Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.

BACKGROUND: We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated. PATIENTS AND METHODS: Patients with advanced breast cancer were randomized to receive oral C (50 mg daily) and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200 mg daily) (arm B). RESULTS: The mean VEGF level decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6) pg/ml at 2 months (P<0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%; P<0.0001) was observed in arm B. CONCLUSIONS: Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.     

多西紫杉醇联合表阿霉素及环磷酰胺治疗晚期乳腺癌的临床观察

目的：观察多西紫杉醇联合表阿霉素及环磷酰胺治疗晚期乳腺癌的疗效与不良反应。方法：采用多西紫杉醇联合表阿霉素及环磷酰胺治疗56例复发或转移的晚期乳腺癌患者,多西紫杉醇75mg/m2,d1,表阿霉素50mg/m2,d1,环磷酰胺500mg/m2,d1,21天为1周期,连续治疗2周期。结果：56例患者TEC方案治疗2周期后CR7例,PR22例,总有效率为51.8%。最常见不良反应为骨髓抑制、消化道反应及脱发,本组无一例发生过敏反应,其不良反应可耐受。结论：TEC方案治疗晚期乳腺癌可作为晚期乳腺癌的一线治疗方案。     

Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer

This phase I was study conducted to establish the maximum tolerated dose, dose-limiting toxicity, and recommended dose of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Twenty-six patients were treated with cyclophosphamide (600 mg m(-2), intravenous bolus) followed by docetaxel (60, 75 or 85 mg m(-2), 1-h intravenous infusion) every 3 weeks. The maximum tolerated dose was docetaxel 85 mg m(-2) with cyclophosphamide 600 mg m(-2), the dose-limiting toxicity being febrile neutropenia. Grade 4 neutropenia was experienced by all patients, but was generally brief. Otherwise, the combination was well tolerated with few acute and no chronic non-haematological toxicities of grade 3/4. Activity was observed at all dose levels and disease sites, and the overall response rate was 42% (95% confidence interval 22-61%). The pharmacokinetics of docetaxel were not modified by cyclophosphamide coadministration. These findings establish a recommended dose of docetaxel 75 mg m(-2) in combination with cyclophosphamide 600 mg m(-2) every three weeks for phase II evaluation.     

术前化疗对乳腺癌组织VEGF表达和血管生成的影响

目的研究术前化疗对乳腺癌血管内皮生长因子(VEGF)表达、肿瘤组织微血管密度的影响.方法36例术前化疗的乳腺癌和32例未做术前化疗的乳腺癌标本,进行VEGF、CD34免疫组织化学标记,并进行微血管计数和统计学处理.结果术前化疗组VEGF阳性率为47.22%(17/36),对照组53.13%(17/32),微血管计数化疗组和对照组分别为23.67±13.45,26.12±11.32,两者差异均无显著性.化疗组VEGF阳性和阴性的标本,MVC均值差异无显著性;对照组VEGF阳性和阴性的标本,MVC均值差异有显著性.结论常规术前化疗并未显示出明显的血管生成抑制作用,也未显示出明显的血管内皮生长因子表达的改变.     

A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk

A common 936 C/T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels. In our case-control study, we investigated the role of this polymorphism for breast cancer risk. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29.4%) than among patients (17.6%; p = 0.000014). The odds ratio for carriers of a 936T-allele for breast cancer was 0.51 (95% confidence interval 0.38-0.70). Additionally, VEGF plasma levels were determined in 21 nonsmoking post-menopausal controls; carriers of a 936T allele had significantly lower levels (median 23 pg/ml; range 6-50 pg/ml) than noncarriers (37; 21-387; p = 0.034). We conclude that carriers of a VEGF 936T-allele are at decreased risk for breast cancer, this, however, requiring further confirmation in a larger study.     

