PubMed Health⌕ Search

Biomedical subjects

A J Neville

Publications and source records attributed to A J Neville.

At least 19 recordsLinked to original sources
PubMed2001

A retrospective analysis of the relationship between changes in serum PSA, palliative response and survival following systemic treatment in a Canadian randomized trial for symptomatic hormone-refractory prostate cancer.

BACKGROUND: To investigate the relationship between changes in serum PSA, palliative response and survival following systemic treatment for symptomatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A retrospective review of 161 patients, treated with mitoxantrone and prednisone (M + P) (n = 80), or prednisone alone (P) (n = 81) from a Canadian randomized phase III clinical trial. PSA response was defined by > or =50% decline compared to baseline. Palliative response was defined by the primary and secondary endpoints of the trial. All responses were required to be maintained on two visits at least three weeks apart. The Cox proportional hazards model and a landmark analysis (at nine weeks) were used to evaluate survival differences between PSA responders and non-responders. RESULTS: Using an intent-to-treat analysis in which patients with missing PSA data are considered non-responders, 34% of M + P and 11% of P patients achieved a PSA response (P = 0.0001). Nineteen of thirty-six (53%) patients with PSA response and twenty-six of ninety (29%) patients without PSA response achieved a palliative response (P = 0.001 Chi-square test, phi coefficient = 0.28). From the landmark analysis. PSA responders had longer survival than non-responders (P = 0.009). In multivariate analysis, better performance status, higher hemoglobin and PSA response (P < 0.001) predicted for survival, but palliative response did not (P = 0.11). CONCLUSIONS: There is significant but imperfect statistical association between PSA response and palliative response. PSA response was associated with longer survival. Patients treated with M + P were more likely to achieve a PSA response and a palliative response than those treated with P.

Aged↗
PubMed1999

Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone.

PURPOSE: A combination of mitoxantrone plus prednisone is preferable to prednisone alone for reduction of pain in men with metastatic, hormone-resistant, prostate cancer. The purpose of this study was to assess the effects of these treatments on health-related quality of life (HQL). PATIENTS AND METHODS: Men with metastatic prostate cancer (n = 161) were randomized to receive either daily prednisone alone or mitoxantrone (every 3 weeks) plus prednisone. Those who received prednisone alone could have mitoxantrone added after 6 weeks if there was no improvement in pain. HQL was assessed before treatment initiation and then every 3 weeks using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ-C30) and the Quality of Life Module-Prostate 14 (QOLM-P14), a trial-specific module developed for this study. An intent-to-treat analysis was used to determine the mean duration of HQL improvement and differences in improvement duration between groups of patients. RESULTS: At 6 weeks, both groups showed improvement in several HQL domains, and only physical functioning and pain were better in the mitoxantrone-plus-prednisone group than in the prednisone-alone group. After 6 weeks, patients taking prednisone showed no improvement in HQL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P =.009), four functioning domains, and nine symptoms (.001 < P <. 01), and the improvement (> 10 units on a scale of 0 to100) lasted longer than in the prednisone-alone group (.004 < P <.05). The addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (.001 < P <.003). CONCLUSION: Treatment with mitoxantrone plus prednisone was associated with greater and longer-lasting improvement in several HQL domains and symptoms than treatment with prednisone alone.

Adenocarcinoma↗
PubMed1996

Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.

PURPOSE: To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. PATIENTS AND METHODS: We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. RESULTS: Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. CONCLUSION: Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Adenocarcinoma↗
PubMed1990

Effect of whole-body hyperthermia on hepatic cytochrome P450.

Currently, the combination of hyperthermia with a variety of chemotherapeutic agents and cytokines for the treatment of disseminated human malignancy is being examined. In this study we investigated the effects of 41 degrees-42 degrees C whole-body hyperthermia (WBH) and the cytokine interleukin-1 (IL-1) on cytochrome P450 in mice. At 24 h following 1 h of 41 degrees-42 degrees C WBH, IL-1 or combined treatment, hepatic microsomal cytochrome b5 and aminopyrine N-demethylation were assayed. Cytochrome b5 activity was not significantly diminished by WBH, IL-1 or WBH + IL-1, but N-demethylation was suppressed by the combination of WBH + IL-1 and, to a lesser extent, by WBH alone.

Animals↗
PubMed1990

Adjunctive therapy (whole body hyperthermia versus lonidamine) to total body irradiation for the treatment of favorable B-cell neoplasms: a report of two pilot clinical trials and laboratory investigations.

