Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer
Herbert Hurwitz, M.D., Louis Fehrenbacher, M.D., William Novotny, M.D., Thomas Cartwright, M.D., John Hainsworth, M.D., William Heim, M.D., Jordan Berlin, M.D., Ari Baron, M.D., Susan Griffing, B.S., Eric Holmgren, Ph.D., Napoleone Ferrara, M.D., Gwen Fyfe, M.D., Beth Rogers, B.S., Robert Ross, M.D., and Fairooz Kabbinavar, M.D.
Background Bevacizumab, a monoclonal antibody against vascularendothelial growth factor, has shown promising preclinical andclinical activity against metastatic colorectal cancer, particularlyin combination with chemotherapy.
Methods Of 813 patients with previously untreated metastaticcolorectal cancer, we randomly assigned 402 to receive irinotecan,bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5mg per kilogram of body weight every two weeks) and 411 to receiveIFL plus placebo. The primary end point was overall survival.Secondary end points were progression-free survival, the responserate, the duration of the response, safety, and the qualityof life.
Results The median duration of survival was 20.3 months in thegroup given IFL plus bevacizumab, as compared with 15.6 monthsin the group given IFL plus placebo, corresponding to a hazardratio for death of 0.66 (P<0.001). The median duration ofprogression-free survival was 10.6 months in the group givenIFL plus bevacizumab, as compared with 6.2 months in the groupgiven IFL plus placebo (hazard ratio for disease progression,0.54; P<0.001); the corresponding rates of response were44.8 percent and 34.8 percent (P=0.004). The median durationof the response was 10.4 months in the group given IFL plusbevacizumab, as compared with 7.1 months in the group givenIFL plus placebo (hazard ratio for progression, 0.62; P=0.001).Grade 3 hypertension was more common during treatment with IFLplus bevacizumab than with IFL plus placebo (11.0 percent vs.2.3 percent) but was easily managed.
Conclusions The addition of bevacizumab to fluorouracil-basedcombination chemotherapy results in statistically significantand clinically meaningful improvement in survival among patientswith metastatic colorectal cancer.
Vascular endothelial growth factor (VEGF), a diffusible glycoproteinproduced by normal and neoplastic cells, is an important regulatorof physiologic and pathologic angiogenesis.1 Preclinical studieshave shown that a murine antihuman monoclonal antibody againstVEGF can inhibit the growth of human tumor xenografts,2 anda humanized variant of this antibody (bevacizumab [Avastin])3is being evaluated in clinical trials as a treatment for variouscancers.
In addition to its direct antiangiogenic effects, bevacizumabmay also improve the delivery of chemotherapy by altering tumorvasculature and decreasing the elevated interstitial pressurein tumors.4,5 In a phase 2 trial of the treatment of colorectalcancer, the addition of bevacizumab to fluorouracil plus leucovorin6increased the response rate, the median time to disease progression,and the median duration of survival. The current phase 3 trialwas designed to determine whether the addition of bevacizumabto a combination of irinotecan, fluorouracil, and leucovorin(IFL)7 improves survival among patients with metastatic colorectalcancer more than does a regimen of IFL plus placebo.
Methods
Patients
Eligible patients had histologically confirmed metastatic colorectalcarcinoma, with bidimensionally measurable disease. Other inclusioncriteria included an age of at least 18 years, an Eastern CooperativeOncology Group (ECOG) performance status8 of 0 or 1, a lifeexpectancy of more than three months, and written informed consent.Adequate hematologic, hepatic, and renal function (includingurinary excretion of no more than 500 mg of protein per day)was also required.
Exclusion criteria included prior chemotherapy or biologic therapyfor metastatic disease (adjuvant or radiosensitizing use offluoropyrimidines with or without leucovorin or levamisole morethan 12 months before study entry was permitted), receipt ofradiotherapy within 14 days before the initiation of study treatment,major surgery within 28 days before the initiation of studytreatment, clinically significant cardiovascular disease, clinicallydetectable ascites, pregnancy or lactation, regular use of aspirin(more than 325 mg per day) or other nonsteroidal antiinflammatoryagents, preexisting bleeding diatheses or coagulopathy or theneed for full-dose anticoagulation, and known central nervoussystem metastases.
The protocol was approved by the institutional review boardsof all participating institutions and carried out in accordancewith the Declaration of Helsinki, current Food and Drug AdministrationGood Clinical Practices, and local ethical and legal requirements.
Study Design
Eligible patients were assigned to treatment with the use ofa dynamic randomization algorithm that was designed to achieveoverall balance between groups; randomization was stratifiedaccording to study center, baseline ECOG performance status(0 vs. 1), site of primary disease (colon vs. rectum), and numberof metastatic sites (one vs. more than one). Initially, patientswere randomly assigned in a 1:1:1 ratio to receive IFL plusplacebo, IFL plus bevacizumab, or fluorouracil and leucovorinplus bevacizumab (Table 1), each of which was to continue untildisease progression or unacceptable adverse effects occurredor for a maximum of 96 weeks.
An interim analysis was scheduled to be performed after 300patients underwent randomization, at which time an unblinded,independent data-monitoring committee was to assess the safetyof IFL plus bevacizumab, on the basis of all the available safetyinformation, including the number of deaths in each group, butin the absence of information related to tumor response. Ifthe data-monitoring committee found no untoward adverse eventsattributable to the addition of bevacizumab to IFL, the enrollmentof patients in the group assigned to receive fluorouracil andleucovorin plus bevacizumab was to be discontinued, and additionalpatients would be randomly assigned in a 1:1 ratio to receiveeither IFL plus placebo or IFL plus bevacizumab. However, ifthe data-monitoring committee concluded that the safety profileof IFL plus bevacizumab was unacceptable, assignment to thattreatment was to be discontinued, and patients would insteadbe randomly assigned in a 1:1 ratio to receive either the combinationof fluorouracil and leucovorin plus bevacizumab or IFL plusplacebo.