Tumor angiogenesis in breast cancer: Its importance as a prognostic indicator and the association with vascular endothelial growth factor expression

Summary The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm² in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm² (p<0.00001). The significance of MVD was found in both node-negative and node-positve patients (p< 0.005 and p<0.01, respectively). Multivariate analysis confirmed that MVD is an independent prognostic indicator for RFS. In the background factor analysis, MVD was significantly correlated with the number of metastatic nodes (p<0.01). In addition, the immunocytochemical analysis for vascular endothelial growth factor (VEGF) demonstrated a close association between the increase in MVD and the expression of VEGF (p<0.001). VEGF status also was a significant prognostic indicator in univariate analysis for RFS (p<0.01). It was concluded that MVD is a potent prognostic indicator in primary breast cancer. Furthermore, it was also suggested that VEGF plays crucial roles in the promotion of angiogenesis in breast cancer.Abbreviations MVD microvessel density - VEGF vascular endothelial growth factor     

Cyclophosphamide-methotrexate 'metronomic' chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation.

BACKGROUND: Metronomic chemotherapy-the chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule of administration at close regular intervals, with no prolonged drug-free breaks-is a potentially novel approach to the control of advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has, as an advantage, the property of significantly reducing undesirable toxic side-effects. The aim of the present study was to evaluate the cost effectiveness of cyclophosphamide-methotrexate 'metronomic' chemotherapy in the palliative treatment of pretreated metastatic breast cancer. METHODS: Low-dose cyclophosphamide-methotrexate 'metronomic' chemotherapy was compared with outcome and resource utilisation data of published phase II trials regarding metastatic breast cancer, performed in western countries, mostly in Europe. All direct costs associated with metastatic breast cancer treatment were included and adjusted to year 2003 values. Sensitivity analyses were performed and variations to the values of key parameters were assessed. RESULTS: Low-dose cyclophosphamide-methotrexate 'metronomic' therapy was assessed to be a cost-effective/cost-saving therapy for palliative treatment for metastatic breast cancer when compared with novel chemotherapy strategies (phase II trials). Compared with the 11 phase II mono- and combination chemotherapies, metronomic treatment showed marked cost savings in each case and improved cost effectiveness. Sensitivity analyses showed the results were robust to variations to the values of key parameters with very few exceptions. CONCLUSIONS: Metronomic cyclophosphamide-methotrexate is significantly cost effective. If validated by prospective randomized trials, the treatment concept could reduce healthcare costs, especially those associated with the combined use of new, highly expensive, molecularly targeted therapies.     

多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床观察

目的：观察多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床疗效及不良反应。方法：回顾性分析40例转移性乳腺癌患者的化疗资料,采用国产多西他赛75mg/m2,表柔比星70-90mg/m2静脉滴注,环磷酰胺500mg/m2每3周1次。观察每次化疗后的不良反应,完成4个疗程后观察疗效。结果：全部病例均按计划完成4个周期的化疗。完全缓解（CR）3例,部分缓解（PR）20例,稳定（SD）12例,进展（PD）5例。总有效率（CR＋PR）为57.5%,控制率（CR＋PR＋SD）87.5%。主要不良反应为中性粒细胞减少、恶心、呕吐、腹泻等。结论：多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌临床疗效较好,不良反应患者可以耐受。     

A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer.

BACKGROUND: Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease. PATIENTS AND METHODS: Thirty-three patients were randomized to either docetaxel (100 mg/m(2)) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m(2)) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately. RESULTS: Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35% [95% confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15% to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment. CONCLUSIONS: Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.     

