Self-reported conflicts of interest (sfCOI) of authors and the interpretation of randomized phase III trials (RCT) and related editorials (REd) in cancer research.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6055-6055
Author(s):  
Giovanni Mendonca Bariani ◽  
Anezka Carvalho Rubin De Celis Ferrari ◽  
Paulo Marcelo Hoff ◽  
Rachel Riechelmann
Keyword(s):  
Cancer Research ◽  
Logistic Regression ◽  
Conflicts Of Interest ◽  
Multivariable Analysis ◽  
Phase Iii ◽  
Experimental Therapy ◽  
Negative Results ◽  
Study Results ◽  
Phase Iii Trials ◽  
Cancer Studies

6055 Background: Growing participation from industry in cancer research has resulted in increased reporting of COI. We aimed to test any association between author’s conclusion and sfCOI in cancer studies. Methods: All RCT and REd published in 6 major cancer journals in a 3.5 year period were selected. Two investigators blinded to COI disclosure independently analyzed each RCT and REd, classifying authors’ conclusions as highly positive, positive, neutral, negative, and highly negative with respect to author’s opinion on the experimental therapy. The agreement rate between investigators for conclusion classification was 90% (consensus was achieved for the remaining 10%). We also collected data on study results, COI and sponsorship. COI was defined as any self-reported financial tie between author and industry except for research funds. Predictors of positive/highly positive conclusions of RCT and of REd were tested separately in logistic regression multivariable models. Results: From Jan 2008 to Oct 2011, 1,485 articles were retrieved: 150 RCT and 140 REd were eligible. Among the RCT, 82 (55%) were positive, and 78 (52%) were entirely or partially funded by industry. Any sfCOI was present in 103 (69%) RCT and in 71 (47%) REd. Conclusions of REd and RCT were: 7.3% and 11.3% highly positive, 42.7% and 57.3% positive, 8.0% and 2.0% neutral, 29.3% and 18.7% negative, and 12.7% and 10.7% highly negative, respectively. Multivariable analysis showed that RCT positive result was the only significant predictor for positive conclusion by RCT authors (OR=109, 95% CI: 21-567; p<0.001). The only factor associated with positive conclusions of REd authors was a positive conclusion by RCT author (OR=42, 95% CI: 7-244; p<0.001). While 64 (43%) RCT reported negative results, 103 (68.7%) RCT authors interpreted studies positively. Logistic regression for discordance between RCT result and RCT conclusion did not find any association with COI. Conclusions: The interpretation of RCT results by authors was not influenced by sfCOI or trial sponsorship. Authors of REd were not influenced by study results or by their sfCOI when discussing cancer RCT.

Self-Reported Conflicts of Interest of Authors, Trial Sponsorship, and the Interpretation of Editorials and Related Phase III Trials in Oncology

2013 ◽  
Vol 31 (18) ◽  
pp. 2289-2295 ◽  
Author(s):  
Giovanni M. Bariani ◽  
Anezka C.R. de Celis Ferrari ◽  
Paulo M. Hoff ◽  
Monika K. Krzyzanowska ◽  
Rachel P. Riechelmann
Keyword(s):  
Cancer Research ◽  
Conflicts Of Interest ◽  
Multivariable Analysis ◽  
Phase Iii ◽  
Experimental Therapy ◽  
Phase Iii Trial ◽  
Research Reporting ◽  
Phase Iii Trials ◽  
Positive Results ◽  
Related Phase

