4′-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data

Ganzina, Fabrizio

doi:10.1016/s0305-7372(83)80029-2

Cited by 182 publications

(55 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Numerous anthracyclines have been developed with the aim of obtaining potent drugs with reduced cardiac toxicity. Epirubicin (4'-epidoxorubicin) and pirarubicin (4'-O-tetrahydropyranyldoxorubicin) have been brought into routine clinical usage after it was observed that they produced less cardiotoxicity than doxorubicin and daunorubicin, the reference molecules, in both preclinical models and early clinical trials (Ganzina, 1983;Maehara et al, 1989;Herait et al, 1992). In addition, several strategies for reducing cardiotoxicity of anthracyclines have been proposed, including the administration of a-tocopherol (Julicher et al, 1986;Mimnaugh et al, 1981), N-acetylcysteine (Villani et al, 1990), glutathione (Villani et al, 1990), and ICRF-187 or dexrazoxane (Herman & Ferrans, 1986;Speyer et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention

Pouna

Bonoron‐Adèle

Gouverneur

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

1 In order to develop a predictive model for the preclinical evaluation of anthracycline cardiotoxicity and the means of preventing it, we have studied the functional parameters of perfused hearts isolated from rats receiving repeated doses of several anthracyclines. 2 The anthracyclines studied were doxorubicin, epirubicin, pirarubicin and daunorubicin, and we also studied a liposomal formulation of daunorubicin (DaunoXome) and the co-administration of dexrazoxane (ICRF-187) and doxorubicin. 3 Anthracyclines were administered i.p. at equimolar doses corresponding to 3 mg kg-' per injection of doxorubicin, every other day for a total of six doses. Dexrazoxane was used at the dose of 30 mg kg-' per injection and was administered either 30 min before or 30 min after doxorubicin. We evaluated any general toxicity towards the animals as well as alterations of left ventricular contractility and relaxation ex vivo.4 Epirubicin and daunorubicin were significantly less cardiotoxic than doxorubicin, and neither pirarubicin nor DaunoXome caused significant alterations in cardiac function. There was a direct relationship between the decrease in cardiac contractility or relaxation and anthracycline accumulation in the heart, evaluated after the same treatment schedule. 5 Dexrazoxane induced a significant protection against doxorubicin-induced cardiac toxicity when administered 30 min before doxorubicin, whereas this protection was ineffective when administered 30 min after doxorubicin. Direct perfusion of DaunoXome in isolated hearts of untreated animals resulted in a 12-fold reduction of the accumulation of daunorubicin in heart tissue as compared to the perfusion of free daunorubicin, and did not cause alterations in cardiac function at a dosage for which free daunorubicin induced major alterations. 6 The isolated perfused rat heart appears to be a valuable model for screening of new anthracyclines and of strategies for circumventing anthracycline cardiotoxicity.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention

Pouna

Bonoron‐Adèle

Gouverneur

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Four patients presented symptoms of cardiovascular toxicity; in three patients their condition required hospitalization. 'Chills', as experienced by five of our patients, should be viewed on the background of previously reported temperature rise associated with high-dose EPR (Ganzina et al, 1983;Martoni et al, 1990;Brausi et al, 1995). Although the development of angioedema in one of two patients was related in time to EPR infusions, it was most probably related to the use of EMP.…”

Section: Toxicitymentioning

confidence: 57%

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study

Hernes

Fosså²,

Vaage³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg-1, and intravenous epirubicin (EPR) infusions, 100 mg m-2, every third week up to a cumulative dose of 500 mg m-2. Biochemical response [. 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of 2 3 weeks' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a . 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response.Biochemical progression (. 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of . 50% PSA decrease in patients with HRPC.

show abstract

“…Deamination of daunorubicin (1), doxorubicin (2) and their L-arabino isomers (3,4) resulted in an almost quantitative formation of a single ringcontracted aldehyde (8 and 10, respectively, as reported in Scheme 1) likely because of its high insolubility in the aqueous reaction medium. The formation of ring-contracted aldehydes as major BDF; mice received 10'' ascites cells on day 0 ip or iv.…”

Section: Discussionmentioning

confidence: 99%

New anthracycline glycosides obtained by the nitrous acid deamination of daunorubicin, doxorubicin and their configurational analogues.

et al. 1985

View full text Add to dashboard Cite

The new anthracyclines 7-0-(2,3,5-trideoxy-3-C-formyl-a-L-threo-pentofuranosyl)daunomycinone (8) and -adriamycinone (10) have been obtained upon nitrous acid deamination of daunorubicin and doxorubicin respectively. Deamination of the L-ribo analogue of daunorubicin (6) gave a mixture of 2,3,6-trideoxy-L-glycero-hexopyranosid-4-ulose (a-L-cinerulosyl) (11) and 2,6-dideoxy-a-L-arabino-hexopyranosyl (12) glycosides. The corresponding adriamycinone glycosides 13 and 14, obtained by deamination of the doxorubicin L-ribo analogue 7, were found to display an outstanding antileukemic activity in mice.

show abstract

4′-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data

Cited by 182 publications

References 15 publications

Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention

Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study

New anthracycline glycosides obtained by the nitrous acid deamination of daunorubicin, doxorubicin and their configurational analogues.

Contact Info

Product

Resources

About