口服小剂量环磷酰胺联合卡培他滨维持治疗晚期三阴性乳腺癌的疗效

目的:观察小剂量环磷酰胺（CTX）联合卡培他滨（CAP）维持治疗晚期三阴性乳腺癌的疗效及安全性。方法:回顾性分析我院收治的经含卡培他滨方案两药联合化疗后达临床稳定的晚期三阴性乳腺癌患者68例,实验组34例给予口服环磷酰胺 50 mg/d,d8~21,每3周重复,联合卡培他滨1 000 mg/m2,bid,d1~14,休息7天。对照组34例患者仅给予口服卡培他滨单药维持治疗。观察2组患者的ORR、DCR、TTP、安全性及对生活质量的影响。结果:经维持治疗后实验组ORR 为29.4%,DCR为85.3%;对照组ORR 为14.7%,DCR为64.7%。实验组中位TTP为12个月,明显高于对照组中位TTP 6.9个月(P＜0.05)。两组的主要不良反应为手足综合征,实验组的胃肠道反应及血液学毒性稍高于对照组,均为Ⅰ-Ⅱ度。两组患者的生活质量评分均较治疗前明显提高,治疗后组间差异无统计学意义(P＞0.05)。结论:口服小剂量环磷酰胺联合卡培他滨维持治疗晚期三阴性乳腺癌有较好的疗效,不良反应可以耐受,可作为复发转移较快的晚期三阴性乳腺癌患者维持治疗的一种选择,具有一定的临床推广应用价值。     

多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床观察

目的:观察多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床疗效及不良反应。方法:回顾性分析40例转移性乳腺癌患者的化疗资料,采用国产多西他赛75mg/m2,表柔比星70-90mg/m2静脉滴注,环磷酰胺500mg/m2每3周1次。观察每次化疗后的不良反应,完成4个疗程后观察疗效。结果:全部病例均按计划完成4个周期的化疗。完全缓解(CR)3例,部分缓解(PR)20例,稳定(SD)12例,进展(PD)5例。总有效率(CR+PR)为57.5%,控制率(CR+PR+SD)87.5%。主要不良反应为中性粒细胞减少、恶心、呕吐、腹泻等。结论:多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌临床疗效较好,不良反应患者可以耐受。     

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer

The purpose of the study was to evaluate the efficacy and safety of docetaxel plus epirubicin (ET) and of 5-fluorouracil plus epirubicin and cyclophosphamide (FEC) as first-line chemotherapy for metastatic breast cancer. A total of 142 patients (intent-to-treat (ITT)) with at least one measurable lesion were randomised to receive docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) or 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles. Prophylactic granulocyte-colony-stimulating factor was only permitted after the first cycle, if required. Per-protocol analysis (n=132) gave an overall response rate for ET of 63.1% (95% confidence interval (CI), 50-78%) and for FEC 34.3% (95% CI, 23-47%) after a median seven and six cycles, respectively. Intent-to-treat population (n=142) gave an overall response rate for ET of 59% (95% CI, 47-70%) and for FEC 32% (95% CI, 21-43%) after a median seven and six cycles, respectively. The median response duration for ET was 8.6 months (95% CI, 7.2-9.6 months) and for FEC 7.8 months (95% CI, 6.5-10.4 months). The median time to progression (ITT) for ET was 7.8 months (95% CI, 5.8-9.6 months) and for FEC 5.9 months (95% CI, 4.6-7.8 months). After a median follow-up of 23.8 months, median survival (ITT) for ET and FEC were 34 and 28 months, respectively. Nonhaematologic grade 3-4 toxicities were infrequent in both arms. Haematologic toxicity was more common with ET and febrile neutropenia was reported in 13 patients (18.6%) in the ET group. Two deaths in the ET group were possibly related to study treatment. In conclusion, both ET and FEC were associated with acceptable toxicity. ET is a highly active first-line therapy for metastatic breast cancer.     

