Vincristine, prednisone and L-asparaginase in the induction of remission in children with acute lymphoblastic leukemia following relapse

Kung, Faith; Nyhan, W. L.; Cuttner, Janet; Falkson, Geoffrey; Lanzkowsky, Philip; Duca, V. Del; Nawabi, IW; Koch, Kjell; Pluess, Hansjuerg; Freeman, Arnold I.; Burgert, E. Omer; Leone, Louis A.; Ruymann, Frederick B.; Patterson, Richard B.; Degnan, Thomas J.; Hakami, Nasrollah; Pajak, Thomas F.; Holland, James F.

doi:10.1002/1097-0142(197802)41:2<428::aid-cncr2820410208>3.0.co;2-c

Cited by 37 publications

(3 citation statements)

References 7 publications

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“…At low doses, prednisone is involved in the treatment of emergency rescues such as acute asthma (3). At relatively high doses, prednisone is prescribed for the treatment of pediatric cancer (4). Although prednisone has therapeutic uses for many pediatric diseases, there are several challenges that should be addressed with the oral delivery of this drug.…”

Section: Introductionmentioning

confidence: 99%

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

et al. 2013

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Abstract. The purpose of this study is to enhance the dissolution rate of prednisone by co-grinding with Neusilin to form a complex that can be incorporated into a mini-tablet formulation for pediatrics. Prednisone-Neusilin complex was co-grinded at various ratios (1:1, 1:3, 1:5, and 1:7). The physicochemical properties of the complex were characterized by various analytical techniques including: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), particle size, surface area, solubility, and dissolution rate. The co-grinded prednisone-Neusilin complex (1:7) was blended with other excipients and was formulated into a 2-mm diameter mini-tablet. The minitablets were further evaluated for thickness, weight, content uniformity, and dissolution rate. To improve taste masking and stability, mini-tablets were coated by dip coating with Eudragit® EPO solution. DSC and XRPD results showed that prednisone was transformed from crystalline state into amorphous state after co-grinding with Neusilin. Particle size, surface area, and SEM results confirmed that prednisone was adsorbed to Neusilin's surface. Co-grinded prednisone-Neusilin complex (1:7) had a solubility of 0.24 mg/ mL and 90% dissolved within 20 min as compared to crystalline prednisone which had a solubility of 0.117 mg/mL and 30% dissolved within 20 min. The mini-tablets containing co-grinded prednisoneNeusilin complex (1:7) exhibited acceptable physicochemical and mechanical properties including dissolution rate enhancement. These mini-tablets were successfully dip coated in Eudragit® EPO solution to mask the taste of the drug during swallowing. This work illustrates the potential use of co-grinded prednisone-Neusilin to enhance solubility and dissolution rate as well as incorporation into a mini-tablet formulation for pediatric use.

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Section: Introductionmentioning

confidence: 99%

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

et al. 2013

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“…Patients were informed of the investigational nature of the treatment and an informed consent was signed in accordance with institutional and federal guidelines. Treatment toxicity and therapeutic effects were evaluated and classified according to CALGB criteria [8].…”

Section: Methodsmentioning

confidence: 99%

Sequential intermediate‐dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia

1990

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Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.

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“…83 At relatively high doses, Prednisone is prescribed for the treatment of pediatric cancer. 84 Although Prednisone has therapeutic uses for many pediatric diseases, there are several challenges that should be addressed with the oral delivery of this drug. These challenges include: (1) this drug is sparingly soluble in water and has low bioavailability; any liquid formulation must include organic solvents; (2) this drug has low tolerance depending on the dose strength and can cause fluctuation in overall absorption; (3) this drug should be in a dosage form that could be swallowed readily; (4) this drug is extremely bitter which requires better palatability through taste masking.…”

Section: Introductionmentioning

confidence: 99%

A Series of Pharmaceutical Technology Concepts Applied to Pediatric Formulations

Lou¹

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Pediatric formulations have received great attention from regulatory agencies in the United States and Europe. Since solid dosage forms such as tablets and capsules will not be able to improve pediatric patients' compliance, customized pediatric formulations are needed. In response, formulators in the pharmaceutical industry have made significant effort into developing various pediatric formulations. However, developing satisfactory pediatric formulations is a process that is guided by case by case basis. The objective of this current study was to apply the scientific pharmaceutical technology concepts into developing modern pediatric formulations. We have shown that the drug delivery design will be affected by the route of administration and by the type of dosage form utilized. We are hopeful that our approach will serve as a tool to assist formulations development. Three drug molecules and an anion were utilized in this work (Chlorpheniramine Maleate, Prednisone, Sulfamerazine, and Iodide ion). Each drug molecule was utilized according to its physicochemical properties along with the pediatric patients' needs. As a result, several pediatric formulations were developed. Here is the list: taste masked orally disintegrating tablet, taste masked orally disintegrating film, taste masked mini-tablet, reconstituted nanocrystals and a transdermal microemulsion. We are hopeful that these dosage forms will serve as good examples for specialized pediatric formulations and will attract pharmaceutical industry to adapt some these delivery systems into their development strategy. vi TABLE OF CONTENTS CHAPTER 1.

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Vincristine, prednisone and L-asparaginase in the induction of remission in children with acute lymphoblastic leukemia following relapse

Cited by 37 publications

References 7 publications

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

Sequential intermediate‐dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia

A Series of Pharmaceutical Technology Concepts Applied to Pediatric Formulations

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