Leonard B Saltz

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..As knowledge of molecular and biochemical mechanisms of action and resistance continues to expand, newer and better camptothecin-based strategies for treatment of malignant disease are likely to evolve...

..Stage III colorectal cancer (TanyN₁₋₂M₀) represents a group at a higher risk of recurrence, and this population is routinely given adjuvant chemotherapy in the absence of a medical or psychiatric contraindication...

..We assessed the safety and efficacy of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy...

..We present in detail these recent advances and provide some insight into several promising future strategies...

..To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor...

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..A discussion of palliative care in a patient with rectal cancer must therefore be based on the assumption that the patient does not have a realistic chance of undergoing a curative intervention...

..We evaluated the safety and efficacy of concurrent administration of two monoclonal antibodies, cetuximab and bevacizumab, in patients with metastatic colorectal cancer...

..We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer...

..role for continuing bevacizumab in subsequent regimens? Is there a role for cetuximab (Erbitux) in standard first-line chemotherapy? Are there practices in colorectal cancer that have become widely accepted without direct supportive data?..

..No patient should be refused treatment with an EGFR-targeting agent solely on the basis of a negative EGFR IHC test and no patient should be given anti-EGFR therapy simply on the basis of a positive or strongly positive EGFR test result...

..We examine in detail the data on which current recommendations for adjuvant treatments are based. We also review some of the more promising experimental approaches currently under investigation...

..In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction...

..S. and European approval of irinotecan/5-FU/LV for this indication. An overview of the findings of these two pivotal studies provides insights regarding the application of this new combination in clinical practice...

..We performed a phase I study of 5-fluorouracil (5-FU), cisplatin and irinotecan...

..Locoregionally recurrent squamous-cell carcinoma of the anal canal is managed with salvage surgery. High-dose-rate intraoperative radiation therapy has been used in selected patients with this disease to reduce the risk of local recurrence...

..At present there is no defined role for routine FDG-PET in the preoperative evaluation of nonmetastatic rectal cancer...

..We prospectively evaluated tumor response with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT...

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..Patients with pathologically node-negative tumors have an improved prognosis, but recurrence patterns and independent prognostic factors in these patients have been incompletely characterized...

..The extent of metastatic disease and the response to chemotherapy are the major determinants of survival. Effective systemic chemotherapy should be given high priority in the treatment of stage IV rectal cancer...

..Therefore, the authors of this report evaluated the safety and efficacy of MK-0646, a fully human monoclonal antibody (MoAb) that binds to the IGF-1R, as monotherapy in patients with metastatic, well-differentiated NETs...

..To determine the maximum tolerated dose (MTD), toxicities, and suitable dose for weekly 1-h paclitaxel combined with weekly cisplatin and irinotecan to treat advanced gastrointestinal malignancies...

..Either antibody may be used for immunohistochemical detection of EGFR in colorectal carcinomas. In addition, manual scoring had an excellent correlation with automated scoring...

..This phase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC) patients...

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..The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial...

..These tumors are clinically aggressive. Prospective studies using defined diagnostic criteria are needed to determine their biologic characteristics and optimal management...

..To compare the mutational and copy number profiles of primary and metastatic colorectal carcinomas (CRCs) using both unpaired and paired samples derived from primary and metastatic disease sites...

..Participation of eligible patients in clinical trials must continue to be actively encouraged. Only in this way will we be able to continue to build and expand on the progress that has been made thus far...

..To better define the CTV for IMRT, we evaluated patterns and predictors of LRF in SCCAC patients given conventional radiation treatment...

..Although easy to implement, there remains significant heterogeneity within each stage grouping. In the era of multimodality treatment, a more refined tool is needed to predict recurrence...

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..Perioperative bev is now commonly used in patients undergoing hepatic resection. Little is known, however, about the safety of perioperative bev use in the setting of hepatic resection...

..08, 0.02 and p = 0.03, 0.01, respectively). CONCLUSIONS: Our results indicate that FDG-PET assessment of locally-advanced rectal cancer response to preoperative chemoradiation may predict longterm outcomes...

..In this study, the authors examined recurrence patterns and survival after resection of SLMRC...

..Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown...

..These results also provide a rationale for broader KRAS testing beyond the most common hotspot alleles in exons 2 and 3...

..However, these agents are not without substantial potential for toxicity. This review will discuss the available therapies and the data to justify the appropriate use and nonuse of targeted therapies in patients with metastatic CRC...

..Expression of p27 in the residual rectal cancer may therefore identify patients with disease likely to be refractory to standard therapy and for whom investigational approaches should be strongly considered...

..We sought to determine if the initial prolonged infusion was still necessary and if an infusion time of fewer than 30 minutes could be safely used...

..Chemotherapy and radiation afford disappointing results, however, and novel therapies are needed...

..The cause of the possible relationship between rash and clinical benefit remains unclear at this time, and additional studies are needed to determine the clinical utility of this observation...

