Smart Drug Erbitux
INTRODUCTION
Section:
Management of metastatic colorectal cancer (mCRC) has evolved over the past decade. Patients receiving irinotecan (Camptosar; Pfizer Inc, New York, NY),one-4 oxaliplatin (Eloxatin; Sanofi-aventis U.Southward. LLC, Bridgewater, NJ)v-7 and fluorouracil (FU) achieve the best outcomes (median survival (MS), approximately 21 months), regardless of handling sequence.7,8 Biologic therapies provide further improvements. The antiangiogenic monoclonal antibody bevacizumab (Avastin; Genentech Inc, South San Francisco, CA) improves survival in bevacizumab-naïve patients when added to first-lineix or 2d-line chemotherapy,10 but seems inactive in refractory affliction.10,eleven Biologics targeting the epidermal growth factor receptor (EGFR) are constructive in disease refractory to FU, irinotecan, and oxaliplatin.12,13
Cetuximab (ERBITUX; ImClone Systems Inc, New York, NY, and Bristol-Myers Squibb Co, Princeton, NJ), a chimeric monoclonal immunoglobulin 1 that binds to the EGFR, blocks signal transduction, modulates tumor growth,14,fifteen and may mediate antibody-dependent cell-mediated cytotoxicity.16 Cetuximab and irinotecan have produced amid the highest response rates (RR; approximately 23%) observed in refractory patients, and the blueprint of action in irinotecan-refractory patients suggests cetuximab restores chemosensitivity.14 Cetuximab is also active every bit a single agent, producing objective RR betwixt 9% and 12%,12,xiv,17 and improving survival when compared with best supportive intendance in refractory patients.eighteen The role of cetuximab-based combinations in outset-line therapy is under investigation.19,20
The ERBITUX Plus Irinotecan for Metastatic Colorectal Cancer (EPIC) study was designed to determine whether calculation cetuximab to irinotecan as second-line therapy would prolong survival in irinotecan-naïve patients with EGFR-expressing mCRC. 2nd-line was defined every bit failure of prior fluoropyrimidine and oxaliplatin therapy.
PATIENTS AND METHODS
Department:
Study Design and Eligibility Criteria
In this open-label, randomized, phase III study, patients from 221 sites worldwide were randomly assigned 1:i to receive cetuximab/irinotecan or irinotecan alone. The randomization was stratified by study site and Eastern Cooperative Oncology Group (ECOG) performance status (PS, 0 to 1 v 2).
Eligibility required bidimensionally measurable (≥ 1 tumor with 1 diameter ≥ twenty mm and the other ≥ 10 mm), histologically documented mCRC with immunohistochemical evidence of EGFR expression. Failure (disease progression/discontinuation due to toxicity) within half dozen months of the last-dose of first-line fluoropyrimidine and oxaliplatin handling for metastatic disease was required. Previous irinotecan or anti-EGFR therapies were excluded; prior bevacizumab was immune.
This study was performed after approving by a local human investigations committee and in accord with an assurance filed with and approved by the department of health and human being services where appropriate. Informed consent was obtained from each participant.
Treatment
The only irinotecan regimen approved past the United states Food and Drug Administration and the European Medicines Agency for pretreated patients at the fourth dimension of design was irinotecan monotherapy (every 3 weeks), therefore it was chosen as comparator. Patients assigned to the irinotecan and cetuximab arm received an initial 400-mg/grand2 cetuximab dose (ii-60 minutes intravenously [4]), and then 250 mg/mii (1-hour Four) weekly, preceded by premedication with antihistamine. Irinotecan 350 mg/m2 (xc-minute IV; 300 mg/gii for patients ≥ lxx years, those with ECOG PS of 2, or with prior pelvic/intestinal irradiation) was administered every three weeks in both treatment arms, starting i hr after cetuximab-infusion completion for patients in the cetuximab arm. Treatment continued until affliction progression or unacceptable toxicity. At that place were no poststudy treatment limitations.
Dose Modifications
Grade 3/4 hypersensitivity required cetuximab discontinuation; infusion was slowed to ane half of the initial charge per unit in case of form 1/ii allergic/hypersensitivity reactions. Cetuximab was withheld for grade 3 acneform rash, until resolution to form 2 or lower. Severe toxicities warranting irinotecan and/or cetuximab dose reductions included grade 3/iv neutropenia, thrombocytopenia, neutropenic fever, diarrhea, or grade 3 nausea/airsickness. Both agents were discontinued for course 4 nonhematologic toxicities, and patients were observed until resolution.
