Yttrium-90 radioembolization in patients with unresectable liver metastases: determining the factors that lead to treatment efficacy.

INTRODUCTION: Locoregional treatments, such as radioembolization, can be used to treat patients with unresectable liver metastases. We aimed to determine the progression-free survival and factors that predict survival of patients with liver metastases whose response to selective internal radiation therapy (SIRT) with Y-90 was assessed by positron emission tomography-computed tomography (PET-CT). PATIENTS: Our study included 78 liver cancer patients who were treated with Y-90 radioembolization. RESULTS: The post-treatment response rates were as follows: 7 patients (9%) had stable disease (SD), 26 patients (33.3%) had a partial response (PR), 4 patients (5.1%) had a complete response (CR). The median hepatic progression-free survival (HPFS) was 4.4 months while median overall survival was 10.1 months. Univariate analysis revealed that HPFS is significantly affected by international normalized ratio (INR) levels and age (Hazard Ratio(HR)=0.54 (95%CI:0.30-096), P=0.034, HR=1.03(95%CI:1.00-1.05), P=0.051). However, only INR levels retained significance with multivariate analysis (HR=0.53 (95%CI:0.30-0.93), P=0.028), while age had limited significance (HR =1.02 (95% CI:1.00-1.05), P=0.051). CONCLUSIONS: We determined that Y-90 radioembolization is effective as a salvage therapy in patients with predominant liver metastases. For the first time, we showed that age and INR values reflecting the functional hepatic reserve can be used as positive predictive factors for HPFS.

Differential expression and activation of epidermal growth factor receptor 1 (EGFR1), ERK, AKT, STAT3, and TWIST1 in nonsmall cell lung cancer (NSCLC).

Lung cancer is the leading cause of death of both men and women across the world. Overexpression and activating mutations of the epidermal growth factor receptor-1 (EGFR1) are frequently observed and associated with poor prognosis. To inhibit the function of EGFR1, multiple antibodies and small-molecule tyrosine kinase inhibitors (TKI) that target EGFR1 have been developed. Even though some patients respond to these TKI, subsequent studies reveal that this is not the case for all nonsmall cell lung cancer (NSCLC) patients. In this study, we determine whether activation and expression levels of EGFR1, ERK, AKT, STAT3, and TWIST1 are dependent on the activating mutations of EGFR1. Protein lysates and DNA have been isolated from tumor and corresponding normal tissues of 16 NSCLC patients. Genomic-DNA is used to sequence the exons 18, 19, and 21 of EGFR1, and exon 2 of k-RAS. Protein lysates were used to determine the expression or phosphorylation levels of EGFR, STAT3, ERK, AKT, and TWIST1. Our results revealed that 16 tumor samples of NSCLC patients showed no mutation in any of the indicated exons of EGFR1 and k-RAS albeit significant levels of activation or expression of the above-mentined oncogenes. In NSCLC patients, the tumor micro-environment can be as important as the activating mutations of EGFR1. TK therapy may also be considered for patients who show high levels of activation of EGFR1 even in the absence of activating mutations.

Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer.

BACKGROUND: Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors) are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum-soluble TNF-related apoptosis-inducing ligand) and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: sTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes. RESULTS: Elevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown). CONCLUSIONS: Serum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment.

Interaction of allergic disease and (immune) response to cancer in patient with stage-4 adenocarcinoma of the lung.

A 50 year old male patient who was watched because of penicillin and venom allergy in the allergy unit had been admitted to the medical oncology polyclinic with cough, expectoration and hemoptysis 10 years ago. His symptoms had first begun 1 month prior to that admission, and he was then diagnosed with stage IV adeno carcinoma. The first allergic reaction occurred at 1 hour following the last transfusion, while the second transfusion reaction occurred within the first 10 minutes of the transfusion and was associated with respiratory arrest. Also, he reported both penicillin and venom allergy history, and, subsequent to diagnosis and treatment, developed an anaphylactic reaction to a European Cornet sting on two occasions. Our aim in publishing this case is that after diagnosis of metastatic lung adeno cancer, our patient developed anaphylactic reactions associated with bee stings and on 2 occasions suffered transfusion associated anaphylactic reactions. His subsequent survival (9 years to date with stable disease) is extraordinary.