Purpose Growing participation by industry in cancer research has resulted in increased reporting of conflicts of interest (COI). We aimed to test any association between authors' conclusions and self-reported COI or trial sponsorship in cancer studies. Methods Editorials and related phase III trials published in six clinical oncology journals in the last 3.5 years were analyzed independently by two investigators who classified study conclusions according to authors' endorsement of the experimental therapy. Logistic regression multivariable models were used to assess predictors of favorable conclusions of editorialists and of phase III authors. Results From January 2008 to October 2011, 1,485 articles were retrieved: 150 phase III trials and 150 editorials were eligible. Among the phase III trials, 82 (54.7%) had positive results, and 78 (52.0%) were entirely or partially funded by industry. Any COI were disclosed in 103 phase III trials (68.7%) and in 71 editorials (47.3%). Multivariable analysis showed that phase III trial results were the only significant predictor for a positive conclusion by trial authors (odds ratio [OR], 92.2; 95% CI, 19.7 to 431.6; P < .001). Sponsorship did not predict for positive conclusion by phase III authors (OR, 0.86; 95% CI, 0.3 to 2.5; P = .788). The only factor associated with positive conclusions by editorial authors was a positive conclusion by phase III trial authors (OR, 36.3; 95% CI, 6.8 to 194.2; P < .001). Conclusion The interpretation of recently published phase III cancer trials by their authors or by editorialists was not influenced by financial relationships or industry sponsorship. Increased awareness of COI policies may have led to more integrity in cancer research reporting.

Comparing the outcomes of noninferiority (NI) and superiority phase III trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13055-e13055
Author(s):  
Everardo D. Saad ◽  
Marc E. Buyse
Keyword(s):  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Experimental Therapy ◽  
Tumor Type ◽  
Margin Width ◽  
Number Of Patients ◽  
Significant Difference ◽  
Phase Iii Trials ◽  
Superiority Trials

e13055 Background: We compared the outcomes of NI and superiority trials on advanced breast cancer (BC), non-small-cell lung cancer (NSCLC), and colorectal cancer (CRC). Methods: We searched PubMed for phase III trials on systemic antineoplastic treatments for advanced BC, NSCLC and CRC published between 1/1998 and 12/2009 in 11 leading journals. We categorized primary endpoints (PEP) as time-to-event (overall survival or any variant of progression-free survival), response rate, or other (quality of life or toxicity). We used the PEP (defined as the one stated explicitly, used for N calculation, or cited first) to ascertain trial positivity. Results: We retrieved a total of 262 trials (93 on BC, 102 on NSCLC, and 67 on CRC), 36 of which (13.7%) used a NI design (12 in each tumor type). There was no significant trend in the proportion of NI trials in the two 6-year periods compared (1998-2003 vs 2004-9). The median number of patients/arm for NI and superiority trials were 284 and 164, respectively (p<0.001). There was no significant difference in the distribution of the PEP categories between NI and superiority trials. We could ascertain trial positivity in all but six trials: 24 (66.7%, 95% confidence interval [CI], 49.1% to 81.2%) NI trials were positive, compared with 89 (39.4%, 95% CI, 33.0% to 46.1%) superiority trials (p<0.001). NI trial positivity could be determined by finding a CI for the estimated treatment effect that excluded the NI margin in 15 of 27 trials (otherwise, positivity was based on authors’ conclusions, or the experimental therapy was superior to control for the PEP). The overall rates of trial positivity varied across tumor types: 48.4% for BC, 31.4% for NSCLC, and 53.7% for CRC (p=0.002). When adjusted for trial size, NI design (vs. superiority; odds ratio [OR]=4.2; 95% CI, 1.7 to 10.3) and tumor type (BC [OR=2.2; 95% CI, 1.2 to 4.0] and CRC [OR=2.8; 95% CI, 1.4 to 5.5] vs. NSCLC as reference) remained significantly associated with trial positivity. Conclusions: NI trials are more likely than superiority trials to yield positive results. The influence of NI margin width on trial results should be investigated.

