FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1975442922> ?p ?o ?g. }

• W1975442922 endingPage "179" @default.
• W1975442922 startingPage "178" @default.
• W1975442922 abstract "Sir,We appreciate the interest of O'Donnell et al in our report on temsirolimus in neuroendocrine cancers (NEC). They suggest that based on the tumour control rate observed in our study, temsirolimus may have activity in advanced NEC ‘beyond the natural course of disease'. We completely agree with this observation. In fact, as discussed in our manuscript, at the end of stage I in this two-staged trial, we had amended the protocol despite not meeting the originally set criteria, and proceeded to stage II based on the observed decrease in tumour progression rate and clinical benefit in some patients. We concluded the manuscript by declaring that temsirolimus appears to have modest activity in NEC, and advocating the development of combination studies with this agent.We also share the enthusiasm of O'Donnell et al for efficient clinical trial designs to evaluate the activity of new molecularly targeted compounds. However, we would respectfully disagree with their statement that this is best achieved by abandoning single-arm phase II studies.Phase II trials play a pivotal screening role in the drug development process (Mariani and Marubini, 2000; Taylor et al, 2006). Given that patient and financial resources are precious, and there is a pressing need to rapidly bring true advances to the clinic, efficient phase II trial designs that reliably retain promising agents while quickly discard inactive ones are critical. This is particular true when we have such a wide range of novel agents undergoing evaluation. Traditional single-arm phase II trials that focused solely on response might underestimate the cytostatic activity of some molecular targeted agents; however including tumour control within the primary end point can overcome this limitation, as can referencing the tumour control rates to other studies of less-active agents in the same population (as was done by O'Donnell et al in coming to the conclusion that temsirolimus does have some activity against NEC based upon our study results). In our study, after the accrual of 37 patients over 18 months, we were able to draw useful conclusions about the antitumour activity of temsirolimus in NEC, thus reaffirming that single-arm phase II trials remain a good choice for promptly determining if a drug should advance to further development.The randomised discontinuation design has been proposed as an alternate more complex option to evaluate the efficacy of cytostatic drugs (Ratain et al, 2006). This design represents an appealing alternative with some limitations (Freidlin and Simon, 2005). These studies tend to be much larger than other phase II designs; as an example, 368 patients were entered on a clinical trial of carboxyaminoimidazole in renal cell carcinoma that used the randomised discontinuation design and concluded that the drug was inactive (Stadler et al, 2005). Given the multitude of interesting options for renal cell cancer under evaluation, a design that requires over 350 patients to conclude that a drug is inactive lacks the efficiency we are all seeking. As an interesting comparison, two multikinase inhibitors, sorafenib and sunitinib, have now been approved for advanced renal cell cancers. The phase II development of sorafenib utilised the randomised discontinuation design and enrolled 202 patients, 36% of patients had tumour shrinkage of ⩾25% and 32% achieved stable disease at 12 weeks (Ratain et al, 2006). The phase II development of sunitinib utilised a single-arm phase II design and enrolled 106 patients, 34% of patients had partial responses by RECIST criteria and 29% achieved stable disease for ⩾3 months (Motzer et al, 2006). Both trials led to further phase III evaluations due to the promising activity detected by their respective phase II designs.Lastly, O'Donnell et al draw analogies between renal cell carcinoma and NEC. One needs to be cautious in extrapolating from an experience in a tumour that has a different biology, natural history and response to therapy." @default.
• W1975442922 created "2016-06-24" @default.
• W1975442922 creator A5000204204 @default.
• W1975442922 creator A5003643368 @default.
• W1975442922 creator A5036620887 @default.
• W1975442922 date "2006-12-12" @default.
• W1975442922 modified "2023-10-16" @default.
• W1975442922 title "Reply: Evaluating the activity of temsirolimus in neuroendocrine cancer" @default.
• W1975442922 cites W1496244746 @default.
• W1975442922 cites W1822621519 @default.
• W1975442922 cites W2145537131 @default.
• W1975442922 cites W2149026055 @default.
• W1975442922 cites W2152618785 @default.
• W1975442922 cites W2156408558 @default.
• W1975442922 doi "https://doi.org/10.1038/sj.bjc.6603514" @default.
• W1975442922 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2360211" @default.
• W1975442922 hasPublicationYear "2006" @default.
• W1975442922 type Work @default.
• W1975442922 sameAs 1975442922 @default.
• W1975442922 citedByCount "2" @default.
• W1975442922 countsByYear W19754429222012 @default.
• W1975442922 countsByYear W19754429222017 @default.
• W1975442922 crossrefType "journal-article" @default.
• W1975442922 hasAuthorship W1975442922A5000204204 @default.
• W1975442922 hasAuthorship W1975442922A5003643368 @default.
• W1975442922 hasAuthorship W1975442922A5036620887 @default.
• W1975442922 hasBestOaLocation W19754429221 @default.
• W1975442922 hasConcept C121608353 @default.
• W1975442922 hasConcept C126322002 @default.
• W1975442922 hasConcept C142724271 @default.
• W1975442922 hasConcept C143998085 @default.
• W1975442922 hasConcept C183713625 @default.
• W1975442922 hasConcept C190283241 @default.
• W1975442922 hasConcept C2776820818 @default.
• W1975442922 hasConcept C2779066768 @default.
• W1975442922 hasConcept C55493867 @default.
• W1975442922 hasConcept C71924100 @default.
• W1975442922 hasConcept C86554907 @default.
• W1975442922 hasConcept C86803240 @default.
• W1975442922 hasConceptScore W1975442922C121608353 @default.
• W1975442922 hasConceptScore W1975442922C126322002 @default.
• W1975442922 hasConceptScore W1975442922C142724271 @default.
• W1975442922 hasConceptScore W1975442922C143998085 @default.
• W1975442922 hasConceptScore W1975442922C183713625 @default.
• W1975442922 hasConceptScore W1975442922C190283241 @default.
• W1975442922 hasConceptScore W1975442922C2776820818 @default.
• W1975442922 hasConceptScore W1975442922C2779066768 @default.
• W1975442922 hasConceptScore W1975442922C55493867 @default.
• W1975442922 hasConceptScore W1975442922C71924100 @default.
• W1975442922 hasConceptScore W1975442922C86554907 @default.
• W1975442922 hasConceptScore W1975442922C86803240 @default.
• W1975442922 hasIssue "1" @default.
• W1975442922 hasLocation W19754429221 @default.
• W1975442922 hasLocation W19754429222 @default.
• W1975442922 hasLocation W19754429223 @default.
• W1975442922 hasOpenAccess W1975442922 @default.
• W1975442922 hasPrimaryLocation W19754429221 @default.
• W1975442922 hasRelatedWork W1995193840 @default.
• W1975442922 hasRelatedWork W2057935885 @default.
• W1975442922 hasRelatedWork W2061143535 @default.
• W1975442922 hasRelatedWork W2122132792 @default.
• W1975442922 hasRelatedWork W2139969317 @default.
• W1975442922 hasRelatedWork W2145731612 @default.
• W1975442922 hasRelatedWork W2150458600 @default.
• W1975442922 hasRelatedWork W2154171266 @default.
• W1975442922 hasRelatedWork W2166010840 @default.
• W1975442922 hasRelatedWork W2515988937 @default.
• W1975442922 hasVolume "96" @default.
• W1975442922 isParatext "false" @default.
• W1975442922 isRetracted "false" @default.
• W1975442922 magId "1975442922" @default.
• W1975442922 workType "article" @default.