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Biomedical subjects

J L Mansi

Publications and source records attributed to J L Mansi.

At least 55 records · Page 3Linked to original sources
PubMed1991

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer.

Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.

Adenosine Triphosphate↗
PubMed1991

Anthrapyrazole CI941: a highly active new agent in the treatment of advanced breast cancer.

Thirty-one patients with advanced breast cancer were treated with CI941, an anthrapyrazole structurally related to mitoxantrone. Patients had not previously been treated with anthracyclines or mitoxantrone, and 15 patients had not received any previous cytotoxic chemotherapy. CI941 was given at a dose of 50 mg/m2 by intravenous bolus injection every 21 days. Thirty patients were assessable for response, and all were assessable for toxicity. Two patients (7%) had complete responses (CRs), and 17 (56%) achieved partial responses (PRs; overall response rate, 63%; 95% confidence interval, 46% to 81%). The response rates in patients with and without prior chemotherapy were 63% and 64%, respectively. The median response duration was 37 weeks from start of treatment, with a maximum response duration of greater than 70 weeks. Median survival has not yet been reached. Leukopenia was the most frequently encountered toxicity, with a World Health Organization (WHO) grade greater than 3 occurring in 74% of courses. Thrombocytopenia and anemia were negligible. Only 10 patients (32%) had alopecia severe enough to wear a wig. There were no cardiac symptoms or events in any patient, but a slight median fall in left ventricular ejection fraction (LVEF) of 6% (from +7 to -12) during stress and 6% (from +14 to -14) at rest occurred. Other toxicities were mild, and the drug was generally well tolerated. CI941 is a very active and well-tolerated new agent in the treatment of advanced breast cancer, with neutropenia being the main toxicity.

Adult↗
PubMed1990

Ifosfamide with and without adriamycin in advanced uterine leiomyosarcoma.

Uterine leiomyosarcomas are rare tumours and the results of treatment of advanced disease are poor. Ifosfamide and Adriamycin are both known to be active drugs in soft-tissue sarcomas. We present our experience using ifosfamide alone and in combination with Adriamycin in advanced or recurrent uterine leiomyosarcomas. Ifosfamide alone was given as a 24-h infusion at doses ranging from 5 to 7.5 g/m2, with mesna rescue. In the combination regimen, ifosfamide was given at a dose of 5 g/m2 and Adriamycin, at a dose of 40 or 60 mg/m2. Ten patients were treated with ifosfamide alone, with only one partial response lasting 6 months. In all, 11 patients were treated with ifosfamide and Adriamycin, which resulted in 1 complete response that lasted 11 months. Although many of the patients had extensive disease and some had undergone prior treatment with other chemotherapy, ifosfamide would appear to have only modest activity at the dose and schedule used.

Adult↗
PubMed1990

Endometrial stromal sarcomas.

The case histories of 15 patients with endometrial stromal sarcoma attending the Royal Marsden Hospital between 1973 and 1987 were reviewed. Eight patients were classified as having low-grade and seven as high-grade tumors using specific histological criteria. Those patients with low-grade tumors had a long relapse-free and overall survival in the absence of receiving specific therapy after initial surgery. Five are alive and disease free, one has shown a partial response to hormonal manipulation, and one is alive with disease on no therapy. Only one patient has died and this occurred 111 months postdiagnosis. Conversely, all seven patients with high-grade tumors relapsed with local disease and three have died. Thus, after surgical resection patients with low-grade tumors probably do not require treatment until relapse, whereas adjuvant radiotherapy should be given to those patients with high-grade tumors. On relapse, hormone therapy should be the treatment of first choice for patients with low-grade tumors, whereas chemotherapy is more appropriate for patients with high-grade tumors.

Adult↗
PubMed1989

Prolonged survival in a patient with disseminated malignant teratoma in the presence of a persistently elevated serum alpha-fetoprotein level.

The authors report a patient with disseminated malignant teratoma who has survived for 3.5 years after discontinuation of treatment despite a persistent and nonprogressive elevation of his serum alpha-fetoprotein level. Potential sources of the marker in his case are discussed and the possibility of a chemotherapeutically induced evolution of his tumor considered.

Adult↗
PubMed1989

Primary medical therapy for operable breast cancer.

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy. With a median follow-up of 19 months (range 6-42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease. Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.

Adult↗
PubMed1989

The fate of bone marrow micrometastases in patients with primary breast cancer.

Using an immunocytochemical technique, micrometastases have been found in the bone marrow of approximately 26% of patients with primary breast cancer at the time of initial surgery. To determine the fate of these cells, both in patients receiving and not receiving adjuvant therapy, multiple bone marrow aspirates were repeated in 82 patients at a median time of 18 months after surgery but prior to overt relapse. In both treated and untreated patients micrometastases were only found in one of 45 (2%) and one of 37 (3%) patients, respectively. However, when multiple marrow aspirates were taken from patients with local recurrence the incidence of micrometastases was 19% (three of 16), and this increased to 30% (three of ten) in patients with disease at distant sites other than bone, and 100% (ten of ten) in patients with radiologically proven bony disease. Three of 11 (27%) patients in whom the primary tumor remained in situ while receiving adjuvant therapy before definitive surgery had micrometastases at the time of diagnosis and at follow-up 3 months later. These results suggest that many of the micrometastases from breast cancer patients are the result of "shedding" of cells from the primary carcinoma and that a proportion are not viable. The technique is currently insufficiently sensitive to accurately monitor adjuvant therapy in breast cancer patients.