Tumor responses and progression were determined with the useof the Response Evaluation Criteria in Solid Tumors.9 At thetime of disease progression, the treatment assignment was revealedand patients could be offered second-line treatment. Such patientsin the group assigned to bevacizumab-containing treatment hadthe option to continue bevacizumab during this second-line treatment.No crossovers were allowed in the group given IFL plus placebo.Patients assigned to a treatment containing bevacizumab whohad no signs of progressive disease at the end of the 96-weekstudy period could continue to receive bevacizumab in a separateextension study. Patients in a group receiving bevacizumab whohad a confirmed complete response or unacceptable adverse effectsfrom chemotherapy could discontinue chemotherapy and receivebevacizumab alone.
Bevacizumab (or placebo) was administered concomitantly withchemotherapy. Doses of bevacizumab and chemotherapy were recalculatedif a patient's weight changed by at least 10 percent duringthe study. Standard intracycle and intercycle dose modificationsof irinotecan and fluorouracil (according to the package insert)10were permitted in patients with treatment-related adverse events.The doses of leucovorin and bevacizumab were not altered.
In the analysis of survival and subsequent treatment, all patientswere followed until death, loss to follow-up, or terminationof the study.
Assessments
After the baseline evaluation, tumor status was assessed every6 weeks for the first 24 weeks of the study and then every 12weeks for the remainder of therapy. All complete and partialresponses9 required confirmation at least four weeks after theywere first noted.
Safety was assessed on the basis of reports of adverse events,laboratory-test results, and vital-sign measurements. Adverseevents were categorized according to the Common Toxicity Criteriaof the National Cancer Institute, version 2, in which a gradeof 1 indicates mild adverse events, a grade of 2 moderate adverseevents, a grade of 3 serious adverse events, and a grade of4 life-threatening adverse events. Prespecified safety measuresincluded the incidence of all adverse events, all serious adverseevents, and adverse events that have been associated with bevacizumab— hypertension, thrombosis, bleeding of grade 3 or 4,and proteinuria — as well as diarrhea of grade 3 or 4,and changes from baseline in various laboratory values and vitalsigns.
To monitor the safety of the regimen of IFL plus placebo andof IFL plus bevacizumab, the incidence of death, serious adverseevents, diarrhea of grade 3 or 4, bleeding of grade 3 or 4 fromany source, and thrombosis was monitored during the study inan unblinded fashion by the data-safety monitoring committeeuntil the completion of recruitment or the time of the interimanalysis of efficacy, whichever came first.
Statistical Analysis
The primary outcome measure was the duration of overall survival;survival was measured without regard to subsequent treatments.There was no crossover between groups, however. Secondary outcomemeasures were progression-free survival, objective responserates (complete and partial responses), the duration of responses,and the quality of life.
For patients who were alive at the time of analysis, data onsurvival were censored at the time of the last contact. Progression-freesurvival was defined as the time from randomization to progressionor death during the study, with death during the study definedas any death that occurred within 30 days after the last doseof bevacizumab or chemotherapy. For patients without diseaseprogression at the time of the final analysis, data on progression-freesurvival were censored at the last assessment of tumor statusor on day 0 if no further assessment was performed after baseline.Patients without adequate follow-up data were categorized ashaving no response.
To detect a hazard ratio of 0.75 for death in the group givenIFL plus bevacizumab as compared with the control group, approximately385 deaths were required. All calculations were performed withthe log-rank test and involved two-sided P values, with an alphavalue of 0.05, a statistical power of 80 percent, and one interimanalysis of efficacy.
Interim analyses were conducted in an unblinded fashion by anindependent data-monitoring committee. An interim analysis ofsafety was conducted after the random assignment of approximately100 patients to each group. A second interim analysis of safetyand efficacy was performed after 193 deaths had occurred (halfthe number of required events). According to the protocol, theseinterim efficacy analyses were governed by a formal group sequentialstopping rule based on an O'Brien–Fleming spending function.
Efficacy analyses were performed according to the intention-to-treatprinciple. Safety analyses included all patients who receivedat least one dose of study medication.
The study was designed by Genentech in collaboration with theinvestigators. Genentech collected and analyzed the data; allauthors had access to the primary data. The decision to publishthe paper was made by all the investigators. The article waswritten by Dr. Hurwitz.
Results
Characteristics of the Patients
Between September 2000 and May 2002, 923 patients underwentrandomization at 164 sites in the United States, Australia,and New Zealand. After 313 patients had been randomly assignedto one of the three groups — 100 to IFL plus placebo,103 to IFL plus bevacizumab, and 110 to fluorouracil, leucovorin,and bevacizumab — assignment to the group given fluorouracil,leucovorin, and bevacizumab was halted (the results in thisgroup are not reported). This step was required by the protocolafter the first formal interim analysis of safety concludedthat the regimen of IFL plus bevacizumab had an acceptable safetyprofile and that assignment to this group could continue.
The intention-to-treat analysis of the primary end point ofoverall survival included 411 patients in the group given IFLplus placebo and 402 patients in the group given IFL plus bevacizumab.Table 2 shows selected demographic and baseline characteristics,which were well balanced between the groups. Similar numbersof patients in each group had previously undergone surgery orreceived radiation therapy or adjuvant chemotherapy for colorectalcancer.
Table 2. Selected Demographic and Baseline Characteristics.
Treatment
The median duration of therapy was 27.6 weeks in the group givenIFL plus placebo and 40.4 weeks in the group given IFL plusbevacizumab. The percentage of the planned dose of irinotecanthat was given was similar in the two groups (78 percent inthe group given IFL plus placebo and 73 percent in the groupgiven IFL plus bevacizumab).
As of April 2003, 33 patients in the group given IFL plus placeboand 71 in the group given IFL plus bevacizumab were still takingtheir assigned initial therapy. The rates of use of second-linetherapies that may have affected survival, such as oxaliplatinor metastasectomy, were well balanced between the two groups.In both groups, approximately 50 percent of patients receivedsome form of second-line therapy; 25 percent of all patientsreceived oxaliplatin, and less than 2 percent of patients underwentmetastasectomy.
Efficacy
The median duration of overall survival, the primary end point,was significantly longer in the group given IFL plus bevacizumabthan in the group given IFL plus placebo (20.3 months vs. 15.6months), which corresponds to a hazard ratio for death of 0.66(P<0.001) (Table 3 and Figure 1), or a reduction of 34 percentin the risk of death in the bevacizumab group. The one-yearsurvival rate was 74.3 percent in the group given IFL plus bevacizumaband 63.4 percent in the group given IFL plus placebo (P<0.001).In the subgroup of patients who received second-line treatmentwith oxaliplatin, the median duration of overall survival was25.1 months in the group given IFL plus bevacizumab and 22.2months in the group given IFL plus placebo.
