New Antifungal Drugs and the Pediatric Cancer Patient: Current Status of Clinical Development
Bibliographic record
Abstract
Invasive mycoses are important causes for treatment related morbidity and mortality in severely immunocompromised pediatric patients with hematological malignancies or hematopoietic stem cell transplantation. The past decade has witnessed a major expansion of antifungal drug research, which has resulted in the development of the novel class of echinocandin lipopeptides (anidulafungin, micafungin, caspofungin) and a new generation of antifungal triazoles with improved pharmacological properties (posaconazole, ravuconazole, voriconazole). Whereas caspofungin and voriconazole have been licensed in the European Union, the United States, Canada and several other countries throughout the world, posaconazole, ravuconazole, anidulafungin and micafungin are under regulatory review or in advanced stages of clinical development. Caspofungin and voriconazole are increasingly prescribed in pediatric patients, although pediatric dosage finding and safety evaluations have not been completed. This article reviews the clinical pharmacology of the new antifungal agents and the status of their clinical development in immunocompromised pediatric patients. Zusammenfassung Invasive Pilzinfektionen sind wichtige Ursachen von Morbidität und Mortalität bei der Behandlung abwehrgeschwächter Kinder und Jugendlicher mit hämatologischen Neoplasien oder hämatopoetischer Stammzell-Transplantation. Das vergangene Jahrzehnt hat eine intensivierte Forschung auf dem Gebiet der antimykotischen Chemotherapie erlebt, die zu der Entwicklung der neuen Substanzklasse der Echinocandine (Anidulafungin, Micafungin, Caspofungin) und einer neuen Generation von antimykotischen Triazolen mit verbesserten pharmakologischen Eigenschaften (Posaconazol, Ravuconazol, Voriconazol) geführt hat. Während Caspofungin und Voriconazol in der Europäischen Union, den Vereinigten Staaten, Kanada und mehreren anderen Ländern zugelassen ist, befinden sich Posaconazol, Ravuconazol, Anidulafungin und Micafungin in Evaluation durch die Zulassungsbehörden bzw. in fortgeschrittenen Stadien der klinischen Entwicklung. Caspofungin und Voriconazole werden zunehmend bei pädiatrische Patienten eingesetzt, obwohl Dosisfindung und Prüfung von Sicherheit und Verträglichkeit in dieser Population nicht abgeschlossen sind. Die vorliegende Arbeit gibt eine Übersicht über die klinische Pharmakologie der neuen antimykotischen Substanzen und über den derzeitigen Stand ihrer klinischen Entwicklung bei abwehrgeschwächten Kindern und Jugendlichen.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".