Adriamycin cardiomyopathy—risk factors

Minow, Robert A.; Benjamin, Robert S.; Lee, Elisa T.; Gottlieb, Jeffrey A.

doi:10.1002/1097-0142(197704)39:4<1397::aid-cncr2820390407>3.0.co;2-u

Cited by 234 publications

(83 citation statements)

References 8 publications

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“…In the case of doxorubicin and cisplatin, side effects such as cardiomyopathy (doxorubicin) and nephrotoxicity (cisplatin) have been partly attributed to high levels of peak free drug (Minow et al, 1977;Nagai et al, 1986). In a study by Nagai et al (1986), the plasma C max of ultrafiltrated Pt was the most useful pharmacokinetic marker for cisplatin nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

et al. 2006

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To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0 -2. The first cohort received SPI-77 at 100 mg m À2 , the second 200 mg m À2 and the final cohort 260 mg m À2 . Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m À2 dose level for an overall response rate of 4.5% (7.1% at X200 mg m À2 ). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.

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Section: Discussionmentioning

confidence: 99%

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

et al. 2006

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“…It is used for the treatment of a wide range of malignant diseases ranging from the leukaemias to solid tumours such as lung and ovarian carcinomas (Davis & Davis 1979). The major dose-limiting toxicity of ADM is cardiomyopathy which appears to be dependent upon the total accumulated drug dose (Minow et al, 1975). There is also a variety of evidence which suggests that clinical effectiveness of ADM may be limited by the development of cellular resistance to the drug (Hubbard et al, 1978;Kaye & Merry, 1985).…”

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confidence: 95%

The in vitro effects and cross-resistance patterns of some novel anthracyclines

Twentyman¹,

Fox²,

Wright³

et al. 1986

Br J Cancer

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Summary A range of new anthracyclines, structurally related to adriamycin (ADM), has been synthesised and studied in vitro. Three compounds described in this paper (Ro 31-1215; Ro 31-1741; Ro 31-2035) are all 4-demethoxyanthracyclines. In the mouse mammary tumour cell line, EMT6/Ca/VJAC, using a 1 h drug exposure followed by colony formation as the response endpoint, we found Ro 31-1215 and Ro 31-1741 to be 2-3 x and 4-7 x more potent then ADM, whilst Ro 31-2035 was 3-4 x less potent. For continuous drug exposure and suppression of population growth as the endpoint, the potency of Ro 31-1741 was similar to that of ADM, whereas that of Ro 31-1215 was 1.5-2 x higher and that of Ro al., 1978;Kaye & Merry, 1985). The mechanism of such resistance is currently the subject of much ongoing laboratory work and a variety of strategies for overcoming resistance are being investigated (Tsuruo et al., 1983;Skovsgaard et al., 1984).Over the last 10 years a large number of analogues of ADM have been produced with the major objective of finding a drug which is less cardiotoxic for a given amount of anti-tumour effect (Naff et al., 1982

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“…Among this class of compounds, doxorubicin has shown significant activity against a wide range of human cancers, including leukaemia, lymphomas and a variety of solid tumours (Tan et al, 1973;Frederickson et al, 1974). Unfortunately, the clinical use ofthe agent is limited by an unusual cardiomyopathy, which is related to the total cumulative dose of the drug (Minow et al, 1977). Doxorubicin also produces acute toxicity in the form of bone marrow depression, alopecia and oral ulceration (O'Bryan et al, 1977).…”

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confidence: 99%