The median duration of survival (indicated by the dotted lines) was 20.3 months in the group given irinotecan, fluorouracil, and leucovorin (IFL) plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001).
The addition of bevacizumab to IFL was associated with increasesin the median duration of progression-free survival (10.6 monthsvs. 6.2 months; hazard ratio for progression, 0.54, for thecomparison with the group given IFL plus placebo; P<0.001);response rate (44.8 percent vs. 34.8 percent; P=0.004); andthe median duration of response (10.4 months vs. 7.1 months;hazard ratio for progression, 0.62; P=0.001) (Table 3). Figure 2shows the Kaplan–Meier estimates of progression-freesurvival. Treatment effects were consistent across prespecifiedsubgroups, including those defined according to age, sex, race,ECOG performance status, location of the primary tumor, presenceor absence of prior adjuvant therapy, duration of metastaticdisease, number of metastatic sites, years since the diagnosisof colorectal cancer, presence or absence of prior radiotherapy,baseline tumor burden, and serum concentrations of albumin,alkaline phosphatase, and lactate dehydrogenase (data not shown).
Figure 2. Kaplan–Meier Estimates of Progression-free Survival.
The median duration of progression-free survival (indicated by the dotted lines) was 10.6 months in the group given irinotecan, fluorouracil, and leucovorin (IFL) plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo, corresponding to a hazard ratio for progression of 0.54 (P<0.001).
Safety
Table 4 presents the incidence of selected grade 3 or 4 adverseevents during the assigned treatment, without adjustment forthe median duration of therapy (27.6 weeks in the group givenIFL plus placebo and 40.4 weeks in the group given IFL plusbevacizumab). The incidence of any grade 3 or 4 adverse eventswas approximately 10 percentage points higher among patientsreceiving IFL plus bevacizumab than among patients receivingIFL plus placebo, largely because of an increase in the incidenceof grade 3 hypertension (requiring treatment) and small increasesin the incidence of grade 4 diarrhea and leukopenia. However,there was no significant difference in the incidence of adverseevents leading to hospitalization or to the discontinuationof study treatment or in the 60-day rate of death from any cause.
Phase 1 and 2 trials had identified hemorrhage, thromboembolism,proteinuria, and hypertension as possible bevacizumab-associatedadverse effects. However, in our study, only the incidence ofhypertension was clearly increased in the group given IFL plusbevacizumab, as compared with the group given IFL plus placebo.All episodes of hypertension were manageable with standard oralantihypertensive agents (e.g., calcium-channel blockers, angiotensin-converting–enzymeinhibitors, and diuretics). There were no discontinuations ofbevacizumab therapy, hypertensive crises, or deaths relatedto hypertension in the bevacizumab group.
Rates of grade 2 or 3 proteinuria (there were no episodes ofgrade 4 proteinuria or nephrotic syndrome) and grade 3 or 4bleeding from any cause were similar in the two groups, althoughall three cases of grade 4 bleeding were in the group givenIFL plus bevacizumab. The incidence of all venous and arterialthrombotic events was 19.4 percent in the group given IFL plusbevacizumab and 16.2 percent in the group given IFL plus placebo(P=0.26).
Gastrointestinal perforation occurred in six patients (1.5 percent)receiving IFL plus bevacizumab. One patient died as a directresult of this event, whereas the other five recovered (threeof them were able to restart treatment without subsequent complications).Of the six patients with a perforation, three had a confirmedcomplete or partial response to IFL plus bevacizumab. Factorsother than the study treatment that may have been associatedwith gastrointestinal perforation were colon surgery withinthe previous two months in two patients and peptic-ulcer diseasein one patient.
Discussion
The results of this phase 3 study provide support for the useof antiangiogenic agents in the treatment of cancer. When thistrial was designed and initiated, the addition of irinotecanto fluorouracil and leucovorin had just been shown to prolongsurvival in patients with metastatic colorectal cancer and wasconsidered the new standard first-line therapy for this disease.Our randomized trial was designed to compare the relative safetyand efficacy of two regimens for metastatic colorectal cancer:IFL alone and with bevacizumab, a humanized monoclonal antibodyagainst VEGF.
We found that the addition of bevacizumab to IFL improved overallsurvival. Furthermore, the increase of 4.7 months in the medianduration of survival attributable to bevacizumab is as largeas or larger than that observed in any other phase 3 trial forthe treatment of colorectal cancer.11 The median survival of20.3 months in the bevacizumab-treated population occurred inspite of the limited availability of oxaliplatin for second-linetherapy during this trial.
As compared with IFL alone, the regimen of IFL plus bevacizumabincreased progression-free survival from a median of 6.2 monthsto 10.6 months, the overall response rate from 34.8 percentto 44.8 percent, and the median duration of response from 7.1months to 10.4 months. These improvements are clinically meaningful.We would not have predicted that the absolute improvement inthe response rate of 10 percent with IFL plus bevacizumab wouldhave been associated with an increase in survival of this magnitude.This observation suggests that the primary mechanism of bevacizumabis the inhibition of tumor growth, rather than cytoreduction.
This clinical benefit was accompanied by a relatively modestincrease in side effects of treatment, which were easily managed.There was an absolute increase of approximately 10 percent inthe overall incidence of grade 3 and 4 adverse effects, attributablelargely to hypertension requiring treatment, diarrhea, and leukopenia.The 60-day rates of death from any cause, hospitalization, anddiscontinuation of treatment were not significantly increasedby the addition of bevacizumab to IFL.
