Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

BACKGROUND: To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. TREATMENT: EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. RESULTS: Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). CONCLUSIONS: Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

Mayo regimen plus three different second-line chemotherapy regimens in sequential therapy in patients with advanced colorectal cancer (ACRC).

As the number of active drugs for colorectal cancer increases, we continually revisit the question of how best to integrate them. We investigated whether sequential chemotherapy consisting of only bolus plus infusional 5-fluorouracil/folinic acid could be comparable, concerning overall survival, to sequential chemotherapy consisting of bolus 5-fluorouracil/folinic acid plus "new-generation" drugs like CPT-11 or oxaliplatin. Patients with histologically verified locally advanced disease and/or metastatic colorectal adenocarcinoma, without possibility for surgical resection, were eligible for the study. The treatments were: Cohort A--Mayo Clinic Regimen (MCR) in first line, "de Gramont" regimen in second line; Cohort B--MCR in first line, CPT-11 (350mg/m2) in second line; Cohort C--MCR in first line, oxaliplatin (85mg/m2) plus "de Gramont" regimen in second line. A total of 89 patients received first plus second line chemotherapy and all of them were analyzed for survival. Number of patients/cohort: A-32 B-27; C-30. The median survival time of the patients was 15, 11, and 17 months for the patients in cohorts A, B, and C, respectively. Survival of the patients in cohort C was significantly better than survival of the patients in cohort B (log-rank test, p=0.04). There was not a significant difference in overall survival between the cohorts A vs. C (log-rank test, p=0.52) and B vs. C (log-rank test, p=0.27). It is conceivable that infusional HD 5-FU could serve as a basis for first and second-line protocols in which other drugs are added to this regimen. Infusional 5-FU plus oxaliplatin in sequential pattern of application after bolus 5-FU has the best overall survival in comparison to other cohorts. CPT-11 applied as a single drug, was not effective enough in comparison to other treatment options.

Serum gonadotropin levels in patients with germ-cell tumors of the testis: interrelations, possible cross-reactions and interpretation of beta-HCG level.

The concentration of FSH, LH, LTH, testosterone and beta-hCG was estimated in 177 serum samples from 86 patients with malignant germ-cell tumors of the testis. The objectives of the investigation were the following: the detection of interrelations of hypophyseal gonadotropins at different beta-hCG levels; the determination of the significance of borderline values of beta-hCG; the analysis of the effect of elevated concentrations of beta-hCG on pituitary gonadotropins: the detection of possible cross-reactions during gonadotropin determinations. The RIA method was used to estimate levels of three gonadotropins. The results revealed that there was no cross-reaction between FSH and beta-hCG at RIA assays. When the serum level of beta-hCG of tumor origin exceeded 100 U/l a subtotal inhibition of FSH secretion was observed. Pathologically increased values of beta-hCG were found not only in serum with subnormal-FSH levels, but also when FSH levels were excessively elevated (exceeding 50 U/l). In the latter case the elevated beta-hCG levels could possibly be the consequence of the secretion of beta subunits by the hypophysis or a cross-reaction with LH, and not of a tumor. With values of beta-hCG over 100 U/l cross-reaction with LH occurs, so the true LH levels cannot be assessed. For an adequate interpretation of elevated values of beta-hCG in the serum (i.e. whether they are tumor-derived or not), it is necessary to have values of FSH from the same serum sample.

Therapeutic and endocrine effects of Decapeptyl, synthetic LH-RH agonistic analogue in premenopausal women with metastatic breast cancer. A pilot phase II study.

Twelve premenopausal patients with advanced breast cancer were entered into pilot phase II study to assess efficacy, toxicity and influence of the synthetic LH-RH agonistic analogue D-Trp6-LH-RH (Decapeptyl) on the patients' hormonal status. The patients, aged 33-50, with newly diagnosed stage IV or recurrent breast cancer were not previously treated by any kind of endocrine therapy. Steroid receptor status was known in 9 patients. Decapeptyl was applied monthly at a dose of 3.75 mg i.m. until progression. The therapeutic response was evaluated in 11/12 patients. Partial remission was achieved in 5, stabilization in 3, and 3 consecutive patients failed to respond. The best therapeutic response was obtained in patients with pleuropulmonal and soft-tissue involvement, aged 41-45, including those with incomplete ovarian suppression, and regardless of steroid receptor status. The mean serum gonadotropins and estradiol levels were suppressed. The treatment was free of any side effects, except hot flushes in 7 patients.