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Biomedical subjects

P Selby

Publications and source records attributed to P Selby.

At least 109 records · Page 6Linked to original sources
PubMed1990

ChlVPP combination chemotherapy for Hodgkin's disease: long-term results.

Two hundred and eighty-four patients with advanced Hodgkin's disease (HD) (stage II with poor prognostic features and stage III/IV) have been treated with the ChlVPP combination chemotherapy regimen (chlorambucil, vinblastine, procarbazine and prednisolone) in a single-centre unselected series. Median follow up is 92 months. Fifty-five patients had previously received radiotherapy but none had received previous chemotherapy. Eighty-five per cent of previously untreated patients and 91% of previously irradiated patients entered complete remission (CR); 71% and 68% of these respectively remain in CR at 10 years and 65% and 64% of each group respectively are alive at 10 years. On univariate analysis, age, stage, site of visceral disease and lymphocyte count predicted survival and on multivariate analysis age, absence of symptoms, absence of lung, liver or bone marrow disease and achieving a CR remained important predictors of survival. Acute toxicity was mild. The 10 year actuarial risk of acute leukaemia was 2.7%. This study adds further support to the view that chlorambucil is as effective and less toxic than mustine in combination chemotherapy for HD. We suggest that MOPP chemotherapy is no longer routinely indicated for HD.

Adolescent↗
PubMed1990

Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo.

The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation.

Animals↗
PubMed1990

Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit.

In a consecutive series of studies, 164 patients with symptomatic and/or visceral metastatic malignant melanoma were treated with single agent vindesine, high dose melphalan with autologous bone marrow transplantation (AMBT), high dose BCNU with ABMT or the BOLD (bleomycin, vincristine, CCNU and DTIC) combination. The high dose treatments and the combination chemotherapy resulted in significantly higher response rates but no prolongation of survival. Factors associated with longer survival included the absence of visceral metastases, the absence of bulky disease and good performance status. For all treatments, life table estimates of survival at 1 and 2 years were only 10% and 4% respectively.

Adolescent↗
PubMed1989

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.

Adolescent↗
PubMed1989

Clinical applications of tumour necrosis factor.

Tumour necrosis factor (TNF) is a polypeptide hormone produced in vivo by activated macrophages and lymphocytes. TNF has diverse effects in vivo and has a physiological role as an immune modulator, as a mediator of the immune response, both through activation of neutrophils and eosinophils, and also affects the vascular endothelium. TNF also has antiviral activity and causes alterations in lipid metabolism. In disease states excessive production of TNF may have adverse affects. TNF has been implicated as a mediator of endotoxic shock, inflammatory joint disease, immune deficiency states, allograft rejection, and in the cachexia associated with malignant disease and some parasitic infections. When used in pharmacological doses, TNF is cytotoxic to many malignant cells in vitro and in vivo. The mechanisms underlying cytotoxicity are not fully elucidated but involve both a direct toxic effect to the cell and an indirect effect on tumour vasculature. Cytotoxicity is not universal and TNF may act as a differentiating agent or growth factor for some haematological cell types. So far the clinical application of TNF has been as a treatment for cancer in Phase I and II trials in patients with advanced disease and its efficacy here is still unproven. TNF may have potential for clinical application in combination therapy for cancer. There is experimental evidence for its interaction with other biological agents and cytotoxic drugs. The use of specific antibodies to inhibit production of TNF, or other agents to antagonise the toxic effects of TNF may have clinical relevance in counteracting septic shock and the clinical manifestations of TNF in inflammatory and neoplastic disease.

Animals↗
PubMed1989

High dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease.

Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140 mg m-2 and the dose of BCNU from 300 to 600 mg m-2. The response rate was 76% with 53% complete remission. Forty-five per cent of the patients are free of disease at 4-20 months follow-up. There were eight (26%) treatment-related deaths due to lung damage (seven cases) and irreversible cardiac failure (one case). Fatal lung damage occurred only in patients receiving 600 mg m-2 of BCNU with high dose melphalan. The dose of BCNU given with high dose melphalan should not exceed 500 mg m-2. This treatment is effective against relapsed Hodgkin's disease but must be used cautiously. The best time for its use remains to be determined.

