Trilostane in the treatment of advanced breast cancer.

The combination of trilostane 960 mg daily and either dexamethasone 0.5 mg b.d. or hydrocortisone 10 mg b.d. has been used to treat advanced metastatic breast cancer in post-menopausal women. Twenty-three patients had assessable disease and received treatment for a minimum of 8 weeks. Six (26%) showed an objective response and three (13%), stabilisation of previously progressive disease, sustained for at least 3 months. Side-effects were mainly gastrointestinal. Biochemical studies suggest that the mechanism of action may be inhibition of conversion of androstenedione to oestrone.

Cyclophosphamide and nandrolone decanoate in the treatment of advanced carcinoma of the breast--results of a comparative controlled trial of the agents used singly and in combination.

A random trial in which cyclophosphamide, nandrolone decanoate and the two drugs in combination were used in the treatment of advanced breast carcinoma is described. The results suggest that it is preferable to use cyclophosphamide on its own.

A preliminary trial of doxorubicin in advanced breast cancer and other malignant disease.

Doxorubicin in a dose of 60 mg/m(2) has been used in the treatment of 23 patients with advanced malignant disease, 18 of whom had carcinoma of the breast. The drug has significant clinical activity on its own, prolonged dosage may be required to obtain a response, and there is a risk of cerebral metastases becoming manifest during treatment which is otherwise successful. Cardiac toxicity appears to be acceptably low with this dose regimen.

Mycosis fungoides--response to therapy and survival patterns in 85 cases.

The clinical course and management of 85 cases of mycosis fungoides presenting over a 20-year period are described. The extent of skin involvement and presence of lymphadenopathy were seen to be important prognostic factors. The following survival patterns were observed. In eight cases with limited plaque disease there was prolonged disease-free survival after treatment with kilovoltage X-rays; after a median follow-up of 64 months there was only one case of progression to generalized disease. In 49 cases of generalized skin disease (plaque disease +/- tumours; erythroderma) treated with total skin electron beam therapy there was a 24% 5-year disease-free survival; this potential for long-term survival was seen in cases with generalized plaque disease without lymphadenopathy. The remainder of the cases showed a continuously relapsing course. The extent of skin involvement and presence of lymphadenopathy can both be used as known prognostic factors to adopt a logical plan of treatment.

A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474.

An introductory clinical trial of the anti-oestrogenic agent IC146474 in late or recurrent carcinoma of the breast is described.Forty-six patients have been treated, of whom 10 have shown a good response. This is of the same order as that seen with oestrogens and androgens.The particular advantage of this drug is the low incidence of troublesome side effects.

Chemotherapy of metastatic carcinoma of the breast.

Thirty-four patients with metastatic breast carcinoma were treated with the following combination: methotrexate 60 mg/m2 i.v. days 1 and 8,5-fluorouracil 500 mg/m2 i.v. days 1 and 8, cyclophosphamide 100 mg/m2 daily for 14 days, and prednisolone 25 mg b.d. by mouth daily for 14 days. In 21/34 (62%) patients regression of tumour was maintained for at least three months and in six (18%) this was complete. The median duration of response was 15 months (range 6--33) and there was a significant difference in survival between responders and non-responders (P<0.01). Toxicity was acceptable although dose reduction was necessary in eight patients and in three patients treatment had to be discontinued.

Spinal-cord compression in myeloma.

Clinical records of 47 patients in whom spinal-cord compression was the presenting feature of plasma-cell myeloma were analysed retrospectively. Patients were referred during 1954-78. Median survival was 30 months and prognosis was best for those in whom the site of cord compression was the thoracic region. Early laminectomy and decompression followed by adequate radiotherapy resulted in complete or good partial response in over a third of patients who presented with complete paraplegia. Improvements in supportive care and more effective chemotherapy allow spinal-cord compression in myeloma to be treated promptly and vigorously, thus improving duration and quality of survival in a substantial proportion of patients.

A prospective study of the treatment of high-grade histology non-Hodgkin's lymphoma involving the gastrointestinal tract.

Thirty-six patients presenting with stage II-IV primary gastrointestinal non-Hodgkin's lymphoma of high-grade pathology were treated in a prospective study from 1975 to 1983 with combined modality therapy. A complete response rate of 56% was obtained and the overall 5-yr survival rate was 36%. The 5-yr relapse-free survival rate of the complete remitters was 79%. Multivariate analysis revealed that the remission achieved (P less than 0.001) and the completeness of primary surgery (P = 0.018) would reliably predict the duration of overall survival. The finding of diffuse histiocytic histology (Rappaport) predicted longer relapse-free survival. The majority of deaths were related to intra-abdominal complications and not to disseminated lymphoma. Gastrointestinal tract non-Hodgkin's lymphoma of high-grade pathology of all stages is curable with a combination of chemotherapy and radiotherapy following surgery to remove as much macroscopic disease as is possible.

Computed tomography of abdomen in staging and clinical management of lymphoma.

During July 1976 to Demember 1977, 150 patients with Hodgkin's disease and 138 with non-Hodgkin's lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin's lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin's disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin's disease.

The prognostic significance of mediastinal bulk in patients with stage IA-IVB Hodgkin's disease: a report from the Manchester Lymphoma Group.

