In order to determine the natural history and results of treatment of intracerebral metastases in solid-tumor patients, the records of 191 patients with an antemortem diagnosis of intracerebral metastasis made during the period from August 1974 to November 1978 were reviewed. Malignancies included lung (122 patients), breast (26), unknown primary (16), melanoma (8), colorectal (6), hypernephroma (4), and others (12). Favorable prognostic factors included solitary brain metastasis (P less than 0.001), ambulatory performance status (P less than 0.001), symptoms of headache (P less than 0.001), or visual disturbances (P less than 0.02), and estrogen receptor positivity in breast cancer patients (P = 0.055). Poor prognostic factors included advanced age (P less than 0.04) and evidence of impaired consciousness, i.e., disorientation, lethargy, stupor, or coma (P less than 0.007). Median survival time after diagnosis of intracerebral metastasis was 3.7 months for the entire series. In those patients with a single intracerebral metastasis and minimal tumor burden, the type of treatment used had a significant impact on survival. Those cases treated with surgery and radiation had a median survival time of 9.7 months versus 3.7 months for those treated with radiation alone (P less than 0.02). When using a proportional hazard regression analysis to adjust for the three most important prognostic factors, treatment (surgery and radiation versus radiation alone) still appeared to be important. Intracerebral metastases were the immediate or contributing cause of death in 50% of the patients in this series. Patients at greater risk of dying of intracerebral metastases included those in whom the brain was the first site of distant metastasis, those with an intracerebral metastasis from an unknown primary site, and those whose presentation of malignancy was with symptoms of a brain metastasis. Although the therapeutic goal in intracerebral metastases is generally palliative, it appears that there are categories of cases that may benefit from more aggressive treatment.
Antiestrogen therapy may offer the possibility of useful and, occasionally, long-term palliation of refractory epithelial ovarian carcinoma, with little toxicity. There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial.
Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH, 3,4-NH2, 2,3,4- and, 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50 = 3.5 microM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg)/day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.
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