Phase I trial of irofulven (MGI 114) in pediatric patients with solid tumors

Bomgaars, Lisa; Megason, Gail; Pullen, Jeanette; Langevin, Anne Marie; Weitman, Steve; Hershon, Linda; Kuhn, John G.; Bernstein, Mark L.; Blaney, Susan M.

doi:10.1002/pbc.20686

Cited by 3 publications

(4 citation statements)

References 24 publications

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“…Thus, in heavily pretreated patients dose-limiting thrombocytopenia was observed at 6–8 mg/m 2 /day. In less heavily pretreated patients, doses of 13–17 and 10 mg/m 2 /day were proposed as the MTD …”

Section: Hmaf Clinical Trials: Current Status and Resultsmentioning

confidence: 99%

“…In less heavily pretreated patients, doses of 13−17 and 10 mg/m 2 /day were proposed as the MTD. 273 A population pharmacokinetic model for and evaluation of variables that might affect HMAF pharmacokinetics were derived from phase I studies with 59 cancer patients. HMAF was administered by 5-or 30-min intravenous infusion, and blood samples were collected over 4 h. Plasma samples were analyzed to quantitate HMAF, and population pharmacokinetic analysis was performed using a nonlinear mixed effects modeling program, MP2.…”

Section: Population Pharmacokinetics and Phase I Clinical Trialsmentioning

confidence: 99%

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Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

Tanasova

Sturla

2012

Chem. Rev.

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Section: Hmaf Clinical Trials: Current Status and Resultsmentioning

confidence: 99%

Section: Population Pharmacokinetics and Phase I Clinical Trialsmentioning

confidence: 99%

Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

Tanasova

Sturla

2012

Chem. Rev.

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“…). Sixty‐one trials investigated 53 targeted drugs and 82 trials evaluated 48 cytotoxic agents (Supplementary Table S1) . Several studies involved multiple strata due to differences in eligibility criteria or drug‐dosing schemes.…”

Section: Resultsmentioning

confidence: 99%

A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials

Dorris

Liu

Li³

et al. 2016

Pediatric Blood & Cancer

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“…This selectivity depends on a fast energy-dependent uptake mechanism which exists in sensitive cells, contrasting passive diffusion in relatively resistant cells (e. g., bone marrow progenitor cells or some solid tumour cells) [58]. Irofulvene has entered diverse phase I and II clinical trials to investigate the treatment of hormone-refractory prostate cancer, ovarian cancer, metastatic thyroid cancer and inoperable liver cancer [59], [60], [61]. Furthermore, irofulvene has been studied for synergistic effects when used in combination with gemcitabine, cisplatin, and others to treat patients suffering from a variety of solid tumours [62], [63].…”

Section: Antitumourmentioning

confidence: 99%

Fungal Genetics, Genomics, and Secondary Metabolites in Pharmaceutical Sciences

Misiek

Hoffmeister

2007

Planta Med

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Natural products represent the traditional source of new drug candidates [1]. A global overview on the metabolic wealth of fungal secondary metabolites ± prominent and less prominent ones ± is provided in diverse compilations [2], [3]. From the systematic viewpoint, the most prolific producers of pharmaceutically relevant molecules are the ascomycetes. Their evolutionary counterpart, the basidiomycetes, are equally rich and often unique in their secondary metabolism, however, they cannot compare for significance in terms of clinically used compounds. We open our review with spotlights in the history of pharmacy to underline the Janus-faced nature of fungal metabolites.The Eleusinian Mysteries, initiation ceremonies in the ancient Greek culture that have been established about 1500 BC, climaxed when the initiates reached a visionary state. Their revelatory state of mind was mediated by a drink called ªkykeonº. Today's research attributes this preparation to rye, parasitised by the ergot fungus Claviceps ± a classic in the history of pharmacy. Ergot fungi are known to produce hallucinogenic lysergic acid amides [4]. In the medieval Europe, the sclerotia of the same fungus posed a severe threat to human health when continued ingestion of contaminated bread caused horrible symptoms, like gangrene of the extremities. The order of St. Anthony, in particular, cared for those who were ailing from these symptoms colloquially referred to as ªholy fireº or ªSt. Anthony's fireº. Created in 1515 for an Antonitarian monastery, one painting of the Isenheim Altar symbolises the suffering and the pain of those affected by the toxic metabolites of the ergot fungus. The Isenheim Altar is one of the most outstanding pieces of art ever and marked the onset of the Renaissance. Starting in the 18 th centuryClaviceps sclerotia were pharmaceutically used to induce contractions of the uterus. In the 1930 s, the ergot alkaloids served as a molecular template for the synthesis of the lysergic acid diethylamide (LSD) by Albert Hofmann and co-workers at the San- AbstractFilamentous fungi produce a plethora of bioactive natural products. These metabolites display a broad range of useful activities for pharmaceutical purposes, exemplified best by the antibiotic penicillin. Yet, many more have been isolated, characterised, and tested, and some have made their way in clinical trials and into pharmaceutical practice. Through genomics, we become increasingly aware that the biosynthetic abilities for natural products are much richer than expected. The first part of our review highlights selected metabolites that filamentous fungi offer to pharmacists for drug development. This is followed by a summary on the potential of fungal genetics and genomics for pharmaceutical sciences and natural product research.

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Phase I trial of irofulven (MGI 114) in pediatric patients with solid tumors

Abstract: The MTD of irofulven administered daily x 5 every 28 days with concomitant ondansetron and dexamethasone is 6 mg/m(2)/day in heavily pre-treated patients and 10 mg/m(2)/day in less heavily pre-treated patients.

Cited by 3 publications

References 24 publications

Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials

Fungal Genetics, Genomics, and Secondary Metabolites in Pharmaceutical Sciences

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