Previous phase 1 and 2 clinical trials suggested that treatmentwith bevacizumab alone or with chemotherapy resulted in an increasedincidence of thrombosis, bleeding, proteinuria, and hypertension.6,12With the exception of hypertension, we did not find an excessof these side effects as compared with their incidence in thegroup given IFL plus placebo — thus highlighting the importanceof randomized, placebo-controlled studies for the evaluationof safety as well as efficacy. One new potential adverse effectthat we did find was gastrointestinal perforation. This complicationwas uncommon and had variable clinical presentations. Severebowel complications, particularly in patients with neutropenia,have been reported with IFL and other chemotherapy regimensfor colorectal cancer,7,13 and in one series, fistulas werereported in over 2 percent of patients treated with fluorouracil-basedregimens.14 No such events occurred in the group given IFL plusplacebo, whereas six cases were observed in the group givenIFL plus bevacizumab (1.5 percent), sometimes in the settingof overall tumor responses. Although three of these six patientswere able to restart treatment without subsequent complications,one patient died and two discontinued therapy permanently asa result of this complication. VEGF is associated with woundhealing,15,16 and VEGF inhibitors can inhibit dermal-wound angiogenesisin patients with cancer. Although infrequent and associatedwith colorectal cancer and its complications, the risk of thisadverse event may be increased by bevacizumab therapy.
Recently, oxaliplatin has been approved in the United Statesfor both second-line and first-line treatment of colorectalcancer.17 Although there are not yet sufficient long-term dataon the efficacy of bevacizumab in combination with oxaliplatin-basedregimens, studies addressing the role of these combinationsare ongoing.18 The improvement in the clinical outcome affordedby the addition of bevacizumab to IFL or to fluorouracil alone6,19suggests that blocking VEGF may be a broadly applicable approachto the treatment of colorectal cancer.
In summary, the addition of bevacizumab to bolus IFL conferreda clinically meaningful and statistically significant improvementin overall survival, progression-free survival, and responserate. These results suggest that bevacizumab plus fluorouracil-basedchemotherapy should be considered a new option for the treatmentof metastatic colorectal cancer.
Funded by Genentech. Dr. Hurwitz was supported in part by aCareer Development Grant (K23 CA085582–04).
Dr. Hurwitz reports having received consulting fees from Genentech,Pfizer, and Imclone; lecture fees from Genentech and Pfizer;and research support from AstraZeneca, Cephalon, Bristol-MyersSquibb, Genentech, GlaxoSmithKline, and Sanofi-Synthelabo; Dr.Cartwright consulting fees from Genentech; Dr. Hainsworth lecturefees from Genentech and research support from Genentech, Sanofi-Synthelabo,and Novartis; Dr. Heim consulting fees from Genentech and havingequity in Genentech; Dr. Berlin consulting fees from Genentechand Pfizer and lecture fees from Sanofi-Synthelabo; and Dr.Kabbinavar lecture fees from Genentech. Ms. Griffing and Ms.Rogers and Drs. Ferrara, Novotny, Holmgren, and Fyfe are employeesof Genentech and report having equity in Genentech. Dr. Rosswas an employee of Genentech during the trial.
We are indebted to the patients who participated in this study,their families, and their support teams; to the health careteams at each center; to the members of the Data and SafetyMonitoring Board — Richard Schilsky (chair), Robert Mayer,Alan Venook, and Lee-Jen Wei — and to the members of theData Coordinating Center (Statistics Collaborative) for theirinvaluable assistance in the conduct of this study.
Source Information
From Duke University, Durham, N.C. (H.H.); Kaiser Permanente, Vallejo, Calif. (L.F.); Genentech, South San Francisco, Calif. (W.N., S.G., E.H., N.F., G.F., B.R., R.R.); Ocala Oncology, Ocala, Fla. (T.C.); Sarah Cannon Cancer Center, Nashville (J.H.); Hematology and Oncology Associates of Northeastern Pennsylvania, Scranton, Pa. (W.H.); Vanderbilt University, Nashville (J.B.); California Pacific Medical Center, San Francisco (A.B.); and the University of California at Los Angeles, Los Angeles (F.K.).
Address reprint requests to Dr. Hurwitz at the Department of Medical Oncology and Transplantation, Rm. 3802 Red Zone, Duke South Clinics, Box 3052, Duke University Medical Center, Durham, NC 27710, or at hurwi004{at}mc.duke.edu.
References
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-676. [CrossRef][ISI][Medline]
Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993;362:841-844. [CrossRef][Medline]
Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593-4599. [Free Full Text]
Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7:987-989. [CrossRef][ISI][Medline]
Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004;10:145-147. [CrossRef][ISI][Medline]
Kabbinavar F, Hurwitz H, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21:60-65. [Free Full Text]
Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2000;343:905-914. [Free Full Text]
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655. [ISI][Medline]
Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205-216. [Free Full Text]
Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004;22:23-30. [Free Full Text]
Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial cell growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427-434. [Free Full Text]
Rothenberg ML, Meropol NJ, Poplin EA, Van Cutsem E, Wadler S. Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 2001;19:3801-3807. [Free Full Text]
Tebbutt NC, Norman AR, Cunningham D, et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut 2003;52:568-573. [Free Full Text]
Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL, DiPietro LA. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 1998;152:1445-1452. [Abstract]
Hurwitz H, Holden SN, Eckhardt SG, et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling, in patients with solid tumors. Prog Proc Am Soc Clin Oncol 2002;21:82. abstract.
Oxaliplatin. (Eloxatin). New York: Sanofi-Synthelabo, 2004 (package insert).
Benson AB, Catalano PJ, Meropol NJ, O'Dwyer PJ, Giantonio BJ. Bevacizumab (anti-VEGF) plus FOLFOX4 in previously treated advanced colorectal cancer (advCRC): an interim toxicity analysis of the Eastern Cooperative Oncology Group (ECOG) study E3200. Prog Proc Am Soc Clin Oncol 2003;22:243. abstract.
Hurwitz H, Fehrenbacher L, Cartwright T, et al. A phase III trial of bevacizumab in combination with bolus IFL (irinotecan, 5-fluorouracil, leucovorin) as first-line therapy in subjects with metastatic CRC: efficacy results in arm 3 (5-FU/LV/BV) and other exploratory analyses. Presented at the 94th AACR Annual Meeting, Washington, D.C., July 11–14, 2003. abstract. (Accessed on May 10, 2004, at http://www.aacr.org/1132ag.asp.)
Bevacizumab in Colorectal Cancer
Sonpavde G., Sharieff W., Hurwitz H. I., Novotny W., Kabbinavar F., the Bevacizumab Study Team
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351:1690-1691, Oct 14, 2004.
