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Background: The aim of our study was to compare healthcare-related costs of treatment with XELOX and FOLFOX4 chemotherapeutic regimens in patients with colorectal cancer. We have evaluated costs claimed to the health insurance by the hospital administering these cancer therapies. This study is a pilot project utilising the new I-COP database developed by the Institute of Biostatistics and Analyses of the Masaryk University in Brno, Czech Republic., Patients and Methods: First, we estimated the costs based on current prices of procedures, medication, and materials from public sources. Using the I-COP database, we then carried out a matched-pair comparison of 26 patients treated with FOLFOX4 or XELOX for colorectal cancer. We evaluated a period of three months of therapy (i.e. 6 cycles of FOLFOX4 or 4 cycles of XELOX). Statistical analysis was done using the Wilcoxon matched pairs test., Results: The estimated cost for three months of therapy was 148,288 Czech crowns (CZK) for FOLFOX4 (including CZK 101,064 for chemotherapy drugs) and CZK 123,756 for XELOX. The overall costs claimed to the insurance companies were CZK 160,158 and CZK 151,176 for FOLFOX4 and XELOX, respectively (p = 0.221). The XELOX regimen had significantly higher costs for chemotherapy drugs (CZK 131,705 versus 114,531, p = 0.023) whereas other costs were lower than those for FOLFOX4., Conclusions: FOLFOX4 and XELOX regimens can be considered as equivalent in terms of costs claimed by the hospital administering cancer treatment.

Hemopoietic growth factors (HGF) and leukapheresed peripheral progenitor cells (PBPC) are increasingly used for supportive care in high-dose chemotherapy (HDC) of solid tumors. Presently, therapeutic protocols with cyclic HDC plus PBPC support are successfuly used in breast cancer patients. Administration of PBPC significantly influences hemopoietic recovery in terms of shortening the pancytopenia period which reduces the risk of dangerous complications, especially the risk of infection. As a certain controversy exists about efficacy of this therapy, large randomized studies are conducted to find more accurate conclusions. In 1998 National Cancer Institute (NCI) gave top priority to four randomized studies of HDC with PBPC support. In recent years, rising yields of PBPC are obtained. The use of new combinations and dosages of hemopoietic growth factors leads to a significant increase of progenitor cells circulating in peripheral blood. Effective mobilization regimens combinations of chemotherapy and cytokines - enable to increase the numbers of circulating progenitors as much as 100-fold. Another aspect, how to minimize the risks is to reduce the transplant volume and so reduce the amount of cryoprotective agent DMSO (dimethyl sulfoxide) and hemolysed erythrocytes. This led to the idea to use only whole blood enriched for PBPC. At present it has been used also in our patients. The results show that enriched whole blood can be used as sufficient substitution for support in intensive cyclic chemotherapy in breast cancer patients.

The aim of our project was to compare the efficacy of mobilised whole blood versus cryopreserved PBPC (peripheral blood progenitor cells) obtained by leukapheresis in the support of hematopoietic recovery in cyclic intensive chemotherapy. Twenty-nine women with breast carcinoma were treated. The mean age was 46 years. In stage III were 23, in stage IV were 6. They received 6 cycles of epirubicin 150 mg/m2 and cyclophosphamide 1250 mg/m2. In the first cycle, 24 hours after chemotherapy, application of G-CSF 5 microg/kg/day was started, and discontinued when leukaphereses and whole blood collections were done. Leukapheresed progenitors were then divided into 3 aliquots, cryopreserved and reinfused after the 4th, 5th and 6th chemotherapy cycles. Mobilised whole blood was collected on day 14 of the 1st and 2nd cycles and reinfused 24 hours after chemotherapy. The occurrence of grade IV leukopenia was 1.82 times higher with whole blood support and grade IV thrombocytopenia 2.64 times higher than in cycles with cryopreserved PBPC support. This resulted from the fact that in one application the numbers of CD34+ cells and CFU-GM were nearly double in cryoconcentrates. The yields of CD34+ cells in 450 ml of whole blood were 1.8 x 10(6)/kg, which is not sufficient for optimal hemopoietic recovery.

