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Biomedical subjects

H T Ford

Publications and source records attributed to H T Ford.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lactic acidosis. A presentation of metastatic breast cancer arising in pregnancy.

Lactic acidosis B is a rare metabolic complication of malignancy. It usually is associated with advanced and extensive metastatic disease. The authors report a case in which lactic acidosis was the presenting feature of a previously undiagnosed case of metastatic breast cancer in a pregnant woman and that resolved with successful antineoplastic treatment. The authors review the likely cause and management of the condition.

Acidosis, Lactic↗
PubMed1992

A preliminary clinical study of gossypol in advanced human cancer.

A total of 34 patients with advanced cancer were given weekly or daily escalating doses of oral gossypol, a cottonseed-oil constituent showing evidence of antineoplastic activity in pre-clinical studies. No major adverse events occurred and there was no evidence of haematological or biochemical disturbance. As determined by dose escalation in 17 patients, the dose-limiting toxicity was emesis in 16 patients. There was no evidence of tumour regression in any of the 20 patients assessed for response. We conclude that gossypol is safe but unlikely to be clinically useful in patients with advanced cancer.

Adult↗
PubMed1992

Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the treatment of advanced breast cancer: a randomised clinical trial.

Patients with advanced breast cancer were randomised to 3M (mitozantrone 6.5 mg/m2q 21 days, methotrexate 30 mg/m2q 21 days, mitomycin C 6.5 mg/m2q 42 days) or 2M (as 3M but without mitomycin C). The objective response rates of 30% in 51 evaluable patients receiving 3M and 26% of 54 patients receiving 2M were not significantly different. 4/16 patients not responding to 2M responded to 3M on crossover. Both regimes were well tolerated but there was significantly less haematological toxicity and fewer dose reductions and delays with 2M. We conclude that patients should initially be treated with 2M and that non-responding patients should be crossed to 3M.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Adjuvant aminoglutethimide for postmenopausal patients with primary breast cancer: analysis at 8 years.

PURPOSE: The study purpose was to evaluate aminoglutethimide (AG) as adjuvant therapy in patients with primary node-positive breast cancer in a randomized double-blind placebo-controlled trial. PATIENTS AND METHODS: In a multicenter trial, 354 postmenopausal women with early breast cancer and histologically confirmed positive axillary lymph nodes were randomized after surgery to received aminoplac. Patients were prescribed either AG 250 mg four times per day and hydrocortisone 20 mg twice per day or placebos of identical appearance for 2 years. RESULTS: After a median follow-up of 8.1 years, there has been no overall benefit for AG in terms of either event-free survival or overall survival (OS). However, the results are consistent with interim analyses with a significantly improved event-free survival for patients who received AG for up to 4 years, although this benefit subsequently disappears. Similarly, there is an improved OS for patients who received AG for up to 4 years, but this also subsequently disappears. There was a marginal advantage for estrogen receptor (ER)-positive patients who received AG (n = 74; P = .054). There was no difference in the sites of relapse. There was a significant increase in toxicity for patients who received AG. CONCLUSION: The lack of survival benefit with long-term follow-up for AG may indicate that aromatase inhibitors have less of an impact on early breast cancer than tamoxifen and may imply different biologic mechanisms of action.

Aged↗
PubMed1991

Topical calcipotriol treatment in advanced breast cancer.

19 patients with locally advanced or cutaneous metastatic breast cancer were treated with the topical vitamin D analogue calcipotriol 100 micrograms daily. 14 patients completed 6 weeks' treatment; 3 showed a 50% reduction in the bidimensional diameter of treated lesions and 1 other patient showed a minimal response. 2 patients became hypercalcaemic during treatment. In all patients who responded the tumours contained receptors for 1,25-dihydroxyvitamin D3, shown by immunocytochemistry.

Administration, Topical↗
PubMed1991

Diagnosing breast carcinoma in young women.

