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Biomedical subjects

J L Mansi

Publications and source records attributed to J L Mansi.

At least 37 records · Page 2Linked to original sources
PubMed1996

A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer.

Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity.

Adenocarcinoma↗
PubMed1995

A randomised study to determine whether routine intravenous magnesium supplements are necessary in patients receiving cisplatin chemotherapy with continuous infusion 5-fluorouracil.

Cisplatin is an effective antineoplastic agent, but can cause renal tubular damage leading to urinary magnesium wasting and hypomagnesaemia. Cisplatin and 5-fluorouracil, when used in combination, have synergistic antitumour activity in upper gastrointestinal malignancies, but it is unclear whether they have additive effects on renal magnesium loss. To determine the optimal regimen for magnesium supplementation in these patients, we have conducted a randomised trial of routine intravenous magnesium supplements compared with magnesium given on an 'as required' basis. 32 patients were randomised to receive magnesium intravenously in prehydration and posthydration fluids with cisplatin chemotherapy, or to receive magnesium only when the serum level was low. 5-fluorouracil was given as a continuous infusion. Serum magnesium was measured on admission for each cycle of chemotherapy and an interim measurement performed between each cycle. 28 patients were evaluable. All patients randomised to receive magnesium on an 'as required' basis had at least one episode of hypomagnesaemia. On subsequent admissions for chemotherapy (cycles 2 and 3), the mean serum magnesium level was significantly lower in these patients compared with patients who received magnesium routinely (P < 0.05). After omission of magnesium from the first cycle of cisplatin, magnesium supplements were necessary in 50% of subsequent cycles, usually by the second or third cycle. Moreover, there were several instances of symptomatic hypomagnesaemia requiring further intravenous supplements in mid-cycle. Patients treated with a combination of cisplatin and 5-fluorouracil should be given intravenous magnesium supplements with each cycle of cisplatin chemotherapy. Nevertheless, episodes of hypomagnesaemia still occur, and additional intravenous supplements may be required, highlighting the importance of measuring this electrolyte.

Adult↗
PubMed1995

Oesophageal varices: a potentially fatal complication of liver metastases.

Haemorrhage from oesophageal varices is a common and potentially life-threatening complication of portal hypertension, which is usually due to cirrhosis of the liver. Although liver metastases and hepatic dysfunction frequently occur in malignant disease, reports of oesophageal varices arising as a consequence of metastatic liver disease are sporadic, suggesting that this complication is unusual. Indeed, one review of the literature identified only 23 cases, although a few others have subsequently been reported. The management of such patients bleeding from oesophageal varices is clearly very different from bleeding due to other causes such as peptic ulceration. We report three cases and review the literature. All of our cases presented to us within a period of one year, suggesting that this complication of metastatic liver disease is more common than originally considered to be the case.

Aged↗
PubMed1995

Primary non-Hodgkin's lymphoma of the thyroid with bone marrow infiltration at presentation.

Primary non-Hodgkin's lymphoma of the thyroid is predominantly a disorder of elderly females. Most patients present with limited disease and receive local irradiation. Presentation with advanced disease is uncommon and, consequently, bone marrow examination is not always done. We report a patient with primary thyroid lymphoma who had bone marrow infiltration at presentation and discuss the importance of this investigation in management.

Aged↗
PubMed1995

Adjuvant chemotherapy for colorectal cancer.

Colorectal cancer is the second most common cancer in the Western world, and yet the survival after potentially curative excisional surgery has improved little over the last half century. Newer tumour prognostic markers are not superior to conventional Dukes' staging and there are currently no markers which predict response to chemotherapy. Adjuvant chemotherapy has had a chequered past, but recently a number of important prospective studies have demonstrated its proven benefit in patients with Dukes' stage C colorectal cancer. However, several issues still require clarification. (1) Do immunomodulators such as levamisole have a significant role in adjuvant chemotherapy? (2) Which patients derive most benefit from adjuvant chemotherapy? (3) Do prognostic markers have a role in predicting these patients? Approximately 30% of patients with Dukes' stage B cancers die of metastatic disease and the role of adjuvant chemotherapy in patients with these tumours seems worth exploring. Only a large randomised trial can give answers to these important questions. Such a trial would also encourage the widespread introduction of standard methods of surgical and pathological assessment.

Chemotherapy, Adjuvant↗
PubMed1994

Eosinophilic folliculitis occurring after bone marrow autograft in a patient with non-Hodgkin's lymphoma.

Eosinophilic pustular folliculitis is a rare disorder previously reported predominantly in Japanese people who are otherwise healthy. Recently, the disorder has been noted in patients with acquired immune deficiency syndrome, as has eosinophilic folliculitis, a similar but distinct entity. The authors report a patient with eosinophilic folliculitis who was immunocompromised after high dose chemotherapy and bone marrow autograft for treatment of non-Hodgkin's lymphoma.

Adult↗
PubMed1994

Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.

This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.

Administration, Oral↗
PubMed1994

Breast carcinoma: measurement of tumor response to primary medical therapy with color Doppler flow imaging.