High-dose chemotherapy (HDC) in high-risk breast cancer is one of the possible approaches how to improve therapeutic results, eventually, to overcome the incurability of the disease. In recent randomized studies superiority of HDC to conventional therapy has not been unambiguously established. Nevertheless, many oncologists, as well as, patients are so convinced of HDC benefits, that they are not willing to take part in randomized studies. At an ASCO Annual Meeting (American Society of Clinical Oncology) in May 1999 in Atlanta - preliminary results of five large randomized studies phase III were presented (2 studies on metastatic breast cancer and 3 studies on high-risk breast cancer with more than 10 positive lymph nodes). The ASCO was informed of an investigation into serious scientific misconduct in a clinical trial that was presented in a plenary session of its Annual Meeting. The results of Dr. Bezwoda's research were presented at ASCO's Meeting as one of four plenary papers on the investigational therapy and was the only one to clearly indicate a survival benefit in the high-dose regimen. Preliminary results presented there, however, did not confirm the original hypothesis of the high efficacy of HDC. It is necessary to wait for definite results (within two or three years, because enrollment of patients either has been finished or is being finished just now) and several parameters may change. In view of hitherto results, some investigators think that there is no need to continue in similar intensive studies. Still some believe that different modifications of therapeutic regimens or new, less toxic drugs should be tested which may lead to more effective and safer HDC.

AC133 antibody provides an alternative to CD34 for the selection and characterization of cells necessary for engraftment in transplant situations. We studied the effect of stem cell factor (SCF), interleukin 3 (IL-3) and interleukin 11 (IL-11) on the ex vivo expansion of human CD34+/AC133+ progenitors isolated from leukapheresis products from chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) -mobilized adult donors. MiniMACS AC133+ isolated cells contained a mean of 85% (80-90) AC133+ cells. Enriched AC133+ cells co-expressed CD34+ 80%, CD71low 36.6% and CD33+ 6.6%. After a seven-day ex vivo expansion in the presence of SCF + IL-3 + IL-11, the number of cells increased 19 times. These cells expressed a mean 12% CD34+ and 74% CD71+ (23% CD 71high) and 59% CD33+. This means that the absolute number of CD34+ cells increased slightly, the number of CD33+ increased 100 times and cells with high density CD71high (23%) appeared. These cells represent the cells committed to erythroid differentiation. The increase in the number of CFU-GM with various combinations of cytokines SCF + Il-3 + IL-11 will be discussed. The number of CFU-GM in culture after a seven-day ex vivo expansion in the presence of SCF + IL-3 + IL-11 increased 45 times.

The role of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) combination in hemopoietic recovery was studied in patients with high-risk breast carcinoma and compared to a control group of previously treated identical patients who were not given EPO plus G-CSF. Eleven consecutive patients admitted to this study had Stage III or IV breast cancer. They received 6 cycles of intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2). The 1st cycle served for mobilization of peripheral blood progenitor cells (PBPC). At its end leukaphereses collections of PBPC were performed to be used as hematologic support (PBPCT) in the 5 remaining cycles. The administration of EPO plus G-CSF was started when leukocyte (WBC) count in peripheral blood dropped below 1 x 10(9)/l and hemoglobin (Hb) level fell below 100 g/l. The treatment was stopped when leukocyte count rose to 5 x 10(9)/l and Hb to 130 g/l. EPO plus G-CSF combination after PBPCT produced significant effects in terms of hemopoietic recovery, clinical benefit and supportive care requirements when compared with 12 historic control patients: Periods of leukopenia were shorter which resulted in reduced risk of infectious complications. The grades of leukopenia in the study and control groups were as follows: grade 4 (36 vs. 18%), grade 3 (57 vs. 30%), grade 2 (7 vs. 13%) respectively. Significantly shorter was the time of PLT recovery < 50 x 10(9)/l (p < 0.001). The grades of thrombocytopenia were: grade 4 (29 vs. 11%), grade 3 (21 vs. 12%), grade 2 (25 vs. 36%) respectively. The number of necessary transfusions was significantly reduced as well as the length of hospital stay (p < 0.001). In conclusion, our results obtained in this study confirm that combination of EPO plus G-CSF not only increases the rate of hemopoietic recovery, reduces the number of necessary red blood cell and platelet transfusions but, at the same time, simplifies the clinical management and is more tolerable for the patients.

