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Biomedical subjects

S M Crawford

Publications and source records attributed to S M Crawford.

At least 19 recordsLinked to original sources
PubMed1996

Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

PURPOSE: In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS: After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS: The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION: Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effects of exercise modality on metabolic rate and body composition.

This study was designed to investigate the effects of exercise as a strategy for weight management in overweight women. Specifically, the effects of exercise modality on resting energy expenditure (REE) and body composition [sum of skinfolds and fat-free mass (FFM)] were examined. Participants included 41 overweight, sedentary women aged 25-49 years who had a defined history of dieting. Experimental (n = 26) and control (n = 15) participants were recruited separately. Participants in the experimental group were randomly assigned to either an endurance- or a resistance-training exercise class. Exercise classes designed for a sedentary population were scheduled three times per week for a duration of 3 months. Results indicated that exercise modality had no effect on REE. Exercise, regardless of modality, had a significant effect on body composition (p = 0.0001) as shown by a significant decrease in the sum of skinfolds for the two exercise groups relative to the control group (p < 0.0001). No differences in fat-free mass were observed between groups. Regardless of modality, exercise also resulted in an increased estimated maximum oxygen uptake (VO2max), based on a 1-mile walking test (p = 0.012). The pattern of weight change of the groups was different (p = 0.029) over the 3-month period. Whereas the exercise groups maintained their weight, the control group gained weight (approximately 2.5 kg). Thus, although exercise modality had no effect, the benefits of exercise per se, such as decreased body fat, increased fitness level, and weight maintenance, were observed in this population.

Adult↗
PubMed1994

Determination of altretamine in human plasma with high-performance liquid chromatography.

A fast, simple, and sensitive isocratic HPLC method has been developed and validated for the determination of the anticancer drug altretamine in human plasma. Spiked serum samples and clinical plasma samples are extracted with acetonitrile at 4 degrees C and the precipitate removed by filtration. The plasma sample volume required (ca. 0.2 ml) is small and the total analysis time is less than 15 min per sample (including batch-wise pre-treatment). Recovery of altretamine is 99 to 106% for pooled human serum spiked with altretamine in the range 200 ng/ml to 10 mg/ml. In this concentration range, the R.S.D. varies from 1 to 8%. The limit of quantitation is ca. 150 ng/ml for an R.S.D. of 10%. The intra-day R.S.D. for human samples spiked at 5 mg/ml varied between 1.7 and 4%; the inter-day R.S.D. at this concentration was ca. 3%. A preliminary study with one patient receiving 260 mg/m2 by mouth indicated that the peak altretamine concentration was significantly lower after a standard breakfast than in the fasting state.

Altretamine↗
PubMed1994

Growth characteristics of early passage cell lines compared with established TCC bladder lines.

The growth patterns of established cell lines from bladder transitional cell carcinoma (TCC) were compared with early passage cell lines. The growth of established cell line 5637 was uninhibited in both serum free (basal) and serum containing media. The early passage line (DR) grew only in serum containing medium. This confirms the unreliability of results from biological studies on established (continuous) cell lines.

Carcinoma, Transitional Cell↗
PubMed1994

Cushing's syndrome associated with recurrent endometrioid adenocarcinoma of the ovary.

Ectopic production of adrenocorticotrophic hormone (ACTH) by malignant neoplasms is a well recognised cause of Cushing's syndrome but is extremely rare in ovarian carcinoma. A patient who underwent surgery for ovarian carcinoma followed by a course of chemotherapy is reported. The tumour was a bilateral moderately differentiated endometrioid adenocarcinoma and contained numerous chromogranin immunoreactive endocrine cells as well as small foci of ACTH immunoreactivity. She subsequently presented with Cushing's syndrome in association with extensive pelvic recurrence of the tumour.

Carcinoma, Endometrioid↗
PubMed1993

Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody.

BACKGROUND: Many patients with non-Hodgkin's lymphomas are not cured by current therapies, and new approaches to treatment are needed. As part of an ongoing phase 1 study, we examined the effect of radioimmunotherapy with 131I-labeled B-cell-specific anti-CD20 monoclonal antibody in 10 patients with CD20-positive B-cell lymphomas in whom primary chemotherapy had failed. METHODS AND RESULTS: Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with 131I (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, without pretreatment with unlabeled anti-B1 antibody, to all 10 patients; then, with pretreatment with 135 mg of unlabeled antibody, to 8 patients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactivity were obtained after each tracer dose. All known disease sites larger than 2 cm could be imaged. The effect of a pretreatment dose of unlabeled anti-B1 antibody on targeting of the tumor with the radiolabeled antibody was variable. The pretreatment dose of unlabeled antibody that produced the highest ratio of the tumor dose to the whole-body dose in tracer studies was then used to deliver higher doses of radioactivity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treated twice, six to eight weeks apart), four patients received 35 cGy (one patient treated twice), and two patients received 45 cGy (one patient treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients with bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objective responses to tracer infusions before they received radioimmunotherapeutic doses. Of the four patients with complete remissions, one remained in remission for eight months and the other three continue to have no disease progression (for 11, 9, and 8 months). There was mild or no myelosuppression. CONCLUSIONS: Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.

