Efficacy Of Adjuvant Treatment Research Articles

Cytochrome P450 2D6 polymorphisms of Thai patients with breast cancer and their outcomes of adjuvant tamoxifen.

e11037 Background: The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamoxifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. We evaluated Cytochrome P450 2D6 SNPs and the influences of tamoxifen efficacy in adjuvant treatment of breast cancer in Ramathibodi hospital. Methods: Peripheral blood DNA samples from 38 patients who had disease recurrence during adjuvant tamoxifen treatment, and from 38 patients who had completed 5 years of tamoxifen without recurrence of breast cancer were isolated and genotyped for CYP2D6*4 by RFLP method, and CYP2D6*10 by PCR and DNA sequencing method. Disease free survival and correlation with genotypes were analyzed by Kaplan-Meier method, and log-rank test. Results: Of 76 analyzed patients, 42%, 36% and 22% of the patients carried the CYP2D6 *10/*10, wt/*10 and wt/wt genotypes respectively. There was no discernible correlation between clinicopathological parameters and the patterns of CYP2D6 *10 genotype. We found no significant difference in DFS among these three groups of patients (the mean DFS were 42.94 months for *10/*10 patients, not reach for wt/*10 patients and 60 months for wt/wt patients, p=0.128). One patient had both CYP2D6 wt/*4 and *10/*10. We found common SNPs of CYP2D6*10 188C>T with allele frequency 59.87 %. SNP of CYP2D6*4 1934G>T was detected with allele frequency 0.66%. Both SNPs frequencies were concordance to previous reports in Asian population. Conclusions: The polymorphisms of CYP2D6*10 do not influence the clinical outcomes of Thai breast cancer patients receiving adjuvant tamoxifen.

Zhisou Powder and three children to support pro-Decoction efficacy of adjuvant treatment of elderly pneumonia Analysis

Objective To Observe Zhisou Powder and three sub-biological parent Decoction efficacy of adjuvant therapy for pneumonia in the elderly.Methods Choose from January 2007 to January 2009 hospitalized patients with pneumonia,116 cases of elderly ,56 cascs were randomly divided into treatment group and control group 60 cases.The control group were treated with conventional Western medicine treatment,including antibacterial drugs,cough phlegm,asthma,oxygen,etc.,the treatment group in the control group supplemented with oral administration on the basis of the third son of Yang Zhisou Powder and pro-decoctiou decoction were compared cough,sputum improves the time patients,pulmonary rales reduce the time and the X-ray absorption degree of difference in inflammation.Results The treatment group improved time to cough sputum,pulmonary rales reduce the time and the X-ray absorption level of inflammation were better than that in the control group,the difference was significant,P ＜ 0.05.Conclusion And other antibacterial drugs in Western medicine on the basis of conventional therapy supplemented by oral administration Zhisou Powder and three sons to support the pro-Tang Decoction senile pneumonia,efficacy is better and be able to short the course,reduce the usc of antimicrobial drugs,thereby reduce the drug-resistant generation and improve the prognosis has important clinical significance. Key words: Zhisou Powder; Three sons,the pro-Tang Yang; Senile Pneumonia

Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders

Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. This randomized, double-blind, placebo-controlled study was conducted between May 2004 and August 2007. Seventy antipsychotic-treated inpatients and outpatients from 10 psychiatric hospitals in The Netherlands with a DSM-IV-diagnosed schizophrenia spectrum disorder were included. Patients were randomized to adjuvant treatment with aspirin 1000 mg/d or placebo. During a 3-month follow-up, psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Other assessments included cognitive tests and immune function. The primary efficacy outcome was the change in total PANSS score. Secondary outcomes were changes in the PANSS subscales and cognitive test results. Mixed-effect models showed a 4.86-point (95% CI, 0.91 to 8.80) and 1.57-point (95% CI, 0.06 to 3.07) larger decrease in the aspirin group compared to the placebo group on the total and positive PANSS score, respectively. Similar but not statistically significant results were observed for the other PANSS subscale scores. Treatment efficacy on total PANSS score was substantially larger in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded. Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development. controlled-trials.com Identifier: ISRCTN27745631.

