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Biomedical subjects

C Viner

Publications and source records attributed to C Viner.

16 recordsLinked to original sources
PubMed1992

Gut protection by cyclophosphamide "priming" in patients receiving high-dose melphalan--effect of drug scheduling.

A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan.

Bone Marrow Transplantation↗
PubMed1992

A randomised phase II study of carmustine alone or in combination with tumour necrosis factor in patients with advanced melanoma.

Laboratory data suggest a synergistic interaction between carmustine (BCNU) and tumour necrosis factor (TNF) in melanoma. We therefore studied the activity of 200 mg/m2 BCNU given alone or in combination with 88 micrograms/m2 recombinant human TNF-alpha (rhTNF alpha) as a daily i.v. infusion for 5 days at 48-day intervals to patients with metastatic melanoma. In this randomised phase II trial, the rate of response to BCNU alone was 20% [95% confidence interval (CI), 2%-38%], and this was not improved by the addition of TNF (response rate, 10.5%; 95% CI, 1.3%-33%). Toxicity was higher in the combination arm, and there was no difference in survival.

Adolescent↗
PubMed1992

High-dose chemotherapy and autologous bone marrow transplantation for relapsed and refractory Hodgkin's disease.

The results of high-dose chemotherapy with melphalan or melphalan (carmustine) etoposide for 66 consecutive patients with relapsed or resistant Hodgkin's disease are described. 55 patients were evaluable for response and 22% of these achieved complete remission and 59% partial remission. The actuarial survival at 2 years was 45% and the principal factors determining survival were the sensitivity of the disease to therapy given before high-dose chemotherapy and the type of treatment received. Intensive chemotherapy with autologous bone marrow transplantation can produce long-term survivors among patients for whom long-term survival would otherwise be improbable. However, this treatment remains toxic with an uncertain place in management.

Adolescent↗
PubMed1992

High-dose busulfan in patients with myeloma.

PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS: Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS: Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.

Adult↗
PubMed1990

Colony stimulating activity in the serum of patients with multiple myeloma is enhanced by interleukin 3: a possible role for interleukin 3 after high dose melphalan and autologous bone marrow transplantation for multiple myeloma.

Sera from 36/37 multiple myeloma patients and 19/21 sera from patients with other solid or liquid tumours had granulocyte-macrophage colony stimulating activity (CSA) towards normal human donor bone marrow whereas 1/16 sera from normal donors had this activity. Unlike human rhGM-CSF and GM-CSF from 5637 (human bladder cell line) conditioned medium which is heat stable, CSA from serum is heat labile (56 degrees C/30 min). In multiple myeloma patients, CSA was detectable more than 2 years after treatment with 'high dose melphalan. Although multiple myeloma patients, at relapse, have sufficient CSA in their serum to produce maximal stimulation of GM-CFUc from normal donor bone marrow in vitro, their own GM population responds poorly. The results suggest that the failure of patients own bone marrow to respond to endogenous CSA may be due to damage to the stem cells of the marrow or the failure of precursor cells to respond to CSA. Addition of rhIL-3 to myelomatous serum increased the number of GM-CFUc from both normal and myelomatous bone marrow but did not stimulate the growth of MY-CFUc significantly. The results suggest that rhIL-3 may assist bone marrow recovery in multiple myeloma patients after intensive chemotherapy.

Bone Marrow↗
PubMed1989

Intensive treatment of multiple myeloma and criteria for complete remission.

50 previously untreated patients with multiple myeloma received two-phase treatment: repeated cycles of 4 day infusion with vincristine, doxorubicin, and methylprednisolone (VAMP) followed by high-dose melphalan (HDM), with autologous bone marrow transplantation where possible. The overall response rate was 74% (37/50), with 25 patients (50%) achieving complete haematological and biochemical remission. These remissions were associated with a good quality of life as measured by performance status, pain grade, and the reversal of humoral immunosuppression. 6 patients died during the VAMP phase and there was 1 death related to HDM. The achievement of complete remission, as defined here, in such a high proportion of patients is exceptional and may represent a useful advance in the management of myeloma.

Adult↗
PubMed1989

High-dose chemotherapy and autologous bone marrow transplantation for myeloma.

In three studies we have attempted to increase the complete remission rate in a series of patients with multiple myeloma under the age of 69. A CR rate of 27% was seen in 63 patients treated with intravenous high-dose melphalan 140 m/m2 with or without the addition of high-dose methyl prednisolone 1 g/m2 for 5 days (in 22 patients). In a third study a CR rate of 50% was seen in 50 patients treated in a programme in which vincristine, adriamycin and methyl prednisolone was first given and patients then received high-dose melphalan 140-200 mg/m2 with an autologous bone marrow transplant where possible. Median remission duration in the first two studies was 19 months with a median survival of 5 years. A definition of complete remission in myeloma is proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

VAMP followed by high dose melphalan and autologous bone marrow transplantation for multiple myeloma.

Fifty previously untreated patients with myeloma were entered into a 2-phase treatment programme: vincristine, adriamycin and methyl prednisolone (VAMP) followed by high dose intravenous melphalan (HDM) with autologous bone marrow transplantation where possible. The complete remission rate of 50% was associated with very good quality of life and the reversal of humoral immunosuppression. Complete remission is important in younger patients with myeloma as it represents a first step in achieving long, symptom- free survival.

Adult↗
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↗
PubMed1987

Tumour necrosis factor in man: clinical and biological observations.

Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 10(5) units (400 micrograms)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of approximately 20 minutes but non-linear pharmacokinetics lymphoma, improvements in their tumours were recorded. RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients. TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock.

Adolescent↗
PubMedDate not supplied

Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone.

A study of 32 patients receiving cyclophosphamide (CY) and verapamil (VER) in addition to the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) was made in which the clinical response and growth of clonogenic myeloma cells (MY-CFUc) from bone marrow aspirates were compared. At presentation, MY-CFUc were grown from 72 per cent (23/32) of the patients. After treatment with CY-VAMP or VERCY-VAMP, MY-CFUc were grown from 25 per cent (8/32) of patients of whom only 50 per cent responded clinically. The overall clinical response rate for patients receiving CY-VAMP and VERCY-VAMP was 64 per cent (9/14) and 72 per cent (13/18) respectively of whom 14 per cent in each group achieved complete remission. There was no concomitant increase in normal tissue toxicity as measured by granulocyte-macrophage colony (GM-CFUc) formation. Comparison of these data with our previous study of patients receiving VAMP alone, suggests that the addition of CY to the regimen may increase the tumour cell kill. Further clinical studies will determine whether there is a significant increase in the complete remission rate.

Antineoplastic Combined Chemotherapy Protocols↗