Charles L. Wiseman

Management of breast cancer patients failing adjuvant chemotherapy with adriamycin‐containing regimens

Sixty‐two patients with breast cancer treated with Adriamycin‐containing adjuvant chemotherapy developed recurrent disease. Four patients refused to take any form of systemic therapy at the time of relapse. Fifty‐eight patients were managed with various treatment modalities, and of these 33 (57%) achieved on objective remission, 11 (19%) had stable disease and 14 patients (24%) did not respond to any form of therapy. Twenty‐four patients received more than one treatment modality. Thirty‐eight patients were treated with chemotherapy and 35 received endocrine therapy. Eight of 20 patients (40%) achieved objective remission upon retreatment with higher dose of 5‐fluorouracil, Adriamycin, and cyclophosphamide at time of relapse, and seven of 18 patients (38%) treated with other chemotherapeutic agents showed objective remission. Fourteen of 35 patients (40%) achieved objective remission with hormonal therapies. The median survival from first relapse was 15 months for all patients, and was 25.7 months for responding patients. Survival was significantly longer in asymptomatic patients compared with those who were symptomatic from recurrent disease.

Electrocardiographic changes after adriamycin chemotherapy

The electrocardiograms of 146 patients with metastatic carcinoma of the breast were reviewed before, during, and after the patients received Adriamycin (Doxorubicin) chemotherapy (AD). The most significant electrocardiographic change occurred in the amplitude of the QRS voltage. Seven patients developed cardiomyopathy after AD and showed a significant decrease in QRS voltage. This decrease, however, was more severe at the onset of congestive heart failure than at conclusion of Adriamycin. In 35 patients with pleural effusion, there was an inverse relation between the extent of the effusion and the amplitude of QRS voltage in the absence of congestive heart failure. These results indicate that 1) the sudden and relatively severe decrease in QRS voltage with the onset of CHF limits the value of this ECG criterion for predicting early Adriamycin toxicity, and 2) caution should be exercised in the interpretation of QRS voltage changes in patients with significant pleural effusion. Cancer 43:465–471, 1979.

Phase II trial of bruceantin in metastatic breast carcinoma.

A PHASE II EVALUATION OF BRUCEANTIN was carried out in 15 patients with refractory metastatic breast cancer. All patients had received extensive prior therapy including adriamycin, cytoxan, 5-FU, methotrexate, and a vinca alkaloid. Except for two patients with stable disease, no complete or partial response was observed. Drug toxicity, mainly nonhematologic, was severe, with nausea, vomiting, mild hypotension, and fever being the most frequently encountered.

Combination chemotherapy with vincristine and methotrexate for advanced refractory breast cancer

Eighteen patients with advanced breast cancer refractory to combination chemotherapy with 5‐FU, Adriamycin, Cytoxan (FAC) were treated with methotrexate 30 to 40 mg/m2 iv and vincristine 1.5 mg/m2 iv at weekly intervals. Of 17 evaluable patients, 4 (23%) achieved a partial remission with a median duration of remission of 6 months and a median survival of 10 months. In another seven of seventeen patients (41%) the disease remained stable. Toxicity was minimal.

Phase II evaluation of vinblastine, methotrexate, and calcium leukovorin rescue in patients with refractory metastatic breast cancer

Seventy‐five evaluable patients with metastatic breast cancer refractory to frontline chemotherapy were treated with vinblastine 1.5 mg/m2 by continuous intravenous infusion for five days, intravenous infusion of methotrexate 200 mg/m2, and appropriate calcium leukovorin rescue. Thirty‐eight patients were treated with vinblastine followed by methotrexate and calcium leukovorin, while 37 patients were treated with these same drugs in reverse sequence. In 17 patients (23%) an objective remission was achieved, while 39 remained stable for a period in excess of eight weeks. The median duration of remission was two months, and the median duration of survival was six months. The two regimens were well balanced for commonly used pretreatment prognostic factors. There was no difference in response rate and duration of response between the two treatment regimens. In patients with no prior exposure to methotrexate, the remission rate was 37% (11 of 30) compared with 13% (6 of 45). The treatment was well tolerated, and the dose‐limiting toxicity was myelosuppression. This combination of drugs is effective in patients who have not been exposed to either drug, while it is only marginally effective in patients previously treated with methotrexate or vinblastine.

Preparation of suspensions of single cells from monolayer cell cultures without enzymatic dissociation

0 Most human epithelial tumors are maintained in vitro as monolayer cultures. Utilization of cell lines to s tudy cell kinetics and the factors that may influence cell proliferation requires the preparation of single cells in suspension, if cell counting techniques are employed. Single cell suspensions can be obtained from many cell lines by enzymatic t reatment (1), e.g. with trypsin, disodium ethylenediamine tetraacetic acid or collagenase. The effects of proteolytic enzymes on the sensitive cell membrane and its numerous receptors are not completely understood (2). We describe here a method for the preparation of suspensions of single cells from cell lines maintained as monolayers, without using enzymatic dissociation.