Impact of Selection Bias on the Utilization of Adjuvant Therapy for Pancreas Adenocarcinoma

Improved outcomes have been associated with the use of adjuvant therapy after resection of pancreas adenocarcinoma. However, the frequency with which patients receive adjuvant therapy and the factors impacting its use remain largely undefined. We hypothesized that nonutilization of adjuvant therapy was primarily associated with patient comorbidity and onset of postoperative complications. A prospectively maintained database was reviewed to identify patients who underwent potentially curative resection of histologically confirmed pancreas adenocarcinoma at our institution from January 1996 to May 2007. Clinicopathological data and postoperative treatment history were collected to identify variables associated with receipt of adjuvant therapy. Of 119 patients, 33% did not receive adjuvant therapy. The frequency with which patients underwent adjuvant therapy did not change over time. On multivariate analysis, patient age 70 years or greater, major postoperative complications, distal pancreatectomy, absence of nodal metastases, and absence of perineural invasion were associated with decreased utilization of adjuvant therapy. One-third of patients in this contemporary dataset of patients did not go on to receive adjuvant therapy. The likelihood of receiving adjuvant treatment is negatively impacted by the course of postoperative recovery. Moreover, the fact that adjuvant therapy was undertaken less often for older patients and patients with favorable pathological features highlights the selection bias impacting the decision to pursue postoperative therapy for this disease. This selective utilization of postoperative therapy for patients with adverse oncological characteristics is likely to bias any retrospective analysis attempting to measure the efficacy of adjuvant treatment for pancreas adenocarcinoma.

Minimal change disease with IgM+ immunofluorescence: a subtype of nephrotic syndrome

Immunoglobulin (Ig) M nephropathy is defined by electron-dense mesangial deposits and mesangial IgM visible by immunofluorescence (IF) without other histopathologic and immunofluorescent microscopic abnormalities. Certain patients have only immuno-positive (IgM+) IF. Children presenting with steroid-dependent or steroid-resistant nephrotic syndrome have a high prevalence of IgM+ IF with or without electron-dense deposits. We reviewed the clinical course of children with steroid-dependent or steroid-resistant nephrotic syndrome who underwent renal biopsy at Texas Children's Hospital from 1989 to 2006 to further characterize IgM+ IF in children with nephrotic syndrome. Of the 55 children with steroid-resistant or -dependent minimal change disease (MCD), 23 had IgM+ IF. Of these 23 children, 61% had microscopic hematuria at presentation, 48% (11/23) were steroid-dependent, and 48% (11/23) steroid-resistant (one underwent biopsy prior to steroid therapy). We compared the efficacy of adjuvant treatment with cyclophosphamide and cyclosporine: 18% initially treated with cyclophosphamide obtained remission, while 55% had no response; 83% obtained subsequent remission with cyclosporine. Of those initially treated with cyclosporine, 88% obtained complete or partial remission. IgM+ IF may be surrogate marker for the severity of MCD. Based on our results, children with MCD and IgM+ IF have a better response to cyclosporine than cyclophosphamide.

Addressing fertility needs of breast cancer patients: oncology perspective

Premenopausal women represent approximately 23% of women diagnosed with breast cancer. As the medial age of first pregnancy increases in developed countries, a greater proportion of women are diagnosed with breast cancer at a time when they have not yet completed their family. For these women, the impact of breast cancer treatment on their reproductive capacity can be of significant concern and may influence their treatment decisions. Despite these concerns only a proportion of premenopausal women with breast cancer are informed about their treatment choices in light of their reproductive needs. The diagnosis of cancer itself as well as systemic cancer treatments, including chemotherapy and hormonal therapy, can delay and/or reduce the reproductive capacity. Treatment decisions need to consider not only adjuvant treatment efficacy but also its risks, including impact on fertility. The risk of chemotherapy-associated amenorrhea varies according to the regime and is age-dependent. Hormonal treatments may delay reproduction further. A variety of fertility preservation strategies have been tried including gonadal protection during chemotherapy, ovarian cryopreservation and in vitro fertilization, but their potential benefits need to be considered in light of risks and, for most of them, the evidence for efficacy is limited. Special fertility considerations are required in women with family history and/or evidence of genetic predisposition to breast cancer as strategies for risk reduction may impact on their fertility choices. Finally, as survival of women with metastatic breast cancer increases, women with advanced cancer who become pregnant pose unique management challenges for oncologists and obstetricians alike.