OBJECTIVE: To assess the individual and combined diagnostic accuracy of clinical examination, mammography, and fine needle aspiration biopsy in young women with breast cancer. DESIGN: Analysis based on case notes of patients presenting with breast cancer during 1971-89. SETTING: A combined breast clinic. PATIENTS: Consecutive series of 81 women aged less than 36 with histologically proved breast cancer presenting with a discrete mass over 19 years. MAIN OUTCOME MEASURES: Results of clinical examination, xeromammography or conventional mammography, fine needle aspiration biopsy, and examination of tissue removed by surgery. RESULTS: The clinical diagnosis was correct in 47 women and radiography in 35. Fine needle aspiration biopsy was correct in 47 of the 63 women in whom it was successfully performed. Fine needle aspiration was significantly more accurate than mammography (78% v 45%, p less than 0.01). Ten (16%) patients had negative results on clinical examination, mammography, and fine needle aspiration. CONCLUSION: Mammography alone seems inadequately sensitive to detect breast cancer in young patients. When all investigations give negative results excision biopsy is the only way of obtaining a definitive diagnosis.

Adult↗
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

Randomised trial of chemotherapy versus endocrine therapy in patients presenting with locally advanced breast cancer (a pilot study).

Sixty patients with locally advanced breast cancer, but with no evidence of distant metastases were randomised to receive primary endocrine therapy or chemotherapy after assessment and 'Trucut' biopsy of the primary tumour. After 12 weeks all patients were assessed. Eight out of 30 (27%) of the patients who received chemotherapy showed complete clinical regression of the primary cancer, eight patients' tumours had regressed by more than 50%, and ten showed a 25-50% reduction in bi-dimensional diameter. Only four (13%) patients' tumours failed to reduce in size. Seven patients were judged to require mastectomy at the end of the 12 week period of treatment with chemotherapy. In contrast, only three out of 30 (10%) patients receiving endocrine therapy showed a greater than 50% reduction in tumour size, and four patients had a 25-50% reduction at 12 weeks. The remaining patients' tumours either stabilised (12 patients) or enlarged (11 patients). We conclude that primary chemotherapy in patients with primary breast cancer is more effective in rapidly reducing the size of the primary breast cancer than endocrine therapy (P = 0.001) and alters significantly the future management of these patients. However, at 65 weeks on completion of the follow-up, there is no significant difference in the number of patients' disease-free, locally or distant recurrent, or dead.

Adult↗
PubMed1990

Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A.

Thirty-one postmenopausal women with advanced breast cancer have been treated with the nonsteroidal competitive aromatase inhibitor CGS 16949A at p.o. doses of 0.3, 1, and 2 mg twice a day. All patients were assessed for response. Five patients, all treated with 1 mg twice daily, had objective evidence of response (two complete responses and three partial responses); disease stabilized in 17 patients. Minor side effects were reported by ten patients. Two further patients treated with 2 mg twice a day experienced persistent nausea which improved after dose reduction, and one patient, treated with 0.3 mg twice daily, developed a vasculitic rash requiring discontinuation of CGS 16949A. Estradiol levels measured in 24 patients were significantly suppressed 2 wk after starting CGS 16949A treatment at all doses used. Treatment with 2 mg twice a day lowered estradiol levels to a mean of 29% of pretreatment values which was significantly lower than the corresponding figure of 57% for patients treated with 0.3 mg twice daily. Aldosterone levels were significantly lowered below pretreatment values by the 1- and 2-mg twice daily doses. No clinically apparent cases of adrenocortical insufficiency occurred, although small changes in serum electrolyte levels were noted. The results indicate that CGS 16949A is an effective aromatase inhibitor, requiring further evaluation in the treatment of advanced breast cancer. The optimal dose is likely to be 1 mg twice a day.

Aldosterone↗
PubMed1990

Treatment of advanced breast cancer in postmenopausal women with 4-hydroxyandrostenedione.

