摘要:

The combination chemotherapy including mitoxantrone, fluorouracil and leucovorin has proven to be effective and well-tolerated in advanced breast cancer (ABC). No data are available on the association with navelbine, a new vinka alkaloid, which has demonstrated high activity in ABC. The trial was designed to evaluate feasibility and efficacy of the association of vinorelbine to mitoxantrone, fluorouracil and L-leucovorin in patients who failed a previous regimen for ABC or who relapsed within 6 months of adjuvant chemotherapy. The schedule was as follows: mitoxantrone 6 mg/m2 days 1 and 8; L-leucovorin 250 mg/m2 days 1 and 8, fluorouracil 600 mg/m2 days 1 and 8, vinorelbine 25 mg/m2 days 1 and 8, cycles being repeated every 21 days. Twenty-five patients were enrolled and are evaluable for response and side effects. One hundred cycles of therapy have been delivered (median/patient, 4 cycles). In 41 cycles a delay was required and in 38 cycles it was necessary to administer granulocyte colony-stimulating factor for neutropenia. Seven partial remissions (28%; 95% confidence interval, 12–49%), 10 stabilizations of disease and 8 progressions were observed. Although grade 4 neutropenia was observed in 44% of the patients, no grade 3-4 infections were observed. Nonhemato-logic toxicities were mild or moderate and included alopecia, mucositis and phlebitis. In conclusion, the schedule employed, although correlated with a moderate activity, does not seem to be superior to other regimens with mitoxantrone, fluorouracil, and leucovori

ISSN:0030-2414    

DOI:10.1159/000227506

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

It has been demonstrated that breast surgery may induce prolactin (PRL) increase. Because of the potential stimulatory role of PRL on breast cancer cells, its postoperative increase may influence the prognosis of breast cancer patients. This study was performed to evaluate the influence of surgery-induced hyperprolactinemia on recurrence rate in operable breast cancer. The study included 250 consecutive breast cancer patients, clinical stage Tl-3 N0-2M0, who were observed for a median follow-up of 72 months. Surgery-induced hyperprolactinemia occurred in 108/250 patients (43%). Irrespectively of node involvement, hormonal receptor, type of surgery and adjuvant therapies, the relapse rate was significantly higher in patients who had no surgery-induced hyperprolactinemia than in those with postoperative PRL increase (64/142 vs. 23/108; p < 0.001). This difference was also significant in relation to node status (NO: 22/63 vs. 5/56, p < 0.001; N+: 42/79 vs. 18/52, p < 0.05). The present study shows that a surgery-induced rise of PRL, despite its potential stimulation of cancer cell growth, is paradoxically associated with a longer disease-free survival in operable breast carcinoma in both patients with or without axillary node involvement. Moreover, this study suggests that the prognosis of node-negative patients who did not show postoperative hyperprolactinemia tends to be similar to that of patients with node involvement and surgery-induced PRL enhancement. Therefore, the lack of surgery-induced hyperprolactinemia would have to be grouped together with the unfavorable prognostic factors of breast cancer.

ISSN:0030-2414    

DOI:10.1159/000227507

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Sequential thermoradiotherapy was given to 24 patients with locally advanced breast carcinoma. The outcome of treatment was analyzed in relation to the thermal dose as well as clinical stage, tumor volume, vascular density and necrotic fraction prior to treatment. Complete or partial response was seen in all patients. Three of the patients showed local recurrence following treatment. One of the recurrences was due to a geographic miss of the radiation therapy whereas the other two recurrences were ‘true’ local treatment failures. Local treatment failure could not be attributed to an advanced clinical stage, large tumor masses or poor tumor heating. The recurrent tumors had a low vascular density and significant necrotic fraction prior to treatment, suggesting that treatment failure was due to the presence of chronic hypoxia. The radiothera-peutic problem of treatment resistance caused by chronically hypoxic cells is probably not eliminated with sequential thermoradiother