Impact of single agent daily prednisone on survival and toxicities in post-docetaxel men with metastatic castration-resistant prostate cancer (mCRPC): An analysis of 2 phase III trials.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 213-213
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Arnoud J. Templeton ◽  
Eugene D. Kwon ◽  
Johann S. De Bono
Keyword(s):  
Statistical Significance ◽  
Oral Prednisone ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Multivariable Analysis ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Grade 3 ◽  
Combination Regimens ◽  
The Impact

213 Background: Daily oral prednisone (P) has been employed for the therapy of mCRPC, alone or in combination regimens. Despite palliative benefits and PSA responses, the overall clinical impact of P is unknown and it may foster resistance mechanisms. We performed a pooled analysis of control arms of randomized trials which either did or did not administer single agent P to evaluate its impact on overall survival (OS) and toxicities. Methods: Individual patient data from control arms ofrandomized trials of post-docetaxel men receiving placebo or P + placebo were eligible for analysis. Patient demographics, survival, and toxicity data were collected. The impact of P on OS and toxicities was investigated in Cox regression models adjusted for known clinical and laboratory prognostic factors. Statistical significance was defined as a p-value < 0.05 and all tests were two-sided. Results: The control arms of 2 randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n = 394) administered P plus placebo and the CA184-043 trial (n = 400) administered placebo alone. P plus placebo was not significantly associated with OS compared to placebo alone in a multivariable analysis (HR = 0.89 [95% CI 0.72-1.10], p = 0.27). Other factors associated with poor OS were Eastern Cooperative Oncology group (ECOG)-performance status (PS) ≥ 1, Gleason Score ≥ 8, liver metastasis, high PSA, hypoalbuminemia, and elevated LDH.In contrast, CTCAE grade ≥ 3 therapy-related toxicities were significantly increased with P plus placebo compared to placebo alone (HR = 1.48 (1.03-2.13), p = 0.034) in a multivariable analysis. Other baseline factors significantly associated with a higher risk of grade ≥ 3 toxicities were ECOG-PS ≥ 1, hypoalbuminemia and elevated LDH. Conclusions: P plus placebo compared with placebo alone for post-docetaxel men with mCRPC was not associated with extension of OS, but was associated with higher grade ≥ 3 toxicities. With the exception of the use of P in combination with abiraterone, P alone or in combination regimens should be questioned given its unclear palliative benefits and association with increased toxicities.

scholarly journals Measuring vaccine efficacy against infection and disease in clinical trials: sources and magnitude of bias in COVID-19 vaccine efficacy estimates

2021 ◽  
Author(s):  
Lucy R. Williams ◽  
Neil M. Ferguson ◽  
Christl A. Donnelly ◽  
Nicholas C. Grassly
Keyword(s):  
Vaccine Efficacy ◽  
Asymptomatic Infection ◽  
Phase Iii ◽  
Uncertainty Interval ◽  
Considerable Uncertainty ◽  
Study Results ◽  
Phase Iii Trials ◽  
Asymptomatic Infections ◽  
Protection Against Infection ◽  
Induced Immunity

Background Phase III trials have estimated COVID-19 vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections. Methods We developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic and any SARS-CoV-2 infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections. Results VE against asymptomatic infection measured by PCR or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias towards underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4 to 77.1) and 70.9% (95% UI 49.8 to 80.7) respectively. Conclusion Multiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.

Compendium of Unpublished Phase III Trials in Oncology: Characteristics and Impact on Clinical Practice

2011 ◽  
Vol 29 (23) ◽  
pp. 3133-3139 ◽  
Author(s):  
Vincent C. Tam ◽  
Ian F. Tannock ◽  
Christine Massey ◽  
Jennifer Rauw ◽  
Monika K. Krzyzanowska
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Phase Iii ◽  
Institutional Review Boards ◽  
Negative Results ◽  
Institutional Review ◽  
Subsequent Publication ◽  
Phase Iii Trials ◽  
Asco Meeting ◽  
American Society