Predictive value of MRP2, p53, bcl2 and topoisomerase II immunostainings for the efficacy of anthracyclines-based adjuvant chemotherapy in breast cancer: Results from two randomized trials

616 Background: The identification of predictive biomarkers for the efficacy of adjuvant treatments could allow to better tailor adjuvant treatments. We evaluated the predictive value of MRP2, bcl2, topoisomerase IIα (Topo IIα) expression and p53 status for the efficacy of adjuvant anthracyclines (A)-based chemotherapy. Methods: Tumor samples from 823 patients included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no treatment were used to perform a tissue-array. Chemotherapy consisted of 5FU (500mg/m2), farmorubicine (90% of patients) or doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) (D1=D28) for 6 cycles. Immunostainings (cut-off: >10% stained cells) were performed for MRP2 (M2III-6; 1:300; Alexis), p53 ( DO-7; 1:50; Dako), bcl2 (124; 1:50; Dako), and Topo IIα (KI-S1; 1:5000; Chemicon). We previously reported predictive values of ER, HER2 expression and molecular subclassification using the same tissue-array (Conforti, Annals of Oncology, 2007). Results: After a median follow-up of 10 years, 174 patients (22%) have presented a relapse and 186 patients (24%) died. Chemotherapy improved DFS (HR = 0.77, 95% CI: 0.63- 0.9), but not OS (HR = 0.88, 95% CI: 0.66–1.1). A positive staining for MRP2, p53, Topo IIα and bcl2 was observed in 122 (16%), 157 (20%), 267 (35%) and 251 (34%) assessable samples respectively. P53 and Topo IIα were more frequently expressed in patients with basal-like (51% and 53%) or HER2-overexpressing tumors (44% and 57%), as compared to other groups (HER2- and nonbasal BC) (11% and 28%). Bcl2 was more frequently positive in patients with luminal-like breast cancer (47% versus 16%, p<0.01). No significant interaction was observed between the four biomarkers expression and treatment efficacy for both DFS and OS (adjusted p values for interaction ranged between 0.30 and 0.85). Conclusions: In this study, we did not detect significant interaction between MRP2, p53, bcl2 and Topo Iia expressions and treatment efficacy. Nevertheless, such study cannot exclude a possible interaction with a higher number of events or different methods (DNA sequencing for p53 mutations and lower dilution [1:200] for S1 Ab). No significant financial relationships to disclose.

Colon Cancer: Update on Adjuvant Therapy

Colon cancer is a public health problem worldwide. Although potentially curable at early stages, a substantial number of patients will inevitably present with or eventually develop metastatic disease, which is often incurable. Despite the progress achieved with the introduction of new cytotoxic agents, recurrence rates for patients with resected stage II/III disease remain > 20%. Therefore, a great deal of effort and resources have been put into improving early diagnosis and prevention tools as well as the efficacy of adjuvant treatment. Oxaliplatin-based chemotherapy is now considered the standard of care in node-positive colon cancer, but there remains controversy with regard to the indication and type of adjuvant treatment in patients with nodenegative disease. Oral fluoropyrimidines play a growing role in the management of colorectal cancer and can be currently considered an alternative to 5-fluorouracil. Numerous reports have suggested that elderly patients benefit equally from chemotherapy, but the growing numbers of octogenarian and nonagenarian patients in our clinics, many of whom occasionally struggle through treatment, are a reminder of the challenges ahead. Finally, as we might have reached a plateau in terms of cytotoxic chemotherapy, numerous clinical trials are now focusing on the role of biologic agents in the adjuvant setting.

