Analysis of clinical trials with biologics using dose-time-response models

2015 ◽  
Vol 34 (22) ◽  
pp. 3017-3028 ◽  
Author(s):  
Markus R. Lange ◽  
Heinz Schmidli
Keyword(s):  
Clinical Trials ◽  
Time Response ◽  
Response Models ◽  
Dose Time

Optimal design of clinical trials with biologics using dose-time-response models

2014 ◽  
Vol 33 (30) ◽  
pp. 5249-5264 ◽  
Author(s):  
Markus R. Lange ◽  
Heinz Schmidli
Keyword(s):  
Clinical Trials ◽  
Optimal Design ◽  
Time Response ◽  
Response Models ◽  
Dose Time

Dose–time response association between occupational asbestos exposure and pleural mesothelioma: authors’ response

2017 ◽  
Vol 75 (2) ◽  
pp. 161-162 ◽  
Author(s):  
Aude Lacourt ◽  
Emilie Leveque ◽  
Marcel Goldberg ◽  
Karen Leffondre
Keyword(s):  
Asbestos Exposure ◽  
Time Response ◽  
Pleural Mesothelioma ◽  
Dose Time

Diarrhea events in cancer patients (pts) treated with lapatinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9125-9125 ◽  
Author(s):  
M. Koehler ◽  
S. Chan ◽  
B. O. Newstat ◽  
A. Preston ◽  
H. A. Burris
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Kinase Inhibitor ◽  
Median Number ◽  
Low Grade ◽  
Cancer Clinical Trials ◽  
Dose Time ◽  
Delayed Onset ◽  
Gastrointestinal Adverse Events ◽  
Time To Onset

9125 Introduction: Lapatinib (L) is an oral dual ErbB1/ErbB2 tyrosine kinase inhibitor administered to > 5,000 pts in clinical trials. Low grade gastrointestinal adverse events: diarrhea, nausea and vomiting were recorded. We characterize here the diarrhea events related to L. Methods: Diarrhea events were recorded in 1,514 pts from 8 completed MBC and non-breast cancer clinical trials. Non-L treated pts in these trials were the comparator for analysis of toxicity grades, relationship to dose, time to onset, duration, required interventions and outcomes. Results: The L dose ranged from 1,000–1,500mg daily as monotherapy (n=928) or in combination with chemotherapy (n=198). Capecitabine alone (n=191)and tamoxifen alone (n=197) pts served as controls. For L and non-L groups the per pt diarrhea rates were: any grade 50%v33%; of those G1 54%v53%; G2 30%v30%; G3 15%v17%; G4 <1%v0% and SAEs 3% v 3%; respectively. There were no fatal L-related SAEs. For L, early diarrhea presentation <6 days(d) was 2x more frequent (44%v21%). In the non-L grp, diarrhea presented at 6–14 d in 30% pts. Delayed onset (>28 d) was similar: 22% on L v 26%, non-L. Initial G3 diarrhea or progression from G1/G2 to G3 was similar (Lv non-L): 4%v 3% and 4% v3%, respectively. The median number of events/pt (2) was the same for both groups and median duration was 5d (L) v 6d (non-L). Events (L v non-L) resolved in 89%v93%; and resolved with sequelae <1% v 1%; resolution was not recorded in 7%v4%. Events were managed in approximately 30% of pts with standard anti-diarrhea medications (loperimide and lomitil) and when more sever with hydration, octreotide & antibiotics. Majority of G1/G2 events were not treated. Most pts (85%) did not have L interrupted or dose adjusted and both group only 2% (L)v 2% (non-L) discontinued therapy due to diarrhea. Conclusions: Diarrhea related to L therapy (mostly used as monotherapy in this analysis) is usually mild to moderate, frequently does not require intervention, but pts monitoring is crucial. Importantly, L-related diarrhea appears as early events (before day 6) and is generally responsive to standard interventions. Analyses are ongoing to further identify its natural history, characteristics and pts at risk for serious events. No significant financial relationships to disclose.

scholarly journals Efficient Analysis of Dose—Time—Response Assays

BioScience ◽  
2013 ◽  
Vol 63 (6) ◽  
pp. 490-498
Author(s):  
Ann Yellowlees ◽  
Chris S. LeButt ◽  
Karie J. Hirst ◽  
Peter C. Fusco ◽  
Kelly J. Fleetwood
Keyword(s):  
Time Response ◽  
Dose Time
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