R.K. Knight

Combined chemotherapy and radiotherapy for locally advanced breast cancer

Abstract To test the feasibility of combining radiotherapy and chemotherapy as the primary management of locally advanced breast cancer, 24 patients were allocated to receive either 4 courses of adriamycin and vincristine (AV) followed by radiotherapy, followed by 8 courses of cyclophosphamide, methotrexate and 5 -florouracil (CMF) (group A) or radiotherapy followed by 4 courses of AV followed by 8 courses of CMF (group B). The objective regression rate after AV and radiotherapy was 10/12 ( 83% ) in group A and 11/12 ( 92% ) in group B, but the subsequent relapse rate was high being 6/12 ( 50% ) in group A and 7/12 ( 58% ) in group B. The pattern of relapse, duration of objective regressions and survival in groups A and B were the same. No serious adverse side effects arose from combining chemotherapy and radiotherapy in either group. In a retrospective comparison of groups A and B with patients treated previously by radiotherapy alone, the median duration of response in this series of 33 months was significantly longer than in patients treated by radiotherapy alone ( 10.5 months ); P ≤ 0.001. Although the survival experience of the combined groups A and B (median 36 months ) was higher than that in the previous series (25 months) this difference is not statistically significant. While these retrospective comparisons give rise to optimism that combining radiotherapy and chemotherapy may be helpful in the treatment of locally advanced breast cancer, prospective randomized controlled trials are now necessary to determine whether a true improvement in results can be achieved by this approach.

CONTROLLED TRIAL OF ADJUVANT CHEMOTHERAPY WITH MELPHALAN FOR BREAST CANCER

370 patients who had carcinoma of the breast with involved axillary lymph-nodes were randomised after total mastectomy and axillary clearance to receive either no additional treatment or melphalan 6 mg/m2 daily for 5 days every 6 weeks for sixteen cycles. There was a trend towards longer relapse-free survival (RFS) in patients treated with melphalan, but this was not significant either in the whole series or in sub-groups according to menopausal status or extent of nodal involvement. In patients receiving melphalan RFS was not significantly affected by either the occurrence of amenorrhoea or the dosage of melphalan received. Overall survival did not differ significantly between the two groups. The results of this trial suggest that there is no place for the use of melphalan as adjuvant therapy in the management of early breast cancer.

Adriamycin alone or combined with vincristine in the treatment of advanced breast cancer

One hundred and nineteen women with advanced breast cancer treated previously by endocrine therapy but no prior chemotherapy were given adriamycin 70 mg/m2 i.v. on day 1 of a 3-weekly cycle for 8 courses, followed by a regimen of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) until relapse. They were allocated randomly to receive either no treatment (group A) or vincristine 1.4 mg/m2 i.v. on days 1 and 8 during treatment with adriamycin (group AV). In 107 evaluable patients objective responses were seen in 30/53 patients (57%) in group A and in 28/54 patients (52%) in group AV. The projected dose of adriamycin received was 78% in group A and 75% in group AV; and 60% for vincristine in group AV. The subjective and haematological toxicity for adriamycin was similar in both groups, but 65% of patients treated with vincristine developed neurotoxicity. The median duration of objective regressions was the same for both groups (7 months), and the median time to failure was 5 months for group A and 6 months for group AV respectively. The median survival of the responders tended to be longer in group AV (17.5 months) than in group A (13 months), but this difference was not statistically significant (P = 0.112). It is concluded that there is no advantage therapeutically in combining vincristine and adriamycin in patients with advanced breast cancer.

Combined cytotoxic and progestogen therapy for advanced breast cancer

Sixty‐nine patients with advanced breast cancer treated with cytotoxic chemotherapy were randomized to receive concomitantly either norethisterone acetate (progestogen group) or a placebo (placebo group). Objective responses were seen in 53% of patients in the progestogen group and 61% of patients in the placebo group. The median duration of response was the same for both groups (38 weeks). Three out of ten patients in the placebo group, who received subsequently the progestogen on relapse, had a further objective regression. The overall survival in the two groups was similar, although in a sub‐group of patients who had operable tumors, but a subsequent short disease‐free interval, survival was significantly better in the placebo group. There was less myelosuppression in the progestogen group, who were able to receive higher doses of cytotoxic drugs. Less nausea and vomiting occurred in the progestogen group, but other subjective side effects were similar. It is concluded that there is no advantage therapeutically in combining cytotoxic chemotherapy and progestogen therapy and, in some patients, better results are obtained using the two treatments sequentially. Cancer 42:1680–1686, 1978.

