The present phase III trial was carried out to verify whether a kinetic recruitment induced by low doses of diethylstilbestrol (DES) could increase the killing efficacy of chemotherapy in patients with locally advanced breast cancer. One-hundred and seventeen untreated patients with locally advanced breast cancer (stage IIIA/IIIB) were randomized to receive 3 courses of primary chemotherapy consisting of cyclophosphamide (600 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.) and fluorouracil (600 mg/m2 i.v.) (CAF) on day 1, or DES-CAF (DES, 1 mg orally days 1-3, CAF on day 4). The courses were repeated every 3 weeks. The patients who achieved an objective response were submitted to mastectomy followed by 3 courses of CAF alternated with 3 courses of CMF (cyclophosphamide, 600 mg/m2 i.v.; methotrexate, 40 mg/m2 i.v.; fluorouracil, 600 mg/m2 i.v.), with or without DES. The two treatment arms were well balanced in terms of clinical and pathologic features. There was no significant difference in response rates to induction chemotherapy between the two treatment arms (objective response rate, 63.3% for CAF and 56.1% for DES-CAF). Median overall survival was 49 and 47 months and median progression-free survival was 24 and 21 months for CAF and DES-CAF patients, respectively. Toxicity was not significantly different in the two groups, with the exception of leukopenia: DES chemotherapy was significantly more myelotoxic than the standard treatment, which resulted in a significant reduction in the actual dose intensity. In spite of the attractive experimental evidence, we conclude that so far there is no clinical advantage in the combination of estrogen and chemotherapy. Further research is needed to investigate different schedules of chemotherapy and hormones, or to test the possibility of combining various mitogens.

Few and conflicting reports have so far been published on the urinary excretion of luteinizing hormone (LH) in childhood (for reference, see Leone & Sciarra (1966 a) and Rifkind, Kulin & Ross (1967). Further investigation seemed therefore indicated.The daily excretion of LH was determined semiquantitatively in 24 normal, healthy and non-hospitalized prepubertal children (12 boys and 12 girls), aged 5\p=n-\10 yr. A complete 48 hr. urine specimen (1000\p=n-\2000 ml.) was collected from every subject without the use of a preservative and stored in a cold room at 4\ s=deg\ .Within 3 days of the urine collection, each sample was extracted by Johnsen's tannic acid method (1958) but using, as a rule, the highest concentrations of reagents suggested by the Danish author. Twenty-four hours before assay, the dry precipitates were ground to fine powder and redissolved in a 0\m=.\9% NaCl solution. As described by Sciarra, Pastorino & Leone (1968) the powders proved so soluble that they could be dissolved in very small amounts of saline 0\m=.\5\p=n-\ml.); consequently, urinary LH was concentrated up to 1000-4000 times with a 67 + 5 % recovery rate. After centrifugation, the supernatants were serially diluted with intervals of 1:1-5. LH was assayed by the immunological method of Wide & Gemzell (1962) but using the reagents of the Pregnosticon Test (Organon), the sensitivity of which was previously established at 1-6 i.u. LH (2nd IRP-HMG)/ml. (Leone & Sciarra, 1966&). The excre¬ tion results were corrected for the 33 % mean methodological loss by tannic acid extraction.In order to evaluate the results, reliability criteria for the method and regression of LH excretion on age for both males and females, with 95 % confidence limits, were calculated. Tests for deviation from parallelism were carried out. The accuracy of the method was in the region of 100 % ; its precision was high (mean = 0-12, range 0-08 to 0-15); its sensitivity was in the range of 0-6-1-2 i.u. LH/24 hr. urine vol. With regard to specificity, the test failed with several urinary extracts from two hypophysectomized young women; virtually no LH activity could be detected in the same extracts by the ventral prostate weight method as modified by McArthur (1952). However, the results were positive in pregnant women. Figure 1 shows that LH was detected in all the children investigated ; the mean urinary hormone level in boys was 2-9/i.u. LH/24 hr. (range 1-2-5-4) and 2-8 i.u./ 24 hr. in girls (range 0-6-5-4); it increased with age in both sexes and more rapidly in females than in males.These results, together with the observations of previous workers who demon-

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