Assessments
Tumor response was evaluated every 6 weeks (computed tomography/magnetic resonance imaging scans of abdomen, pelvis, and chest; x-rays acceptable to confirm os-scan findings) using modified WHO criteria. Objective responses required a ≥ l% reduction (relative to baseline) in the area of all index lesions (investigator selected), confirmed ≥ 4 weeks subsequently. Affliction progression was defined by a 25% increase in the index-lesion area relative to the smallest expanse recorded, past progression of nonmeasurable lesions, or by advent of new lesions. Quality of life (QOL) was assessed at baseline, after 3 weeks, and then every 6 weeks until the outset post-therapy follow-upwards visit using the European System for Enquiry and Handling of Cancer Quality of Life Questionnaire C-30,21 administered before report-related procedures or clinician assessments. Physical examinations and toxicity assessments were performed before each cycle and subsequently therapy completion. Claret counts were evaluated weekly during the first two cycles and so before each cycle. A protocol amendment in February 2005 initiated routine monitoring of claret magnesium levels, as function of laboratory testing. Adverse events and laboratory examinations were graded using the National Cancer Plant Common Toxicity Criteria version ii.0. Follow-upward assessment was conducted 6 weeks after handling completion. Subsequent therapy and survival were monitored every 3 months.
Interim Analyses
Two independent interim analyses (subsequently 400 and 800 randomly assigned patients) were conducted past the data safety monitoring board: a safety review, and a survival comparison/condom review, respectively. Both result sets were unknown by the sponsors until after database lock.
Statistical Analyses
The main study end signal was survival. This written report required 850 events to complete and had ninety% power for demonstrating a statistically pregnant survival divergence, assuming a truthful 60 minutes (cetuximab and irinotecan to irinotecan) of 0.80. An O'Brien and Fleming blazon α spending part was used to ensure an overall, ii-sided, blazon I error rate of v%. Survival was compared between treatment artillery using a ii-sided log-rank test stratified by ECOG PS (0 to ane 5 two). This assay was supplemented by Kaplan-Meier curves, and estimates of OS, 60 minutes, and associated confidence intervals (HR CI level was adapted for the interim assay).
Progression-costless survival (PFS; divers as time to progression or death, and evaluated similar to survival) and rates of tumor response were determined from study-investigator assessments, without independent review for these secondary end points. Tumor response was compared between handling arms using a Cochran-Mantel-Haenszel test stratified by ECOG PS (0 to 1 v 2). The duration of treatment was the menstruum from the first dose until the last plus 21 days for irinotecan and plus 7 days for cetuximab. Time to response was computed for those patients with a response (complete or partial).
European Organisation for Inquiry and Treatment of Cancer Quality of Life Questionnaire C-30 score changes from baseline were compared betwixt treatment artillery by a Wei-Lachin exam. Adverse events were categorized using the MedDRA lexicon, version 9.1. Analyses of survival, PFS, tumor response, and QOL were done on an intent-to-care for footing. Safety analyses were restricted to treated subjects.
RESULTS
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Patient Characteristics and Disposition
From May 2003 to February 2006, 1,587 patients were enrolled; 1,410 with EGFR-positive tumors past immunohistochemistry. After meeting all eligibility criteria, 1,298 patients were randomly assigned, 648 to cetuximab and irinotecan and 650 to irinotecan lone (Fig 1 ). Demographic and clinical characteristics of written report patients were well balanced between treatment arms (Table 1).
Treatment Exposure
Median treatment duration was longer for the cetuximab and irinotecan combination: cetuximab for 14.0 weeks (range, 0.vii to 97.9), irinotecan for xiii.1 weeks (range, 0.7 to 89.1), versus 9.9 weeks for irinotecan lonely (range, 0.4 to 71.0). Irinotecan delivery (handling delay rates and median dose intensity) was comparable in the ii groups, but the irinotecan cumulative dose was higher with cetuximab and irinotecan (median, one,395 v 1,048 mg/m2).
Reductions in irinotecan dose were more frequent in the cetuximab and irinotecan arm (43.7% v 36.2%), generally due to toxicity such as gastrointestinal events (13.2% v ix.five%) and delayed hematologic recovery (12.5% five 9.7%). The cetuximab dose was reduced in 129 patients (20.2%), including 28 patients (4.4%) due to peel toxicity.