Adolescent↗
PubMed1989

Cytomegalovirus pneumonia: the use of ganciclovir in marrow transplant recipients.

Sixteen bone marrow transplant recipients with cytomegalovirus pneumonia diagnosed by rapid, non-invasive methods were treated with ganciclovir. Seven patients survived the acute infection and there were five long term survivors. Excellent in-vivo suppression of cytomegalovirus was observed. Marrow toxicity was noted in four patients but was rapidly reversible and not life threatening. Clinical features common to surviving patients included good clinical condition, insidious development of infection and evidence of normal alveolar gas exchange. The fulminant onset of symptoms, radiographic abnormalities and hypoxaemia were characteristic of non-survivors. These results offer some encouragement towards further study of ganciclovir for the early treatment of cytomegalovirus pneumonia. To identify such patients, the use of rapid diagnostic methods and aggressive viral surveillance is recommended. Convincing evidence for the efficacy of this drug will only emerge from randomized prospective studies.

Acyclovir↗
PubMed1989

Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women.

We compared the effect of administering oestradiol via the transdermal or oral routes in six and eight postmenopausal women respectively. Although both treatments achieved similar plasma levels of oestradiol, oral administration led to much greater increases in plasma levels of oestrone and the sulphates and glucuronides of oestradiol, oestrone and oestriol than transdermal treatment (P less than 0.001). Both treatments reduced plasma FSH; from 42 +/- 10 (SE) IU/l to 30 +/- 2 IU/l with oral and from 46 +/- 7 IU/l to 28 +/- 6 IU/l with transdermal treatment. Urine calcium excretion fell from 0.41 +/- 0.06 (molar ratio to creatinine) to 0.17 +/- 0.02 with oral and from 0.25 +/- 0.06 to 0.13 +/- 0.02 with transdermal treatment. Patients' symptoms were improved by both treatments. These changes were related to the plasma oestradiol concentration but not to that of oestrone. Oral, but not transdermal, treatment stimulated hepatic protein synthesis as shown by increased plasma levels of both vitamin-D-binding globulin and sex-hormone-binding globulin. We conclude that although both oral and transdermal oestradiol reduce postmenopausal bone loss, gonadotrophin secretion and symptoms, oral treatment also leads to hepatic stimulation and extensive metabolism of oestradiol, both of which may increase side-effects without conferring additional benefit.

Administration, Oral↗
PubMed1989

Tumour necrosis factor: clinical relevance.

The anticancer effect of tumour necrosis factor (TNF) in murine tumours and in vitro has stimulated great enthusiasm for investigating its possible therapeutic role in humans. Results have now indicated that 400-800 micrograms ng/m2 of TNF may be given to patients and further dose increases are limited by hypotension and hepatic damage. At this dose, no consistent anticancer effects have yet been seen and measurement of TNF serum concentrations suggests that these effects are less than those required to induce regression of mouse tumours. TNF as a single agent is unlikely to have a major role in the treatment of cancer in humans and further studies will explore combination with other agents. During the investigation of the clinical role of TNF, observations have clarified its biological role as a mediator of inflammation and shock, cachexia and organ dysfunction.

Animals↗
PubMed1988

Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients.

Forty-five patients with relapsed or refractory multiple myeloma received continuous infusions of vincristine (0.4 mg total dose daily for 4 days) and adriamycin (9 mg m-2 daily for 4 days) with a high dose of methylprednisolone (1 g m-2 i.v. or p.o. daily by 1 h infusion), the VAMP regimen. Sixteen (36%) responded, with a median duration of remission of 11 months and median survival of 20 months. Major toxicities encountered were infective and cardiovascular. Two smaller groups of myeloma patients were treated with high dose methylprednisolone (HDMP) alone, or VAMP plus weekly low dose cyclophosphamide (Cyclo-VAMP). HDMP produced short responses in 25% of patients with less toxicity than VAMP. Cyclo-VAMP was used in a highly selected group of patients who had previously responded to high dose melphalan. It was well tolerated and produced responses in 61% of this group.

Adult↗