ISSN:0030-2414    

DOI:10.1159/000227508

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In this study, we analyzed 105 paired sporadic primary breast tumor and normal tissue samples for loss of heterozygosity (LOH) on chromosome 17, using 12 polymorphic markers. We have identified partial or interstitial LOH in five separate regions of chromosome 17. Two of the deleted regions lie on the short arm of the chromosome, the first (region I, D17S5) in the telomeric part, distal to TP53 and the second spanning the TP53 gene (region II). Three of the five deleted regions lie on the long arm of chromosome 17: region III, on the proximal long arm between D17S250 and THRA1; region IV, between D17S776 and D17S579, including the BRCA1 gene, and region V, located distal to D17S733. No statistically significant correlations were observed between clin-icopathological characteristics or steroid hormone receptor status and deletion of either region I or II. However, patients whose tumors had LOH for region I showed relapse or death more frequently than patients with tumors informative for this region but without LOH (p = 0.002). Statistically significant correlations between LOH at each of the three deleted regions of 17q and a high mitotic index were observed (region III, p = 0.005; region IV, p = 0.02, and region V, p = 0.004). In addition, LOH at region IV showed a significant association with paucity of estrogen receptors (p = 0.01). Our results show a complex pattern of LOH on chromosome 17 in breast cancer and a correlation of these events with different clinical parameters. This pattern suggests that particular subsets of allele loss may contribute specifically to different clinically defined subsets of sporadic breast tumors.

ISSN:0030-2414    

DOI:10.1159/000227509

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In order to assess the feasibility of a sequential hormonal treatment after tamoxifen failure, 24 postmenopausal advanced breast cancer patients (median age 60 years; ECOG PS ≤ 1) were treated with formestane (4-hydroxyan-drostenedione) 250 mg i.m. fortnightly; 19 patients were estrogen receptor-positive. The sites of metastatic disease were soft tissue in 22 patients, viscera in 9 and bone in 18. The patients were considered evaluable for tumor response after four doses of formestane. Objective responses were observed in 8/24 patients (33%) with one complete and seven partial responses. The median response duration was 9.5 months. The complete response was obtained on skin. We conclude that although the number of complete responses appears to be unsatisfactory, de novo tamoxifen-resistant breast cancer patients are suitable for further hormonal treatment with formestan

ISSN:0030-2414    

DOI:10.1159/000227510

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We investigated the in vitro effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with or without the addition of linoleic acid (LA), on cell growth and prostaglandin E (PGE) and leukotriene B (LTB) secretion by a human breast cancer cell line (MDA-MB-231). With or without the addition of LA, EPA and DHA suppressed cell growth and thymidine incorporation and reduced the secretion of PGE and LTB. In a univariate analysis, cell growth was significantly associated with both LTB and PGE concentrations when cells were treated with DHA or EPA, independent of the addition of LA. However, multivariate regression analysis showed that cell growth was more closely associated with the PGE concentration rather than the LTB concentration. These data suggest that both EPA and DHA suppress cell proliferation in the MDA-MB-231 cell line by inhibition of the cyclooxygenase rather than the lipoxygenase pathways. However, the exact mechanism underlying the antitumor activity of EPA and DHA remains unclear.

ISSN:0030-2414    

DOI:10.1159/000227511

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Conflicting reports have been published on the anti-tumour activities of acetylsalicylic acid in various cancers. Therefore, the effect of acetylsalicylic acid and its major metabolites has been studied on human prostatic carcinoma DU-145 cells. Investigations concentrated on the influence of acetylsalicylic acid, salicylic acid and salicyluric acid, on cell proliferation, DNA– and protein synthesis of DU-145 cells. DNA and protein synthesis determinations were done in vitro by [3H]thymidine and [3H]glycine incorporation, respectively. No effect on cell plating efficiency was observed, however proliferation studies showed that acetylsalicylic acid and salicylic acid inhibited cell growth (10 mM, 100% inhibition). No significant effect on cell proliferation was ascertained with salicyluric acid. Both DNA and protein synthesis were 40% inhibited by 0.1 mM acetylsalicylic acid. This study demonstrates that acetylsalicylic acid exhibits a significant influence on cell growth of prostatic DU-145 cells. These preliminary results may contribute to a better understanding of the anti-tumour capabilities of acetylsalicylic aci