Efficacy
At the time of the information cutoff, 203 patients in the cetuximab and irinotecan arm (31.three%) and 221 patients in the irinotecan arm (34.0%) were alive. OS was comparable between treatments (log-rank P = .71): the HR was 0.975 (95% CI, 0.854 to i.114, adjusted for an acting analysis). MS was 10.7 months (95% CI, ix.vi to eleven.3) with cetuximab/irinotecan and x.0 months (95% CI, 9.1 to 11.3) with irinotecan lone (Fig 2 ). The survival results may take been confounded by poststudy therapy: 46.9% of patients assigned to the irinotecan arm went on to receive cetuximab poststudy (87.2% of those, in combination with irinotecan).
PFS was significantly longer in the cetuximab and irinotecan arm (log-rank P ≤ .0001): the Hr of cetuximab/irinotecan to irinotecan was 0.692 (95% CI, 0.617 to 0.776), indicating a 31% reduction in take chances of progression. Median PFS was 4.0 months (95% CI, 3.2 to 4.1) with cetuximab and irinotecan and two.6 months (95% CI, ii.1 to two.seven) with irinotecan alone; 6-month PFS rates were 27.4% (95% CI, 23.9 to thirty.9) and xvi.3% (95% CI, thirteen.3 to 19.2), respectively, and ix-month PFS rates were 12.6% (95% CI, 10.0 to 15.3) versus 6.v% (95% CI, iv.5 to 8.5; Fig iii ).
The overall RR with cetuximab and irinotecan was 16.four% (95% CI, 13.six to 19.4), compared with iv.2% (95% CI, ii.eight to 6.0) with irinotecan alone (P < .0001; Table 2). Nine patients receiving the combination had consummate responses versus 1 patient receiving irinotecan alone. The median time to response (2.5 v 2.seven months) and the median duration of response (5.7 v 5.v months) did not differ between handling groups.
Consistent with the overall results, predetermined subgroup analyses showed superior PFS and RR with cetuximab and irinotecan regardless of age (< 65 v ≥ 65 years), sex, race, and PS strata (not shown).
QOL
Cetuximab and irinotecan were significantly more effective in maintaining overall QOL. Advantages were seen with cetuximab and irinotecan in 10 of 15 scales, including fatigue (P = .005), nausea/vomiting (P < .001), insomnia (P = .04), pain (P < .001), and diarrhea (P = .02), as well equally domains such as global wellness condition (P = .047), concrete functioning (P = .002), function functioning (P = .003), emotional functioning (P = .002), and cognitive functioning (P < .001) (Fig four ); no differences were seen in the social-functioning domain (P = .774). Compliance with the questionnaire was not significantly dissimilar between treatment arms (56.3% five 56.1% at 15 weeks); the differences in QOL, apparent by the end of the start treatment cycle, remained throughout the study.
Safety
Overall, the safety profile of the cetuximab and irinotecan combination was consistent with prior studies,14 without meaningful increases in toxicity over irinotecan alone except for acneform rash and diarrhea. Ninety-seven patients died inside 30 days of the last treatment: 57 patients in the cetuximab and irinotecan arm (eight.9%) and 40 patients in the irinotecan arm (6.4%). Vii deaths (five and two patients, respectively) were attributed to study drug toxicity.
Neutropenia and diarrhea were the most common class three/iv adverse events, consistent with the profile of irinotecan; both occurred more than oftentimes with cetuximab and irinotecan (Table 3). Severe febrile neutropenia was reported in 8.3% and 6.iv% of patients in the cetuximab and irinotecan and irinotecan groups, respectively. Course 3/iv infusion reactions occurred in 1.4% of cetuximab and irinotecan patients and 0.viii% of those on irinotecan alone. Drug-related acneform rash occurred in most patients (76.3%) receiving cetuximab, becoming severe in 51 cases (8.0%). Hypomagnesemia (and other electrolyte imbalances) was more frequent with cetuximab and irinotecan (33.8% v 8.4% with irinotecan), merely with few severe cases (iii.3% v 0.4%) and no clinically relevant adervse effects.