Treatment of advanced, refractory breast cancer with alternating docetaxel and epirubicin/cyclophosphamide plus human granulocyte colony-stimulating factor

Purpose.A phase II study was performed to investigate the efficacy and tolerance of alternating docetaxel and epirubicin/cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with advanced breast cancer who failed previous non-anthracycline/taxane-containing palliative chemotherapy. Patients and methods.Between November 96 and June 98, a total of 45 patients participated in this trial. Chemotherapy consisted of docetaxel 100mg/m² given as a 1-h infusion on day 1, and epirubicin 100mg/m² plus cyclophosphamide 800mg/m² both adminstered on day 21. G-CSF 5g/kg/day was given subcutaneously from days 22–28 during each cycle. Treatment courses were repeated every 42 days for a total of three courses unless prior evidence of progressive disease. Results.The overall response rate was 57.8% (95% confidence interval, 42.1–72.3%), including seven complete (15.5%) and 19 partial remissions (42.3%); nine patients (20%) had stabilization of disease and 10 (22.3%) progressed. The median time to treatment failure was 7.0 months (range 1.5–26.0), and the median overall survival time 15.0 months (range 2.0–37.0+) with 12 patients (27%) currently still alive with metastatic disease. Myelosuppression was commonly observed with WHO grade 3/4 neutropenia in 20 patients (44%) complicated by septicemia in five (11%). Severe nonhematologic toxicity included stomatitis in five patients (11%), skin and peripheral neurotoxicity each in one patient; alopecia was seen in all 45 patients with complete hair loss in 26 (58%). Conclusions.Our data suggest that alternating docetaxel and epirubicin/cyclo-phosphamide plus G-CSF is an effective and tolerable second-line combination regimen for the treatment of advanced breast cancer.     

Vinorelbine, methotrexate and fluorouracil (VMF) as first-line therapy in metastatic breast cancer: a randomized phase II trial.

BACKGROUND: The purpose of this study was to determine the best tolerated and efficacious dose of vinorelbine given once or twice in 3-week cycles in combination with methotrexate and fluorouracil (VMF). PATIENTS AND METHODS: Vinorelbine 40 mg/m(2) was given as follows: 20 mg/m(2) on days 1 and 8 (group 1); 30 mg/m(2) on day 1 and 10 mg/m(2) on day 8 (group 2); or 40 mg/m(2) on day 1 (not exeeding 60 mg/m(2)) (group 3). The methotrexate dose was 40 mg/m(2) on day 1 and the fluorouracil dose 600 mg/m(2) on days 1 and 8. Thirty patients with evaluable metastases were randomly allocated to the groups (first step). The second step was to exclude the worst tolerated regimen and then to expand the study to 60 patients. Thus, group 1 had 26 patients, group 2 had 24 patients and group 3 had 10 patients. RESULTS: World Health Organization (WHO) grade 3 hematological toxicity occurred in 23%, 36% and 50% of patients and grade 4 in 39%, 32% and 50% of patients in groups 1, 2 and 3, respectively; grade 3 infections were observed in 15%, 9% and 10% of patients in groups 1, 2 and 3, and grade 4 infections in 5% and 10% of patients in groups 2 and 3, respectively. Nonhematological toxicity included a mild to moderate neurotoxicity manifesting as constipation, abdominal colics and myalgia in the majority of patients. One patient in group 3 had serious convulsions after vinorelbine administration; she also developed neutropenic sepsis; all symptoms were reversible. No patient died from side-effects. The objective response rates were 50%, 55% and 44% for groups 1, 2 and 3, respectively. Median time to progression was 7, 10 and 8 months and median survival time was 26, 23 and 16 months in groups 1, 2 and 3, respectively. CONCLUSION: VMF regimens where the vinorelbine dose (40 mg/m(2)) is divided (20 + 20 mg/m(2) and 30 + 10 mg/m(2)) between days 1 and 8 of a 3-week cycle are equally well tolerated and the efficacy is comparable to other modern first line regimens used in the treatment of metastatic breast cancer.     

Multiple cycles of high-dose doxorubicin and cyclophosphamide with G-CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer

Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen.Patients and methods: For mobilisation of PBPC, G-CSF 15 µg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m² and cyclophosphamide 1000 mg/m². Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort.Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m². The MTD in this combination was 110 mg/m² for doxorubicin, and 4 g/m² for cyclophosphamide, with haemorrhagic cystitis being the dose-limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%–97%), with 22% (95% CI: 3%–41%) complete responses.Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m² and cyclophosphamide 4 g/m² with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.     