Based on earlier clinical and preclinical investigations, we designed two different pilot trials for patients with nodular lymphoma or chronic lymphocytic leukemia. These studies evaluated the use of either 41.8 degrees C whole body hyperthermia (WBH), or the nonmyelosuppressive chemotherapeutic drug, lonidamine (LON), as an adjunct to total body irradiation (TBI) (12.5 cGy twice a week, every other week for a planned total dose of 150 cGy). Whole body hyperthermia was initiated approximately 10 min after total body irradiation; lonidamine was administered orally (420 mg/m2) on a daily basis. Although entry to the studies was nonrandomized, the two patient populations were accrued during the same time frame and were comparable in terms of histology, stage of disease, performance status, and prior therapy. Of 8 patients entered on the TBI/WBH study, we observed 3 complete responses (CR), 4 partial responses (PR), and 1 improvement (i.e., a 48% decrease in tumor burden). Of 10 patients entered in the TBI/LON study, there was 1 CR and 4 PR. For the TBI/WBH study, myelosuppression was not treatment-limiting; there were no instances of infection or bleeding and platelet support was never required. The median survival time for the TBI/WBH study is 52.5 months based on Kaplan Meir estimates. Two patients remain in a CR. The median time to treatment failure (MTTF) is 9.4 months (90% confidence interval = 7-15.4 months). In the TBI/LON study, 50% of patients receiving TBI required treatment modification due to platelet-count depression during therapy, but there were no instances of infection or bleeding. Frequently observed LON-related toxicities included myalgias, testicular pain, photophobia and ototoxicity. For the TBI/LON study, median survival is 7.6 months; MTTF was 2.4 months. In analyzing the results of these pilot studies, our subjective clinical impressions lead to the hypothesis that WBH protected against TBI-induced thrombocytopenia during therapy, whereas LON had no effect on TBI-induced myelosuppression. This speculation was tested and confirmed in a series of in vitro and in vivo experiments.

Adult↗
PubMed1988

Phase I trial of lonidamine with whole body hyperthermia in advanced cancer.

Lonidamine is a dechlorinated derivative of indazole-3-carboxylic acid which preclinically synergizes with hyperthermia. Clinically, this nonmyelosuppressive drug (given p.o. daily) is active as a single agent in a variety of malignancies. On this basis, a Phase I study which incorporates a drug escalation schema as well as an escalation in temperature, i.e., 41.0 degrees C for 85 min to 41.8 degrees C for 75 min, was executed. Induction therapy included seven whole-body hyperthermia treatments. Whole-body hyperthermia was delivered using a radiant heat system. Twenty-four patients were entered on study. Of these, 20 were evaluable for response. Group A (60 mg/m2) had three patients with three no responses. Group B (180 mg/m2) consisted of three patients: one lymphoma, partial response; two gastrointestinal adenocarcinomas, one partial response and one improvement, i.e., less than a partial response. Group C (360 mg/m2) had 17 patients: two lung cancers, one complete response and one improvement; one melanoma, improvement; one ovarian, disease stabilization (greater than 100 days); two adenocarcinomas of the gastrointestinal tract, two disease stabilizations; 11 patients, no responses; one patient entered at this level was ineligible for study and did not receive lonidamine. Therapy was well tolerated. Of 16 patients reporting myalgias, two required a lonidamine dose reduction; one patient required dose reduction for central nervous system toxicity. Results obtained encourage Phase II clinical trials.

Adult↗
PubMed1988

A pilot study of whole body hyperthermia and local irradiation for advanced non-small cell lung cancer confined to the thorax.

Six patients with Stage III non-small cell lung cancer completed therapy which consisted of 4 whole body hyperthermia (WBH) treatments during the first 2 weeks of a 6 week course of radiotherapy (60 Gy). A radiant heat system was used to deliver the 41.8 degree C WBH. To reduce the danger of transverse myelitis, the spinal cord (and therefore part of the mediastinum and contralateral hilar region) was not irradiated during the first 2 weeks of radiotherapy and concurrent WBH. Subsequent treatments (weeks 3-6) included conventional irradiation to the primary tumor, mediastinal lymph nodes and spinal cord. Areas of gross disease responded to therapy in 5/6 patients. No radiation pneumonitis was observed. In 2/6 patients, relapse (after 10 months and 6 months, respectively) occurred with malignant pericardial effusions. The mediastinum in these patients was not an area of bulky disease involvement initially. To eliminate such WBH-radiation sanctuary zones, the protocol was modified to include greater combined WBH-radiation treatment. This is accomplished by having one WBH treatment "sandwiched" between 2 radiation fractions. The preclinical basis for the revised protocol is presented.

Adult↗
PubMed1988

Whole body hyperthermia (41-42 degrees C) induces interleukin-1 in vivo.

