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Herbert I Hurwitz

Publications and source records attributed to Herbert I Hurwitz.

At least 19 recordsLinked to original sources
PubMed2006

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma.

PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. RESULTS: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m(2) twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m(2) weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m(2)). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. CONCLUSIONS: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m(2) weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis.

Adenocarcinoma↗
PubMed2006

A phase I study of the safety and pharmacokinetics of edotecarin (J-107088), a novel topoisomerase I inhibitor, in patients with advanced solid tumors.

PURPOSE: To assess the maximum tolerated dose, safety, and pharmacokinetic (PK) profile of escalating doses of the novel topoisomerase I (topo I) inhibitor edotecarin (J-107088) given as a 2-h intravenous (IV) infusion once every 21 days in patients with advanced solid tumors who had not responded to standard therapy. PATIENTS AND METHODS: Twenty-nine patients (18M:11F) received a 2-h IV infusion of edotecarin in doses of 6, 8, 11, 13, or 15 mg/m(2) every 21 days (with an additional 1-2 weeks permitted for recovery) and were evaluated for safety, PK, and tumor response. RESULTS: The most common non-hematologic toxicities were grade 1-2 nausea, fatigue, anorexia, vomiting, and fever. The most common hematologic toxicities were grade 1-2 thrombocytopenia and grade 3-4 neutropenia, leukopenia, and anemia. No grade 3-4 diarrhea was reported. Dose-limiting toxicities were observed in four patients at the 15 mg/m(2) dose and one patient at the 13 mg/m(2) dose. These toxicities included grade 3 nausea, vomiting, headache, and fatigue, as well as grade 4 neutropenia and febrile neutropenia. The maximum tolerated dose was declared at 15 mg/m(2). One patient with bladder cancer had a confirmed partial response at a dose of 13 mg/m(2). There was a trend to dose-proportional increases in edotecarin peak plasma concentrations and area under the curve values. Renal excretion of edotecarin was minimal (3-8% of the dose). CONCLUSION: The recommended Phase II dose of edotecarin is 13 mg/m(2) once every 21 days. The toxicities in this study were those typical of cytotoxic chemotherapy and less severe than those associated with other topo I inhibitors. The observed safety profile and preliminary evidence of clinical benefit warrant further investigation of this drug as monotherapy or part of combination therapy in patients with solid tumors.

Adult↗
PubMed2006

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. PATIENTS AND METHODS: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. RESULTS: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. CONCLUSION: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

Adenocarcinoma↗
PubMed2006

A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract.

PURPOSE: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. METHODS AND MATERIALS: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m(2) q12h)/5-FU (starting at 0.6 mg/m(2) q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. RESULTS: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m(2) q12h/1 mg/m(2) q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. CONCLUSION: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.

Aged↗
PubMed2006

Long-term treatment with bevacizumab for patients with metastatic colorectal cancer: case report.

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor that has demonstrated increased overall survival when added to standard chemotherapy regimens for metastatic colorectal cancer. Herein we report the cases of 2 patients who demonstrated prolonged survival times of almost 5 and 6 years, respectively, on various chemotherapy regimens that also included bevacizumab. Throughout most of their disease course, these patients maintained a good quality of life, with some adjustments of chemotherapy doses because of side effects. Bevacizumab was generally well tolerated in long-term use.

Adenocarcinoma↗
PubMed2006

The role of targeted therapy in the treatment of colorectal cancer.

Recent years have brought significant advances in the treatment of metastatic colorectal cancer. Combination regimens with standard chemotherapeutic agents have extended survival to nearly 2 years, and recent studies suggest that chemotherapy-free intervals may be feasible in some patients without compromising survival outcomes. The most significant recent progress has centered on the use of targeted biologic therapies. The first targeted agent to show a significant benefit in metastatic colorectal cancer was bevacizumab. This monoclonal antibody is directed against vascular endothelial growth factor, a molecule known to be involved in the angiogenic process that is central to cancer growth and metastasis. In clinical trials, bevacizumab has improved survival when added to multiple chemotherapy regimens. The second targeted agent to be approved for colorectal cancer is the monoclonal antibody cetuximab, which is directed against the epidermal growth factor receptor, another key mediator of cancer growth. Cetuximab has been shown to increases the efficacy of irinotecan in irinotecan-refractory patients, indicating that cetuximab may make tumors more sensitive to chemotherapeutic agents. Bevacizumab and cetuximab continue to be evaluated alone as maintenance therapy and in combination in different settings to determine their optimal use in colorectal cancer. Additional targeted agents are also being developed and are showing promise in clinical trials.