Purpose Many phase III trials presented at annual meetings of the American Society of Clinical Oncology (ASCO) remain unpublished. The results of these unpublished trials, if more generally known, might have an impact on clinical practice. Methods Abstracts of large phase III trials evaluating systemic cancer treatment were identified from conference proceedings of the 1989 to 2003 ASCO annual meetings. PubMed, Medline, and Embase were searched for corresponding publications. A compendium of unpublished phase III trials was assembled. Clinical significance of nonpublication was determined by disease site-specific oncology experts from two academic cancer centers in Canada. Results A total of 709 phase III trials were identified of which 66 (9.3%) remain without a subsequent publication at a minimum of 6.5 years of follow-up and 94 (13%) were published after a delay of ≥ 5 years from their initial presentation. Of the unpublished trials, 48% were presented as oral sessions at an ASCO meeting, and 71% of the abstracts reported negative results. The experts judged that 70% of the unpublished trials addressed an important question and 59% might have had clinical impact if their results had been published promptly. Conclusion A substantial number of cancer clinical trials with potential influence on clinical practice remain unpublished and many other trials are published after a substantial delay. Nonpublication of clinical trials breaks an implicit contract with participants, institutional review boards, and sponsors.

Outcomes and Prognostic Factors Following Double-Induction Chemotherapy in AML – A Large, Single Institutional Experience,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3605-3605
Author(s):  
Jeffrey E. Lancet ◽  
Alan F. List ◽  
Celeste M. Bello ◽  
Najla H Al Ali ◽  
Rami S. Komrokji
Keyword(s):  
Bone Marrow ◽  
Logistic Regression ◽  
Induction Chemotherapy ◽  
Odds Ratio ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Categorical Variables ◽  
High Dose ◽  
Cox Regression Analysis

Abstract Abstract 3605 Background: Although a majority of patients with AML achieve complete response (CR) following 1 or 2 cycles of induction chemotherapy, rates of relapse-free and overall survival remain poor. In the US, typically the decision to administer re-induction chemotherapy depends upon the degree of leukemic cell clearance from the bone marrow at 10–14 days after initial induction. In this single-institution study, we assessed patients who underwent double induction chemotherapy for AML in an attempt to delineate specific clinical variables that might influence outcomes and decisions to utilize re-induction chemotherapy. Methods: Between 2004 and 2010, patients who received 2 courses of induction chemotherapy for AML at the H. Lee Moffitt Cancer Center were analyzed. Individual charts were reviewed. Chi square test was used to compare categorical variables in univariate analysis. Kaplan Meier estimates were used to calculate OS. Log rank test was used for comparison between the 2 groups and Cox regression analysis was used for multivariable analysis of survival. Binomial logistic regression was used for multivariate assessment of response rates. All analyses were conducted using SPSS version 19.0 software. Results: We identified 164 patients with previously untreated AML who underwent double-induction chemotherapy at our center, 127 of whom had residual blasts ≥ 10% following initial induction. Baseline characteristics (%): male:female (68%:32%), age less than:greater than 60 (57%:43%), adverse:non adverse karyotype (39%:58%), de-novo:secondary AML (66%:32%). The majority (97%) initially received anthracycline + cytarabine (“7+3”) based induction chemotherapy. Second induction utilized a high-dose cytarabine based regimen in 65% of patients. Overall response rate (CR + CRi) was 62%. Median survival for the entire cohort was 13.3 months (95% CI 11.4–15.3). Univariate analysis of prognostic variables associated with response and survival are shown in Table 1. On multivariate analysis, only adverse karyotype (p=0.02, HR 1.67) and non-hypocellular (≥ 20%) bone marrow at day 14 after 1st induction (p=0.002, HR 1.934) were statistically significant predictors of inferior survival (figure 1), but there was a trend toward inferior OS for re-induction beginning after day 21. The only statistically significant predictors for response (CR+CRi) in the logistic regression model were age < 60 (p=0.034, odds ratio 2.850) and hypocellular day 14 bone marrow after 1st induction (p <0.005, odds ratio 7.87). Conclusions: In patients who received double induction therapy for AML, response was achieved in the majority, and the bone marrow cellularity at day 14 after induction cycle 1 was the strongest predictor of response and survival, strongly suggesting its consideration as a prognostic/stratification factor in future outcomes studies as well as studies testing new agents in refractory disease. Future analyses will include direct comparisons of outcomes and analysis of risk factors between patients receiving 1 versus 2 cycles of induction. Disclosures: No relevant conflicts of interest to declare.

