Adjuvant chemotherapy (CMF) for stage III breast cancer: a randomized trial.

A randomized trial of the effect of adjuvant CMF chemotherapy in patients with Stage III breast cancer receiving primary local radiation or local radiation plus surgery, failed to reveal a survival benefit from early systemic treatment. The subset of premenopausal patients receiving chemotherapy did, however, show a significant prolongation of disease-free survival from 23 to 55 months. Overall survival of this subgroup was not increased. The study included the use of two dose levels of CMF to assess whether higher chemotherapy doses would be more effective. No dose effect was observed. Initial local control with radiation therapy or radiation plus surgery was achieved in the majority (90.9%). Distal recurrence and death from metastatic disease were the major causes of treatment failure. Treatment benefit among premenopausal patients was mainly delayed onset of distal metastatic disease. Among premenopausal patients, salvage therapy for metastatic disease appeared more effective in those not previously exposed to systemic treatment.

High-dose weekly fractionation radiotherapy in advanced cancer of the uterine cervix.

A trial comparing two different radiotherapy techniques and schedules in the treatment of 83 patients with advanced cancer of the uterine cervix (stage IIIB) employing external irradiation alone is described. The one technique, used routinely in this department, employed a conventional daily fractionation schedule while the other used a high-dose weekly fractionation regimen. The techniques are described. The aim of the trial was to compare the efficacy and morbidity of these two methods of treatment. Dose distribution curves in cross-section and midsagittal planes are shown and calculations or equivalent doses at various selected points using Ellis's nominal single-dose formula are tabulated. The 2-year survival figures were 33% for the daily fractionation technique and 22% for the weekly regimen. Serious late complication rates were 6% for the daily regimen and 22% for the weekly schedule. These differences are not statistically significant. Late complication rates in the weekly fractionation regimen appeared to be lower than figures quoted by other authors. Local control within the irradiated volume was better in the group treated by the daily fractionation method.

Radiotherapy and surgery in the management of stage IB and IIA carcinoma of the cervix.

Ninety-two consecutive patients with stages IB and IIA carcinoma of the cervix were treated by one of two regimens: pre-operative intracavitary caesium-137 followed by a Wertheim hysterectomy (group 1) or staging laparotomy with biopsy of suspicious lymph nodes (group 2) (if there was no evidence of tumour on examination of a frozen section of the lymph nodes a Wertheim hysterectomy was performed, but if a tumour was present the abdomen was closed and a course of radical irradiation given). When there was evidence of extracervical spread on examination of the specimen after the Wertheim hysterectomy, postoperative irradiation was given. It was found that clinical staging had been incorrect in 38,5% of patients thought to have stage IB disease and in 71,4% of those thought to have stage IIA disease. The actuarial survival curves showed no significant statistical difference between group 1 and group 2. When examination of the operative specimen showed tumour invasion of the parametrium only, the disease was well controlled by postoperative irradiation (all 7 such patients survived). On the other hand, when there was evidence of tumour invasion of pelvic lymph nodes the 4-year survival rate fell to 31% (4 out of 13 patients), despite the use of postoperative irradiation.

Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

Surgical excision of lung metastases from squamous carcinoma of the cervix. A report of 2 cases.

These 2 case reports serve to emphasize two important points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; and (ii) in selected cases surgical excision of a secondary deposit in the lung is the treatment of choice and may even result in cure.

Treatment of metastatic breast cancer in estrogen receptor positive patients. A randomized trial comparing tamoxifen alone versus tamoxifen plus CMF.

In a controlled clinical trial, 52 patients with ER positive metastatic breast cancer were randomly assigned to receive initial treatment with either tamoxifen alone followed by sequential cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after tumour progression of concurrent tamoxifen plus CMF, All 52 patients entered are eligible and 50 patients were currently assessable. Response rates (CR + PR) were similar for the two treatment groups (15/24 tamoxifen alone, 17/26 tamoxifen + CMF). The median durations of survival for the two treatment groups 17.7 months and 17.1 months were also not significantly different. Significant correlations were found between level of ER and response rate and also between level of ER and response duration. From the result of this investigation it would appear that there is no advantage to the addition of chemotherapy prior to an adequate trial of hormone therapy in patients with metastatic ER positive breast cancer.

Treatment of small cell lung cancer: intensive remission induction, radiation therapy, and maintenance chemotherapy.