The role of endogenous mediated fever and exogenous hyperthermia as modulators of immunological processes against infection and neoplasms remains poorly understood. Hyperthermia appears to modulate the activity of a number of immunological cytokines including Interleukin-1 (IL-1). Using a recently developed Radiant Heat technology for safely producing 41-42 degrees C Whole Body Hyperthermia in mice, we have investigated the effect of 1 hour of 41 +/- 0.5 degrees C WBH on the production of cutaneous IL-1. After a transient fall in IL-1 production 4 hours post WBH, significant elevations (up to twice control levels) were noted with a peak at 16-20 hours post WBH. IL-1 levels remained elevated for 5-6 days post-WBH. The potential clinical significance of this finding is discussed with particular reference to human malignant melanoma.

Animals↗
PubMed1987

Rise in plasma beta-endorphin, ACTH, and cortisol in cancer patients undergoing whole body hyperthermia.

It has been previously reported that sauna-induced fevers (approximately 39 degrees C) result in rises of beta-endorphins in normal volunteers. This report describes changes in plasma beta-endorphins in cancer patients undergoing whole body hyperthermia (40.5 degrees C to 41.8 degrees C). Results presented show that there is a linear relationship between thermal stress, defined in terms of core temperature and/or duration of hyperthermia, and the quantitative rise in plasma beta-endorphin levels. Data relating to changes in ACTH and cortisol levels are in a single temperature range (41.5 degrees C--41.8 degrees C) are also reported.

Adolescent↗
PubMed1987

Phase II trial evaluating continuous infusion of etoposide, cisplatin, and hexamethylmelamine in extensive-disease small cell carcinoma of the lung.

A total of 27 untreated and 24 previously treated patients with extensive-disease small cell lung cancer (SCLC) were treated with a combination chemotherapeutic regimen of continuous-infusion etoposide for 5 days, cisplatin, and hexamethylmelamine. of 25 evaluable patients with untreated SCLC, three (12%) achieved a complete response and 16 (64%) achieved a partial response. Among 23 evaluable patients with relapsed SCLC there were no complete responses and nine (39%) achieved a partial response. Median survival times were 252 and 109 days for the above groups, respectively. Myelotoxicity, especially thrombocytopenia, was moderately severe. Other toxic effects, including renal and neurologic, were minimal. These results compare favorably with other regimens including etoposide and cisplatin. Our results further confirm the activity of etoposide and cisplatin as both initial therapy and as a salvage regimen in the management of patients with extensive-stage SCLC.

Adult↗
PubMed1985

A nontoxic system for 41.8 degrees C whole-body hyperthermia: results of a Phase I study using a radiant heat device.

A Phase I study of whole-body hyperthermia (WBH) (52 treatments/12 patients) was completed with no significant clinical toxicity. The study incorporated a thermal dose escalation scheme from 39.5 degrees-41.8 degrees C for up to 151 min. A radiant-heat device was utilized for producing WBH. During WBH, patients were sedated; endotracheal intubation was not required. No changes in cardiovascular, respiratory, hematological, or biochemical indices requiring clinical intervention occurred during the study. We conclude the radiant-heat device coupled with a defined pharmacological approach to WBH with appropriate patient screening yields a system for 41.8 degrees C WBH which is safe and efficient, is not labor intensive, and does not require general anesthesia and endotracheal intubation. This system is appropriate for a multimodality approach to various systemic cancers.

Adolescent↗
PubMed1985

Massive skeletal muscle invasion by lymphoma.

Three patients had diffuse enlargement of skeletal muscle of the thigh as the result of infiltration by diffuse large-cell lymphoma. One case presented de novo as diffuse lymphoma, but the other two had previous diagnoses of nodular lymphoma and Hodgkin's disease. Computed tomographic scanning disclosed an enhancing mass in the thigh with infiltration of skeletal muscle groups; abnormal medullary cavities were noted in the adjacent long bones. Muscle biopsy established the diagnosis in two of the patients.

Adult↗
PubMed1984

The chemotherapy of granulosa cell tumors of the ovary: experience of the Wisconsin Clinical Cancer Center.

We reviewed the clinical records of 32 patients with granulosa cell tumor of the ovary treated at the Wisconsin Clinical Cancer Center (WCCC) between 1970 and 1982. Eleven of these patients were treated with one or more chemotherapeutic regimens, yielding a total of 22 treatment trials. Objective response was observed in 7 of 17 evaluable treatment trials (41%). The response to chemotherapy could not be assessed in five treatment trials due to the concomitant administration of radiotherapy. We conclude that granulosa cell tumor of the ovary is responsive to chemotherapy. However, the optimal chemotherapeutic regimen for this rare neoplasm remains to be established on the basis of prospective clinical trials.

Adult↗