Health-related quality of life measures in melanoma patients receiving pulsed high-dose intravenous interferon alpha 2b (IFNα2b)

8536 Background: Major problems of high-dose interferon (HDI) in patients with malignant melanoma (MM) result from side effects and impairment of quality of life (QoL). Up to now it is unclear whether intraveneous (iv), subcutaneous (sc), or both components of HDI treatment are necessary for the efficacy in adjuvant treatment of MM. The adjuvant phase III DeCOG MM-ADJ-5 trial evaluates efficacy, safety, and tolerability of pulsed high-dose intravenous IFNa2b. In this prospective, randomized trial, 3 courses of IFNa2b 20 Mio IU/m2 iv on 5 days a week for 4 weeks repeated every 4 months are compared to the standard HDI regimen. The higher iv dosage produces more toxicity, but for a shorter period of time, since patients in the pulsed treatment arm are 9 months off treatment as compared to the conventional sc treatment with 10 Mio IU/m2 three times a week given for 11 months after 4 weeks of iv therapy. Methods: With a planned recruitment of 600 patients, an interim analysis of QoL has been performed after half of the patients completed treatment. EORTC QLQ- C30 questionnaire modified for interferon side effects was obtained before therapy, and at 4, 16, 24, and 40 weeks of treatment. The global QoL items were obtained weekly by a visual analogue scale over the whole year of treatment. Additionally, the side effects were scored using CTC- AE toxicity levels, and dose modifications were recorded. Results: A total of 300 patients were evaluated. After 4 weeks of initial iv HDI treatment the global QoL score decreased similarly in both treatment groups (35% vs. 41%). Four weeks after the initial iv pulse, the global QoL score completely recovered in the experimental arm (104%). In the conventional HDI, QoL remained reduced by an average 22% during the whole subcutaneous treatment phase. During the second and third iv-pulse in the experimental arm, QoL again decreased and completely recovered thereafter. Overall, the cumulative QoL score measured for 12 months treatment was significantly in favour of the pulsed regimen (+16% AuC value). Conclusions: Patients under pulsed adjuvant HDI treatment experience significantly less impairment of QoL and may therefore have a higher rate of completing the scheduled dosage. [Table: see text]

Significance of ERCC1 and HER2 expression in human colon carcinomas

14534 Background: Predictive and prognostic markers need to be established in colon cancer in order to tailor chemotherapy and, therefore, improve efficacy of adjuvant treatment. In this study, expression of the excision repair cross-complementing 1 (ERCC1) and HER2 tyrosine kinase receptor genes was evaluated in human colon carcinomas. Moreover, expression levels were associated with survival, time to disease progression and various clinicopathologic parameters. Methods: Fifty formalin fixed paraffin embedded tissues of primary colon carcinomas, resected from an equal number of patients at the University Hospital of Patras, Greece were studied. Forty four patients were treated with adjuvant chemotherapy and four patients with chemotherapy for advanced disease. Total RNA was extracted from tissues, quantified and reverse transcribed. Levels of ERCC1 and HER2 mRNA were quantified using Taqman probes in real time PCR and expressed relative to a calibrator. Results: ERCC1 and HER2 mRNA were detected in 92% and 82% of cases respectively, although overexpression was observed in 43.5% and 26.8%. Levels of expression were not related to age, stage, grade and overall survival. There was a significant association between overexpression of ERCC1 and time to disease progression (p&lt;0.05) although this was not observed for HER2. There was a trend towards decreased relapse following adjuvant therapy in patients with low expression levels of ERCC1 and HER2 mRNA levels. However this difference failed to reach significance. Expression levels of ERCC1 and HER2 were not correlated with each other. Furthermore, coexpression of the two molecules was not related to time to disease progression. Additionally, 99.5% and 93.7% of patients with low expression of ERCC1 and HER2, respectively, having received adjuvant therapy were alive at the 36 months follow up. Conclusions: These data suggest that overexpression of ERCC1 is significantly associated with time to disease progression in colon cancer. Further studies of ERCC1 as a prognostic or predictive marker are warranted. No significant financial relationships to disclose.