Forty-eight patients with small cell lung cancer were treated with an intensive therapy regimen which included induction chemotherapy with vincristine, adriamycin, procarbazine, and methotrexate. This was followed by radiation therapy given to areas of residual disease after restaging. Maintenance chemotherapy with cyclophosphamide, methotrexate, and procarbazine was then given to patients who had entered complete remission (CR). Fifteen out of 17 patients with limited disease (88%) achieved complete remission. Remission rates for patients with extrathoracic metastases were somewhat lower. Seven of 11 patients (64%) of patients with a single extrathoracic metastatic site achieved CR, while only 6/20 (30%) with multiple extrathoracic metastases went into remission. Median survival for patients who achieved complete remission was 17 months.

The surgical treatment of the radiation-damaged rectum.

Details are given of 37 consecutive patients with radiation damage to the rectum. Twenty-eight presented with rectovaginal fistulas, 3 with haemorrhage from ulcerative proctitis, 3 with low rectal strictures, 2 with a painful rectal ulcer and 1 with a rectal carcinoma. Thirty-five of the 37 had been treated for carcinoma of the cervix, and of these, 30 were Black South African women in whom this disease forms approximately 70 per cent of all malignancies. Associated pathology in these patients included urinary fistulas, small bowel fistulas or stenoses and a variable degree of fibrosis of the pelvic cellular tissue. Treatment involved subtotal rectal resection with restoration of continuity by means of a peranal sleeve anastomosis between healthy colon and the rectal stump denuded of its mucosa. Technical success was achieved in 35 of the 37 patients, with no mortality. The functional results were assessed both subjectively and objectively in 31 patients followed up for more than 6 months. Full continence was achieved in 54 per cent initially, improving to 75 per cent (21 of 28) at 1 year postoperatively. At 1 year, variable degrees of incontinence for a liquid stool persisted in 7 of 9 patients who had low fistulas with a low anastomosis at dentate line level. Where anastomosis was possible at a higher level, all 19 patients cured of fistula, ulcer, stenosis or haemorrhagic proctitis were fully continent at 1 year.

Cytosolic oestrogen receptor content of breast cancer tissue in blacks and whites.

We have examined the oestradiol receptor (ER) content of cytosols from 560 Black and White patients. The tumours from the White group contained a significantly lower proportion on ER-negative tumors (35.4%) compared with those from the Black group (46.5%). The proportion of ER-positive tumours is significantly greater in the post- than in th premenopausal White group. The frequencies of ER-positive tumours in the post- and premenopausal Black groups are not significantly different, resembling the situation described by others in Japanese women.

Serum prolactin after chest wall surgery: elevated levels after mastectomy.

Galactorrhea is a recognized sequel of chest injury, but serum PRL levels in these patients have not been systematically documented. Therefore, we examined the PRL responses over 5 days in patients undergoing either mastectomy (10 patients) or thoracotomy (10) and in seven patients undergoing elective laparotomy (controls). Basal serum PRL levels were normal in every subject. There were no consistent or significant alterations in PRL levels after laparotomy or thoracotomy. After mastectomy, PRL levels rose from a mean preoperative level of 7.1 +/- 1.3 to 16.0 +/- 3.3 ng/ml (P < 0.01) on the first postoperative day. Mean levels continued to rise to 35.6 +/- 6.6 ng/ml (P < 0.005) on day 5; levels were supranormal in eight subjects. Hyperprolactinemia persisted in the four subjects evaluated 4 weeks postoperatively and in one of five patients evaluated at 6 months. In a retrospective study, serum PRL levels were measured months to years after thoracotomy (31 patients) and mastectomy (53 patients) and compared to levels in 41 normal female controls. Mean serum PRL levels were 8.4 +/- 1.3 ng/ml in the control group, 13.1 +/- 0.9 ng/ml in the thoracotomy group (P < 0.005), and 20.6 +/- 3.1 ng/ml in the mastectomy group (P < 0.001). One thoracotomy patient and 18 mastectomy patients (34%) had supranormal PRL levels. It is concluded that mastectomy acutely stimulates PRL secretion in most subjects, and levels may remain elevated for months, perhaps for years, in a proportion of patients. Both the acute and chronic hyperprolactinemic states are probably the result of neurogenic PRL release mediated via the suckling reflex.

Hodgkin's disease in South African children.

