Drug-associated cardiotoxicity.
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Doxorubicin↗
Biomedical subjects
G R Blumenschein
Publications and source records attributed to G R Blumenschein.
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 that 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.
Breast Neoplasms↗
Combined chemoimmunotherapy for advanced breast cancer: a comparison of BCG and levamisole.
One hundred and fourteen evaluable patients with metastatic breast cancer were treated with a program consisting of 5-FU, Adriamycin, cyclophosphamide (FAC) and nonspecific immunotherapy with Levamisole. The results of this treatment program were compared to those observed with FAC and Bacillus Calmette Guerin (BCG) and FAC chemotherapy alone, both groups treated prior to the study reported in this paper. The overall response rates and complete response rates for all three treatment regimens were identical. The duration of remission, survival of all patients and survival of responders was similar for both chemoimmunotherapy regimens, being superior to the FAC chemotherapy alone group. Immunotherapy with Levamisole was well tolerated and side-effects were experienced by less than one-fourth of the patients. Overall, Levamisole was better tolerated than BCG and was easier to administer than the latter drug. These results suggest than nonspecific immunotherapy with Levamisole might prolong remission and survival of patients with metastatic breast cancer. Since the results achieved with BCG and Levamisole appear similar, the therapeutic ratio favors the use of Levamisole.
Antineoplastic Agents↗
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 vincristing 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.
Adult↗
Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer.
Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.
Adult↗
Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG.
One hundred five patients with metastatic breast cancer were treated with 5-fluorouracil, Adriamycin, cyclophosphamide and BCG (FAC-BCG). The results were compared to those observed in a group of 44 patients treated with FAC chemotherapy alone. Although the overall response rates were similar (76% for FAC-BCG and 73% for FAC), the duration of remission was of 9 months for FAC and 14 months for FAC-BCG (p = 0.008). Similarly, survival of responding patients treated with FAC-BCG was significantly longer (24 months) than that observed in the chemotherapy alone treated group (15 months). There was no difference in survival or duration on study for nonresponders. Analysis of response rates by known prognostic factors was unrewarding. The duration of remission and survival, however, were significantly longer for patients with bone soft tissue involvement than for patients with visceral metastasis. Similarly patients with 1 or 2 metastatic sites survived significantly longer than those with more than 3 organ sites involved (p = 0.02). This chemotherapeutic combination is highly effective in inducing remissions. In addition, nonspecific immunotherapy with BCG appears to prolong duration of remission and survival for responding patients.
Adult↗
Combined chemoimmunotherapy and radiation therapy of inflammatory breast carcinoma.
Thirty-two patients with a diagnosis of primary inflammatory breast carcinoma were treated with combination chemoimmunotherapy consisting of 5-fluorouracil, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (FAC) plus BCG followed by radiation therapy. This group of patients was compared to a group of 32 consecutive historical controls treated with radiation therapy alone. The estimated mean disease-free interval for the FAC-BCG group was 16 months, compared to 9 months for the radiation therapy alone group (P less than 0.01). The estimated median survival for the FAC-BCG treated group was 24 months, compared to 18 months for the radiation therapy alone group (P = less than 0.03). The combined modality approach consisting of chemoimmunotherapy and radiation therapy significantly improved the disease-free interval and survival of patients with inflammatory breast carcinoma.
Adult↗
Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.
Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.
BCG Vaccine↗
Hormonal therapy with tamoxifen in male breast cancer.
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Aged↗
High-dose methotrexate for advanced breast cancer.
High-dose infusions of methotrexate with citrovorum factor rescue were evaluated in 27 patients with advanced recurrent breast cancer who had previously been treated with various Adriamycin-containing regimens. Eight of 27 patients (29%) achieved objective tumor regression with a median duration of response of 26 weeks. Nineteen patients had previously received standard doses of methotrexate (less than 50 mg/m2/dose), while eight patients had had no prior exposure to methotrexate. The response rates observed in these two groups of patients were similar. Except for two drug-related deaths, toxic effects were acceptable. Myelosuppression was mild, transient, and noncumulative. Gastrointestinal toxic effects did not appear to be dose-related and were mild in most instances. Central nervous system dysfunction with lethargy, fatigability, confusion, and disorientation was the most significant toxic effect of this high-dose methotrexate therapy and was observed in six (22%) of the patients. In two patients treatment with this program was discontinued because of the development of renal dysfunction. High-dose methotrexate with citrovorum factor rescue appears to be an effective regimen in patients with advanced refractory breast cancer. However, in view of the enormous cost necessitated by this treatment approach, we do not feel further studies would be worthwhile.
Age Factors↗
Ifosfamide versus cyclophosphamide in combination drug therapy for metastatic breast cancer.
A combination of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) was compared to a combination of 5-FU, adriamycin, and ifosfamide (FAI) in the treatment of metastatic breast cancer. All patients in the FAC and FAI groups also received nonspecific immunotherapy with bacillus Calmette-Guérin (BCG) and levamisole. Of 117 evaluable FAC patients, 19 (16%) achieved complete remission and 66 (56%) achieved partial remission. In the FAI group, eight of 49 (16%) evaluable patients achieved complete remission and 24 (50%) achieved partial remission. The response rates, durations of remission, and survival were similar in both groups. The combination of two immunotherapeutic agents (BCG and levamisole) did not have an additive effect since their results were similar to our previous experience with FAC-BCG and FAC-levamisole. In the FAI group, 25% of the patients had hematuria, while none of the patients in the FAC group had urinary complications. Nausea and vomiting were more severe in FAI-treated patients and some patients required iv fluids to correct dehydration. Ifosfamide in combination with 5-FU and adriamycin was more toxic than and not superior to cyclophosphamide.