Postoperative Adjuvant Irradiation With or Without Chemotherapy for Rectal Carcinoma.

p atients with rectal carcinoma who are candidates for adjuvant treatment, in spite of complete surgical resection with negative margins, are those with a moderate to high risk of local or systemic failure or decreased survival when treated with surgery alone. The high-risk factors include primary tumor extension beyond the rectal wall, involved nodes, or both (Dukes' stage B or C; Astler-Coller B2, Cl, or C2; modified Astler-Coller B2.3, C1.3; TNM T3-4 NO, Tis-4 N1-3). The ideal adjuvant treatment for resectable highrisk rectal cancer would preferably decrease both local and systemic failures, increase both disease-free and overall survival, and accomplish such with acceptable tolerance. At the 1990 National Institutes of Health (NIH) Consensus Conference on Adjuvant Therapy of Large Bowel Cancer, 1 the efficacy of adjuvant treatment for rectal cancer was evaluated by outcomes of three scientific endpoints: (1) incidence of pelvic (local) recurrence, (2) disease-free survival (time to relapse), and (3) overall survival. Inclusion of local recurrence as a separate endpoint is based on the significant morbidity of pelvic recurrence 2 and the difficulty in achieving subsequent salvage for cure. Standard treatment of pelvic recurrence results in short-term palliation (usually 6 to 12 months) and infrequent cure. 3 Although distant metastases result in less patient months of morbidity than local recurrence in high-risk patients treated with surgery alone, 2 subsequent cure can be achieved only when solitary or adjacent metastases can be resected. Reduction in the incidence of distant metastases with effective systemic adjuvants would be a justifiable separate endpoint in future trials.

Toll like receptor 3 expression and efficacy of adjuvant treatment with polyadenylic-polyuridylic acid in patients with axillary node positive breast cancer: Results from two randomized trials

10563 Background: Toll like receptor 3 (TLR3) are transmembrane receptors involved in the cellular response to danger signal and specifically activated by double stranded RNA. Based on these data, we hypothesized that the TLR3 expression by tumor cells is associated with the efficacy of a treatment with double stranded RNA in cancer patients. Patients and Methods: TLR3 expression was assessed by immunohistochemistry in 336 patients with axillary node positive breast cancer. These patients were selected to have been included in two randomized trials that compared a post-operative administration of polyadenylic-polyuridylic acid (polyAU) to either no treatment (n = 174, trial I) or an adjuvant chemotherapy by CMF regimen (n = 162, trial II). In the trial II, locoregional and pelvic radiotherapy were given in the polyAU arm. Results: TLR3 was found to be overexpressed in 45 tumors (13%). Median follow-up were 23 and 17 years for living patients included in the trials I and II respectively. When the analysis focused on the first trial, the 20 year overall survival rates were 87% (95% CI: 53–97%) and 32% (95% CI: 12–63%) for patients with TLR3-overexpressing tumour treated (n = 8) or not (n = 11) with polyAU (p = 0.03). In the same trial, the 20 year overall survival rates were 43% (95% CI: 33–54%) and 35% (95% CI: 25–46%) for patients with TLR3-negative tumor treated (n = 81) or not (n = 74) with polyAU (p = 0.32). When the analysis focused on the Trial II, the 15 year overall survival were 62% (95% CI: 45%-91%) and 21% (95% CI: 8%-47%) for patients with TLR3-overexpressing tumors treated (n = 12) or not (n = 14) with polyAU (p = 0.005). In the same trial, 15 year overall survival rates were 31% (95% CI: 21%-42%) and 39% (95% CI: 28%-51%) for patients with TLR3-negative tumors treated (n = 66) or not (n = 70) with polyAU (p = 0.39). Conclusion: This study suggests that the post-operative administration of polyadenylic-polyuridylic acid improves outcome of patient with TLR3-overexpressing, node-positive breast cancer. [Table: see text]

Condrossarcoma de ramo púbico superior simulando hérnia inguinal

Primary pelvic tumors are relatively rare, representing no more than 5% of primary bone tumors. We presented a case of a chondrosarcoma of the superior pubic ramus initially managed as an inguinal hernia and then operated under oncological principles. Special attention is attributed to the importance for the correct diagnosis and surgical treatment given the low efficacy of adjuvant treatments for this type of neoplasia.