Erratum to "IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer" [Clin. Lab. 2012; 58:501-505].

BACKGROUND: Colorectal cancer is the third most common human cancer and the third leading cause of cancer related death. BevacizumAb is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancers. Our goal was to evaluate the possibility of using serum sTRAIL and IL8 as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: The study was conducted in Denizli between November 10, 2009 and September 20, 2010. 25 patients (6 female, 19 male) with metastatic colon cancer whose mean age was 58.7 years, were selected and included in the study. All patients received therapy with BevacizumAb. All patients were followed in the Oncology Clinic of Denizli State Hospital and were evaluated by clinical status. sTRAIL and IL8 levels were measured by ELISA in the sera of 25 BevacizumAb treated metastatic colon cancer patients and 20 healthy age-gender matched controls. Measurements were taken before and after treatment. RESULTS: The serum sTRAIL concentrations in patients before therapy were similar to those of healthy age-gender matched controls, namely 1.23 +/- 0.06 ng/mL and 1.21 +/- 0.04 ng/mL, respectively. After BevacizumAb treatment, sTRAIL ratios were increased significantly in 11 of 25 patients. 14 patients showed progressive disease with median overall survival of only 8.1 +/- 0.4 months. These 14 patients were the same ones who showed no increase in sTRAIL levels after BevacizumAb treatment. We explored evidence for a correlation between sTRAIL levels and overall survival rates and observed that elevated sTRAIL levels after the BevacizumAb treatment were significantly associated with increased median overall survival up to 22.6 months. Serum IL8 levels were decreased in all patients who received BevacizumAb therapy. CONCLUSIONS: In BevacizumAb therapy, serum IL8 levels were decreased in all patients, and thus, changes in such levels were not correlated with disease outcome. Our data suggest measurement of changes in sTRAIL following BevacizumAb treatment may have prognostic value in metastatic colon cancer patients.

IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer.

BACKGROUND: Colorectal cancer is the third most common human cancer and the third leading cause of cancer related death. BevacizumAb is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancers. Our goal was to evaluate the possibility of using serum sTRAIL and IL8 as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: The study was conducted in Denizli between November 10, 2009 and September 20, 2010. 25 patients (6 female, 19 male) with metastatic colon cancer whose mean age was 58.7 years, were selected and included in the study. All patients received therapy with BevacizumAb. All patients were followed in the Oncology Clinic of Denizli State Hospital and were evaluated by clinical status, sTRAIL and IL8 levels were measured by ELISA in the sera of 25 BevacizumAb treated metastatic colon cancer patients and 20 healthy age-gender matched controls. Measurements were taken before and after treatment. RESULTS: The serum sTRAIL concentrations in patients before therapy were similar to those of healthy age-gender matched controls, namely 1.23 +/- 0.06 ng/mL and 1.21 +/- 0.04 ng/mL, respectively. After BevacizumAb treatment, sTRAIL ratios were increased significantly in 11 of 25 patients. 14 patients showed progressive disease with median overall survival of only 8.1 +/- 0.4 months. These 14 patients were the same ones who showed no increase in sTRAIL levels after BevacizumAb treatment. We explored evidence for a correlation between sTRAIL levels and overall survival rates and observed that elevated sTRAIL levels after the BevacizumAb treatment were significantly associated with increased median overall survival up to 22.6 months. Serum IL8 levels were decreased in all patients who received BevacizumAb therapy. CONCLUSIONS: In BevacizumAb therapy, serum IL8 levels were decreased in all patients, and thus, changes in such levels were not correlated with disease outcome. Our data suggest measurement of changes in sTRAIL following BevacizumAb treatment may have prognostic value in metastatic colon cancer patients.

Effects of two plant growth regulators, indole-3-acetic acid and ß-naphthoxyacetic acid, on genotoxicity in Drosophila SMART assay and on proliferation and viability of HEK293 cells from the perspective of carcinogenesis.

