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The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline and/or taxanes, were treated with mitoxantrone 10 or 12 mg m(-2) intravenously on day 1 plus gemcitabine in escalating doses from 600 to 1200 mg m(-2) intravenously on days 1 and 8, every 3 weeks. In phase I, on 23 patients entered on study, dose-limiting toxicity occurred at the dosage of 1200 mg m(-2) gemcitabine and 10 mg m(-2) mitoxantrone, with three out of five patients developing grade 4 neutropenia. In phase II, with gemcitabine administered at 1000 mg m(-2) and mitoxantrone at 10 mg m(-2), 12 (30%) out of 40 assessable patients responded, even if no complete response was obtained. Moreover, stable disease was observed in eight (20%) patients. The median time to treatment failure was 22 weeks (range, 2-33), and median survival was 42 weeks (range, 2-92). Grade 3 and 4 neutropenia were observed in 12 (30%) and one (2.5%) cases respectively; grade 3 thrombocytopenia was observed in two patients (5%), grade 2 mucositis in two patients (5%), grade 3 anaemia in two patients (5%), grade 3 alopecia in one patient (2.5%) and asymptomatic cardiotoxicity in three patients (8%), respectively. In conclusion, the doses of 10 mg m(-2) (day 1) for mitoxantrone and 1000 mg m(-2) for gemcitabine (days 1-8) every 3 weeks resulted active and safe in MBC. Further investigations in less heavily pretreated patients are warranted. [ABSTRACT FROM AUTHOR]

In the present study, the primary tumor angiogenesis characteristics of 81 stage IV previously untreated breast cancers with synchronous metastasis to different distant sites (10 patients with soft tissue metastases, 31 with bone metastases, and 40 with visceral metastases) were analyzed. The primary intratumor microvessel density was assessed by immunohistochemical assay on paraffin-embedded primary tumor samples, using a monoclonal anti-CD34 antibody. The mean primary intratumor microvessel density (at 400× fields) was 78±39 (SD) microvessels per field. The microvessel density was not significantly related to the main clinical/pathological features of the tumor (age, cytohistological grade, DNA ploidy, diameter, and receptor status). The percentage of tumor cases with high primary intratumor microvessel density (cut-off median value of the series 73±39 microvessels/field) did not significantly differ in patients with bone, soft tissue, or visceral metastatic disease. Aanalysis of clinical outcome showed a significantly shorter time to progression and overall survival for patients with visceral metastases ( P<0.001 and P<0.0002 by log-rank, respectively). Presence of visceral metastases was confirmed to be the only independent prognostic factor related to a worse TTP (hazard risk 2.15, 95% confidence interval 1.14–4.03, P<0.02) and overall survival (hazard risk 1.81, 95% confidence interval 0.98–3.35, P<0.06) by multivariate analysis. In conclusion, the assessment of neoangiogenesis of primary breast cancer by CD34 expression does not provide information predictive of different distant sites of metastasis. [ABSTRACT FROM AUTHOR]

The value of combination chemotherapy with HEXA-CAF was analyzed in 31 patients with histologically documented epithelial ovarian cancer in advanced stages (minimal or gross disease). No patient had been previously treated with chemotherapy. Peritoneoscopy with diaphragmatic inspection, peritoneal cytology, lymphography, and chest X-ray were routinely used in staging and restaging the patients. Complete (CR) plus partial (PR) responses were obtained in 13/31 fully restaged patients (41.9%). CR was recorded in seven patients (22.5%) and PR in six patients (19.3%). Remission duration was significantly longer in patients who achieved CR (20 months) than in those who attained PR (9.5 months) (P Less Than 0.01). In all treated patients the median duration of survival was 16.5 months. Survival was significantly longer in patients with CR than in patients who did not achieve CR (P Less Than 0.05). Nevertheless, considering the rate of CR in patients with gross disease (20.6%), HEXA-CAF combination seems a useful but not yet a hopeful treatment for patients with advanced ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Combined treatment modality was applied in 110 consecutive women with primary inoperable (T3b-T4) Breast cancer. Treatment was started with four cycles of adriamycin plus vincristine (AV). This was followed in responders by high-energy radiotherapy (RT). At the end of combined therapy, patients in complete remission (CR) were randomized to either no further treatment or six more cycles of chemotherapy. AV induced objective response in 89% of patients (complete 15.5%, partial 54.5%, improvement 19%). At the end of RT, 81% of 98 (82.7%) patients responding to AV were classified in CR. The median duration of CR was 15 months. The median free interval was statistically prolonged by additional chemotherapy. The three-year survival was 52.8%. Altogether, present findings indicate that combined treatment modality has improved the three-year survival compared to the previous series treated with radiotherapy alone. However, to achieve a satisfactory control of T3b-T4 breast cancer a more aggressive and prolonged treatment is required. [ABSTRACT FROM AUTHOR]

Using a new immunoradiometric assay, a total of 100 cytosols obtained from primary breast tumors were examined for content of pS2, an estrogen-regulated protein. In our series, the median pS2 value was 5 ng/mg protein cytosol which was used as the cut-off. pS2 content was not correlated with menopausal status, tumor size, nodal involvement or tumor proliferative activity expressed as labeling index (tritiated thymidine LI). A positive correlation was found between pS2 and estrogen (ER) and progesterone (PgR) hormone receptors. pS2 in association with ER and PgR seems to identify tumor subgroups with diverse hormone responsiveness. Moreover, in favorable and unfavorable prognostic subgroups, LI and pS2 further emphasize this prognostic diversity. Copyright © 1993 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]