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.

Incomplete operative removal of colorectal liver metastases followed by chemotherapy decreases survival in comparison to chemotherapy alone.

Metastatic colorectal carcinoma (CRC) has an inevitable fatal outcome except in a small percentage of selected patients, approximately 10-20%, with good prognosis after successful complete operative removal of the liver metastases. In patients not eligible for surgical resection of the liver metastases, chemotherapy is currently the only widely available treatment option. Controversy still exists about the criteria for operability of CRC liver metastases, and some patients, still undergo ineffective, i.e. unnecessary surgery. The aim of this paper is to analyse and compare the overall survival (OS) and time to progression (TTP) in patients who underwent incomplete removal of liver CRC metastases followed by chemotherapy, and patients treated with chemotherapy alone. Seventy-three patients with CRC liver metastases underwent incomplete operative removal of the metastases followed by FOLFIRI (Cohort A - 27 patients) or with FOLFIRI alone (Cohort B - 46 patients). Patients received FOLFIRI until progression. FOLFOX4 was used as second line chemotherapy. The median OS in Cohort A was 8 months, the median TTP was 5 months, and the response rate was 44%; the median OS in Cohort B was 19 months, the median TTP was 8m, and the response rate was 39%. There was a significant difference in OS and in TTP (p < 0.01) in favour of the chemotherapy alone group (B). Patients undergoing incomplete removal of the liver metastases had shorter survival and TTP in comparison with patients treated with chemotherapy alone.

Colorectal cancer care in the Balkan countries.

PURPOSE: The aim of this survey was to assess the status of colorectal cancer (CRC) care in the Balkans by contacting cancer care specialists in the Balkan Union of Oncology (BUON) member states. MATERIALS AND METHODS: The authors searched the 2004 membership directories of the ASCO and ESMO and identified members from the Balkan countries. They then sent them a 3-page questionnaire via e-mail or fax. RESULTS: Fifty-two responses from 8 countries were received and analysed. The response rate varied from 25% (Turkey) to 3% (Bulgaria). No Bosnian (n=13), Croatian (n=16) and Albanian (n=1) participated. The results showed that, despite variations on the state of development among Balkan countries, there were some striking similarities and also some similar difficulties that CRC specialists are facing in their individual countries. CONCLUSION: Combined and coordinated efforts at solving some of these common problems may help CRC patients receive better and higher quality care.

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.

[Effect of cytochrome c on the activity of lysosomal enzymes in the rat liver under hypobaric hypoxia]. / Vliianie tsitokhroma c na aktivnost' fermentov lizosom v pecheni krys pri gipobaricheskoi gipoksii.

Under conditions of three-hour hypobaric hypoxia the total activity of acid phosphatase and DNase in the rat liver somewhat lowers. The activity of free enzymes increases by 27 and 37%, and that of bound ones decreases by 42 and 24 %, respectively. Cytochrome c being introduced to hypoxic animals, the total activity of the enzymes does not significantly change. Under these conditions the activity of free acid phosphatase increases by 16%, and bound one decreases by 24 %. The activity of free acid DNase somewhat rises (by 12%) and that of bound one lowers (by 15%). A preliminary administration of cytochrome c to the organism prevents the development of pronounced changes in the activity of the studied lysosomal enzymes in the liver under grave hypoxia.

[Iron, copper, zinc and cobalt content and activity of respiratory metalloenzymes in animal tissues under toxic hypoxia]. / Issledovanie soderzhaniia zheleza. Medi, tsinka, kobal'ta i aktivnosti dykhatel'nykh metallofermentov v tkaniakh zhivotnykh pri toksicheskoi gipoksii.

The rabbits being repeatedly poisoned with small doses of sodium cyanide, the activity of succinic dehydrogenase in the tissues does not essentially change. The activity of NAD.H2-cytochrome-c-reductase and NAD.H2-diaphorase in the brain, myocardium and kidneys increases. Under histotoxic hypoxia the level of iron in the tissues increases by 52-93%, that of copper--by 28-36%, of zinc--by 21-74% and of cobalt by 28-40%. There existed a positive correlation between the content of iron and the activity of NAD-dependent enzymes. In nonlethal form of histotoxic hypoxia the content of nonhemin iron and the activity of NAD.H2-cytochrome-c-reductase in the mitochondria of the brain increases by 25% and 17%, respectively, and a direct correlation is revealed between them.