PURPOSE: To assess the ability of color Doppler flow imaging to help evaluate the response of breast cancer to medical therapy. MATERIALS AND METHODS: Thirty-four patients with large or centrally located breast carcinomas were studied. All tumors had been treated medically. Tumor size was assessed at clinical examination, volume at B-mode ultrasound (US), and vascularity at color Doppler flow imaging. The changes seen during the treatment course were cross compared and correlated with final tumor response. RESULTS: In 97 of the 126 treatment cycles (77%), changes in vascularity were concordant with changes in the size of the tumors (reduction in the vascularity with response to therapy and an increase in tumor size with lack of response or progression). Changes seen at color Doppler flow imaging occurred at least 4 weeks before those seen at clinical and B-mode US examination in 40% and 38% of cases, respectively. Changes in vascularity could be assessed in every patient. CONCLUSION: Color Doppler flow imaging can help assessed and predict the response of breast cancer to medical treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Mammography in the assessment of response to medical treatment of large primary breast cancer.

The sequential mammograms of 48 patients (median age: 54 years, range: 24-84 years) undergoing primary medical treatment for large operable breast cancer at this institution were reviewed, and compared to the findings at clinical assessment. Twenty-six patients underwent endocrine therapy using tamoxifen, and 22 chemotherapy (CMF or MMM). All had more than two mammograms which were reviewed blindly by two independent radiologists. Response to treatment by both evaluation modalities was recorded using WHO definitions (NC, PR, CR, PD). Some 81% of patients achieved an objective clinical response to treatment, whilst 63% showed mammographic response. Overall comparison of clinical examination with mammography showed agreement in 38 patients (79%) and disagreement in 10 (21%). Agreement in type of response but not in its degree was found in 22 cases (46%). The results suggest that in the majority of cases mammography provides a useful adjunct to clinical examination in monitoring response to primary medical treatment for breast cancer. However, radiological factors such as unchanging microcalcification, and the continuing presence of mammographic density contribute to the discrepancy with clinical response in some tumours, and the search for alternative modalities of assessment should continue.

Adult↗
PubMed1993

Response of metastatic anal carcinoma to single agent carboplatin.

The management of locoregional squamous cell carcinoma of the anus with a combined modality approach comprising chemotherapy and radiotherapy is well established. However, the optimum regimen for the management of metastatic disease has yet to be determined. Cisplatin has been shown to have some efficacy in this disease. We report a case of partial response of metastatic disease to single agent carboplatin, and discuss its role in this situation.

Anus Neoplasms↗
PubMed1993

Repeat administration of high dose melphalan in relapsed myeloma.

At a median time of 20 months following high dose melphalan for myeloma, 29 patients relapsed and were treated with induction chemotherapy to maximum response followed by a second course of high dose melphalan. The majority (90%) of patients received 200 mg m-2 with an autologous bone marrow transplant. Sixteen (55%) patients achieved complete remission and 11 (38%) a partial response. The median duration of remission was 17 (4-42) months. The median survival has not been reached, with 50% of patients alive at 58+ months after presentation. The period of neutropenia was similar during both first and second high dose procedures, but the duration of thrombocytopenia was longer in patients receiving melphalan for a second time (median 22 (16-56) days and 41 (18-69) days respectively). There was one treatment-related death due to thrombocytopenic haemorrhage. Repeated administration of high dose melphalan is a feasible approach for patients with relapsed myeloma.

Adult↗
PubMed1993

The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study.

BACKGROUND: 5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. PATIENTS AND METHODS: Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. RESULTS: Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007). CONCLUSIONS: MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years' follow-up.

Using an antiserum to epithelial membrane antigen we have screened multiple bone marrow aspirates from 350 patients with primary breast cancer taken at the time of initial surgery. 89 (25%) patients were found to have micrometastases and their presence was related to pathological size (P less than 0.01), the presence of peritumoral vascular invasion (P less than 0.001), and positive lymph nodes (P less than 0.005) but not menopausal status. At a median follow-up of 76 months (range 34-108) 107 patients had relapsed with distant metastases. 48% (43 of 89) of these patients had micrometastases initially compared with 25% (64 of 261) who did not (P less than 0.005). The test predicts for relapse in bone (P less than 0.01) and other distant sites excluding bone (P less than 0.001) and is associated with a shorter overall survival (P less than 0.005). We conclude that the detection of micrometastases signals a high likelihood of early relapse and decreased survival in breast cancer.

Adult↗
PubMed1991

A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/methotrexate/5 FU (CMF) in the treatment of advanced breast cancer.

Mitozantrone (Novantrone) has recently been incorporated into a new combination chemotherapy regimen with mitomycin-C and methotrexate (MMM) against advanced breast cancer. We have compared MMM (mitozantrone 8 mg m-2 i.v. q 3 weekly, methotrexate 35 mg m-2 i.v. q 3 weekly, mitomycin-C 8 mg m-2 i.v. q 6 weekly) with CMF (cyclophosphamide 100 mg orally, days 1-14, methotrexate 35 mg m-2 i.v., days 1 and 8, 5-FU 1,000 mg i.v., days 1 and 8, q 4 weekly), each regimen with folinic acid rescue, in a randomised trial, 29/57 evaluable patients treatment with MMM achieved an objective response (51%) compared with 33/55 treated with CMF (60%). Overall median survival was 16 months for MMM and 12 months for CMF. Subjective toxicity was low for both regimens and the only significant difference was in incidence of diarrhoea (50% for CMF vs 21% for MMM). Haematological toxicity was similar, leading to treatment delays and/or dose reductions in 35% patients with CMF vs 43% with MMM. Thrombocytopenia was significantly increased in MMM (34% vs 14%). No clinical cardiotoxicity was seen, but a significant reduction in left ventricular ejection fraction occurred in four patients on CMF vs 2 on MMM. MMM is an active, well tolerated new chemotherapy regimen for advanced/metastatic breast carcinoma with an efficacy and toxicity spectrum very similar to CMF.

Adult↗