The prevalence and prognostic significance of autoantibodies detected in patients with high risk melanoma receiving adjuvant therapy with high-dose interferon

7519 Background: Immunotherapies that have shown a benefit in advanced melanoma have been shown to induce the collateral appearance of autoimmune responses as thyroid autoantibodies and depigmentation. The purpose of this study was to assess the prevalence of autoantibodies in the serum of stage IIB and III melanoma patients on high dose adjuvant interferon and the appearance of vitiligo, and address their prognostic significance. Patients and Methods: Two hundred patients were included in the study. Peripheral blood was obtained prior to initiation of adjuvant interferon at completion of 1 month of intravenous interferon and at three monthly intervals. Serum samples were tested for antithyroid, antinuclear, anti-DNA, anticardiolipin antibodies by enzyme linked immunosorbant assay (ELISA). Patients were examined for the appearance of vitiligo. Results: The patients were followed for a median time of 36 months. Autoantibodies were detected in fifty two (26%) of 200 patients. 111 patients have relapsed and 78 have died. The median time to progression was 24 months and the median survival was 43.9 months. The median time to progression for the patients who tested negative for autoantibodies was 14.8 months and has not been reached yet for the 52 patients who developed autoantibodies (105 vs 6 p<0.0001). The median survival was 30.7 months for those who were negative and has not been reached yet for the other group (76 vs 2 p<0.001). In multivariante analysis the presence of autoimmunity was an independent favorable prognostic marker. Conclusion: The detection of autoantibodies and appearance of vitiligo was associated with a lower risk of relapse, longer disease free and overall survival. The induction of autoimmunity may be a surrogate marker for monitoring the efficacy of adjuvant treatment with interferon in stage IIB and III melanoma patients. No significant financial relationships to disclose.

Dietary Genistein Reduces Metastasis in a Postsurgical Orthotopic Breast Cancer Model

Metastatic spread, not primary tumor burden, is the leading cause of breast cancer deaths. For patient prognosis to improve, new systemic adjuvant therapies that are capable of effectively inhibiting the outgrowth of seeded tumor cells after surgical treatment of the primary breast tumor are needed. To facilitate the preclinical development of such therapies, relevant animal models of breast cancer metastasis that can mimic the postsurgical adjuvant setting are required. Here we developed a preclinical xenograft model of breast cancer metastasis where the primary tumor was removed by surgical resection before systemic adjuvant treatment. We used this model to assess the antimetastatic effect of postsurgical dietary intervention with the soy isoflavone genistein. The anticancer activity of genistein has been established in vitro and in vivo, however, few studies have tested the potential of genistein as an antimetastatic therapy. Using our model, we tested the efficacy of adjuvant treatment with genistein to inhibit the outgrowth of metastases postsurgery. To establish primary tumors, human breast carcinoma cells, MDA-MB-435/HAL, were implanted into the mammary fat pad of female nude mice. Primary tumors were left to grow for 5 weeks before being surgically removed. Mice were then randomized into two diet groups: control soy-free diet versus genistein-supplemented diet. Five weeks later, metastatic burden was assessed. Genistein reduced the percent metastatic burden in the lungs by 10-fold. These results indicate that dietary intervention following cancer surgery can affect the outgrowth of seeded tumor cells. The availability of well-characterized, clinically relevant animal models for studying factors that regulate metastatic outgrowth postsurgery will provide an important tool for developing new systemic adjuvant therapies.

Large-cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighteen cases and the efficacy of adjuvant treatment with octreotide

This study was undertaken to evaluate the efficacy of a new adjuvant protocol with octreotide, alone or in combination with radiotherapy, in radically resected large cell neuroendocrine carcinomas of the lung. Between 1990 and 2001, a total of 18 consecutive patients affected by large cell neuroendocrine carcinomas of the lung were operated on. Lobectomy and systemic lymphadenectomy were performed in all cases. Postoperative radiotherapy was performed when stage was higher than Ib. Ten patients with positive results of preoperative indium In-111 pentetreotide scintigraphy received octreotide after the operation. Nine patients (50%) had local recurrences or distant metastases (mean recurrence time 14 months); palliative chemotherapy was given, but all patients died. In 10 cases (55.5%) octreotide alone or in combination with radiotherapy was administered as adjuvant treatment; 9 of these patients (90%) are alive and free of disease ( P = .0007), and the other had liver and brain metastases 21 months after surgery. Our preliminary results seem to demonstrate the efficacy of octreotide as adjuvant therapy in large cell neuroendocrine carcinomas of the lung when results of preoperative indium In-111 pentetreotide scintigraphy were positive. Further study are required to assess the utility of octreotide in patients with negative results of indium In-111 pentetreotide scintigraphy.