Mitoxantrone in advanced breast cancer—a phase II study with special attention to cardiotoxicity

Thirty-four patients with advanced breast cancer, who had not received previous chemotherapy for metastatic disease, were treated with mitoxantrone 14 mg/m2 i.v. every 21 days. Eleven of 33 evaluable patients (33%) achieved a partial response; there were no complete responders. Before commencing mitoxantrone, and 3-monthly thereafter, radionuclide assessment of ventricular performance was obtained at rest and in response to stress. Ten patients showed a deterioration in ejection fraction, two of whom developed congestive cardiac failure. Dose-limiting toxicity was myelosuppression. Nausea and vomiting were generally mild and transient. Alopecia was minimal in most patients. Mitoxantrone is an active, well-tolerated new drug in the treatment of advanced breast cancer, but cardiotoxicity may occur in a proportion of patients. Further investigation is required to determine the precise nature, incidence and prognosis of cardiotoxicity encountered with mitoxantrone.

Contribution of prednisolone to the primary endocrine treatment of advanced breast cancer

Two hundred and four patients with progressive locally advanced or metastatic breast cancer not controllable by local therapy alone, and who had had no prior systemic therapy for advanced disease, were treated by primary endocrine therapy according to menopausal status. Premenopausal patients received ovarian irradiation (O) whilst postmenopausal patients received tamoxifen 10 mg b.d. (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg b.d. (P). In 180 evaluable patients, T + P induced significantly more responses than T alone (26/73 vs 9/72, P less than 0.01) and the addition of P to O in premenopausal patients also induced more responses than O alone (7/16 vs 4/19), but this difference was not significant and accrual of premenopausal patients continues. There was a trend for patients receiving T + P to have a longer survival than those receiving T alone (median 25 vs 16 months). These trends occurred in patients with tumours positive for oestrogen receptors and when receptor status was unknown; patients with receptor-negative tumours had a negligible response to endocrine treatment. P mitigated the occurrence of hypercalcaemia and tumour flare sometimes seen with T alone.

Corticosteroids for elderly patients with breast cancer

Ninety‐one assessable elderly women (⪖65 years) with advanced breast cancer were treated with prednisolone 15 mg (or cortisone 75 mg) daily after primary endocrine treatment (estrogens, androgens or tamoxifen). Thirteen (14%) achieved an objective regression, and 19 (21%) others showed no change for ⪖six months. Hence, 32 patients (35%) had control of disease for about one year. Responses were mainly in soft tissue and skeletal lesions and were independent of response to prior endocrine treatment. Toxicity was low. Low‐dose corticosteroid treatment is of value in controlling advanced breast cancer in elderly women.

Diagnosis and management of malignant pleural effusion

Pleural effusions are a common clinical problem in patients with metastatic malignant disease. Management is sometimes difficult but it is usually possible to relieve the distressing breathlessness suffered by such patients with local treatment. Surprisingly, in spite of a wealth of experience, the ideal treatment of this condition is still controversial. In addition, little data exist regarding patient selection for what is necessarily a palliative procedure. This article aims to review the management of malignant pleural effusion and considers what features may help the selection of patients suitable for different forms of available treatment.

Mitomycin C and vinblastine in the treatment of advanced breast cancer

Forty-nine women with progressive metastatic breast cancer, extensively pretreated, received mitomycin C 12 mg/m2 and vinblastine 6 mg/m2 intravenously every 3 weeks. Eleven patients responded, giving a response frequency of 22%. Considering only the 40 patients evaluable after two or more courses of treatment, the response frequency is 27.5%. Responses occurred predominantly at soft tissue sites. Subjective toxicity was mild.

Norethisterone acetate in the treatment of advanced breast cancer

One hundred and twenty-five patients with progressive advanced carcinoma of the breast were treated with norethisterone acetate 20 mg tds orally after prior hormonal treatment or chemotherapy. Ninety-nine patients are evaluable for response. Sixteen patients (16%) achieved a partial response (median duration 4.5 months), 26 (26%) had stable disease (median duration 3 months) and 57 (58%) developed progressive disease on treatment. Patients who responded to norethisterone acetate had more often responded to prior hormonal or ablative treatment (56% vs 25%) and had received less prior treatment than those who did not respond (p less than 0.05). There was no statistically significant correlation between response and age, menopausal status, disease-free interval, stage at diagnosis, or distribution of disease. Side effects led to cessation of therapy in nine patients (9%).