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7: 3029-3037
[Abstract][Full Text]
Fan, F., Gray, M. J., Dallas, N. A., Yang, A. D., Van Buren, G. II, Camp, E. R., Ellis, L. M.
(2008). Effect of chemotherapeutic stress on induction of vascular endothelial growth factor family members and receptors in human colorectal cancer cells. Molecular Cancer Therapeutics
7: 3064-3070
[Abstract][Full Text]
Willmann, J. K., Lutz, A. M., Paulmurugan, R., Patel, M. R., Chu, P., Rosenberg, J., Gambhir, S. S.
(2008). Dual-targeted Contrast Agent for US Assessment of Tumor Angiogenesis in Vivo. Radiology
248: 936-944
[Abstract][Full Text]
Meulenbeld, H. J., van Steenbergen, L. N., Janssen-Heijnen, M. L. G., Lemmens, V. E. P. P., Creemers, G. J.
(2008). Significant improvement in survival of patients presenting with metastatic colon cancer in the south of The Netherlands from 1990 to 2004. Ann Oncol
19: 1600-1604
[Abstract][Full Text]
Ager, E. I., Neo, J., Christophi, C.
(2008). The renin-angiotensin system and malignancy. Carcinogenesis
29: 1675-1684
[Abstract][Full Text]
Karanjia, R, Eng, K T, Gale, J, Sharma, S, Hove, M W t.
(2008). Electrophysiological effects of intravitreal Avastin (bevacizumab) in the treatment of exudative age-related macular degeneration. Br. J. Ophthalmol.
92: 1248-1252
[Abstract][Full Text]
Kabbinavar, F. F., Wallace, J. F., Holmgren, E., Yi, J., Cella, D., Yost, K. J., Hurwitz, H. I.
(2008). Health-Related Quality of Life Impact of Bevacizumab When Combined with Irinotecan, 5-Fluorouracil, and Leucovorin or 5-Fluorouracil and Leucovorin for Metastatic Colorectal Cancer. The Oncologist
13: 1021-1029
[Abstract][Full Text]
Aranda, E., Valladares, M., Martinez-Villacampa, M., Benavides, M., Gomez, A., Massutti, B., Marcuello, E., Constenla, M., Camara, J. C., Carrato, A., Duenas, R., Reboredo, M., Navarro, M., Diaz-Rubio, E.
(2008). Randomized study of weekly irinotecan plus high-dose 5-fluorouracil (FUIRI) versus biweekly irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as first-line chemotherapy for patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors Study. Ann Oncol
0: mdn557v1-mdn557
[Abstract][Full Text]
Salama, J. K., Chmura, S. J., Mehta, N., Yenice, K. M., Stadler, W. M., Vokes, E. E., Haraf, D. J., Hellman, S., Weichselbaum, R. R.
(2008). An Initial Report of a Radiation Dose-Escalation Trial in Patients with One to Five Sites of Metastatic Disease. Clin. Cancer Res.
14: 5255-5259
[Abstract][Full Text]
Adam, R., de Haas, R. J., Wicherts, D. A., Aloia, T. A., Delvart, V., Azoulay, D., Bismuth, H., Castaing, D.
(2008). Is Hepatic Resection Justified After Chemotherapy in Patients With Colorectal Liver Metastases and Lymph Node Involvement?. JCO
26: 3672-3680
[Abstract][Full Text]
Carden, C. P., Larkin, J. M.G., Rosenthal, M. A.
(2008). What is the risk of intracranial bleeding during anti-VEGF therapy?. Neuro Oncol
10: 624-630
[Abstract][Full Text]
Koldehoff, M., Beelen, D. W., Elmaagacli, A. H.
(2008). Small-molecule inhibition of proteasome and silencing by vascular endothelial cell growth factor-specific siRNA induce additive antitumor activity in multiple myeloma. J. Leukoc. Biol.
84: 561-576
[Abstract][Full Text]
Kooby, D. A.
(2008). Patterns of Recurrence Following Liver Resection for Colorectal Metastases--Invited Critique. Arch Surg
143: 749-750
[Full Text]
Tijink, B. M., Laeremans, T., Budde, M., Walsum, M. S.-v., Dreier, T., de Haard, H. J., Leemans, C. R., van Dongen, G. A.M.S.
(2008). Improved tumor targeting of anti-epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology. Molecular Cancer Therapeutics
7: 2288-2297
[Abstract][Full Text]
Melichar, B., Koralewski, P., Ravaud, A., Pluzanska, A., Bracarda, S., Szczylik, C., Chevreau, C., Filipek, M., Delva, R., Sevin, E., Negrier, S., McKendrick, J., Santoro, A., Pisa, P., Escudier, B.
(2008). First-line bevacizumab combined with reduced dose interferon-{alpha}2a is active in patients with metastatic renal cell carcinoma. Ann Oncol
19: 1470-1476
[Abstract][Full Text]
Finn, R. S.
(2008). Targeting Src in breast cancer. Ann Oncol
19: 1379-1386
[Abstract][Full Text]
Wallgard, E., Larsson, E., He, L., Hellstrom, M., Armulik, A., Nisancioglu, M. H., Genove, G., Lindahl, P., Betsholtz, C.
(2008). Identification of a Core Set of 58 Gene Transcripts With Broad and Specific Expression in the Microvasculature. Arterioscler. Thromb. Vasc. Bio.
28: 1469-1476
[Abstract][Full Text]
Etienne-Grimaldi, M.-C., Formento, J.-L., Francoual, M., Francois, E., Formento, P., Renee, N., Laurent-Puig, P., Chazal, M., Benchimol, D., Delpero, J.-R., Letoublon, C., Pezet, D., Seitz, J.-F., Milano, G.
(2008). K-Ras Mutations and Treatment Outcome in Colorectal Cancer Patients Receiving Exclusive Fluoropyrimidine Therapy. Clin. Cancer Res.
14: 4830-4835
[Abstract][Full Text]
McKibbin, T., Frei, C. R., Greene, R. E., Kwan, P., Simon, J., Koeller, J. M.
(2008). Disparities in the Use of Chemotherapy and Monoclonal Antibody Therapy for Elderly Advanced Colorectal Cancer Patients in the Community Oncology Setting. The Oncologist
13: 876-885
[Abstract][Full Text]
Santoro, A., Comandone, A., Rimassa, L., Granetti, C., Lorusso, V., Oliva, C., Ronzoni, M., Siena, S., Zuradelli, M., Mari, E., Pressiani, T., Carnaghi, C.