4-Hydroxyandrostenedione (4-OHA), a new specific aromatase inhibitor, was used to treat 57 postmenopausal women with advanced breast cancer at a dose of 250 mg by i.m. injection every 2 weeks; 55 women were assessable for response. In all, 18 patients (33%) had objective evidence of a response to treatment, with a median duration of 12 months; the disease stabilised in 8 (14%) patients. Serum oestradiol levels, which were measured weekly in nine of the patients, were found to be suppressed to a mean of between 36% and 51% of pretreatment levels during the first 6 weeks of treatment. Three patients were withdrawn from treatment because of toxicity (pain at injection site, sterile abscess and rash). One patient had an isolated episode of anaphylaxis after 6 months of treatment. In comparison with our previous reports of 4-OHA treatment, a dose of 250 mg given i.m. fortnightly appears to be the optimal dose regimen. The efficacy of the drug seems to be similar to that of tamoxifen and aminoglutethimide.

Adult↗
PubMed1990

The influence of extent and local management on the outcome of radiotherapy for brain metastases.

The results of cranial irradiation for brain metastases in 164 consecutive patients have been reviewed to evaluate a policy of localized high dose irradiation for solitary metastases. Fifty of the 164 patients receiving whole brain irradiation (35 Gy in 15 daily fractions) were selected for boosts delivering 15 Gy in 8 daily fractions to the site of solitary deposits. No difference in overall survival or the incidence of death from progressive brain metastases was seen between the patients receiving a boost and those who did not. Overall median survival was 112 days with 62% of patients dying from metastatic disease outside the brain. Factors associated with increased survival were early response to radiotherapy and, in breast cancer patients, a disease-free interval of 2 years. Palliation of presenting symptoms was achieved in 86% of patients at 3 weeks from starting radiotherapy. It is concluded that whereas whole brain irradiation results in useful symptom control, there is no advantage for high dose treatment in the majority of patients with solitary metastases even in the absence of metastatic disease elsewhere.

Adult↗
PubMed1990

Radical radiotherapy for carcinoma of the anal canal.

The treatment of squamous cell carcinoma of the anal canal remains controversial, and recent reports have recommended combined chemotherapy and radiotherapy rather than radiotherapy alone as primary treatment. In order to define the role for more aggressive local therapy we have performed a retrospective analysis on patients with squamous cell carcinoma of the anal canal treated at the Royal Marsden Hospital between 1958 and 1986. Among 42 patients who received radical radiotherapy (RRT) the overall 5-year caused specific survival (CSS) was 52%. Tumour stage and node involvement were the most important prognostic factors. The 5 year CSS were T1 100%, T2 59%, T3 40% and T4 0% (P less than 0.05). The 5-year CSS for node-negative patients was 64% compared to 23% for node-positive patients (P less than 0.095). A minimum tumour dose of 60 Gy in 30 fractions over 6 weeks was essential to achieve local control and was associated with minimal late morbidity and with the retention of anal continence in all patients locally controlled.

Adult↗
PubMed1990

The clinical and endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer.

The aromatase inhibitor, 4-hydroxyandrostenedione (4OHA) is an effective treatment for advanced post-menopausal breast cancer. The clinical and endocrine effects of 4OHA treatment were studied in five pre- and perimenopausal women with metastatic breast cancer. Serum oestradiol levels were not significantly reduced as a result of treatment with 500 mg of 4OHA by weekly i.m. injections and no patient had a tumour response. Four patients were subsequently treated with the luteinising hormone releasing hormone (LHRH) analogue, gosereline, and three had objective responses. The endocrine effects of combined treatment with goserelin (Zoladex), and 4OHA were studied in a further five premenopausal women. Serum oestradiol levels after treatment with goserelin alone were typical of post-menopausal women. Addition of 4OHA led to a further suppression of oestradiol to within the range observed in post-menopausal patients treated with further suppression of oestradiol to within the range observed in post-menopausal patients treated with 4OHA. Six patients whose tumours had regressed as a result of goserelin treatment and who subsequently relapsed were then given combined treatment. Four of the six experienced a second remission. We conclude that while 4OHA alone is unlikely to be a satisfactory treatment for premenopausal patients with advanced breast cancer, 4OHA in conjunction with goserelin leads to profound suppression of oestradiol. The combination of LHRH analogue and aromatase inhibitor may prove to be a superior treatment to LHRH analogue alone in these patients.