Rates of toxicity-related therapy discontinuation were like across treatment arms (half-dozen.v% for irinotecan and cetuximab v 4.8% for irinotecan). Hospitalizations for gastrointestinal (15.4% 5 12.6%) and hematologic toxicities (9.7% v 7.9%) were slightly college in the cetuximab and irinotecan arm.
Drug-related serious adverse events were reported in 186 patients (29.2%) and 142 patients (22.6%) in the cetuximab and irinotecan and irinotecan groups, respectively, most commonly diarrhea (eleven.9% v 9.4%), febrile neutropenia (7.vii% v 6.two%), and vomiting (4.4% 5 3.3%).
Post-Hoc Analyses
Two analyses were washed in order to elucidate the potential effect of poststudy therapy. An exploratory analysis evaluated survival in patients randomly assigned earlier cetuximab received regulatory approval in each study country (n = 459), censoring alive subjects in one case cetuximab was approved in their markets. MS was 10.five months in the cetuximab and irinotecan arm and 8.vi months in the irinotecan solitary arm (Fig A1A, online only). This deviation was not statistically significant (P = .60). This exploratory analysis, however, was highly underpowered (number of events, 123).
A second mail hoc exploratory analysis was a nonrandomized examination of survival outcomes in patients from the irinotecan-only arm. Those without whatsoever poststudy therapy (due north = 229) had a MS of iii.9 months (95% CI, 3.five to 4.9), those treated poststudy, but without cetuximab (n = 116) had a MS of x.1 months (95% CI, 9.0 to 13.ii), and MS for those who received subsequent cetuximab (n = 305) was thirteen.0 months (95% CI, 12.two to xv.0; Fig A1B, online only). There is an inherent potential for bias in a nonrandomized comparing such as this, however, the two patient subgroups of interest (those receiving subsequent therapy with or without cetuximab) seemed to be reasonably balanced. Baseline features (such every bit age, sex activity, or race) were similar in both groups, equally were prognostic characteristics, such equally time until discontinuation of study therapy (median, 2.eight months for both groups) and the distribution of performance status at fourth dimension of concluding report dose (PS 0 for 46% and 47% of patients, PS ane for 50% in both groups, and PS ii for 4% and 3%, respectively). In the interest of completeness, a like analysis was carried out in the experimental arm. For patients treated with cetuximab and irinotecan on study who did not receive any poststudy therapy (n = 279), MS was half-dozen.31 months (95% CI, v.3 to seven.one); for those that received therapy poststudy but without cetuximab (n = 296), MS was thirteen.0 months (95% CI, xi.six to 13.nine); finally, for patients in the experimental arm receiving poststudy therapy with cetuximab (north = 73), MS was sixteen.2 months (95% CI, 12.viii to 27.4; Fig A1C, online only). For this posthoc analysis of survival in patients in the experimental arm that went to receive poststudy therapy, the median fourth dimension to study-therapy discontinuation for patients with or without poststudy cetuximab was 4.viii and four.1 months, respectively; the distribution of performance condition at fourth dimension of final report dose was PS 0 for 43.eight% and 55.7% of patients, PS 1 for 48.0% and 43.6%, and PS two for 8.2% and 1.7%, respectively.
Discussion
Section:
Ballsy demonstrated meaning improvements in PFS and RR with the addition of cetuximab to irinotecan. This study, still, failed to come across its main end point, showing no statistically meaning differences in survival betwixt cetuximab and irinotecan and irinotecan alone.
Postprotocol treatment may have affected survival, given the substantial proportion (46.9%) of initial irinotecan patients who subsequently received a cetuximab-based regimen, an effective standard treatment afterward irinotecan failure.14 Posthoc exploratory analyses suggest that poststudy cetuximab may have reduced any potential difference beyond treatment arms, prolonging survival in the patients who received it. These findings are inconclusive, but consequent with those from the recent phase Three NCIC-017 report, in which cetuximab significantly improved survival compared to best supportive care (Hour, 0.766; 95% CI, 0.637 to 0.921; P = .0046) in patients previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin.eighteen The lack of survival divergence, however, may not be entirely due to a cross-over result, since, in other settings, trials have documented survival differences fifty-fifty after cross-over.22,23
The effect of poststudy therapies on early on-line clinical trials in mCRC is not unprecedented,24 with some authors questioning the reliability of OS versus PFS as end betoken in early therapy settings.viii,25 Survival was the appropriate option as primary end point for a trial designed to affect clinical practice. However, this study illustrates the challenges of studying commercially available agents early in the course of disease, and the complicating effects of postprotocol factors.