Die systemische Therapie des Kolonkarzinoms 2004

This article reviews the available data regarding the acticity of postoperative adjuvant systemic therapy for colorectal cancer as first and second-line treatment in metastatic disease. The efficacy of adjuvant treatment of patients with stage III colorectal cancer is well established. 5-fluorouracil (5-FU) and folic acid over 6 months (still) represent todays standard and should serve as comparison in randomized studies. The risk of relapse is low in stage II colon carcinoma and consequently the efficacy is relatively small compared to stage III. New investigation indicate, Capecitabene has the potential to replace 5-FU/FS as standard treatment for patients with colon cancer. Efficacy results are expected to be available in 2004. In metastatic disease combination of 5-FU/folic acid plus CPT-11 or OXA are treatment of choice for the first-line therapy of metastatic colorectal carcinoma. FOLFOX is high-dose intensity oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second- line therapy for metastatic colorectal cancer. It resulted in prolongation of the median progress free survival from 6,8 to 8,8 months and increased the survival for 4,5 months. New perspectives are novel chemotherapeutic and targeted agents in metastatic colorectal cancer: For the first time, there has been a targeted therapy shown convincingly to prolong survival for patients with unresectable metastatic colorectal cancer in a well-performed Phase III trial. This agent is bevacizumab, a humanised monoclonal antibody targeting the circulating proangiogenic growth factor vascular endothelial growth factor. Results with bevacizumab should lead to rapid expansion of the number of strategies targeting tumour neovasculature. Additionally, an antibody against the epidermal growth factor, cetuximab, has been shown to have both single-agent activity and the potential ability to partially reverse resistance to a chemotherapy drug. These advancements, as well as data on other novel treatment agents that have been studied specifically in patients with colorectal neoplasms, are discussed in detail.

Which are the interactions between baseline body mass index (BMI), toxicity of chemotherapy (CT), and efficacy of adjuvant treatments? 9-year follow-up results of French Adjuvant Study Group (FASG) trials

550 Objective: The aim of our analysis was to determine the role of BMI on toxicities of adjuvant CT, and if the efficacy of adjuvant treatments was modified by an abnormal BMI (abBMI). Methods: Among the 8 FASG trials, 3,144 patients (pts) were assessable: 1,618 received adjuvant CT alone, 890 CT plus tamoxifen (Tam), 441 hormonotherapy alone, and 195 no systemic treatment. In 2,508 pts receiving CT, it was FEC regimens (epirubicin [E] 50,75, or 100 mg/m2) in 68%, and other E-based CT in the others. The median follow-up was 9 years. BMI = weight (kg)/[size (m)]2: abBMI value was defined as > 27 (WHO classification). We compared pts characteristics and toxicities according to BMI. Then, disease-free (DFS) and overall survival (OS) were computed in a multivariate model according to adjuvant treatment. Results: Median BMI was 24 kg/m2 with 810 (26%) pts > 27. AbBMI was significantly more frequent in menopausal pts, if tumor size > 2 cm, N > 3, and progesterone receptors positive (PR+). Mean E cumulative dose delivered was higher in abBMI pts (342 v 326 mg/m2, P = .009). AbBMI pts had less grade 3–4 neutropenia (11.2% v 14.7%, P = .001), and more left ventricular dysfunction (1.8% v 0.9%, P = .03). In pts receiving E > 450 mg/m2, abBMI pts had less alopecia (P = .03) and more asthenia (P = .01). The 9-year DFS and OS were significantly worse in abBMI pts (54.7% v 59.8, P = .01; 62.3%v 68.3%, P = .0003, respectively). The multivariate analysis showed that abBMI had no prognostic value for relapse in pts receiving Tam alone or no systemic treatment, but was an independent prognostic factor of relapse in pts receiving CT combined or no with Tam (P = .02, and P = .002, respectively). Conclusion: AbBMI pts had less acute toxicity of CT, but developed more delayed cardiac toxicity irrespective of dose. The efficacy of hormonal treatment was not modified by BMI. It seems that an abBMI decreased the effect of CT whereas these pts received higher E dose. Probably, CT drugs have a modified distribution profile in these pts and these findings questioned about the dose calculation in mg/m2 when BMI is upper normal value. No significant financial relationships to disclose.