Antibodies, Monoclonal↗
PubMed2005

Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer.

PURPOSE: Bevacizumab is a monoclonal antibody to vascular endothelial growth factor-A (VEGF). In the pivotal trial in metastatic colorectal cancer (mCRC), addition of bevacizumab to first-line irinotecan, fluorouracil, and leucovorin (IFL) significantly prolonged median survival. The aim of these retrospective subset analyses was to evaluate VEGF, thrombospondin-2 (THBS-2), and microvessel density (MVD) as prognostic factors and/or predictors of benefit from bevacizumab. PATIENTS AND METHODS: In the pivotal trial, 813 patients with untreated mCRC were randomly assigned to receive IFL plus bevacizumab or placebo. Of 312 tissue samples collected (285 primaries, 27 metastases), outcome data were available for 278 (153 bevacizumab, 125 placebo). Epithelial and stromal VEGF expression were assessed by in situ hybridization (ISH) and immunohistochemistry on tissue microarrays and whole sections. Stromal THBS-2 expression was examined by ISH on tissue microarrays. MVD was quantified by Chalkley count. Overall survival was associated with these variables in retrospective subset analyses. RESULTS: In all subgroups, estimated hazard ratios (HRs) for risk of death were < 1 for bevacizumab-treated patients regardless of the level of VEGF or THBS-2 expression or MVD. Patients with a high THBS-2 score showed a nonsignificant improvement in survival following bevacizumab treatment (HR = 0.11; 95% CI, 0.02 to 0.51) compared to patients with a low score (HR = 0.65; 95% CI, 0.41 to 1.02); interaction analysis P = .22. VEGF or THBS-2 expression and MVD were not significant prognostic factors. CONCLUSION: These exploratory analyses suggest that in patients with mCRC addition of bevacizumab to IFL improves survival regardless of the level of VEGF or THBS-2 expression, or MVD.

Antibodies, Monoclonal↗
PubMed2005

Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience.

PURPOSE: Primary adenocarcinoma of the gallbladder is a rare malignancy. To better define the role of adjuvant radiation therapy and chemotherapy, a retrospective analysis of the outcome of patients undergoing surgery and adjuvant therapy was undertaken. METHODS AND MATERIALS: Twenty-two patients with primary and nonmetastatic gallbladder cancer were treated with radiation therapy after surgical resection. Median radiation dose was 45 Gy. Eighteen patients received concurrent 5-fluorouracil (5-FU) chemotherapy. Median follow-up was 1.7 years in all patients and 3.9 years in survivors. RESULTS: The 5-year actuarial overall survival, disease-free survival, metastases-free survival, and local-regional control of all 22 patients were 37%, 33%, 36%, and 59%, respectively. Median survival for all patients was 1.9 years. CONCLUSION: Our series suggests that an approach of radical resection followed by external-beam radiation therapy with radiosensitizing 5-FU in patients with locally advanced, nonmetastatic carcinoma of the gallbladder may improve survival. This regimen should be considered in patients with resectable gallbladder carcinoma.

Adult↗
PubMed2005

Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab.

BACKGROUND: A recent phase III trial showed that the addition of bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, to first-line irinotecan, 5-fluorouracil, and leucovorin (IFL) prolonged median survival in patients with metastatic colorectal cancer. We carried out a retrospective analysis of patients in the trial to evaluate whether mutation status of k-ras, b-raf, or p53 or P53 expression could predict which patients were more likely to respond to bevacizumab. METHODS: Microdissected tumors from 295 patients (274 primary tumors, 21 metastases) were subject to DNA sequence analysis to identify mutations in k-ras, b-raf, and p53. Nuclear P53 expression was determined by immunohistochemistry. Hazard ratios and 95% confidence intervals (CI) for overall survival were estimated using Cox regression analysis. RESULTS: In all biomarker subgroups, estimated hazard ratios for risk of death were less than 1 for bevacizumab-treated patients as compared with those for placebo-treated patients. Mutations in k-ras and/or b-raf were observed in 88 of 213 patients (41%). Hazard ratios for death among patients with tumors with wild-type k-ras/b-raf status, as compared with those of patients with mutations in one or both genes, were 0.51 (95% CI = 0.28 to 0.95) among those treated with IFL plus bevacizumab and 0.66 (95% CI = 0.37 to 1.18) among those treated with IFL plus placebo. Mutations in p53 were found in 139 of 205 patients (68%), and P53 was overexpressed in 191 of 266 patients (72%); neither p53 mutation nor P53 overexpression was statistically significantly associated with survival. CONCLUSIONS: We did not find a statistically significant relationship between mutations of k-ras, b-raf, or p53 and the increase in median survival associated with the addition of bevacizumab to IFL in metastatic colorectal cancer.