..Toxicity can be predicted by baseline bilirubin. Clinical activity is encouraging and may correlate to changes in p21 and Drg1 levels in patients with wild type p53 tumors following therapy...

..As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome...

..We designed a phase I clinical trial of FU in combination with UCN-01...

..A promising combination of irinotecan with oxaliplatin (Eloxatin) and fluorouracil will be assessed in a Phase III study...

..We will discuss the data on therapies currently used to treat well-differentiated NETs, and the strategies being used in clinical trials...

..South San Francisco, CA, http://www.gene.com) and cetuximab (Erbitux; ImClone Systems, Inc., New York, http://www.imclone.com), in colorectal cancer...

..This review discusses the available therapies in metastatic colorectal cancer and describes some of the molecular markers implicated in activity and resistance to current targeted therapies...

..We therefore designed a phase I clinical trial of sequential paclitaxel and flavopiridol...

..As our molecular knowledge of mcrc advances future therapies will likely tailor an individualized approach based on tumor specific molecular markers...

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..0 mg/m, with manageable toxicity. This combination shows encouraging activity, and survival appears promising in the pre-treated aCRC patient population. Further clinical trials are warranted...

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..Additional studies are needed to determine whether epidermal growth factor receptor gene amplification bears any informative value in predicting response to cetuximab-based therapy...

..However, because the accuracy of this approach has not been established, we conducted a prospective analysis to determine the operating surgeon's ability to assess response using DRE...

..Because symptoms may be rapidly ameliorated with supplementation, we suggest that, when fatigue or hypocalcemia is encountered during cetuximab therapy, serum magnesium level be measured and repleted as necessary...

..Early recognition of diarrhea and early pharmacologic intervention can greatly facilitate successful resolution of this treatment complication...

..CONCLUSIONS: Our data suggest that for patients with locally advanced rectal cancer undergoing resection and preoperative CMT, distal margins < or = 1 cm do not seem to compromise oncological outcome...

..To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy...

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..The presence of poor histopathologic features and positive nodal status are the most important prognostic indicators after neoadjuvant therapy...

..However, patients with cT3 disease that is not downstaged by RT have an increased risk of local failure. These data underscore the impact of tumor response to radiation on long-term oncologic outcome...

..CONCLUSION: Palliative resection of the primary tumor is often performed for elderly US patients with stage IV colorectal cancer. This practice pattern merits re-evaluation, given the improvement in the efficacy of systemic chemotherapy...

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..The innovative therapeutic outcomes associated with novel targeted therapies illustrates the need for biologic and pharmacokinetic end points to define their optimal doses and therapeutic effects...

..Our data suggest that all acceptable-risk patients with a diagnosis of primary rectal cancer should undergo resection, regardless of their response to preoperative therapy...

..Safety and efficacy of tremelimumab (CP-675,206), a fully human anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody, were assessed in patients with treatment-refractory colorectal cancer...

..This article will address these and other trials, as well as data relating to incorporation of biologic therapies into combination chemotherapy for patients with advanced colorectal cancer...

..Nevertheless, patients may receive this treatment despite its uncertain benefit. The objective of this study was to determine the extent to which adjuvant chemotherapy is used for patients with stage II colon cancer...

..Clinical trials addressing the acneiform rash associated with epidermal growth factor receptor inhibitors are lacking...

..To this end, anal cancer is a disease best treated primarily with chemoradiation. Although appropriate treatment can produce acceptable results, further investigation and improvement in therapy are still needed...

..Finally, some newer drugs and strategies currently being tested in clinical trials are discussed...

..persistence) after chemoradiation (when salvage is potentially curative), absence of nodal disease at salvage, and negative margins. Salvage inguinal lymph node dissection after failed chemoradiation therapy also is potentially curative...

..A summary of the major randomized clinical trials spanning the past several decades is provided...

..There have been many advances in the surgical and medical treatment of CRC over the last 10 years. This article reviews the indications, efficacy, and toxicity of chemotherapy and targeted therapy for patients who have CRC...

..However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain...

..However, the influence of body mass index (BMI) on the outcome of patients with established colon cancer remains uncertain. Moreover, the impact of change in body habitus after diagnosis has not been studied...

..FK866 is a potent inhibitor or NAD synthesis. This first-in-human study was performed to determine the maximum-tolerated dose, toxicity profile, and pharmacokinetics on a 96-h continuous infusion schedule...

..To evaluate the antitumor activity, toxicities, and pharmacokinetics (PK) of DX-8951f administered as a 30-min infusion daily for 5 days every 3 weeks in patients with fluorouracil-resistant metastatic colorectal carcinoma...

..Regular physical activity reduces the risk of developing colon cancer, however, its influence on patients with established disease is unknown...

..Dietary factors have been associated with the risk of developing colon cancer but the influence of diet on patients with established disease is unknown...

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