Adult↗
Rubidazone in metastatic breast cancer.
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Adult↗
Phase II study with sequential L-asparaginase and methotrexate in advanced refractory breast cancer.
The combination of sequential L-asparaginase and methotrexate (MTX) was evaluated in 33 patients with advanced refractory breast cancer. There were nine partial responses and one complete response, giving an overall response rate of 30% and a median duration of response of 8 months. Five of 17 patients (28%) who had received prior MTX at doses of less than 50 mg/m2 responded. Toxicity was acceptable. Moderate-to-severe stomatitis occurred in most patients and was the dose-limiting factor. Myelosuppression was minimal until the dose of MTX was escalated to greater than or equal to 180 mg/m2. The maximum tolerated dose of MTX was 280 mg/m2 and the median toxic dose was 220 mg/m2. These data indicate a selective "rescue" from MTX damage to normal target tissue by L-asparaginase. The antitumor effect observed even in patients who had been previously exposed to conventional doses of MTX suggests a possible improved therapeutic index of MTX given sequentially with L-asparaginase in this combination.
Adult↗
Prognostic factors in metastatic breast cancer treated with combination chemotherapy.
Six hundred nineteen patients with metastatic breast cancer, treated with a combination of 5-fluorouracil, Adriamycin, and cyclophosphamide, or close variations of this program, with or without immunotherapy were analyzed retrospectively to identify those host, tumor, or treatment characteristics that might be of prognostic importance in predicting response to chemotherapy and survival from onset of the 5-fluorouracil-Adriamycin-cyclophosphamide treatments. Primary tumor characteristics such as size of primary, number of axillary nodes involved, stage at diagnosis, and type of surgery used for primary treatment were not found to be of prognostic significance. Host characteristics such as age, menstrual status, or family history of breast cancer were similarly unrelated to outcome. Non-Caucasian patients had a lower response rate and somewhat shorter survival than did Caucasians. Pretreatment weight loss, poor performance status, and abnormal biochemical and hematological values were of adverse prognostic significance. An estimate of total extent of disease based on criteria for rating extent of involvement at 12 potential sites was a much more important prognostic factor related to response and survival than actual sites of involvement or the traditional "dominant site" classification. There was a trend, however, for patients with bone involvement to have a longer survival than did patients with metastases to other organ sites. Shorter survival times were observed among patients exposed to extensive prior radiotherapy and those who failed to respond to prior hormonal treatment. The prognostic variables identified in this paper should be used for the design and comparison of clinical trials in the future.
Adult↗
Pituitary-ovarian function in breast cancer patients on adjuvant chemoimmunotherapy.
One hundred thirty-one patients with operable breast cancer were treated with adjuvant chemoimmunotherapy consisting of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG). Fifty-five of 131 patients were premenopausal of which 71% (38/55) became amenorrheic. To determine the mechanism of amenorrhea, we measured the immunoreactive serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and plasma estradiol (E2) before and after intravenous administration of luteinizing hormone-releasing hormone (LH-RH) in 11 unselected premenopausal patients who developed amenorrhea and 11 unselected patients who did not. Serum prolactin (PRL) levels were also measured before and after iv administration of thyrotropin-releasing hormone (TRH). Our results showed that patients who developed amenorrhea had abnormally high serum LH and FSH levels at basal and after LH-RH stimulation and low plasma estradiol. Serum PRL levels were normal. Patients who developed amenorrhea were older than those who did not, but their serum LH and FSH levels were also significantly higher and plasma estrogens were significantly lower than that found in 11 normal women with regular menses of the same age range. These results indicate that amenorrhea that develops in some patients with breast cancer after FAC-BCG therapy is a result of primary ovarian failure.
Adult↗
Immunotherapy with BCG administered by scarification: standardization of reactions and management of side effects.
The method of administering BCG by scarification is described in detail. A system of classifying the intensity of local reactions is proposed to standardize administration. The experience of the M.D. Anderson Hospital involving over 2700 patients is reviewed. Administration of BCG by scarification has been accomplished with safety and has been well tolerated and accepted. The most commonly observed side effects are discussed as well as their management.
Angina Pectoris↗
Adjuvant therapy of stage II, III breast cancer.
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Antineoplastic Agents↗
Thyroid-stimulating hormone and prolactin levels in breast cancer.
Serum thyroid-stimulating hormone (TSH) and prolactin (PRL) levels were measured before and after intravenous administration of protirelin to 148 patients with breast carcinoma. There was a high prevalence (36%) of elevated basal TSH; however, most of the patients were euthyroid and had normal serum thyroxine and T3 resin uptake. The PRL level was elevated in 22% of the cases. Both the mean PRL and the mean TSH levels for the breast cancer patients were significantly elevated above the respective means in a control group. We could find no correlation between serum TSH and PRL levels, suggesting that the purported association between a decreased thyroid state and breast cancer is probably not mediated through an increased PRL level. The mean survival and mean disease-free interval were shorter for patients with either elevated TSH or elevated PRL levels, but in neither case was the difference statistically significant.
Adult↗