cancer.

The current standard for primary chemotherapy in patients with ovarian cancer consists of platinum and taxane combination treatment. The roles of the intraperitoneal delivery of agents, and of the multiple new agents with phase II activity, are currently under investigation. Many new agents and combinations warrant further testing in the primary treatment setting. Recent advances in the treatment of cervical cancer involve the selection of agents for chemoradiation in locally advanced disease, the role of combination versus single agent therapy in recurrent disease, and the identification of a new agent with limited activity in advanced disease. Ongoing trials in patients with endometrial cancer are attempting to improve therapy for advanced disease, and are exploring the role of adjuvant chemotherapy in patients with earlier disease stages.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Regional brain activation in humans during respiratory and blood pressure challenges.

1. The aim of the present study was to determine the brain sites mediating aspects of respiratory and cardiovascular control in adult humans using non-invasive functional magnetic resonance (fMRI) procedures, thereby avoiding the spatial and temporal sampling limitations associated with classic neural assessment techniques. 2. We examined activity changes across the entire brain following application of respiratory loads and upon induction of blood pressure and heart rate alterations. Magnetic resonance signals were visualized with a 1.5 Tesla scanner in healthy volunteers (22-52 years of age) using procedures that optimally assess changes in brain tissue microcirculation. Images were collected during a Valsalva manoeuvre, inspiratory loading, hypercapnia, cold pressor challenges to the hand and forehead and during intervening baseline states. 3. Image values from experimental conditions were compared with corresponding baseline values on a pixel-by-pixel basis to identify brain regions in which the experimental conditions produced physiological activation. 4. Ventilatory and pressor challenges elicited significant changes in regional image signal intensity in areas within the orbital cortex, amygdala, hypothalamus and hippocampus. Cerebellar, medullary and pontine areas were also recruited. However, while particular brain regions were only activated during specific stimuli, other regional signal changes occurred with multiple experimental manipulations. 5. The findings indicate that respiratory and cardiac challenges elicit discrete activity changes over multiple brain sites. Activated regions include structures not often related to respiratory or cardiovascular regulation, such as the cerebellum; a prominent role for limbic forebrain structures in mediating the response is also suggested. The fMRI visualization procedures may greatly assist in the determination of neural structures that mediate respiratory and cardiovascular control in humans.

Adult↗
PubMed1998

Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors.

PURPOSE: In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction. PATIENTS AND METHODS: To maximize the opportunity for synergy, we divided the cisplatin into four consecutive weekly treatments, followed by a 2-week rest. Each dose of cisplatin was immediately followed by a dose of irinotecan. The dose of cisplatin was fixed at 30 mg/m2/wk. The initial irinotecan dose was 50 mg/m2/wk and this was escalated by 30% increments in successive cohorts of three to six patients to establish the maximum-tolerated dose (MTD). Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed. RESULTS: Of 35 patients with solid tumors enrolled onto this trial, 30 were assessable for toxicity and response. The MTD for this regimen was 30 mg/m2/wk of cisplatin plus 50 mg/m2/wk of irinotecan in previously treated patients and 30 mg/m2/wk of cisplatin plus 65 mg/m2/wk of irinotecan in chemotherapy-naive patients. Neutropenia was the dose-limiting toxicity (DLT) encountered in this trial. Diarrhea was infrequent and rarely dose-limiting. Seven of 30 assessable patients achieved a partial response. No alteration in irinotecan, SN-38, or SN-38G pharmacokinetics resulted from the administration of cisplatin with irinotecan. CONCLUSION: The administration of cisplatin and irinotecan on this weekly schedule provides a practical and well-tolerated regimen that has the potential to maximize any clinical synergy between the two agents. Evidence of substantial clinical activity was seen in this phase I study.

Adult↗