Antineoplastic Agents↗
PubMed1988

Automated screening for micrometastases in bone marrow smears.

It is possible to detect micrometastases in primary breast cancer using immunocytochemical staining of bone marrow smears. However, using the light microscope the procedure is time-consuming and laborious because such cells occur rarely (less than 1 in 10,000). Using an image analysis system, the Leytas machine, and a specially prepared reproducible slide it has been possible to automate the technique. A 100% concordance was found between the machine and the light microscope in the identification of slides containing moderate to high numbers of tumour cells in bone marrow, and in those containing no tumour cells. However, in those slides containing low numbers of tumour cells (1-10 tumour cells/10(6) normal bone marrow cells) the sensitivity was decreased to 91%. In the presence of non-specific staining the false positive rate was increased from 0% to 22%. This method represents a potential improvement in the assessment of an important clinical staging procedure.

Bone Marrow↗
PubMed1988

Tests for detecting recurrent disease in the follow-up of patients with breast cancer.

In 141 postmenopausal node-positive patients with primary breast cancer, routine biochemical markers (alkaline phosphatase, gamma-glutamyl transpeptidase, carcinoembryonic antigen), and chest x-ray, in combination with history and clinical examination, have been performed at 3 monthly intervals for at least 2 years. Sixty one patients relapsed at a median time of 14 months. The recurrence was detected at routine follow-up in 40 (66%) patients. Of these 40 patients, 26 (65%) presented with symptoms, 11 (28%) were asymptomatic but were found to have relapsed on clinical examination, and only 3 (8%) had their relapse diagnosed on the basis of an abnormal chest x-ray. The remaining 21 patients presented early with symptoms. Therefore symptoms and clinical examination accounted for the detection of relapse in 58 of the 61 (95%) patients. Of the patients who had relapsed, 49% (30 of 61) had one or more abnormal markers/chest x-rays prior to relapse, rising to 79% (48 of 61) at the time of relapse. Of 80 patients with no evidence of recurrence, 36% (29) had no marker abnormality recorded, whereas in 64% (51) one or more abnormalities were found. These results suggest that history and examination are the important procedures in follow-up, and that abnormal markers are not always due to metastatic disease and may be misleading.

Biomarkers, Tumor↗
PubMed1988

A phase I-II study of ifosfamide in combination with adriamycin in the treatment of adult soft tissue sarcoma.

Fifty-four patients with advanced soft tissue sarcoma were treated with a combination of ifosfamide (5 g/m2) and adriamycin (40-60 mg/m2) at 3 weekly intervals. Of the 50 evaluable patients a response was seen in 11 (22%) patients (3 complete and 8 partial responses), stabilization of disease occurred in 17 patients and the remaining 22 patients progressed whilst on treatment. Of the 22 patients receiving adriamycin 60 mg/m2 12 (55%) required a dose reduction due to toxicity compared to 11 (39%) of the 28 patients who received 40 mg/m2. For the patients who had a response the median relapse-free interval was 7 months (range 2-17+) and the overall median survival was 12 months (range 5-29+). The combination does not appear to show an advantage over either drug used as a single agent.

Adolescent↗
PubMed1988

Detection of tumor cells in bone marrow of patients with prostatic carcinoma by immunocytochemical techniques.

We used a mixture of antisera to prostatic specific acid phosphatase, prostatic specific antigen, epithelial membrane antigen and cytokeratin to examine multiple marrow aspirates from patients with local (15) and metastatic prostatic carcinoma (15), and benign prostatic hypertrophy (10). We found moderate to large numbers of tumor cells in the bone marrow of 11 of 15 (73 per cent) patients with known metastatic disease and small numbers of abnormal cells in 2 of 15 (13 per cent) patients with apparently local disease. No tumor cells were found in patients with benign prostatic hypertrophy, and only 2 patients with metastatic disease had tumor cells in the bone marrow when conventional hematomorphological preparations were examined. These findings suggest that immunocytochemistry can increase the detection rate of metastatic prostatic carcinoma cells. Further followup of larger numbers of patients with local carcinoma will reveal whether the presence of micrometastases denotes a poor prognosis.

Acid Phosphatase↗
PubMed1988

The relationship between micrometastases in the bone marrow, histopathologic features of the primary tumor in breast cancer and prognosis.

The pathologic features of the primary tumors in 285 patients with breast cancer at the time of initial presentation, and with no clinical evidence of distant metastases, have been analyzed. The results have been compared with the detection of tumor cells in the bone marrow by use of an immunocytochemical method using antisera raised against the epithelial membrane antigen (EMA). The authors found EMA-positive cells (i.e., tumor cells) in the bone marrow of 77 (27%) patients and a significant association between the presence of such EMA-positive cells in the bone marrow and tumor size (P = 0.006) and peritumoral vascular invasion (P = less than 0.001). A possible relationship with estrogen receptor negativity (P = 0.06) also was noted.

Adult↗
PubMed1987

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.

Adult↗
PubMed1987

Granulocytic sarcoma: a diagnosis to be considered in unusual lymphoma syndromes.

A series of 7 patients with granulocytic sarcoma is presented to illustrate its varied clinical picture. In particular, this condition may present with features which suggest a non-Hodgkin lymphoma. The diagnosis will only be made if a high index of suspicion is maintained and special histopathological methods are used. Granulocytic sarcoma should be treated like an acute myeloid leukaemia.

Adult↗
PubMed1987

Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.

Adult↗