(2008). A phase II randomized multicenter trial of gefitinib plus FOLFIRI and FOLFIRI alone in patients with metastatic colorectal cancer. Ann Oncol
0: mdn401v1-mdn401
[Abstract][Full Text]
Hochster, H. S., Hart, L. L., Ramanathan, R. K., Childs, B. H., Hainsworth, J. D., Cohn, A. L., Wong, L., Fehrenbacher, L., Abubakr, Y., Saif, M. W., Schwartzberg, L., Hedrick, E.
(2008). Safety and Efficacy of Oxaliplatin and Fluoropyrimidine Regimens With or Without Bevacizumab As First-Line Treatment of Metastatic Colorectal Cancer: Results of the TREE Study. JCO
26: 3523-3529
[Abstract][Full Text]
Shojaei, F., Ferrara, N.
(2008). Refractoriness to Antivascular Endothelial Growth Factor Treatment: Role of Myeloid Cells. Cancer Res.
68: 5501-5504
[Abstract][Full Text]
Kulke, M. H., Lenz, H.-J., Meropol, N. J., Posey, J., Ryan, D. P., Picus, J., Bergsland, E., Stuart, K., Tye, L., Huang, X., Li, J. Z., Baum, C. M., Fuchs, C. S.
(2008). Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors. JCO
26: 3403-3410
[Abstract][Full Text]
Carethers, J. M.
(2008). Review: Systemic treatment of advanced colorectal cancer: Tailoring therapy to the tumor. Therapeutic Advances in Gastroenterology
1: 33-42
[Abstract]
Cohen, S. J., Punt, C. J.A., Iannotti, N., Saidman, B. H., Sabbath, K. D., Gabrail, N. Y., Picus, J., Morse, M., Mitchell, E., Miller, M. C., Doyle, G. V., Tissing, H., Terstappen, L. W.M.M., Meropol, N. J.
(2008). Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients With Metastatic Colorectal Cancer. JCO
26: 3213-3221
[Abstract][Full Text]
Shitara, K., Munakata, M., Muto, O., Sakata, Y.
(2008). Metastatic Rectal Cancer Responding to Third-line Therapy Employing Bevacizumab After Failure of Oxaliplatin and Irinotecan: Case Report. Jpn J Clin Oncol
38: 493-496
[Abstract][Full Text]
Kaempf, S., Johnen, S., Salz, A. K., Weinberger, A., Walter, P., Thumann, G.
(2008). Effects of Bevacizumab (Avastin) on Retinal Cells in Organotypic Culture. IOVS
49: 3164-3171
[Abstract][Full Text]
Borner, M., Koeberle, D., Von Moos, R., Saletti, P., Rauch, D., Hess, V., Trojan, A., Helbling, D., Pestalozzi, B., Caspar, C., Ruhstaller, T., Roth, A., Kappeler, A., Dietrich, D., Lanz, D., Mingrone, W., for the Swiss Group for Clinical Cancer Research (,
(2008). Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol
19: 1288-1292
[Abstract][Full Text]
Chen, M. H., Kerkela, R., Force, T.
(2008). Mechanisms of Cardiac Dysfunction Associated With Tyrosine Kinase Inhibitor Cancer Therapeutics. Circulation
118: 84-95
[Full Text]
Pozzo, C., Barone, C.
(2008). Is There an Optimal Chemotherapy Regimen for the Treatment of Advanced Gastric Cancer That Will Provide a Platform for the Introduction of New Biological Agents?. The Oncologist
13: 794-806
[Abstract][Full Text]
Eyler, C. E., Rich, J. N.
(2008). Survival of the Fittest: Cancer Stem Cells in Therapeutic Resistance and Angiogenesis. JCO
26: 2839-2845
[Abstract][Full Text]
Lee, D. J., Lyshchik, A., Huamani, J., Hallahan, D. E., Fleischer, A. C.
(2008). Relationship Between Retention of a Vascular Endothelial Growth Factor Receptor 2 (VEGFR2)-Targeted Ultrasonographic Contrast Agent and the Level of VEGFR2 Expression in an In Vivo Breast Cancer Model. J Ultrasound Med
27: 855-866
[Abstract][Full Text]
Dineen, S. P., Lynn, K. D., Holloway, S. E., Miller, A. F., Sullivan, J. P., Shames, D. S., Beck, A. W., Barnett, C. C., Fleming, J. B., Brekken, R. A.
(2008). Vascular Endothelial Growth Factor Receptor 2 Mediates Macrophage Infiltration into Orthotopic Pancreatic Tumors in Mice. Cancer Res.
68: 4340-4346
[Abstract][Full Text]
Tatar, O., Yoeruek, E., Szurman, P., Bartz-Schmidt, K. U., Adam, A., Shinoda, K., Eckardt, C., Boeyden, V., Claes, C., Pertile, G., Scharioth, G. B., Grisanti, S.
(2008). Effect of Bevacizumab on Inflammation and Proliferation in Human Choroidal Neovascularization. Arch Ophthalmol
126: 782-790
[Abstract][Full Text]
Takata, K., Morishige, K.-i., Takahashi, T., Hashimoto, K., Tsutsumi, S., Yin, L., Ohta, T., Kawagoe, J., Takahashi, K., Kurachi, H.
(2008). Fasudil-induced hypoxia-inducible factor-1{alpha} degradation disrupts a hypoxia-driven vascular endothelial growth factor autocrine mechanism in endothelial cells. Molecular Cancer Therapeutics
7: 1551-1561
[Abstract][Full Text]
van Iersel, L. B. J., Gelderblom, H., Vahrmeijer, A. L., van Persijn van Meerten, E. L., Tijl, F. G. J., Putter, H., Hartgrink, H. H., Kuppen, P. J. K., Nortier, J. W. R., Tollenaar, R. A. E. M., van de Velde, C. J. H.