In this study, the mutagenic and recombinogenic effects of indole-3-acetic acid (IAA), a plant growth regulator naturally synthesized in plants but produced synthetically, and ß-naphthoxyacetic acid (BNOA), a synthetic plant growth regulator widely used in agricultural regions, were investigated using the somatic mutation and recombination test (SMART) in Drosophila wings. The effect of the same plant growth regulators against the proliferation and viability of a human immortalized embryonic kidney HEK293 cells which is at the early stage of carcinogenesis were also examined with MTT and trypan-blue exclusion assays. For the SMART assay, two different crosses were used: a standard and a high-bioactivation (HB) cross, involving the flare-3 and the multiple wing hairs markers. The HB cross involved flies characterized by an increased cytochrome P-450-dependent bioactivation capacity, which permits the more efficient biotransformation of promutagens and procarcinogens. In both crosses, the wings of the two types of progeny, inversion-free marker heterozygotes and balancer heterozygotes, were analyzed. The results show that IAA and BNOA are not mutagenic or recombinogenic in the wing cells of Drosophila. Furthermore, neither plant growth regulator affected the proliferation rate of HEK293 cells; however, both of them induced cell death at high concentrations.

TRAIL death receptor-4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

PURPOSE: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. METHODS AND MATERIALS: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. RESULTS: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. CONCLUSIONS: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

Epithelioid leiomyosarcoma with rhabdoid features.

Leiomyosarcomas (LMS) are the most common type of uterine sarcoma. Most LMS have typical histologic features, and variants such as epithelioid LMS, myxoid LMS, LMS with osteoclast-like giant cells and LMS with rhabdoid features occur only rarely. Rhabdoid cells were first described in rhabdoid tumor, a distinctive renal neoplasm of infancy. Such tumors are composed of diffuse proliferation of rhabdoid cells that are round or polygonal in shape with eccentric nuclei, prominent nucleoli and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies. In the literature, extrarenal localizations of malign rhabdoid tumors have been described in a variety of primary sites such as the central nervous system, liver, skin and soft tissues. These characteristic rhabdoid cells have been reported in sarcomas and carcinomas of various types and in a few cases of uterine sarcomas. The presence of rhabdoid cells in tumors is considered to be a predictor of aggressive tumor behavior. Our case is that of a 56-year-old woman who was admitted to the state hospital with left inguinal mass. Microscopically the tumor was admixed of three different types of cell with spindle, epithelioid or rhabdoid features. Immunopositive cytoplasmic staining for myoglobulin and desmin was seen in rhabdoid cells, and cytokeratin immunopositivity was observed in epithelioid and some rhabdoid cells. Epithelioid cells and spindle cells were also SMA positive. The histopathologic and immunohistochemical findings support the diagnosis of epithelioid LMS with rhabdoid features. We report this very uncommon LMS variant; to the best of our knowledge there are only a few cases in the English literature.

Lymphokine-activated killer cell susceptibility and adhesion molecule expression of multidrug resistant breast carcinoma.

Reports showing susceptibility of multidrug resistant (MDR) cancer cells to immune effectors, together with P-glycoprotein (P-gp) expression in immune effector subsets, including immature natural killer (NK) cells, and some activated T cells, suggest P-gp or some changes associated with it, have implications in immune-mediated mechanisms. A series of experiments were done to determine the nature of alterations associated with susceptibility to immune effector cells of MDR tumor cells. A cell line isolated from the malignant pleural effusion of a breast cancer patient was transfected with human and murine MDR1 genes, and four variants with different levels of MDR were obtained. Lymphokine-activated killer (LAK) activity was measured by a 51Chromium release, and conjugate formation assays. MDR1 transfectant P-gp+ breast carcinoma lines had increased LAK susceptibility compared to their parent line. Some part of the increased LAK susceptibility of drug-resistant cell lines was at the binding/recognition level as shown by conjugate formation assays. This suggests that differences may exist between paired cell lines with respect to the expression of cell adhesion molecules (CAMs). Monoclonal antibodies (mAbs) to CAMs and flow cytometry were used to quantitate these antigens. The CAMs studied were those previously found to be upregulated by stimulating NK cells with (interleukin-2) IL-2; ICAM-1 (CD54), LFA-3 (CD58), N-CAM (CD56), and the beta chain of LFA-1 (CD18). Although no differences in these CAMs were found between the breast carcinoma line and its MDR1-transfected variants, the target susceptibility results given above suggest that IL-2 treatment could be effective in combination with current protocols using chemotherapeutics, monoclonal antibodies (mAbs) and stem cell transplantation.