Adult↗
PubMed1992

Phase II trials of fosquidone, (GR63178A), in colorectal, renal and non-small cell lung cancer. CRC Phase II Clinical Trials Committee.

A total of 61 eligible patients with metastatic cancer have been treated in a series of Phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were colorectal (23), renal (21), and non small cell lung (17). No patient had received prior chemotherapy. The drug was given intravenously as a 20 min infusion at the dose of 120 mg-2 on days 1 to 5 every 3 weeks. Treatment was well tolerated; the only significant side effects being mild nausea and generalised musculo-skeletal pains. Response was assessed after two cycles of therapy. No patient achieved an objective partial response. A total of nine patients demonstrated stable disease for a median duration of 11 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.

Adult↗
PubMed1992

The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours.

We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed.

Adenocarcinoma↗
PubMed1992

Metabolic and anthropometric changes with weight cycling in wrestlers.

Repeated cycles of weight loss and regain have come to be known as weight cycling. This phenomenon is frequently observed in athletes who must meet specific weight categories to qualify for competition. The purpose of this study was to determine the metabolic and anthropometric changes that occur with rapid weight loss/regain cycles in competitive wrestlers. Collegiate wrestlers were divided into two groups, "cyclers" (N = 8) and "noncyclers" (N = 6), based on their reported dieting history. Measurements included a 3-d diet record, resting energy expenditure (REE), skinfold and girth measures, and biochemical tests at three time points: preseason, peak season, and off-season. All anthropometric measures changed with time, and a diet group by time interaction was observed for the trunk to extremity skinfolds ratio (T/E) (P < 0.05), with greater fat loss and regain from the trunk area of the cyclers. There were no differences in REE within or between groups. Serum triiodothyronine (T3) values decreased over time (P < 0.01). Large weight losses appear to have occurred due to both dieting and short-term dehydration, and although physiological changes were observed, a training effect may have overridden any metabolic influence of weight cycling.

Adult↗
PubMed1990

A phase I/II study of the 5-HT3 antagonist GR38032F in the anti-emetic prophylaxis of patients receiving high-dose cisplatin chemotherapy.

A total of 24 patients who were receiving combination chemotherapy (POMB) including cisplatin at a dose of 100-120 mg/m2 were treated with the 5HT3 antagonist GR38032F (GR) as an anti-emetic prophylaxis. GR was given as a 15-min loading infusion followed by a 24-h infusion at three escalating dose levels of 1, 2 and 4 mg/h. In the first 24 h after commencing treatment, six patients had complete control of nausea and vomiting (CR), two had 1-2 emetic episodes (MR) and five had 3-5 emetic episodes (mR). The major response rate (CR + MR) was thus 35%. Eight responding patients (CR or MR) went on to receive oral GR at 8 or 12 mg t.i.d. for 5 days. In this group there was one CR, one MR, two mRs and four failures (F). There was no evidence of an improved therapeutic effect with increasing dose in either the infusion or the oral section of the study, although numbers were limited in the latter part of the trial. Toxicity was mild, with low-grade headache affecting 25% of patients being the most frequent side effect. Pharmacokinetic data was obtained in six patients at each dose level. There was a progressive rise in clearance with increasing dose, indicating that the kinetics are non-linear. However, there was no evidence of an association between high plasma levels and therapeutic efficacy. GR38032F is well tolerated and has promising single-agent activity in preventing vomiting induced by high-dose cisplatin.

Adult↗
PubMed1990

Treatment of bladder carcinoma using a germ cell chemotherapy protocol.

Elevated levels of circulating beta-human chorionic gonadotrophin (beta-HCG) are commonly associated with a variety of tumours of germ cell origin. Other carcinomas may possess choriocarcinomatous elements but only rarely have there been reports of transitional cell carcinomas of the bladder associated with raised germ cell tumour markers, possibly because assays are not routinely performed. We present 3 patients with advanced transitional cell carcinoma of the bladder, 2 with metastatic and 1 with locally invasive disease, who had raised levels of germ cell tumour markers. These patients were therefore treated with combination chemotherapy appropriate to such tumours, with excellent results, as shown by clinical improvement and return to normal of tumour marker levels. Recent reports of the association between bladder carcinoma and ectopic synthesis of beta-HCG are reviewed. It was concluded that the production of beta-HCG is probably not rare, but that when it is found, the adoption of an appropriate chemotherapeutic regime may be successful.

Antineoplastic Combined Chemotherapy Protocols↗