To support multicyclic, dose-intensive chemotherapy in breast cancer, we assessed the effects of reinfusing hematopoietic progenitors either as a leukapheresis product or as mobilized unprocessed whole blood. In this clinical study, 16 consecutive female breast cancer patients were given six cycles of chemotherapy regimen EC (epirubicin (150 mg/m2) and cyclophosphamide (1250 mg/m2) on day 1). In the first cycle, 24 h after chemotherapy, mobilization of the peripheral blood progenitor cells (PBPC) was started with growth factor G-CSF (Neupogen; Amgen-Roche) at a dose of 5 microg/kg/day for 13 days. In all other cycles G-CSF had been given at the same dose from day 7. On days 11, 12 and 13 the leukaphereses were performed and their products cryopreserved. On day 14 whole blood was collected. The median peak incidence of CFU-GM (granulocyte-macrophage colony-forming unit) in peripheral blood was approximately 50 times the baseline level. The leukapheresed PBPC were divided into portions and reinfused after the fourth, fifth and sixth chemotherapy courses. The support with mobilized whole blood was given after the second and third cycles. The effects of the support of whole blood vs leukapheresed PBPC on hematopoietic recovery were compared. The best yields of leukaphereses were achieved on day 13 after initiation of the chemotherapy. The mean number of CD34+ cells was 4.93 x 10(6)/kg (s.d. 2.7; range 0.36-10.54 x 10(6)/kg) the amount of CFU-GM was 2.18 x 10(5)/kg (s.d. 1.3; range 0.07-4.2 x 10(5)/kg). The yields of CFU-GM in 450 ml whole blood collected on day 14 reached 0.51 x 10(5)/kg (s.d. 0.28; range 0.05-1.5 x 10(5)/kg) and of CD34+ cells were 1.3 x 10(6)/kg (s.d. 0.8, range 0.18-2.58 x 10(6)/kg). PBPC yields in 450 ml of unprocessed whole blood were in some cases not sufficient for good hematopoietic recovery after the EC cycles. Grade 4 leukopenias and thrombocytopenias were two times higher in cycles with whole blood support than in cycles with cryopreserved PBPC support. An increase of PBPC harvest can be simply achieved by collecting larger amounts of unprocessed blood, as used by some authors.

Hematologic effects of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) combination after printing intensive chemotherapy in the treatment of female breast carcinoma are presented. In a previous group treated with G-CSF alone, 36% of patients became anemic and had to be transfused for correction of their anemia. To the present study 11 consecutive patients with different stages of breast carcinoma were admitted. All were given priming intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2 followed by subcutaneous application of G-CSF at a dose of 5 micrograms/kg/day and EPO 250 IU/kg/day. In cases where leucocyte counts dropped below 1 x 10(9)/l and hemoglobin levels fell to 85 g/l administration of growth factors was started. The therapy stopped when normal leucocyte count reached 4 x 10(9)/l for G-CSF and hemoglobin level rose to 115 g/l for EPO. Our results show significant difference between MNC/T1 (min.), CD34+ cells/microliters (min.), CFU-GM/ml (min.), BFU-E/ml (min.) and MNC/microliters (max.), CD34+ cells/microliters (max.), CFU-GM/ml (max.), BFU-E/ml (max.) p < 0.01, with mean peak values of 16.9-fold for circulating MNC/microliters, 7.8-fold for CD34+ cells/microliters 23.4-fold for CFU-GM/ml and 28.7-fold increase for BFU-E/ml. Side effects were minimal, no infectious complications occurred, body temperature did not rise over 38 degrees C and no corrections of anemia were needed. It is concluded that the administration of G-CSF plus EPO combination following intensive chemotherapy reduces hematologic toxicity and induces large amount of hemopoietic progenitors suitable for autologous transplantation in women with breast carcinoma.