ISSN:0030-2414    

DOI:10.1159/000227512

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Results with second-line treatment of advanced colorectal cancer are poor. Preliminary phase I/II results suggest encouraging response rates to high-dose 5-fluorouracil (FU) (2,600 mg/m2) combined with folinic acid (FA) in pretreated patients with advanced colorectal cancer. To determine the significance of weekly high-dose FU/FA in colorectal cancer refractory to weekly standard doses of FU/FA, a phase II study was initiated. 69 patients with metastatic colorectal cancer refractory to first-line weekly standard-dose FU/FA were treated with weekly high-dose FU 2,600 mg/m2 combined with FA 500 mg/m2 as a a 2-hour infusion prior to FU application. Pretreatment was highly homogenous and consisted of weekly FU 500 mg/ m2 combined with FA 500 mg/m2 or FA 20 mg/m2 or the pure stereoisomer of FA (6S-FA) 250 mg/m2. At the time of disease progression under first-line therapy, patients were transferred to high-dose FU/FA within 4 weeks. Treatment was continued until tumor progression under therapy was documented. Of the 69 evaluable patients, 17 (24.6%) achieved partial response (PR), 42 (60.9%) had no change (NC) and 10 (14.5%) had progressive disease under therapy. The median duration of PR was 7 months, the median time to progression of NC was 4 months. Median survival of all patients was 9 months, of patients with PR, 11,5 months. 33/38 patients with tumor-related pain experienced impressive relief under therapy. Prognostic factors for a beneficial outcome were complete response/PR under first-line therapy, a small number of metastatic sites and a good Karnofsky performance status. Moderate toxicity was observed, and the pattern of toxic events and severity did not differ from standard-dose FU regimens. WHO grade III toxic events were diarrhea (9), mucositis (6), nausea (5), hand-foot syndrome (9) and leukopenia (2). Symptomatic treatment was administered in an outpatient setting until recovery. We conclude that weekly high-dose FU/FA is an effective and well tolerated second-line therapy regimen. Patients with advanced colorectal cancer refractory to first-line weekly standard-dose FU/FA treatment may benefit from effective control of tumor-related symptoms and demonstrate prolonged survival.

ISSN:0030-2414    

DOI:10.1159/000227513

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The aim of the present study was to investigate whether the rate of thymidylate synthetase inhibition (TSIR) and the rate of proliferating cell nuclear antigen expression (PCNA-R) in gastric cancer tissues, which can be obtained within a short period after surgery, were predictive and quantitative prognostic factors for locally advanced gastric cancer patients with preoperative down-staging chemotherapy. Curatively resected 30 locally advanced gastric cancer patients with preoperative chemotherapies were studied. Three-year survival analysis showed that the higher TSIR and the lower PCNA-R significantly predicted better prognosis (p < 0.01 and p < 0.05, respectively). Multiple regression test showed that the TSIR was a significantly predictive variable for 1-year survival (p < 0.05). The TSIR and PCNA-R could be predictive and quantitative prognostic factors in advanced gastric cancer patients who received preoperative downstaging chemotherapy.

ISSN:0030-2414    

DOI:10.1159/000227514

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Preoperative serum CEA and CA 19-9 levels in 158 patients with gastric cancer were analyzed with respect to prognostic factors, using univariate and multivariate analysis. The incidence of high preoperative levels of both CEA and CA 19-9 was 10.1% (16/158). 13.9% (22/158) showed high CEA levels and normal CA 19-9 levels, whereas the reverse was true in 16.5% (26/158). Neither marker showed a high level in 59.5% (94/158). The multivariate analysis showed that in addition to tumor stage, the depth of invasion, liver metastasis and peritoneal dissemination, combination assays of preoperative serum CEA and CA 19-9 levels were an independent prognostic factor. Combination assays of preoperative serum CEA and CA 19-9 will allow us to conduct a more careful postoperative follow-up of high-risk patients, and also help determine the optimum adjuvant chemotherapy.

ISSN:0030-2414    

DOI:10.1159/000227515

出版商:S. Karger AG    

年代:1995

数据来源: Karger