Which are the interactions between baseline body mass index (BMI), toxicity of chemotherapy (CT), and efficacy of adjuvant treatments? 9-year follow-up results of French Adjuvant Study Group (FASG) trials

550 Objective: The aim of our analysis was to determine the role of BMI on toxicities of adjuvant CT, and if the efficacy of adjuvant treatments was modified by an abnormal BMI (abBMI). Methods: Among the 8 FASG trials, 3,144 patients (pts) were assessable: 1,618 received adjuvant CT alone, 890 CT plus tamoxifen (Tam), 441 hormonotherapy alone, and 195 no systemic treatment. In 2,508 pts receiving CT, it was FEC regimens (epirubicin [E] 50,75, or 100 mg/m2) in 68%, and other E-based CT in the others. The median follow-up was 9 years. BMI = weight (kg)/[size (m)]2: abBMI value was defined as > 27 (WHO classification). We compared pts characteristics and toxicities according to BMI. Then, disease-free (DFS) and overall survival (OS) were computed in a multivariate model according to adjuvant treatment. Results: Median BMI was 24 kg/m2 with 810 (26%) pts > 27. AbBMI was significantly more frequent in menopausal pts, if tumor size > 2 cm, N > 3, and progesterone receptors positive (PR+). Mean E cumulative dose delivered was higher in abBMI pts (342 v 326 mg/m2, P = .009). AbBMI pts had less grade 3–4 neutropenia (11.2% v 14.7%, P = .001), and more left ventricular dysfunction (1.8% v 0.9%, P = .03). In pts receiving E > 450 mg/m2, abBMI pts had less alopecia (P = .03) and more asthenia (P = .01). The 9-year DFS and OS were significantly worse in abBMI pts (54.7% v 59.8, P = .01; 62.3%v 68.3%, P = .0003, respectively). The multivariate analysis showed that abBMI had no prognostic value for relapse in pts receiving Tam alone or no systemic treatment, but was an independent prognostic factor of relapse in pts receiving CT combined or no with Tam (P = .02, and P = .002, respectively). Conclusion: AbBMI pts had less acute toxicity of CT, but developed more delayed cardiac toxicity irrespective of dose. The efficacy of hormonal treatment was not modified by BMI. It seems that an abBMI decreased the effect of CT whereas these pts received higher E dose. Probably, CT drugs have a modified distribution profile in these pts and these findings questioned about the dose calculation in mg/m2 when BMI is upper normal value. No significant financial relationships to disclose.

Prognostic Variables for Cancer-Related Survival in Node-Negative Colorectal Carcinomas

Background/Aim: The efficacy of adjuvant treatment in node-negative colorectal carcinoma is unproven. The purpose of this study was to analyze the prognostic value of routinely detectable clinicopathological variables in order to identify subgroups of node-negative colorectal cancer patients at a high risk of a recurrence. Methods: Seventy-three patients who did not receive radio- or chemotherapy were selected among 112 node-negative colorectal cancer patients who underwent curative resection. Follow-up was a minimum of 5 years or until death. The influence of 17 demographic, clinical, and pathological variables on the 5-year cancer-related survival was assessed using univariate and multivariate analyses. Results: The compliance with follow-up was 99%. The 5-year survival rate was 81%. Univariate analysis showed that T4 lesions (p < 0.001), age >70 years (p = 0.008), lymphatic invasion (p = 0.001), and neural invasion (p = 0.02) were significantly associated with a decreased survival. T4 stage (hazard ratio 12.75, p < 0.001) and age >70 (hazard ratio 3.08, p = 0.04) significantly affected the cancer-related survival on multivariate analysis. Conclusions: Node-negative colorectal cancer patients with T4 carcinoma or those aged over 70 years have a higher risk of recurrences after resection. They should receive adjuvant or neoadjuvant treatment compatible with their performance status.