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Biomedical subjects

T J Perren

Publications and source records attributed to T J Perren.

48 records · Page 3Linked to original sources
PubMed1988

Prevention of herpes zoster in patients by long-term oral acyclovir after allogeneic bone marrow transplantation.

Following allogeneic bone marrow transplantation for leukemia, herpes zoster infections that are potentially severe with a high risk of dissemination develop in 30 to 50 percent of patients. Intravenous acyclovir is an effective treatment for established zoster in immunocompromised persons. Oral acyclovir has relatively low bioavailability, which has made the value of this route of administration for the treatment or prophylaxis of herpes zoster infections uncertain. In this trial, 82 patients undergoing allogeneic bone marrow transplantation for leukemia were randomly assigned to receive either intravenous acyclovir for 23 days followed by oral acyclovir for six months, or matched placebos; the random groups were well-matched in all clinical characteristics. During the six-month period of acyclovir/placebo administration, no patient receiving acyclovir developed herpes zoster, whereas six patients receiving placebo did so (p = 0.006). During the six-month follow-up, there were six cases of zoster in the treatment arm of the study and two cases in the placebo arm. Herpes zoster was not restricted to those patients who had positive evidence of antibody before transplant. This study shows that oral acyclovir is capable of preventing zoster infection during its period of administration; once the drug treatment is stopped, infections occur. In selected patients, the use of long-term oral acyclovir may be of value in preventing zoster infections during the time of greatest immunosuppression.

Acyclovir↗
PubMed1988

A new approach to the treatment of advanced high-grade non-Hodgkin's lymphoma--intensive two-phase chemotherapy.

A total of 110 patients with high-grade non-Hodgkin's lymphoma (NHL) not previously treated by chemotherapy or by radiotherapy at more than one site of disease underwent a regimen comprising an intensive 6-week initial, induction phase using vincristine, adriamycin, methotrexate, and prednisolone (VAMP) followed by the non-cross-resistant combination cyclophosphamide, etoposide, and vindesine (EEE). The median age of patients was 54 years, the majority having stage IV disease. The median follow-up was 34 months and all patients have completed treatment. The overall complete remission (CR) rate for all patients was 68%. The initial phase of treatment produced a CR rate of 49%. The full regimen was completed by 87 patients, and of these, 66 (76%) achieved CR. Of those achieving CR, 72% were relapse-free, on an actuarial basis, at 2 years. Overall 2-year survival was 53%, with a median survival of 31 months. The survival of older patients and those with lymphoblastic histology was comparable to that of other groups. The survival prospects of patients with stage IV disease was not as good as that of other patients, with a significant trend to shorter survival in patients with more advanced disease. Toxicity was predictable and manageable for both phases of the regimen, although it was more severe for the initial phase. Dose-limiting toxicities were neutropenia and mucositis. This regimen is active in the treatment of advanced high-grade NHL with acceptable toxicity. These results have encouraged us to continue the study of weekly chemotherapy, which we will compare with standard cyclical chemotherapy in a prospective, randomized trial.

Adolescent↗
PubMed1988

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma.

In a series of 22 patients, high dose BCNU (800-1,000mg m-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return. Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified.

Adult↗
PubMed1987

Multiple myeloma treated with high dose intravenous melphalan.

High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).

Adult↗
PubMed1987

Phase II study of Zoladex depot in advanced prostatic cancer with special reference to criteria of response and survival.

Zoladex is a potent decapeptide analogue of luteinising hormone releasing hormone (LHRH). The drug is formulated as a 3.6 mg depot dispersed in a matrix of d,l-lactide-glycolide copolymer, which is totally biodegradable. This formula releases drug continuously for at least 28 days and reliably suppresses serum testosterone into the castrate range. The effect of the depot was studied in 29 patients with locally advanced or metastatic carcinoma of the prostate. Average age at entry was 71 years (range 52-87) and follow-up was from 13.5 to 34.5 months (median 23). Endocrine studies showed that medical castration was maintained in all cases. Three patients experienced bone pain in the first month of treatment and two others had temporary nephrostomies for worsening ureteric obstruction. Subjective improvement was seen in 23/28 cases (82%). There were no complete responses, but partial response was seen in 24/28 (85.7%) using our own criteria, 24/28 (85.7%) using the criteria recommended by the British Prostate Group (BPG) and 15/28 (53.6%) using NPCP criteria. Stable disease was seen in 3/28 patients (10.7%) by our own or BPG criteria, and in 12/28 patients (42.9%) according to NPCP criteria. Progression of disease was measurable in 21 patients (72.4%) whatever criteria were applied; 11/29 (37.9%) have died, giving a median survival of 10 months (range 2.4-26). Following these encouraging results, a multicentre randomised comparative study with stilboestrol 3 mg daily is being undertaken.

