Therapeutic activity of mitoxantrone and ametantrone against murine tumors

Schabel, Frank M.; Corbett, T.H.; Griswold, Daniel P.; Laster, W R; Trader, M W

doi:10.1016/0305-7372(83)90017-8

Cited by 18 publications

(3 citation statements)

References 5 publications

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“…Mitoxantrone (Novantrone~-~), has shown cytostatic effects in both animal and in vitro test systems (1,2). In clinical studies, antitumor activity has been demonstrated in patients with advanced breast cancer, lymphoma and leukemia (3)(4)(5)(6)(7).…”

Section: Introduction Methodsmentioning

confidence: 99%

The pharmacokinetics and metabolism of mitoxantrone in man

et al. 1985

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An HPLC method using paired-ion chromatography on RP C-18 material was developed. After sample clean up on XAD columns, mitoxantrone (Novantrone; dihydroxyanthracenedione) in concentrations below 1 ng/ml in serum and 0.2 ng/ml in urine were measurable with a coefficient of variation less than 9.3% at a wavelength of 658 nm. Four metabolites were separated in urine. The major metabolite cochromatographed with the synthesized dicarboxylic acid of mitoxantrone. Within 48 hours 4.4% of the administered dose was excreted in urine as mitoxantrone, 0.5% as metabolite 1 and 0.3% as metabolite 2. The pharmacokinetic parameters are adequately described by a three-compartment model with a terminal half-life of 214.8 hours, and a volume of distribution (ss) of 3792 litres. The total body clearance was 358 ml/min and the renal clearance was 26.2 ml/min.

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Section: Introduction Methodsmentioning

confidence: 99%

The pharmacokinetics and metabolism of mitoxantrone in man

et al. 1985

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“…Mitoxantrone (Novantrone| dihydroxyanthracencdione) is a new substituted anthraquinone with marked antitumor activity in mouse tumor systems (3), as well as in human tumors, including breast cancer (4). Its efficacy in patients with breast cancer, as defined by several phase II studies, is comparable with that of other single agents, including doxorubicin (4)(5)(6).…”

Section: Introductionmentioning

confidence: 82%

First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer

Periti¹,

Cuna²,

Pannuti³

et al. 1985

Invest New Drugs

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In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate was 43%; five of 30 patients (16%) attained a complete remission, and eight of 30 (27%) had a partial remission. Median response duration was 12+ months. The greater number of responses was seen in skin and soft tissues. Hematologic toxicity was limiting with 75% of patients experiencing substantial-severe leukopenia. Clinically evident heart failure developed in one patient; in three other patients there was minor-moderate alteration of cardiac function during mitoxantrone-cyclophosphamide therapy. Based on these data, it is believed that this regimen may provide significant long-lasting palliation in patients with advanced breast cancer.

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“…A synergistic interaction between FUra and cis-DDP has been reported in murine leukemic cells in culture (6,7) as well as in animals bearing tumors (8,9). Received: 7/31/89 Accepted: 9/11/89 Scanlon and his co-workers (10) provided evidence that in vitro potentiation of the FUra cytotoxicity by pre-treatment with cis-DDP was due to augmentation of the dTMP-S fol ate cofactor pools in ovarian carcinoma cells.…”

mentioning

confidence: 98%

The Role of Drug Sequence in Therapeutic Selectivity of the Combination of 5-Fluorouracil and Cis-Platin

Palmeri¹,

Trave²,

Russello³

et al. 1989

Selective Cancer Therapeutics

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The therapeutic efficacy of 5-fluorouracil (FUra) and cis-dichlorodiamine-platinum (cis-DDP) in mice bearing transplantable leukemia and solid tumors was evaluated using different sequences of combination of these agents. The optimal sequence was cis-DDP administered 24 h after FUra. The administration of FUra at its maximally tolerated dose (MTD) followed 24 h later by low doses of cis-DDP yielded less toxicity and higher response rate against L1210 and colon 26 than the administration of these two agents in the opposite sequence or concurrently at the MTD. The sequence of administration of these two agents was not therapeutically important when the antitumor activity was evaluated against mice bearing lymphoma P388. These results indicate that the importance of sequencing of FUra and cis-DDP varies among different tumors. The biochemical basis for the therapeutic importance of sequencing in treatments with cis-DDP and FUra was investigated in mice bearing leukemia L1210 cells. While cis-DDP has no significant effects on the activity of thymidylate synthase (dTMP-S), the target enzyme for FUra action, recovery of dTMP-S inhibition following pretreatment with FUra was significantly delayed when cis-DDP was administered 12-24 h after the initial dose of FUra.

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Therapeutic activity of mitoxantrone and ametantrone against murine tumors

Cited by 18 publications

References 5 publications

The pharmacokinetics and metabolism of mitoxantrone in man

The pharmacokinetics and metabolism of mitoxantrone in man

First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer

The Role of Drug Sequence in Therapeutic Selectivity of the Combination of 5-Fluorouracil and Cis-Platin

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