Value of estrogenic recruitment before chemotherapy: first randomized trial in primary breast cancer.

PURPOSE: Several preclinical studies showed that short-term pretreatment of breast cancer cells with estrogens can increase the antitumor efficacy of different cytotoxic drugs. Some early clinical studies in patients with advanced breast cancer did seem to support these findings. Therefore, the efficacy of estrogenic recruitment followed by chemotherapy was compared with that of chemotherapy alone in a randomized phase III study in women with lymph node-positive primary breast cancer. PATIENTS AND METHODS: Three hundred twenty-eight patients with stage II/IIIA breast cancer who were younger than 66 years of age were randomly allocated to chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or FAC plus pretreatment with ethinyl estradiol (EE(2)). FAC (500, 50, and 500 mg/m(2), respectively) was administered intravenously once every 4 weeks for four cycles. EE(2) (0.5 mg) was administered orally, both 24 hours and immediately preceding FAC chemotherapy. RESULTS: Patient and tumor characteristics and chemotherapy dosages were comparable in both treatment groups. Of 318 assessable patients, with a median follow-up of 6.8 years, 177 patients had a relapse and 127 died. No significant differences were observed between the two treatment groups with respect to relapse-free, local recurrence-free, and overall survival according to univariate and multivariate analyses adjusted for age, menopausal status, tumor size, grade, number of positive nodes, and steroid-receptor status. The power for the detection of an increase of 50% in the median relapse-free survival was 80%. CONCLUSION: Estrogenic recruitment of breast cancer cells before FAC chemotherapy did not influence the efficacy of adjuvant chemotherapy in stage II/IIIA breast cancer patients after a follow-up of 6.8 years.

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up.

Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase III trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy.

Food impaction in a duodenal diverticulum as an unusual cause of biliary obstruction: case reports and review of the literature.

We present two patients with upper abdominal complaints and symptoms of biliary obstruction. Endoscopic retrograde cholangiopancreatography showed that the common bile duct was obstructed by a juxtapapillary duodenal diverticulum filled with a food bezoar. There were no gallstones or other potential causes of obstruction. The bile flow was restored and symptoms disappeared after rinsing the diverticulum. Eventually, both of the patients were treated surgically because of recurrent symptoms.

A randomized, double-blind, multicentre study comparing daily 2 and 5 mg of tropisetron for the control of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy.

BACKGROUND: This study compares efficacy, safety and tolerability of 2 and 5 mg tropisetron in prevention of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy. PATIENTS AND METHODS: 152 chemotherapy-naïve cancer patients were randomized in a double-blind manner to receive 2 or 5 mg tropisetron intravenously day 1 and orally days 2-6. Primary efficacy criteria were control of acute (day 1) and delayed (days 2-6) vomiting and nausea. Secondary efficacy criteria included overall control (days 1-6) and control of vomiting and nausea by chemotherapy regimen. Safety and tolerability were evaluated clinically, biochemically and by the patient's diary. Only the first cycle was evaluated. RESULTS: 124 of the 144 intention-to-treat patients were evaluable. There was a better total control (no events) of acute vomiting in the 5 mg (73%) than in the 2 mg group (55%, P = 0.02). Total control (< or = 15 minutes) of acute nausea was obtained in 70% of the 5 mg group and in 51% of the 2 mg (P = 0.03). No differences were observed for total control of delayed nausea or vomiting and for the overall outcome of nausea. Less vomiting (days 1-6) occurred in the 5 mg than in the 2 mg group. Efficacy rates ranged widely between chemotherapy regimens, independent of the tropisetron dose groups. There occurred more headache in the 5-mg group (P < 0.05). CONCLUSIONS: Once daily 5 mg tropisetron is superior to 2 mg for prevention of acute vomiting and nausea induced by low-dose cisplatin- or non-cisplatin chemotherapy regimens, but causes more headache.