Aged↗
PubMed1986

Pharmacokinetic and endocrinological parameters of a slow-release depot preparation of the GnRH analogue ICI 118630 (zoladex) compared with a subcutaneous bolus and continuous subcutaneous infusion of the same drug in patients with prostatic cancer.

Seventeen patients with advanced prostatic cancer were treated with the gonadotrophin-releasing hormone analogue DSer (tBU)6 AzaGly 10 GnRH (ICI 118630), either as a constant SC infusion, or in the form of a monthly SC slowrelease depot formulation, in which case patients were randomised to receive one of three doses. Six of these patients also received a 250-microgram SC bolus of ICI 118630, for pharmacokinetic studies, before starting the infusion or the depot. Drug levels were measured using a double-antibody radioimmunoassay. In contrast to the SC infusion, which gave a smooth serum 118630 level profile, drug release from the depot preparation was not constant, levels varying in a predictable manner throughout each 28-day period, reaching a peak proportional to the dose of ICI 118630 received, between days 15 and 18 of each cycle. With all methods of administration there was an initial rise in LH, usually followed by a rise in testosterone, after which the SC infusion and the depot were both effective in reducing serum LH to basal levels and testosterone into the castrate range within 1 month. It is too early to make any assessment of clinical response; however, depot treatment was well tolerated: Four patients experienced an initial flare in bone pain, probably related to the initial rise in testosterone, and twelve patients experienced flushing; one patient with pre-existing hydronephrosis and hydroureter developed renal failure, possibly related to a tumour flare reaction. No patients have experienced cardiovascular side effects or local reaction.

Buserelin↗
PubMed1985

Phase II study of vincristine, mitomycin-C and mitoxantrone in advanced breast cancer: a preliminary report of response and toxicity.

Nineteen patients with advanced, previously treated breast cancer received treatment with vincristine 2 mg i.v., mitomycin-C 6 mg/m2 and mitoxantrone (Novantrone; dihydroxyanthracenedione) 12 mg/m2 i.v. every three weeks. Thirteen patients are evaluable for response and toxicity. Partial remission was seen in six patients, with soft tissue, bone and visceral metastases and static disease in a further four patients. Median duration of response has not yet been reached (8+ months). Toxicity was mild and predictable, with no patient experiencing severe nausea and vomiting, and only four of the patients requiring a wig for alopecia. Malaise and lethargy were common in those patients receiving more than three courses, and an increase in the mean corpuscular volume (MCV) together with a fall in haemoglobin were seen in patients receiving multiple courses of treatment. The study suggests that this combination is active, and may prove useful with other agents in the treatment of breast cancer.

Adolescent↗
PubMed1985

A radioimmunoassay for GnRH agonist analogue in serum of patients with prostate cancer treated with D-Ser (tBu)6 AZA Gly10 GnRH.

A radioimmunoassay is described for D-Ser (tBu)6 AZA Gly10 GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With 125I-118630 as the label, and an anti-GnRH serum, the specificity of the assay is directed to the N-terminal end of the peptide, and putative degradation products have less than 6% cross-reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 micrograms, has a half-time of disappearance from the serum of 4.9 +/- 0.4 h and a volume of distribution of 13.7 +/- 0.8 litres. Continuous subcutaneous infusion of 120 micrograms 118630/d gave stable serum concentrations of between 2-3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the "peak and trough' pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3.6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6-8 ng/ml 15 d after the implant and fell to less than 1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3.6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long-acting formulations, but also for correlation of serum peptide concentrations with pituitary gonadotroph desensitization.

Buserelin↗
PubMed1985

Assessment of bleomycin, adriamycin and mitomycin-C in the treatment of recurrent cervical cancer.

Twenty women with recurrent squamous cell carcinoma of the cervix were treated with bleomycin followed by adriamycin and mitomycin-C. Treatment was repeated every 28 days. In 18 patients who could be assessed there was one complete response and five partial responses (response rate 33%). Two partial responses were seen in 13 lesions arising from previously irradiated sites of disease (response rate 23%). Three complete responses and three partial responses were observed in 10 lesions arising from non-previously irradiated sites of disease (response rate 60%). In all responding cases tumour regression was noted before the end of the third cycle of treatment. Toxicity was predictable and manageable. These results suggest that chemotherapy may be used as a cytoreductive procedure before radical local treatment.

Adult↗
PubMedDate not supplied

Image-guided biopsy in women with breast cancer presenting with peritoneal carcinomatosis.

When women with a history of breast cancer present with peritoneal carcinomatosis, the differential diagnosis lies between recurrent breast cancer or a new primary tumor. This scenario is of particular relevance to women with a BRCA gene mutation, who have a genetic predisposition to develop second primary tumors of the ovary, fallopian tube, and peritoneum. We describe the use of image-guided core biopsy as an alternative to laparoscopy or exploratory laparotomy in providing minimally invasive diagnosis in this increasingly common clinical dilemma.

Adenocarcinoma↗