(2008). Isolated hepatic melphalan perfusion of colorectal liver metastases: outcome and prognostic factors in 154 patients. Ann Oncol
19: 1127-1134
[Abstract][Full Text]
Steeghs, N., Gelderblom, H., Roodt, J. o. t, Christensen, O., Rajagopalan, P., Hovens, M., Putter, H., Rabelink, T. J., de Koning, E.
(2008). Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor. Clin. Cancer Res.
14: 3470-3476
[Abstract][Full Text]
Schwartz, R. N.
(2008). Management of early and advanced colorectal cancer: Therapeutic issues. Am J Health Syst Pharm
65: S8-S14
[Abstract][Full Text]
Hecht, J. R.
(2008). Current and emerging therapies for metastatic colorectal cancer: Applying research findings to clinical practice. Am J Health Syst Pharm
65: S15-S21
[Abstract][Full Text]
Llovet, J. M., Di Bisceglie, A. M., Bruix, J., Kramer, B. S., Lencioni, R., Zhu, A. X., Sherman, M., Schwartz, M., Lotze, M., Talwalkar, J., Gores, G. J., for the Panel of Experts in HCC-Design Clinical Tr,
(2008). Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma. JNCI J Natl Cancer Inst
100: 698-711
[Abstract][Full Text]
Duncan, T. J., Al-Attar, A., Rolland, P., Scott, I. V., Deen, S., Liu, D. T.Y., Spendlove, I., Durrant, L. G.
(2008). Vascular Endothelial Growth Factor Expression in Ovarian Cancer: A Model for Targeted Use of Novel Therapies?. Clin. Cancer Res.
14: 3030-3035
[Abstract][Full Text]
O'Connell, M. J., Campbell, M. E., Goldberg, R. M., Grothey, A., Seitz, J.-F., Benedetti, J. K., Andre, T., Haller, D. G., Sargent, D. J.
(2008). Survival Following Recurrence in Stage II and III Colon Cancer: Findings From the ACCENT Data Set. JCO
26: 2336-2341
[Abstract][Full Text]
Sobrero, A. F., Maurel, J., Fehrenbacher, L., Scheithauer, W., Abubakr, Y. A., Lutz, M. P., Vega-Villegas, M. E., Eng, C., Steinhauer, E. U., Prausova, J., Lenz, H.-J., Borg, C., Middleton, G., Kroning, H., Luppi, G., Kisker, O., Zubel, A., Langer, C., Kopit, J., Burris, H. A. III
(2008). EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal Cancer. JCO
26: 2311-2319
[Abstract][Full Text]
Kerbel, R. S.
(2008). Tumor Angiogenesis. NEJM
358: 2039-2049
[Full Text]
Kim, M., Liao, J., Dowling, M. L., Voong, K. R., Parker, S. E., Wang, S., El-Deiry, W. S., Kao, G. D.
(2008). TRAIL Inactivates the Mitotic Checkpoint and Potentiates Death Induced by Microtubule-Targeting Agents in Human Cancer Cells. Cancer Res.
68: 3440-3449
[Abstract][Full Text]
Mourad, J.-J., des Guetz, G., Debbabi, H., Levy, B. I.
(2008). Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol
19: 927-934
[Abstract][Full Text]
Cassidy, J., Clarke, S., Diaz-Rubio, E., Scheithauer, W., Figer, A., Wong, R., Koski, S., Lichinitser, M., Yang, T.-S., Rivera, F., Couture, F., Sirzen, F., Saltz, L.
(2008). Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer. JCO
26: 2006-2012
[Abstract][Full Text]
Saltz, L. B., Clarke, S., Diaz-Rubio, E., Scheithauer, W., Figer, A., Wong, R., Koski, S., Lichinitser, M., Yang, T.-S., Rivera, F., Couture, F., Sirzen, F., Cassidy, J.
(2008). Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. JCO
26: 2013-2019
[Abstract][Full Text]
Sarkar, C., Chakroborty, D., Chowdhury, U. R., Dasgupta, P. S., Basu, S.
(2008). Dopamine Increases the Efficacy of Anticancer Drugs in Breast and Colon Cancer Preclinical Models. Clin. Cancer Res.
14: 2502-2510
[Abstract][Full Text]
Ellis, L. M
(2008). Resistance to Anti-VEGF Therapy. aacredbook
2008: 203-207
[Abstract][Full Text]
Oldham, R. K., Dillman, R. O.
(2008). Monoclonal Antibodies in Cancer Therapy: 25 Years of Progress. JCO
26: 1774-1777
[Full Text]
Bilchik, A. J., Hecht, J. R.
(2008). Perioperative Risks of Bevacizumab and Other Biologic Agents for Hepatectomy: Theoretical or Evidence Based?. JCO
26: 1786-1788
[Full Text]
Gruenberger, B., Tamandl, D., Schueller, J., Scheithauer, W., Zielinski, C., Herbst, F., Gruenberger, T.
(2008). Bevacizumab, Capecitabine, and Oxaliplatin As Neoadjuvant Therapy for Patients With Potentially Curable Metastatic Colorectal Cancer. JCO
26: 1830-1835
[Abstract][Full Text]
Van Buren, G. II, Yang, A. D., Dallas, N. A., Gray, M. J., Lim, S. J., Xia, L., Fan, F., Somcio, R., Wu, Y., Hicklin, D. J., Ellis, L. M.
(2008). Effect of Molecular Therapeutics on Liver Regeneration in a Murine Model. JCO
26: 1836-1842
[Abstract][Full Text]
Laurie, S. A., Gauthier, I., Arnold, A., Shepherd, F. A., Ellis, P. M., Chen, E., Goss, G., Powers, J., Walsh, W., Tu, D., Robertson, J., Puchalski, T. A., Seymour, L.
(2008). Phase I and Pharmacokinetic Study of Daily Oral AZD2171, an Inhibitor of Vascular Endothelial Growth Factor Tyrosine Kinases, in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non-Small-Cell Lung Cancer: The National Cancer Institute of Canada Clinical Trials Group. JCO
26: 1871-1878
[Abstract][Full Text]
Adam, R., Wicherts, D. A., de Haas, R. J., Aloia, T., Levi, F., Paule, B., Guettier, C., Kunstlinger, F., Delvart, V., Azoulay, D., Castaing, D.
