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.

Earlier studies suggested that the dose of 6-mercaptopurine (6-MP) can be reduced substantially when the drug is given with allopurinol. We studied the effect of allopurinol on the kinetics of oral and intravenous 6-MP. Studies conducted initially in rhesus monkeys and subsequently in man with 6-MP doses of 100 mg/m2 and 75 mg/m2, demonstrated that allopurinol pretreatment resulted in a nearly 400% increase in peak plasma concentration of oral 6-MP in monkeys (from a mean of 0.54 microM to a mean of 2.1 microM) and a 500% increase in man (0.74 microM to 3.7 microM). Allopurinol pretreatment also led to a 300% increase in plasma AUC in monkeys after oral 6-MP (from a mean of 121 microM/min to a mean of 391 microM/min) and a 500% increase in AUC in man (from a mean of 142 microM/min to a mean of 716 microM/min). In contrast, allopurinol pretreatment had no effect on the kinetics of intravenous 6-MP. This difference was found to be due to inhibition of first-pass metabolism of oral 6-MP as the result of the action of allopurinol on liver or intestinal xanthine oxidase. Our results indicate that, although dose reduction of oral 6-MP given in conjunction with allopurinol is appropriate, it is not necessary when 6-MP is injected intravenously.

A randomized clinical trial was performed to determine the effectiveness of scalp hypothermia in the prevention of hair loss associated with doxorubicin. Twenty‐six patients were randomized to receive scalp hypothermia or chemotherapy alone. Data were analyzed on 25 patients: 12 in the treatment group and 13 in the control group. There was acceptable hair preservation in 75% of the patients who received the scalp hypothermia; only 8% of the patients in the control group had acceptable hair preservation (P = 0.0009). The data were further broken down into patients receiving low‐dose doxorubicin and high‐dose doxorubicin. Side effects were minimal. The results support the use of scalp hypothermia in reducing doxorubicin‐induced alopecia.

To better characterize the disposition of cytosine arabinoside (Ara-C) in cerebrospinal fluid (CSF), its kinetics were studied in seven patients with meningeal leukemia in complete remission. After intraventricular injection of 30 mg Ara-C, CSF and plasma samples were obtained over a 24-hr period. Ara-C levels were measured by a reverse-phase HPLC assay (with a sensitivity of 0.5 microM in CSF and 1.0 microM in plasma) that readily separated Ara-C from its major metabolite uracil arabinoside (Ara-U). Elimination of Ara-C from CSF followed a biphasic pattern, with an initial t1/2 of 1 hr and a terminal t1/2 of 3.4 hr. Ara-C clearance from CSF was 0.42 ml/min, suggesting that drug elimination was primarily by CSF bulk flow. The ratio of the AUC of Ara-U to the AUC of Ara-C was 0.08, indicating only minor metabolism of Ara-C to Ara-U in CSF, in contrast to that after systemic Ara-C. Despite initial CSF Ara-C concentrations exceeding 2 mM, Ara-C was not detectable in plasma in any patient. Intraventricular Ara-C results in very high levels in CSF, but systemic tissues are relatively spared from exposure to Ara-C.