Safety summary of panitumumab (pmab) in combination with chemotherapy (ctx) from four clinical trials in patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15005-e15005
Author(s):  
T. J. Price ◽  
M. Peeters ◽  
J. Douillard ◽  
E. Mitchell ◽  
A. Cohn ◽  
...  
Keyword(s):  
Phase Ii ◽  
Safety Data ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Study Results ◽  
Phase Iii Trials ◽  
Phase Iii Studies

e15005 Background: Pmab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody approved in the US and EU (wild-type KRAS) as monotherapy for pts with mCRC. Safety data from 4 studies (Siena et al ASCO 2008; Peeters et al ASCO 2008; Cohn et al ASCO 2008; Mitchell et al WORLD GI 2008) of pmab in combination with ctx are summarized. Methods: Two studies are single-arm, phase II trials and two are randomized, phase III trials with pooled, blinded safety data that include ctx-controls. All studies were multicenter. Common pt eligibility criteria included: diagnosis of mCRC with measurable disease per modified RECIST criteria, age ≥ 18 years, and adequate hematologic, renal, hepatic, and metabolic function. All studies required pts to receive FOLFOX, FOLFIRI, or irinotecan ctx in combination with pmab. Pts received pmab 6.0 mg/kg Q2W with FOLFOX Q2W or FOLFIRI Q2W, or pmab 9.0 mg/kg Q3W with irinotecan Q3W. Results from planned interim analyses are available for 3 studies, and results from the final analysis are available for one study. Results: Among the 4-study safety data, 1213 pts received pmab + ctx; 703 pts received pmab + FOLFIRI, 455 pts received pmab + FOLFOX, and 55 pts received pmab + irinotecan. Approximately 1,200 pts were enrolled in each phase III study, and data are available from 1,003 pts who received pmab + ctx and 997 pts who received ctx alone. All pts in the phase III studies, regardless of treatment group, were included in the pooled, blinded interim analysis sets monitored by the data monitoring committee for each study. Safety results for the two phase II studies of pmab + ctx and two phase III studies of pmab ± ctx are summarized (Table). Conclusions: Phase II data are consistent with expectations, and phase III trials are ongoing. A consistent safety profile was observed across studies. [Table: see text] [Table: see text]

Tolerability and activity of combinations of the PI3Kδ inhibitor idelalisib (GS-1101) with rituximab and/or bendamustine in patients with previously treated, indolent non-Hodgkin lymphoma (iNHL): Updated results from a phase I study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8500-8500 ◽  
Author(s):  
John Leonard ◽  
Nina D. Wagner-Johnston ◽  
Steven E. Coutre ◽  
Ian Flinn ◽  
Marshall T. Schreeder ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Phase I ◽  
Phase I Study ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Non Hodgkin Lymphoma ◽  
Highly Active ◽  
Study Results ◽  
Asco 2012 ◽  
Phase Iii Trials