(2008). Complete Pathologic Response After Preoperative Chemotherapy for Colorectal Liver Metastases: Myth or Reality?. JCO
26: 1635-1641
[Abstract][Full Text]
Seiwert, T. Y., Haraf, D. J., Cohen, E. E.W., Stenson, K., Witt, M. E., Dekker, A., Kocherginsky, M., Weichselbaum, R. R., Chen, H. X., Vokes, E. E.
(2008). Phase I Study of Bevacizumab Added to Fluorouracil- and Hydroxyurea-Based Concomitant Chemoradiotherapy for Poor-Prognosis Head and Neck Cancer. JCO
26: 1732-1741
[Abstract][Full Text]
Frei, B. L., Soefje, S. A.
(2008). A Review of the Cardiovascular Effects of Oncology Agents. Journal of Pharmacy Practice
21: 146-158
[Abstract]
Kobayashi, H., Sugihara, K., Uetake, H., Higuchi, T., Yasuno, M., Enomoto, M., Kuramochi, H., Lenz, H.-J., Danenberg, K. D., Danenberg, P. V.
(2008). Messenger RNA Expression of Vascular Endothelial Growth Factor and Its Receptors in Primary Colorectal Cancer and Corresponding Liver Metastasis. Ann. Surg. Oncol.
15: 1232-1238
[Abstract][Full Text]
Hsu, A. R., Chen, X.
(2008). Advances in Anatomic, Functional, and Molecular Imaging of Angiogenesis. JNM
49: 511-514
[Abstract][Full Text]
Jaissle, G. B., Ulmer, A., Henke-Fahle, S., Fierlbeck, G., Bartz-Schmidt, K. U., Szurman, P.
(2008). Suppression of Melanoma-Associated Neoangiogenesis by Bevacizumab. Arch Dermatol
144: 525-527
[Abstract][Full Text]
Bianciotto, C., Shields, C. L., Kang, B., Shields, J. A.
(2008). Treatment of Iris Melanoma and Secondary Neovascular Glaucoma Using Bevacizumab and Plaque Radiotherapy. Arch Ophthalmol
126: 578-579
[Full Text]
Italiano, A., Massard, C., Bahleda, R., Vataire, A.-L., Deutsch, E., Magne, N., Pignon, J.-P., Vassal, G., Armand, J.-P., Soria, J.-C.
(2008). Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy. Ann Oncol
19: 787-792
[Abstract][Full Text]
Benesch, M., Windelberg, M., Sauseng, W., Witt, V., Fleischhack, G., Lackner, H., Gadner, H., Bode, U., Urban, C.
(2008). Compassionate use of bevacizumab (Avastin(R)) in children and young adults with refractory or recurrent solid tumors. Ann Oncol
19: 807-813
[Abstract][Full Text]
Tol, J., Koopman, M., Rodenburg, C. J., Cats, A., Creemers, G. J., Schrama, J. G., Erdkamp, F. L. G., Vos, A. H., Mol, L., Antonini, N. F., Punt, C. J. A.
(2008). A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol
19: 734-738
[Abstract][Full Text]
Picchio, M., Beck, R., Haubner, R., Seidl, S., Machulla, H.-J., Johnson, T. D., Wester, H.-J., Reischl, G., Schwaiger, M., Piert, M.
(2008). Intratumoral Spatial Distribution of Hypoxia and Angiogenesis Assessed by 18F-FAZA and 125I-Gluco-RGD Autoradiography. JNM
49: 597-605
[Abstract][Full Text]
Brostjan, C., Gebhardt, K., Gruenberger, B., Steinrueck, V., Zommer, H., Freudenthaler, H., Roka, S., Gruenberger, T.
(2008). Neoadjuvant Treatment of Colorectal Cancer with Bevacizumab: The Perioperative Angiogenic Balance Is Sensitive to Systemic Thrombospondin-1 Levels. Clin. Cancer Res.
14: 2065-2074
[Abstract][Full Text]
Meyer-Losic, F., Nicolazzi, C., Quinonero, J., Ribes, F., Michel, M., Dubois, V., de Coupade, C., Boukaissi, M., Chene, A.-S., Tranchant, I., Arranz, V., Zoubaa, I., Fruchart, J.-S., Ravel, D., Kearsey, J.
(2008). DTS-108, A Novel Peptidic Prodrug of SN38: In vivo Efficacy and Toxicokinetic Studies. Clin. Cancer Res.
14: 2145-2153
[Abstract][Full Text]
Folprecht, G., Seymour, M. T., Saltz, L., Douillard, J.-Y., Hecker, H., Stephens, R. J., Maughan, T. S., Van Cutsem, E., Rougier, P., Mitry, E., Schubert, U., Kohne, C.-H.
(2008). Irinotecan/Fluorouracil Combination in First-Line Therapy of Older and Younger Patients With Metastatic Colorectal Cancer: Combined Analysis of 2,691 Patients in Randomized Controlled Trials. JCO
26: 1443-1451
[Abstract][Full Text]
Dang, D. T., Chun, S. Y., Burkitt, K., Abe, M., Chen, S., Havre, P., Mabjeesh, N. J., Heath, E. I., Vogelzang, N. J., Cruz-Correa, M., Blayney, D. W., Ensminger, W. D., Croix, B. St., Dang, N. H., Dang, L. H.
(2008). Hypoxia-Inducible Factor-1 Target Genes as Indicators of Tumor Vessel Response to Vascular Endothelial Growth Factor Inhibition. Cancer Res.
68: 1872-1880
[Abstract][Full Text]
Norden, A. D., Young, G. S., Setayesh, K., Muzikansky, A., Klufas, R., Ross, G. L., Ciampa, A. S., Ebbeling, L. G., Levy, B., Drappatz, J., Kesari, S., Wen, P. Y.
(2008). Bevacizumab for recurrent malignant gliomas: Efficacy, toxicity, and patterns of recurrence. Neurology
70: 779-787
[Abstract][Full Text]
Logan-Collins, J. M., Lowy, A. M., Robinson-Smith, T. M., Kumar, S., Sussman, J. J., James, L. E., Ahmad, S. A.
(2008). VEGF Expression Predicts Survival in Patients with Peritoneal Surface Metastases from Mucinous Adenocarcinoma of the Appendix and Colon. Ann. Surg. Oncol.
15: 738-744
[Abstract][Full Text]
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