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Cardiotoxicity after liposomal anthracyclines
Reflection & Reaction
3 Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429: 457–63. 4 Issa JP, Garcia-Manero G, Giles FJ, et al. Phase I study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2⬘deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; 103: 1635–40. 5 Pakneshan P, Szyf M, Farias-Eisner R,
Rabbani SA. Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. J Biol Chem 2004; 279: 31735–44. 6 Szyf M, Pakneshan P, Rabbani SA. DNA demethylation and cancer:therapeutic implications. Cancer Lett 2004; 211: 133–43. 7 Mette MF, Aufsatz W, van der Winden J, et al. Transcriptional silencing and promoter methylation triggered by
double-stranded RNA. EMBO J 2000; 19: 5194–201. 8 Park CW, Chen Z, Kren BT, Steer CJ. Double-stranded siRNA targeted to the huntingtin gene does not induce DNA methylation. Biochem Biophys Res Commun 2004; 323: 275–80. 9 Zender L, Hutker S, Liedtke C, et al. Caspase 8 small interfering RNA prevents acute liver failure in mice. Proc Natl Acad Sci USA 2003; 100: 7797–802.
Cardiotoxicity after liposomal anthracyclines There is always a danger in claiming to be the first person to observe an event, even in Case reports. Jones and colleagues,1 in a recent issue of The Lancet Oncology, have fallen into this trap by claiming delivery of the highest cumulative dose of liposomal doxorubicin, with no clinical or pathological evidence of cardiac failure. Liposomal anthracyclines were first used widely in the early 1990s for treatment of AIDS-associated Kaposi’s sarcoma (AIDS-KS), before the introduction of highly active antiretroviral therapy. During this era, many patients were given extended courses of liposomal anthracyclines. Indeed, the medical published work includes evidence of patients receiving up to 2749 mg/m2 liposomal daunorubicin and up to 1040 mg/m2 pegylated liposomal doxorubicin without any cardiotoxicity.2,3 The myocardial effects of these cumulative liposomal anthracyclines were investigated by taking endomyocardial biopsy samples and assessing the tissue by use of the Billingham scale. The median
biopsy scores for ten patients with AIDS-KS given pegylated liposomal doxorubicin (cumulative doses of 440–840 mg/m2) were significantly lower than those for historical controls who had received doxorubicin.4 Nevertheless, we support the observations of Jones and colleagues, and others, of the very low incidence of cardiotoxicity despite high cumulative doses of liposomal anthraclines. To date, we have treated 93 patients with AIDS-KS (90 males, two females, one gender reassignment) with lipsomal anthracyclines; the median age of these patients is 37 years (range 24–62). Liposomal anthracyclines were used as first-line systemic chemotherapy for 78 patients (58 liposomal daunorubicin, 30 pegylated liposomal doxorubicin, and five both agents). The patients received a median cumulative dose of 120 mg/m2 (range 20–520) for liposomal daunorubicin and of 240 mg/m2 (80–760) for pegylated liposomal doxorubicin. The maximum cumulative dose delivered to a one of our patients was 640 mg/m2 liposomal daunorubicin
plus 160 mg/m2 pegylated liposomal doxorubicin. We have not recorded any clinically significant episodes of cardiotoxicity in this cohort of patients, and the actuarial 5-year survival from starting liposomal anthracycline chemotherapy is 73% (95% CI 61–85). Anne Marie Young, Tony Dhillon, and Mark Bower Department of Oncology, Chelsea and Westminster Hospital, London, UK. References
1 Jones RL, Berry GJ, Rubens RD, Miles DW. Clinical and pathological absence of cardiotoxicity after liposomal doxorubicin. Lancet Oncol 2004; 5: 575–77. 2 Rosenthal E, Poizot-Martin I, Saint-Marc T, et al. Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma. Am J Clin Oncol 2002; 25: 57–59. 3 Hengge UR, Esser S, Rudel HP, Goos M. Long-term chemotherapy of HIV-associated Kaposi’s sarcoma with liposomal doxorubicin. Eur J Cancer 2001; 37: 878–83. 4 Berry G, Billingham M, Alderman E, et al. The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi’s sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol 1998; 9: 711–16.
