Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors
Bibliographic record
Abstract
Most pediatric solid tumor protocols include daily cisplatin for 3 to 5 days with higher cumulative doses of cisplatin.Furthermore, such protocols do not generally use a 6-hour infusion of cisplatin.Both these considerations are important in addressing the second question appropriately raised by Freyer et al: What is the therapeutic burden associated with giving amifostine?The reported study is a multiinstitutional, international study that was conducted at six centers in the United States and Australia and has recently expanded to eight centers including Canada.Although the supportive care guidelines are extensive, they have been implemented successfully in these institutions with the provision of appropriate education and clear guidelines.Although we did not capture the incidence of grades 1 and 2 toxicities in this protocol, we do not have concerns regarding the ability to export this therapy to other institutions.However, we concur with Freyer et al that administering multiple daily doses of amifostine to patients with other solid tumors receiving cisplatin daily for 3 to 5 days may require new supportive guidelines and close monitoring.A previous study has shown that amifostine leads to rapid, transient suppression of parathyroid hormone, and hence, transient hypocalcaemia. 3 In that study, amifostine was administered at 600 mg/m 2 /dose twice daily for 3 days with ifosfamide, carboplatin and etoposide to six patients.Grade 3 hypocalcemia was documented in two patients. 3Thus, administration of amifostine twice daily with each cisplatin dose for 3 to 5 days will likely lead to more profound hypocalcemia, requiring prolonged prophylactic calcium infusions and modifications of our supportive guidelines.In addition, although the prescribing information for amifostine recommends administration over 15 minutes, 15 to 30 minutes before radiotherapy or chemotherapy, Wagner et al 4 reported the significantly lower incidents of toxicities such as hypotension with bolus administration of amifostine, a strategy which we adopted in the reported study.Finally, we concur with Freyer et al that other otoprotectants such as sodium thiosulfate also deserve investigation.It is important to point out that both sodium thiosulfate and amifostine are thiol drugs that have similar mechanisms of action, in part acting as scavengers of oxygen-free radicals and binding to the active species of platinum agents. 5However, we believe that given the extensive experience with amifostine, this agent may deserve further study in children with other solid tumors with more careful attention to dosing and scheduling issues.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".