The improved efficacy in secondary finish points that are well-documented and valid in mCRC,25,26 and the QOL results obtained with cetuximab must not exist overlooked. In this trial, adding cetuximab to irinotecan reduced the risk of progression by 31%, and improved median PFS past 55%, and RR by nearly four-fold, including a higher number of complete responses (ix v showtime). The QOL assessments also support this benefit. Global health status too as physical, emotional, and cognitive functioning were significantly amend with cetuximab and irinotecan. These results are the best reported to date subsequently oxaliplatin plus FU and leucovorin (FOLFOX) failure.7
The prophylactic profile of cetuximab plus irinotecan in this written report was manageable, predictable, and consequent with prior studies.14 The addition of cetuximab to irinotecan did not result in meaningful increases in toxicity, except for acneform rash, diarrhea, and electrolyte imbalances. Whether these increases are due to cetuximab itself, or a byproduct of the higher cumulative irinotecan dose with the combination, is unclear, and these findings warrant careful evaluation of the patients appropriate for this regimen. Even so the nearly 50% rate of patients even so receiving combination handling at 15 weeks further reassures of its tolerability.
Several caveats surround these results, apart from the potential event of poststudy cross-over. The absence of contained radiology-review arrangement is a weakness of particular concern given the weight of the PFS and RR finish points in the final results of the report. Notwithstanding, the differences observed make a compelling argument for the therapeutic effect of cetuximab. The application of a self-reported questionnaire to assess QOL in a nonblinded study tin can also exist considered problematic. Information technology could be argued, however, that this is a method to assess patients' individual experiences; in this case, the consistency of the results across most scales probably points to a bona-fide outcome. Also, this standard tool lacks specific acneform-rash scores, a limiting attribute for studies of EGFR inhibitors. Until this deficiency is addressed, scores such as social performance may provide a partial indication of the potential effect of acneform rash in the QOL of patients.
It is almost certain that outcomes with cetuximab will be enhanced past patient selection. Remarkably, randomized trastuzumab trials conducted in preselected patients with chest cancer could demonstrate survival benefits, even subsequently a cross-over.23 Contempo reports indicate that the presence of mutations on the KRAS factor is a stiff predictor of nonresponsiveness to cetuximab,27-29 and that overexpression of the EGFR ligands amphiregulin and epiregulin may exist a robust marker of response.28 While trials are ongoing to validate these biomarkers, whether a pronounced benefit could be documented in any of these subpopulations in EPIC is under written report.
Every bit the evaluation of cetuximab continues, with ongoing or recently-completed randomized trials in kickoff-line (Cancer and Leukemia Group B 80203, Oxaliplatin and Cetuximab in First-Line Treatment of Metastatic Colorectal Cancer, and Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer),19,20,thirty with bevacizumab (Cancer and Leukemia Grouping B 80405), and in the adjuvant setting (N Key Cancer Treatment Group N0147), the data from this EPIC study join the contempo NCIC-017 results, showing that cetuximab provides OS and PFS, as well equally RR and QOL, benefits in multirefractory patients.18 EPIC is the largest comparative trial investigating the efficacy and tolerability of cetuximab added to irinotecan later FOLFOX failure, demonstrating PFS and RR improvements in irinotecan-naïve patients consistent with prior studies in refractory disease. With these results, the inclusion of cetuximab amongst the core agents in the optimal management of mCRC8,31 is well supported. Ongoing studies will further ascertain the optimal apply of cetuximab throughout CRC treatment settings.