Adult↗
PubMed1990

Phase I/II study of the anti-oestrogen zindoxifene (D16726) in the treatment of advanced breast cancer. A Cancer Research Campaign Phase I/II Clinical Trials Committee study.

We report a phase I/II study of the indole derivative, zindoxifene, an anti-oestrogen with intrinsic oestrogenic activity. We have treated 28 women with advanced breast cancer of whom 26 had received prior endocrine therapy. Oral zindoxifene doses ranged from 10 to 100 mg daily; doses were escalated in some patients. Twenty-five patients were assessed for response; the remaining three patients completed less than 3 weeks of treatment. There were no objective responses; disease stabilised in seven patients for up to 5 months and progressed in the remaining 18. Five patients (including three treated with tamoxifen) responded to subsequent endocrine therapy. Nausea, which was dose-limiting, affected half of the patients treated with 80 mg daily. Metabolites of zindoxifene were detectable in serum at all doses used, and sex hormone binding globulin (SHBG) levels showed a strong tendency to rise at the higher doses, indicating that zindoxifene is absorbed and has biological activity. We conclude that zindoxifene in the doses used in this study has only marginal therapeutic activity in the treatment of advanced breast cancer.

Aged↗
PubMed1990

Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer.

Thirty-two previously untreated, fit patients with small-cell lung carcinoma (SCLC) were treated with an intensive combination chemotherapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m2 IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m2 IV days 1 to 3, repeating at 28-day intervals for six courses. Limited-disease (LD) patients were given concurrent hyperfractionated radiotherapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% with 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% 2-year survival and for ED patients 9.5 months with a predicted 14% 2-year survival. Hematologic toxicity was severe with 100% developing World Health Organization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of neutropenic infection or thrombocytopenia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than those reported for less toxic conventional regimens.

Adult↗
PubMed1990

Comparison of conservative surgery and radiotherapy with mastectomy in the treatment of early breast cancer.

We have compared overall survival, and local and distant recurrence-free survival in patients with early breast cancer treated by mastectomy, with patients treated by wide local excision and radiotherapy. To do this, we reviewed a consecutive, unselected series of patients presenting with early breast cancer (T0-T2, N0-N1b, UICC) between 1973 and 1981 to one surgeon (J.-C.G.) and one radiotherapist (H.T.F.). The mean follow-up was 9 years (minimum 6 years, maximum 14 years). Only 9 patients received any adjuvant therapy. At 10 years the relapse-free survival was 65% for both groups of patients; the overall 10-year survival was 70% for patients treated by wide local excision and radiotherapy, and 67% for patients treated by mastectomy. The actuarial loco-regional recurrence rate at 10 years was 15% for patients treated by wide local excision and 13% for patients treated by mastectomy. There were no significant differences in overall survival, loco-regional and distant relapse-free survival between the two groups of patients. Our results support other reports that conservative surgery and radiotherapy in early breast cancer does not adversely affect long-term prognosis.

Adult↗
PubMed1989

Hemibody irradiation (HBI) for metastatic bone pain in two histologically distinct groups of patients.

Fifty patients with hemibody irradiation (HBI) for metastatic bone pain have been reviewed. A total of 60 treatments were given (9 upper HBI, 31 lower HBI and 10 both upper and lower HBI). Seventeen patients had metastatic myeloma and 30 had metastatic prostatic carcinoma. The overall response rate was 83% with a 5% complete response rate. Response was seen within 24 hours in 25% of treatments and lasted until death in 74%. No difference in the response characteristics was seen between those patients with myeloma and those with prostatic carcinoma. Significant toxicity occurred in 60% of patients, predominantly gastrointestinal toxicity and bone marrow suppression. One case of fatal pneumonitis occurred. The possibility of maintaining these response rates but reducing toxicity using lower doses of HBI is discussed.

Adult↗