Four-drug sequential regimen in advanced breast cancer

Summary The results of two empirically designed and potentially non-cross-resistant combinations administered sequentially in advanced breast cancer with the intent of achieving a high rate of durable complete remissions were analyzed. The two drug combinations consisted of cyclophosphamide plus Adriamycin and high-dose methotrexate plus cisplatin given for a total of three cycles; twenty evaluable patients, not previously treated with chemotherapy, were entered into the study. Ten patients were allocated to receive cyclophosphamide and Adriamycin first followed by high-dose methotrexate and cisplatin, while the remaining patients received the opposite sequence. The overall response rate for the entire group was 85% (17 of 20). However, only three of 20 (15%) patients achieved complete remission. One additional complete response was observed when treatment was prolonged for an additional complete cycle. The overall median duration of response was 13 months (range, 5–20⁺ months). Responses were similarly distributed among different sites of lesions. Myelosuppression and gastrointestinal toxicity were mild and transient. Reversible acute renal failure was observed after methotrexate administration in three cases. Present results indicate that overall this sequential treatment appears effective in patients with advanced breast cancer. However, the lack of an increased complete remission rate over conventional regimens coupled with a potential risk of renal toxicity prevents further studies with this multiple drug combination.     

VEGF和CD44表达与乳腺癌分期的相关性研究

目的：研究血管内皮生长因子（vascular endothelial growth factor,VEGF）和CD44在不同分期乳腺癌中的表达及其相互关系。方法：共收集79例手术标本和12例正常乳腺组织,用免疫组织化学法（S-P法）检测,用免疫组化图象分析系统进行结果处理。结果：乳腺癌中VEGF和CD44的表达水平与正常乳腺组织相比差异具有显著性（P〈0.05）;Ⅰ期与Ⅱ期及Ⅲ期之间相比,VEGF和CD44的表达水平差异同样具有显著性,并且随分期越晚表达越强（P〈0.05）;不同细胞类型之间的差异无显著性（P〉0.05）,而与肿瘤的浸润深度、淋巴结转移、远处器官转移以及肿瘤的TNM分期密切相关（P〈0.05）。结论：VEGF与CD44的表达水平与乳癌分期成正相关,在排除创伤和炎症的前提下,可能提示肿瘤的活跃生长以及潜在转移。     

Impact of surgery and chemotherapy on von Willebrand factor and vascular endothelial growth factor levels in colorectal cancer

Introduction von Willebrand factor (vWf) is thought to mediate binding of tumour cells to platelets and to favour their systemic spreading capacity. Platelets involved in tumour angiogenesis are capable of releasing vascular endothelial growth factor (VEGF). Hence, levels of vWf and VEGF may correlate with cancer stage. The objectives are determine the impact of surgery and chemotherapy on vWf and VEGF in colorectal cancer (CRC) patients. Material and methods Twenty healthy volunteers (group 1), 14 patients with locally advanced CRC (group 2) and 12 patients with metastatic CRC (group 3) were enrolled. Blood samples were taken at recruitment in group 1, and before and after surgery and chemotherapy in groups 2 and 3, respectively. Blood levels of vWf, VEGF, platelet count, C-reactive protein (CRP), ceruloplasmin and carcinoembrionary antigen (CEA) were measured. Results At baseline, group 3 showed higher concentrations of vWf than the other groups (p<0.05). In group 2, vWf became elevated 40% post-surgery (p=0.016), independently of changes in CRP or ceruloplasmin. In group 3, chemotherapy caused a 42% reduction in VEGF (p=0.015). Conclusions There was a strong correlation between higher vWf levels and more advanced CRC stage at diagnosis. These levels were elevated post-surgery in patients with locally advanced CRC. Chemotherapy significantly decreased VEGF in metastatic CRC patients before CEA showed any significant change.