Linked Life Data

2545349

Source:http://linkedlifedata.com/resource/pubmed/id/2545349

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1989-8-23
pubmed:abstractText
As the dose-limiting toxicity of mitoxantrone is hematological, the drug is suitable for dose escalation and use in intensive chemotherapy followed by autologous bone marrow rescue. Adult patients with therapy-resistant solid tumors received a regimen of high-dose cyclophosphamide (7 g/m2) and escalating doses of mitoxantrone in dose steps of 30, 45, 60, and 75 mg/m2. Both drugs were given i.v. on 3 consecutive days. Despite the addition of mesnum (3.5 to 7 g/m2), hemorrhagic cystitis occurred on the second day in four of eight patients, irrespective of the mesnum or mitoxantrone dose. Therefore, the cyclophosphamide in the combination regimen was replaced by high-dose melphalan (180 mg/m2). Mucositis was dose limiting at 75 mg/m2 of mitoxantrone. Responses were seen in eight of ten evaluable patients with four complete responses. Three responders received, after the autologous bone marrow transplantation program, radiotherapy or surgery on pretreatment bulky tumor localizations. Five patients still have disease-free survival after 9 to 36 mo. Pharmacokinetic studies of mitoxantrone were performed by high-performance liquid chromatography with UV detection. The plasma disappearance of mitoxantrone fitted into a three-compartment model with a mean t1/2 alpha of 10 min, a mean t1/2 beta of 96 min, and a slow elimination phase of 172 h. The mean distribution volume was 4294 +/- 3836 liters. We conclude that the high-dose cyclophosphamide-mitoxantrone regimen led to unexpected bladder toxicity, but the combination of melphalan (180 mg/m2) and mitoxantrone (60 mg/m2) can probably be given without major extramedullary toxicity. However, more patients should be evaluated at this dose before definite conclusions can be drawn about toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4654-8
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
High-dose cyclophosphamide or melphalan with escalating doses of mitoxantrone and autologous bone marrow transplantation for refractory solid tumors.
pubmed:affiliation
Division of Intensive Care, University Hospital, Groningen, The Netherlands.
pubmed:publicationType
Journal Article