Factors related to truth-telling practice of physicians treating patients with cancer in Turkey.

BACKGROUND: In the practice of oncology, effective communication between physician and patient is very important. Although many studies have indicated that a large majority of physicians, especially from Western countries, tell the truth about diagnosis and prognosis, little is known about attitudes of physicians in Turkey toward truth-telling. OBJECTIVE: In this study, we tried to determine the truth-telling practice of physicians and explore potential related factors with a self-reported questionnaire. DESIGN: Using a questionnaire, 131 cancer specialists were interviewed during the 15th National Oncology Meeting in April 2003. RESULTS: The percentage of physicians who never, rarely, generally, and always prefer truthtelling about a cancer diagnosis were 9%, 39%, 45%, and 7%, respectively. In univariate logistic regression analysis for the truth-telling practice, significant variables included "do not tell" requests from family, experiences from medical training and clinical practice, and medical specialty. In the multivariate analysis, "do not tell" requests from relatives and medical training factors retained their significance. CONCLUSION: Professional training in breaking bad news is important and is associated with the self-reported truth-telling practices of physicians.

Quality of life in patients with advanced non-small cell lung cancer.

Quality of life (QOL) has been shown to improve with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), but the determinants of this improvement have not been thoroughly explored. Fifty consecutive NSCLC patients starting chemotherapy with measurable disease and with an Eastern Co-operative Oncology Group (ECOG) performance status of

Multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine sulfoximine.

BACKGROUND: Multidrug resistance mediated by the multidrug resistance-associated protein 1 (MRP1) decreases cellular drug accumulation. The exact mechanism of MRP1 involved multidrug resistance has not been clarified yet, though glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-Buthionine (S,R)-sulfoximine (BSO) is an inhibitor of GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated vincristine resistance in Human Embryonic Kidney (HEK293) and its MRP1 transfected 293MRP cells. Human Embryonic Kidney (HEK293) cells were transfected with a plasmid encoding whole MRP1 gene. Both cells were incubated with vincristine in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. GSH, Glutathione S-Transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs. RESULTS: N-acetylcysteine increased the resistance of both cells against vincristine and BSO decreased NAC-enhanced MRP1-mediated vincristine resistance, indicating that induction of MRP1-mediated vincristine resistance depends on GSH. Vincristine decreased cellular GSH concentration and increased GPx activity. Glutathione S-Transferase activity was decreased by NAC. CONCLUSION: Our results demonstrate that NAC and BSO have opposite effects in MRP1 mediated vincristine resistance and BSO seems a promising chemotherapy improving agent in MRP1 overexpressing tumor cells.

Different clinical features of primary and secondary tumors in patients with multiple malignancies.

Clinical features of the first and second primaries in patients with multiple malignancies have not been extensively studied. We compared patient and treatment characteristics of the primary malignancy in 48 consequent multiple primary cancer patients with those of the second primary in the same cohort. The second primaries comprised fewer breast cancers; 29.2% of primaries as opposed to 10.4% of second tumors were breast cancer (P = 0.049). In addition, primary tumors tended to be at a lower TNM stage than secondary tumors (P = 0.060). The median overall survival after the diagnosis of the first primary for the whole cohort was 22.3 years (95% CI, 2.0-42.5) and the median time to presentation of the second malignancy was 38 months after the diagnosis of the first primary (range, 0 to 384). Therefore, the prognosis of cancers in the multiple malignancy group appears to be good and they appear to have an indolent clinical behavior. Thus, we recommend a long screening time for secondary tumors after a curative treatment in patients with common cancers, taking into account the different occurrence patterns of second primaries with respect to first primaries.

Retrospective analysis of third-line chemotherapy in advanced non-small cell lung cancer.