If you would like to respond to an article in The Lancet Oncology, or share your views on a current topic of interest or concern in oncology, please email your submission to the Editor at: [email protected]
654
Oncology Vol 5 November 2004
http://oncology.thelancet.com
For personal use. Only reproduce with permission from Elsevier Ltd
3 Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429: 457–63. 4 Issa JP, Garcia-Manero G, Giles FJ, et al. Phase I study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2⬘deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; 103: 1635–40. 5 Pakneshan P, Szyf M, Farias-Eisner R,
Rabbani SA. Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. J Biol Chem 2004; 279: 31735–44. 6 Szyf M, Pakneshan P, Rabbani SA. DNA demethylation and cancer:therapeutic implications. Cancer Lett 2004; 211: 133–43. 7 Mette MF, Aufsatz W, van der Winden J, et al. Transcriptional silencing and promoter methylation triggered by
double-stranded RNA. EMBO J 2000; 19: 5194–201. 8 Park CW, Chen Z, Kren BT, Steer CJ. Double-stranded siRNA targeted to the huntingtin gene does not induce DNA methylation. Biochem Biophys Res Commun 2004; 323: 275–80. 9 Zender L, Hutker S, Liedtke C, et al. Caspase 8 small interfering RNA prevents acute liver failure in mice. Proc Natl Acad Sci USA 2003; 100: 7797–802.
Cardiotoxicity after liposomal anthracyclines There is always a danger in claiming to be the first person to observe an event, even in Case reports. Jones and colleagues,1 in a recent issue of The Lancet Oncology, have fallen into this trap by claiming delivery of the highest cumulative dose of liposomal doxorubicin, with no clinical or pathological evidence of cardiac failure. Liposomal anthracyclines were first used widely in the early 1990s for treatment of AIDS-associated Kaposi’s sarcoma (AIDS-KS), before the introduction of highly active antiretroviral therapy. During this era, many patients were given extended courses of liposomal anthracyclines. Indeed, the medical published work includes evidence of patients receiving up to 2749 mg/m2 liposomal daunorubicin and up to 1040 mg/m2 pegylated liposomal doxorubicin without any cardiotoxicity.2,3 The myocardial effects of these cumulative liposomal anthracyclines were investigated by taking endomyocardial biopsy samples and assessing the tissue by use of the Billingham scale. The median
biopsy scores for ten patients with AIDS-KS given pegylated liposomal doxorubicin (cumulative doses of 440–840 mg/m2) were significantly lower than those for historical controls who had received doxorubicin.4 Nevertheless, we support the observations of Jones and colleagues, and others, of the very low incidence of cardiotoxicity despite high cumulative doses of liposomal anthraclines. To date, we have treated 93 patients with AIDS-KS (90 males, two females, one gender reassignment) with lipsomal anthracyclines; the median age of these patients is 37 years (range 24–62). Liposomal anthracyclines were used as first-line systemic chemotherapy for 78 patients (58 liposomal daunorubicin, 30 pegylated liposomal doxorubicin, and five both agents). The patients received a median cumulative dose of 120 mg/m2 (range 20–520) for liposomal daunorubicin and of 240 mg/m2 (80–760) for pegylated liposomal doxorubicin. The maximum cumulative dose delivered to a one of our patients was 640 mg/m2 liposomal daunorubicin
plus 160 mg/m2 pegylated liposomal doxorubicin. We have not recorded any clinically significant episodes of cardiotoxicity in this cohort of patients, and the actuarial 5-year survival from starting liposomal anthracycline chemotherapy is 73% (95% CI 61–85). Anne Marie Young, Tony Dhillon, and Mark Bower Department of Oncology, Chelsea and Westminster Hospital, London, UK. References
1 Jones RL, Berry GJ, Rubens RD, Miles DW. Clinical and pathological absence of cardiotoxicity after liposomal doxorubicin. Lancet Oncol 2004; 5: 575–77. 2 Rosenthal E, Poizot-Martin I, Saint-Marc T, et al. Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma. Am J Clin Oncol 2002; 25: 57–59. 3 Hengge UR, Esser S, Rudel HP, Goos M. Long-term chemotherapy of HIV-associated Kaposi’s sarcoma with liposomal doxorubicin. Eur J Cancer 2001; 37: 878–83. 4 Berry G, Billingham M, Alderman E, et al. The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi’s sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol 1998; 9: 711–16.
If you would like to respond to an article in The Lancet Oncology, or share your views on a current topic of interest or concern in oncology, please email your submission to the Editor at: [email protected]
654
Oncology Vol 5 November 2004
http://oncology.thelancet.com
For personal use. Only reproduce with permission from Elsevier Ltd