Three hundred and two previously untreated patients with Stage IA-IVB Hodgkin's disease were reviewed to determine the prognostic significance of mediastinal involvement. Mediastinal bulk disease was defined as either a maximal mediastinal width of 7.5 cm or more, or a ratio of the maximum width of mediastinal disease to the maximum chest diameter of greater than or equal to 0.33, or a ratio of the maximum width of mediastinal disease to the chest diameter at T5-T6 greater than or equal to 0.33, or as an area of mediastinal disease greater than or equal to 100 cm2. Bulk disease outside the chest was defined as a mass of lymph nodes measuring 5 cm or more in any axis. The presence of mediastinal bulk disease was of adverse prognostic significance for remission duration and survival in patients with Stage IA-IIB Hodgkin's disease, but for patients with more advanced disease the effect of mediastinal bulk on remission duration and survival was not statistically significant. The mediastinal bulk variable which most significantly related to prognosis was the ratio of the maximum mediastinal disease to the chest diameter at T5-T6.

A multivariate analysis of factors affecting survival in patients with high-grade histology non-Hodgkin's lymphoma.

One hundred and eleven patients with advanced-stage, high-grade histology non-Hodgkin's lymphoma were studied over a 7-yr period and were treated with one form of chemotherapy and radiotherapy. Multivariate analyses were carried out to identify factors which could predict a favourable prognosis. A complete response, low serum LDH and absence of clinical evidence of liver involvement were associated with long-term survival. The presence of 'B' symptoms, bone marrow involvement, low serum albumin and male sex predicted a reduced chance of achieving a complete remission. For those patients who achieved a complete response, the subdivision of histologies, particularly according to the Kiel classification, was the only significant factor predictive of prolonged relapse-free and overall survival. This confirms the importance of identifying different histological subgroups of lymphoma when considering treatment planning.

Maintenance chlorambucil after CVP in the management of advanced stage, low-grade histologic type non-Hodgkin's lymphoma. A randomized prospective study with an assessment of prognostic factors.

One hundred sixty-two patients with Stages III and IV non-Hodgkin's lymphoma of low-grade histologic type were treated with combination chemotherapy using cyclophosphamide, vincristine, and prednisolone (CVP) followed by radiotherapy to sites of previous bulk disease. The patients were randomized to receive either follow-up alone or "maintenance" chemotherapy with 2 years of intermittent chlorambucil. A complete remission was obtained in 56% of patients and the median survival was 64 months (median follow-up, 74 months). Multivariate analysis revealed stage (P less than 0.0001) and Karnofsky performance status (P = 0.021) to predict complete response (CR) and the achievement of a CR (P less than 0.0001), female sex (P = 0.008), the absence of bulk disease (P = 0.038) and low serum alkaline phosphatase (P = 0.002) to predict prolonged survival. The median relapse-free survival (RFS) of the complete responders was 41 months. A prolonged RFS was predicted by low stage (P = 0.014), low serum lactic dehydrogenase (LDH) (P = 0.045) levels, and by the administration of maintenance chlorambucil (P = 0.045). A prolonged survival of the complete responders was predicted by a low number of nodal sites of involvement with lymphoma at presentation (P = 0.022) and lack of liver involvement (P = 0.011). The administration of oral maintenance therapy with chlorambucil for a full 2 years was only possible in 38% of patients, mainly because of progression of disease and the induction of thrombocytopaenia, but despite this it prolonged the median RFS by 38 months and its use could be considered when future studies are being designed.

Early clinical experience with bleomycin in the United Kingdom in series of 105 patients.

The results of treating a series of 105 patients (79 with advanced squamous cell carcinoma, 21 with advanced lymphoma, and 5 with miscellaneous tumours) with bleomycin are described. The drug was usually given as a single agent. Four patients with squamous cell carcinoma showed complete regression and there was partial regression in 25. Side effects were frequent, particularly skin changes and stomatitis; death from pneumonitis occurred in one patient.

A randomised study of adjuvant chemotherapy after mantle radiotherapy in supradiaphragmatic Hodgkin's disease PS IA-IIB: a report from the Manchester lymphoma group.

One hundred and fourteen untreated patients with pathological stage (PS) IA-IIB supradiaphragmatic Hodgkin's Disease were randomised to mantle radiotherapy alone (55) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine, vinblastine, prednisolone and procarbazine- MVPP (59). Patients excluded were those outside the age range 16-65 years and those with massive mediastinal disease precluding laparotomy. Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis. Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third. All patients achieved a complete remission. Median duration of follow-up was 62 months (range 16-97). The relapse free survival (RFS) was 81%; 69% for radiotherapy alone and 93% for adjuvant chemotherapy (P = 0.002). RFS was also shown to be adversely affected by B symptoms (P = 0.0003), bulk disease (P = 0.018), abnormal CXR (P = 0.037), and increasing stage (P = 0.039). Age, sex, histology, and number of sites involved had no significant effect upon RFS. A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone, the presence of bulk disease, and B symptoms. The overall 5 year survival was 93% with no statistically significant difference between the two treatment groups (P = 0.54). Survival was adversely affected by three variables - B symptoms (P = 0.02), the presence of bulk disease (P = 0.002), and pathological stage (P = 0.05). High risk groups for relapse are those with bulk and B symptoms. This analysis has shown that RFS was significantly improved by adjuvant chemotherapy, but that overall survival was not.