Adriamycin cardiotoxicity: a survey of 1273 patients.

Valuable information was collected on the medical history and clinical course of 1273 patients entered in clinical trials with Adriamycin (ADR) carried out in 12 European cancer centers. A coded patient form was used for the data collection carried out in each center by a qualified physician following a guideline which was discussed and accepted by all of the participants. The aim of the study was to define the incidence, characteristics, and possible co-factors of the cardiomyopathy (CMP) in patients treated with combination chemotherapy regimens including ADR. The mean total dose of ADR was 268 mg/m2 (range, 15--1251 mg/m2), and 5.1% of the patients received a total dose of greater than 550 mg/m2. A "definite" ADR-related CMP was observed in 1.7% of the cases; another 3% of the cases were reported as "possible" ADR-CMP since the role played by the drug could not be clearly defined. "Definite" ADR-CMP was fatal in eight patients (0.6%) while "possible" ADR-CMP was fatal in 13 patients (1.0%). Among the possible co-factors examined, the following ones were found to be significantly associated with the occurrence of a "definite" ADR-CMP: (a) total dose of ADR; (b) vincristine when given both before and concomitantly with ADR; (c) bleomycin when given before ADR; and (d) radiotherapy to the mediastinum when given concomitantly with ADR. Furthermore, none of 182 patients receiving ADR by slow infusion developed a "definite" ADR-CMP, while 2% of the patients treated by bolus injection did so. The occurrence of a "possible" ADR-CMP was found to be significantly associated with two pre-existing pathologic conditions (electrocardiogram [ECG] abnormalities and hypertension) but not with the treatment-related co-factors for the "definite" ADR-CMP mentioned above. Other variables examined, such as sex, age, cancer type, baseline liver function, and cyclophosphamide treatment, did not seem to influence the risk of ADR-CMP. Data on ECG changes occurring during ADR treatment were also reported and their incidence was found to be strictly related to the frequency of the ECG monitoring.

Hormone interference in metastatic breast cancer patients treated with medroxyprogesterone acetate at massive doses: preliminary results.

PIP: Medroxyprogesterone acetate (MAP) was administered at daily doses of 2000 mg every 12 hours for 30 days to 2 premenopausal and 8 menopausal patients suffering from advanced breast cancer. The average age was 59 years and the range was 42-70. Measurements were carried out on plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), somatotropin (GH), and prolactin (PR) by radioimmunological assay, and on 17-ketosteroids (17-KS) and 17-hydroxycorticoids (17-OCHS) in 24 hour urine samples. In 6 patients, steroid levels were measured for 2-7 months after treatment. 17-KS values dropped considerably during the 1st week of treatment but were higher than the basal values at the end of treatment, although the difference was not significant. A significant increase was observed in urinary 17-OHCS due to MAP metabolites having dihydroxyketonic side-chain. Values were also higher than basal levels in the 6 patients followed for 2-7 months. LH and FSH plasma levels dropped significantly during treatment and remained low throughout the administration periods, and values for 3 patients checked after 3-5 months were still lower than basal levels. Plasma GH, already at low basal levels, decreased further during treatment and showed no further significant changes during or after treatment. MAP at massive intramuscular doses is absorbed, metabolized, and excreted mainly by a urinary route as steroids with a dihydroxyketonic side-chain, and to a lesser extent as 17-KS. Clinically observed hypercortisonism can be explained by transformation of the steroid administered to corticord. MAP caused a strong inhibition of the pituitary, as shown by LH and FSH levels. The results of the study, while not definitive, demonstrate that the antiblastic effect of the drug can be at least partially explained.^ieng

A possible new approach to the treatment of metastatic breast cancer: massive doses of medroxyprogesterone acetate.

The results obtained with a new hormone therapy using medroxyprogesterone acetate (MAP) in previously untested single and total doses in the treatment of advanced breast cancer are reported. Fifty-two postmenopausal patients were treated with an average total dose of 40 g of MAP for a period of 30 days. Nineteen of 44 patients (43%) had complete or partial remission, while the disease remained unchanged in nine of 44 patients (20%). Disease progression occurred in 12 of 44 patients (27%). Partial or complete remission occurred in 12 of 18 (67%) and four of six (67%) of the patients with dominant osseous and soft tissue metastases respectively. Three of ten (16%) of those with visceral metastases had remission. The average duration of remission was 7 months. Average survival times were 15.5 months for patients with remission, 8 months for those with no change, and 2.5 months for those with disease progression. From a subjective standpoint, pain was reduced significantly or disappeared in 34 of 36 patients (94%); this was also the case with respect to dyspnea (13 of 16 patients [81%]), anorexia (24 of 29 [83%]), asthenia (28 of 35 [80%]), and walking impairment (15 of 24 [63%]). When relapse occurred, patients previously treated with massive doses of MAP received further treatment with higher doses of MAP; four of 22 (18%) of the patients attained partial remission once again. Positive effects were also seen in subjective performance status, body weight, and EKG. We also describe the new clinical and toxicologic features of this treatment.