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
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Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject thing under consideration in this commodity. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more data nearly ASCO's disharmonize of interest policy, please refer to the Author Disclosure Annunciation and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: Oliver Kisker, Merck KGaA (C); Angela Zubel, Merck KGaA (C); Christiane Langer, Bristol-Myers Squibb (C); Justin Kopit, Bristol-Myers Squibb (C) Consultant or Advisory Role: Alberto F. Sobrero, Merck KGaA (C), Pfizer (C), Roche (C), Sanofi-aventis (C), Amgen (C); Heinz-Josef Lenz, ImClone Systems (C), Bristol-Myers Squibb (C), Merck KGaA (C); Howard A. Burris Three, Bristol-Myers Squibb (C) Stock Ownership: Christiane Langer, Bristol-Myers Squibb; Justin Kopit, Bristol-Myers Squibb Honoraria: Alberto F. Sobrero, Merck KGaA, Pfizer, Amgen, Roche, Sanofi-aventis; Werner Scheithauer, Merck KGaA, Pfizer; Howard A. Burris III, Bristol-Myers Squibb Research Funding: Alberto F. Sobrero, Merck KGaA; Werner Scheithauer, Merck KGaA; Cathy Eng, Bristol-Myers Squibb, Genentech, Novartis, Sanofi-aventis, AstraZeneca, Pfizer; Heinz-Josef Lenz, Bristol-Myers Squibb; Gabriele Luppi, Merck KGaA, Bristol-Myers Squibb, ImClone Systems Expert Testimony: None Other Remuneration: None
Author CONTRIBUTIONS
Department:
Conception and blueprint: Alberto F. Sobrero, Oliver Kisker, Angela Zubel, Christiane Langer, Justin Kopit
Provision of study materials or patients: Alberto F. Sobrero, Joan Maurel, Louis Fehrenbacher, Werner Scheithauer, Yousif A. Abubakr, Manfred P. Lutz, M. Eugenia Vega-Villegas, Cathy Eng, Ernst U. Steinhauer, Jana Prausova, Heinz-Josef Lenz, Christophe Borg, Gary Middleton, Hendrick Kröning, Gabriele Luppi, Howard A. Burris III
Drove and assembly of information: Louis Fehrenbacher, Werner Scheithauer, Yousif A. Abubakr, Manfred P. Lutz, M. Eugenia Vega-Villegas, Cathy Eng, Gary Middleton, Justin Kopit, Howard A. Burris 3
Data analysis and interpretation: Alberto F. Sobrero, Joan Maurel, Manfred P. Lutz, M. Eugenia Vega-Villegas, Heinz-Josef Lenz, Christiane Langer, Justin Kopit, Howard A. Burris III
Manuscript writing: Alberto F. Sobrero, Joan Maurel, Manfred P. Lutz, Justin Kopit, Howard A. Burris Three
Terminal approval of manuscript: Alberto F. Sobrero, Joan Maurel, Louis Fehrenbacher, Werner Scheithauer, Yousif A. Abubakr, Manfred P. Lutz, K. Eugenia Vega-Villegas, Cathy Eng, Jana Prausova, Heinz-Josef Lenz, Christophe Borg, Gary Middleton, Hendrick Kröning, Gabriele Luppi, Oliver Kisker, Angela Zubel, Christiane Langer, Justin Kopit, Howard A. Burris Three
Appendix
Section:
Department:
Fig ane. Patient disposition.
Fig ii. Kaplan-Meier analysis of overall survival.
Fig 3. Kaplan-Meier analysis of progression-free survival.
Fig iv. Quality-of-life analysis across treatment artillery. Change from baseline in (A) global health status, (B) concrete performance, (C) emotional functioning, (D) fatigue, (E) diarrhea, and (F) hurting on the European Organization for Enquiry and Handling of Cancer Quality of Life Questionnaire C-30. CET, cetuximab; IRI, irinotecan.
Fig A1. Additional posthoc exploratory survival analyses: (A) restricted to the portion of the trial before regulatory approving of cetuximab; (B) nonrandomized comparison across patients in the irinotecan-only arm; (C) nonrandomized comparison across patients in the experimental arm. Subseq., subsequent.
 | Tabular array one. Patient Demographics and Clinical Characteristics |
| | Tabular array 2. Treatment Responses |
| | Table three. Almost Common Drug-Related Nonhematologic AEs and On-Report Laboratory Abnormalities |
© 2008 by American Society of Clinical Oncology
published online ahead of print at www.jco.org on April seven, 2008. Sponsored by Merck KGaA, Bristol-Myers Squibb, and ImClone Systems. Presented in part at the 41st Almanac Meeting of the American Club of Clinical Oncology, Orlando, FL, June 2005; the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2006; safety and efficacy results from this study were presented at the Almanac Coming together of the American Association for Cancer Enquiry, April fourteen-18, 2007, Los Angeles, CA; and the quality of life results from this study were presented at the 43rd Annual Coming together of the American Lodge of Clinical Oncology, Chicago, IL, June 2007. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this commodity.
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Source: https://ascopubs.org/doi/10.1200/JCO.2007.13.1193
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