8500 Background: PI3K-delta signaling is critical for activation, proliferation and survival of B cells, and is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that has shown considerable monotherapy activity in recurrent iNHL (Kahl, ICML 2011), as well as combination therapy (Fowler, ASCO 2012). Methods: This phase I study evaluated the activity of continuous (48 weeks) idelalisib (Id), 100/150 mg BID, in combination with rituximab (R) (375 mg/m2 weekly x 8 doses) (Id+R), with bendamustine (B) (90 mg/m2 x 2, for 6 cycles) (Id+B), or in combination with R (375 mg/m2 monthly x 6) and B (90 mg/m2 x 2), for 6 cycles (Id+BR). Investigators assessed response according to standard criteria (Cheson 2007). Patients who continued to benefit were able to enroll on an extension study. Results: Study enrolled 78 pts with relapsed/refractory iNHL, with 34 (44%) pts continuing on treatment in the ongoing extension protocol. The 3 cohorts included Id+R (N=30), Id+B (N=34), and Id+BR (N=14). Pts were 67% male, median age [range] of 62 [37E84] years, 41% with refractory disease, 88% stage III/IV, and 36% of FL with high FLIPI scores. The median [range] number of prior therapies was 3 [1E10]. The median [range] duration of treatment was 10.6 [0.5-29.2] months. Overall response rate (ORR) was 63/78 (81%), with 22/78 (28%) CR. The ORR/CR for Id+R was 77%/20%, Id+B was 85%/29%, and Id+BR was 79%/43%. At 20 months, the PFS was 66%. For responders, 73% were progression-free at 20 months. Most common adverse events included (total%/≥G3%) pyrexia (56/4), fatigue (45/4), nausea (41/0), rash (40/8), cough (37/0), diarrhea (36/8), chills (18/0), URI (18/1), and pneumonia (17/15). Lab abnormalities included (total%/≥G3%) ALT/AST elevations (56/17). Conclusions: Idelalisib-based combination therapy is highly active and well tolerated in patients with relapsed/refractory iNHL. These data support further clinical development. Phase III trials evaluating the efficacy of idelalisib in combination with R, or BR in iNHL are ongoing (NCT01732913, NCT01732926). Clinical trial information: NCT01732913, NCT01732929.

scholarly journals The Damaging Outcome of the POLAR Phase III Trials Was Due to Avoidable Time-Dependent Redox Interaction between Oxaliplatin and PledOx

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1937
Author(s):  
Jan Olof G. Karlsson ◽  
Per Jynge ◽  
Louis J. Ignarro
Keyword(s):  
Clinical Trial ◽  
Phase Iii ◽  
Polar Phase ◽  
Negative Results ◽  
M Phase ◽  
Phase Iii Trials ◽  
Modified Folfox6 ◽  
Redox Interaction ◽  
Administration Procedure ◽  
Time Point

On 2 July 2021, highly negative results were reported from the POLAR A and M phase III trials in patients with colorectal cancer, treated with an oxaliplatin-based regimen and co-treated with calmangafodipir (CaM; PledOx®; PledPharma AB/Egetis Therapeutics AB) or placebo. The results revealed persistent chemotherapy-induced peripheral neuropathy (CIPN) in 54.8% of the patients treated with PledOx, compared with 40.0% of the patients treated with the placebo (p < 0.05), i.e., a 37% increase in incidence of the side effect that the trial was aimed to prevent. The damaging outcome of the trials differed diametrically from an in-parallel conducted mice study and from a clinical trial with mangafodipir, the active ingredient of CaM. According to the authors of the POLAR report, the etiology of the profound increase in CIPN in the PledOx arm is unclear. However, these devastating effects are presumably explained by intravenous administrations of PledOx and oxaliplatin being too close in time and, thereby, causing unfavorable redox interactions between Mn2+ and Pt2−. In the mice study as well as in the preceding phase II clinical trial (PLIANT), PledOx was administered 10 min before the start of the oxaliplatin infusion; this was clearly an administration procedure, where the devastating interactions between PledOx and oxaliplatin could be avoided. However, when it comes to the POLAR trials, PledOx was administered, for incomprehensible reasons, “on Top of Modified FOLFOX6” at day one, i.e., after the two-hour oxaliplatin infusion instead of before oxaliplatin. This is a time point when the plasma concentration of oxaliplatin and Pt2+-metabolites is at its highest, and where the risk of devastating redox interactions between PledOx and oxaliplatin, in turn, is at its highest.

Sign in / Sign up

Export Citation Format

Share Document