Thirty South African children with Hodgkin's disease were studied over a 7-year period (1970 - 1977). Males outnumbered females by 5:1. The most frequent histological pattern encountered was mixed cellularity (72%). Fourteen patients with stage I, II or IIIA disease were treated with radiation therapy alone, and all achieved a complete remission with a median duration of remission in excess of 48 months. Sixteen patients with stage III or IV disease received combination chemotherapy (MOPP regimen), and 13 achieved a complete remission with a median duration of remission in excess of 48 months. The overall median survival was in excess of 60 months. Seven patients died during the study period, 4 of Hodgkin's disease and 3 of other causes. There was no significant difference in treatment response or survival between Black and White children.

Tamoxifen and hypercalcaemia. A case report.

A patient is reported in whom hypercalcaemia developed when adjuvant hormonal treatment with tamoxifen (Nolvadex) was instituted. The response to withdrawal of the drug and the recurrence of hypercalcaemia on rechallenge with tamoxifen make a causal relationship between hypercalcaemia and tamoxifen therapy probable. Some of the mechanisms of development of hypercalcaemia in cases of breast carcinoma are discussed, and the literature on hypercalcaemia and tamoxifen therapy is reviewed.

Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine.

Two regimens of chemotherapy for metastatic breast cancer were compared in a randomized controlled fashion. Regimen 1 consisted of cyclophosphamide, vinblastine, methotrexate and 5-fluorouracil (CVMF). Regimen 2 consisted of cyclophosphamide, adriamycin, methotrexate and 5-fluorouracil (CAMF). The patient population consisted of both black and white postmenopausal females who had not received any prior chemotherapy. Objective responses were observed in 25/57 patients treated with CVMF and in 28/51 patients treated with CAMF. Neither race nor choice of chemotherapeutic regimen affected prognosis, although there were differences in the pattern of metastatic involvement between the two racial groups. The median duration of survival of patients who responded to therapy has not yet been reached but will be in excess of 12 months.

Treatment of advanced head and neck cancer by means of radiation therapy plus chemotherapy--a randomised trial.

Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing radical radiation therapy to the primary tumour and associated lymph node areas with a combination of radiation therapy plus chemotherapy. The distribution of tumour types and stages was similar in the two treatment groups. The response rates to radiation therapy alone (50% complete plus parital response) and to radiation therapy plus chemotherapy (60% complete plus partial response) were not significantly different. However, a significant difference in survival was found between the two groups. The median duration of survival for the patients treated by means of radiation therapy alone was 18 weeks; that for the combined therapy was 36 weeks. The combination of radical radiation therapy plus intermittent high-dose chemotherapy was well tolerated and appears to be an approach that warrants further trial.

Oestrogen receptors in tumours of breast cancer patients.

Oestrogen receptors were measured in the cytoplasmic fraction of tumours from patients with breast cancer. Receptors were detected in 48% of patients, and 52% showed no receptors. A follow-up study of a small group of patients on hormone therapy is reported.

The hazards of combined chemotherapy and radiotherapy in rhabdomyosarcoma of the mediastinum: a case report.

A total tumour irradiation dose of 2900 rad and a dose of 2500 rad to a metastasis, as well as the administration of 330 mg/m2 adriamycin, successfully eradicated all traces of malignant disease after partial surgical excision in a 12-year-old Black boy with a rhabdomyosarcoma of the mediastinum. The treatment, however, damaged the heart and caused the death of the patient.

Solitary myeloma. A study of 10 black patients during an 8-year period.

Solitary myeloma of bone occurred in 10 Black patients during the 8-year period from 1967 to 1974. In 4 patients, the solitary myeloma involved the bones of the paranasal sinuses, in 3 patients the pelvis, and in 3 others the manubrium sterni. An IgG monoclonal gammopathy was present in the serum of 4 patients and Bence-Joanes proteinuria was found in 1 patient. Radiation therapy was the treatment of choice and the recommended tumour dosage is 4000-5000 rads. Serial measurements of serum and urine protein electrophoresis and immuno-electrophoresis were most helpful in determining when patients had achieved a complete remission. In 3 patients, 1 of whom died, the myeloma disseminated in periods varying from 26 months to 7 years. Nine patients are alive, of whom 7 are in complete remission, and 5 have lived for more than 5 years since the initial diagnosis of solitary myeloma.