Angiogenesis Inhibitors↗
PubMed2005

Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas.

PURPOSE: This study (EGF10004) assessed the safety/tolerability, pharmacokinetics, and clinical activity of daily oral dosing with lapatinib (GW572016) in patients with ErbB1-expressing and/or ErbB2-overexpressing advanced-stage refractory solid tumors. PATIENTS AND METHODS: Heavily pretreated patients with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers were randomly assigned to one of five dose cohorts of lapatinib administered once daily. Pharmacokinetic samples were obtained on days 1 and 20. Clinical response was assessed every 8 weeks. RESULTS: Sixty-seven patients with metastatic solid tumors were treated with lapatinib. The most frequently reported drug-related adverse events were diarrhea (42%) and rash (31%). No grade 4 drug-related adverse events were reported. Five grade 3 drug-related toxicities (gastrointestinal events and rash) were experienced by four patients. Drug-related interstitial pneumonitis or cardiac dysfunction associated with other ErbB-targeted therapies was not reported. Four patients with trastuzumab-resistant metastatic breast cancer-two of whom were classified as having inflammatory breast cancer-had partial responses (PRs). Twenty-four patients with various other carcinomas experienced stable disease, of whom 10 received lapatinib for > or = 6 months. The relationships between lapatinib dose or serum concentration and clinical response could not be adequately characterized due to the limited response data. The incidence of diarrhea increased with increasing dose, whereas the incidence of rash was not related to dose. CONCLUSION: Lapatinib was well tolerated at doses ranging from 500 to 1,600 mg once daily. Clinical activity was observed in heavily pretreated patients with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers, including four PRs in patients with trastuzumab-resistant breast cancers and prolonged stable disease in 10 patients.

Adult↗
PubMed2005

Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer.

PURPOSE: In a phase III trial, combining bevacizumab (BV)--a recombinant, humanized, monoclonal antibody targeting vascular endothelial growth factor--with irinotecan, bolus fluorouracil (FU), and leucovorin (LV; IFL) increased survival compared with IFL alone in first-line treatment of patients with metastatic colorectal cancer (CRC). Results for the parent study of IFL/BV versus IFL/placebo are reported elsewhere. Here, we describe efficacy and safety results for the third patient cohort in this trial, who received BV combined with FU/LV, and compare them with results for concurrently enrolled patients who received IFL. METHODS: Patients (N = 923) were randomly assigned to receive IFL/placebo (control), IFL/BV, or FU/LV/BV. Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA) 5 mg/kg was administered intravenously every 2 weeks. Before an interim analysis confirmed acceptable safety for IFL/BV, 313 patients were concurrently randomly assigned to these three arms; after this analysis, the FU/LV/BV arm was discontinued. RESULTS: Median overall survivals were 18.3 and 15.1 months with FU/LV/BV (n = 110) and IFL/placebo (n = 100), respectively. Median progression-free survivals were 8.8 and 6.8 months, respectively. Overall response rates were 40.0% and 37.0%, and median response durations were 8.5 and 7.2 months, respectively. Adverse events consistent with those expected from FU/leucovorin- or IFL-based regimens were seen, as were modest increases in hypertension and bleeding in the bevacizumab arm, which were generally easily managed. CONCLUSION: The FU/LV/BV regimen seems as effective as IFL and has an acceptable safety profile. FU/LV/BV is an active alternative treatment regimen for patients with previously untreated metastatic CRC.

Adult↗
PubMed2005

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer.

PURPOSE: Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA), a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody that inhibits tumor angiogenesis, has demonstrated survival benefit in patients with previously untreated metastatic colorectal cancer when combined with irinotecan/fluorouracil (FU)/leucovorin (LV; IFL). Three randomized clinical studies have evaluated bevacizumab in combination with FU/LV alone. A combined analysis of raw data from these studies was performed to better assess the efficacy of bevacizumab with FU/LV. PATIENTS AND METHODS: The analysis used primary efficacy data from three independent studies, including 241 patients in a combined control group receiving either FU/LV or IFL and 249 patients receiving FU/LV/bevacizumab (5 mg/kg once every 2 weeks). The efficacy data included response rate, progression-free survival, and overall survival. RESULTS: The median duration of survival was 17.9 months in the FU/LV/bevacizumab group, compared with 14.6 months in the combined control group, corresponding to a hazard ratio for death of 0.74 (P = .008). The median duration of progression-free survival was 8.8 months in the FU/LV/bevacizumab group, compared with 5.6 months in the combined control group, corresponding to a hazard ratio for disease progression of 0.63 (P < or = .0001). The addition of bevacizumab also improved the response rate (34.1% v 24.5%; P = .019). CONCLUSION: The addition of bevacizumab to FU/LV provides a statistically significant and clinically relevant benefit to patients with previously untreated metastatic colorectal cancer.