BACKGROUND: First- and second-line chemotherapies have been demonstrated to be effective in treatment of patients with inoperable, advanced non-small cell lung cancer (NSCLC), although the role of third-line chemotherapy remains unclear. The present investigation assessed treatment outcomes in patients with advanced NSCLC who received third-line and higher chemotherapy. PATIENTS AND METHODS: This retrospective study included consecutive patients with advanced NSCLC who received at least three lines of systemic chemotherapy. RESULTS: A total of 72 patients who had received third-line or higher chemotherapy were included in the analysis. The median age of patients was 49 years (range 41-76), and there were 13 (18.1%) women and 59 (81.9%) men. Estimated median survival was 26 months. Moreover, overall survival was significantly longer in patients for whom disease control was achieved after second-line chemotherapy compared to those with disease progression (34 vs. 17 months, respectively). Survival after third-line treatment was significantly longer in the group with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at the beginning of third-line therapy compared to patients with a status of 2-3. CONCLUSIONS: In patients with advanced stage NSCLC, administration of third-line and higher systemic chemotherapy may be associated with increase in overall survival. Furthermore, greater increases in overall survival were also observed in patients for whom disease control was achieved after second-line therapy and in those with ECOG performance status of 0-1 before third-line treatment.

Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab.

Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20-30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer.

Oral cyclophosphamide and etoposide in treatment of malignant pleural mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. MATERIALS AND METHODS: This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). RESULTS: The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression- free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). CONCLUSIONS: Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.

Determinants of opioid efficiency in cancer pain: a comprehensive multivariate analysis from a tertiary cancer centre.

BACKGROUND: Pain is one of the most terrifying symptoms for cancer patients. Although most patients with cancer pain need opioids, complete relief of pain is hard to achieve. This study investigated the factors influencing persistent pain-free survival (PPFS) and opioid efficiency. MATERIALS AND METHODS: A prospective study was conducted on 100 patients with cancer pain, hospitalized at the medical oncology clinic of Akdeniz University. Patient records were collected including patient demographics, the disease, treatment characteristics, and details of opioid usage. Pain intensity was measured using a patient self-reported visual analogue scale (VAS). The area under the curve (AUC) reflecting the pain load was calculated from daily VAS tables. PPFS, the primary measure of opioid efficacy, was described as the duration for which a patient reported a greater than or equal to two-point decline in their VAS for pain. Predictors of opioid efficacy were analysed using a multivariate analysis. RESULTS: In the multivariate analysis, PPFS was associated with the AUC for pain (Exp (B)=0.39 (0.23-0.67), P=0.001), the cumulative opioid dosage used during hospitalisation (Exp (B)=1.00(0.99-1.00), P=0.003) and changes in the opioid dosage (Exp (B)=1.01 (1.00-1.01), P=0.016). The change in VAS score over the standard dosage of opioids was strongly associated with current cancer treatment (chemotherapy vs. others) (ß=-0.31, T=-2.81, P=0.007) and the VAS for pain at the time of hospitalisation (ß=-0.34, T=-3.07, P= 0.003). CONCLUSIONS: The pain load, opioid dosage, concurrent usage of chemotherapy and initial pain intensity correlate with the benefit received from opioids in cancer patients.

Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma.

Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment with FOLFIRI plus bevacizumab. The study included patients with metastatic colorectal cancer who received FOLFIRI plus bevacizumab as a first-line treatment. Patients who had objective response with FOLFIRI plus bevacizumab treatment after an average period of 6 months received a maintenance treatment with capecitabine plus bevacizumab (capecitabine 2 x 1000 mg/m(2), 1 - 14 days, every 21 days, bevacizumab 7.5 mg/m(2), every 21 days) until disease progression or toxicity. The time to progression on bevacizumab treatment was evaluated. A total of 29 patients (15 male, 14 female) were included. The mean age was 62 years. The mean number of cycles for maintenance treatment with capecitabine plus bevacizumab was 12. The median PFS was 16 ± 3 months, and OS was 42 ± 11 months. PFS and OS were remarkably higher in patients with a complete or near complete response to induction treatment. Fourteen patients (48%) experienced hand-foot syndrome associated with capecitabine plus bevacizumab treatment, without any severe toxicity. Inselected patients with metastatic colorectal carcinoma who had a remarkable objective response to FOLFIRI plus bevacizumab treatment, a maintenance treatment with capecitabine plus bevacizumab following FOLFIRI plus bevacizumab until disease progression may be a suitable, effective and tolerable regimen, which requires further studies.