Adult↗
PubMed2005

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. METHODS: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods. RESULTS: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation. CONCLUSIONS: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Adenocarcinoma↗
PubMed2005

Targeting vascular endothelial growth factor and angiogenesis for the treatment of colorectal cancer.

Angiogenesis, the development and proliferation of new blood vessels, is critical for the growth of tumors. The process of new blood vessel formation is under complex control from a variety of pro- and anti-angiogenesis factors. By identifying and understanding these factors, new therapies have been developed to inhibit tumor growth and survival by blocking tumor-related angiogenesis. Recent success with the monoclonal antibody against vascular endothelial growth factor (VEGF; bevacizumab) in a large, randomized, phase III study has provided a critical proof of principle for this therapeutic area. This review will outline the biology of angiogenesis in colorectal cancer and discuss the current status of angiogenesis inhibition in its treatment.

Angiogenesis Inhibitors↗
PubMed2005

Angiogenesis inhibition in the treatment of colorectal cancer Part 3 of a 3-part series: targeting VEGF--current and future research directions.

Treatment options for advanced colorectal have improved substantially in recent years as a number of agents have been developed that have different targets and mechanisms of action. Significant improvements in outcomes have been observed by combining multiple chemotherapeutic agents instead of the single-agent approach. Some debate still remains regarding which combination is most effective and in what order regimens should be given. In addition to cytotoxic chemotherapy drugs, targeted biologic agents have been developed to inhibit tumor angiogenesis, which may hamper the viability of the tumor. There may also be a synergistic effect between antiangiogenic agents and chemotherapy. Regulation of tumor angiogenesis may actually improve blood flow throughout the tumor, which could enhance delivery of chemotherapy through the circulation. One antiangiogenic agent currently approved for the treatment of advanced colorectal cancer is bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, a ligand known to be important for angiogenesis. The other currently approved biologic agent, cetuximab, targets the epidermal growth factor receptor. The combination of bevacizumab plus cetuximab has a biologic rationale. Randomized trials incorporating combination chemotherapy regimens plus both bevacizumab and cetuximab are currently underway, as are preliminary studies withnovel angiogenesis inhibitors.

Angiogenesis Inhibitors↗
PubMed2004

A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon.

PURPOSE: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer. METHODS AND MATERIALS: Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.0 mg/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) every 12 h). Eniluracil and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500 cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks after completion of chemoradiotherapy. RESULTS: Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was completed in all patients; radiotherapy was completed in 20 patients. The recommended Phase II dose of eniluracil and 5-FU was 8 mg/m(2) every 12 h and 0.8 mg/m(2) every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven of the 17 patients with primary rectal cancer underwent a sphincter-sparing procedure. One patient had a pathologic complete response. CONCLUSION: Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted.

Adenocarcinoma↗
PubMed2004

Targeted therapy of colorectal cancer: clinical experience with bevacizumab.

Advanced colorectal cancer remains an urgent health concern, despite improvements in systemic chemotherapy. Targeted therapeutics promise effective tumor therapy with minimal side effects. Angiogenesis (the formation of new blood vessels) is essential for tumor growth and metastasis and may be an ideal target in the search for new antineoplastic agents. Vascular endothelial growth factor is one of the best characterized of the proangiogenic growth factors that regulate angiogenesis and is a logical target in colorectal cancer therapy. Bevacizumab (Avastin; Genentech Inc.; South San Francisco, CA), a humanized murine monoclonal antibody directed at vascular endothelial growth factor, is being evaluated in the treatment of various types of cancer. It has shown promising efficacy in phase II clinical trials in patients with metastatic colorectal cancer. Addition of bevacizumab at a dose of 5 mg/kg to chemotherapy (5-fluorouracil plus leucovorin) resulted in a higher objective response rate (40% versus 17%), longer time to disease progression (9.0 versus 5.2 months), and longer median survival time (21.5 versus 13.8 months). Hypertension and thrombosis were the principal safety concerns, but were manageable. Further phase II/III studies of bevacizumab, administered with 5-fluorouracil plus leucovorin, with or without irinotecan and/or oxaliplatin, in colorectal cancer, are under way.

Angiogenesis Inhibitors↗