1 / 22

Dottor Liberato Di Lullo Direttore U.O.C. DI ONCOLOGIA P.O. “F. Veneziale” Isernia e P.O. “A. Cardarelli” CB Chieti,

La doxorubicina liposomiale non pegilata nel MBC: dati della letteratura in vari profili di pazienti (naive, pretrattata, anziana). Dottor Liberato Di Lullo Direttore U.O.C. DI ONCOLOGIA P.O. “F. Veneziale” Isernia e P.O. “A. Cardarelli” CB Chieti, 11 Dicembre 2012.

gabi
Download Presentation

Dottor Liberato Di Lullo Direttore U.O.C. DI ONCOLOGIA P.O. “F. Veneziale” Isernia e P.O. “A. Cardarelli” CB Chieti,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. La doxorubicina liposomiale non pegilata nel MBC: dati della letteratura in vari profili di pazienti (naive, pretrattata, anziana) Dottor Liberato Di Lullo Direttore U.O.C. DI ONCOLOGIA P.O. “F. Veneziale” Isernia e P.O. “A. Cardarelli” CB Chieti, 11 Dicembre 2012

  2. RISK FACTORS FOR THE DEVELOPMENT OF CHRONIC ANTHRACYCLINE CARDIOTOXICITY (1) • A number of risk factors for the development of chronic anthracycline cardiotoxicity have been identified. The strongest predictor is cumulative dose • Cumulative dose:The development of anthracycline-related cardiotoxicity is strongly correlated to cumulative dose. Based upon these observations, it has been generally recommended that cumulative doxorubicin doses be limited to 450 to 500 mg/m2 in adults. However, there is variable sensitivity to anthracyclines among patients, with some tolerating doses as high as 1000 mg/m2, and others experiencing cardiotoxicity at doses lower that 300 mg/m2. Early data suggest that inherited polymorphisms in one of the carbonyl reductase genes that catalyze the metabolism of anthracyclines to cardiotoxic metabolites may be involved.  • Age: age extremes predispose to cardiotoxicity at lower cumulative anthracycline dose. In older patients, preexisting heart disease (including hypertension) is a risk factor for anthracycline cardiotoxicity. However, it is not clear whether pre-existing heart disease increases susceptibility to anthracycline-induced damage, or whether there is less functional reserve to tolerate additional myocardial damage

  3. Radiation therapy: prior mediastinal irradiation may increase the susceptibility to anthracycline cardiotoxicity by inducing endothelial cell damage and compromising coronary artery blood flow. This risk of cardiotoxicity is particularly important in women who have received prior chest wall irradiation for left-sided breast cancer. Concurrent irradiation also increases risk • Longer duration of survival: is also a risk factor for cardiac toxicity, emphasizing the importance of monitoring for long-term effects in the growing population of cancer survivors • Concomitant chemotherapy: the administration of nonanthracycline agents that also cause cardiotoxicity may result in synergistic toxicity when anthracyclines are given concurrently. The most important agents in this regard are the taxanes (paclitaxel, docetaxel) and trastuzumab • Hematopoietic cell transplantation: The combination of cyclophosfamide and total body radiation prior to bone marrow transplantation is itself capable of causing myocardial damage. Thus, in patients with prior anthracycline treatment or mediastinal radiation, the risks of developing cardiotoxicity at the time of bone marrow transplantation are even greater N Engl J Med. 1998;339(13):900; Am J Med. 1977;62(2):200 Ann Intern Med. 1979;91(5):710; J Clin Oncol. 2008;26(19):3159 J Clin Oncol. 2007;25(25):3991; Ann Intern Med. 1996;125(1):47 Cancer. 2003;97(11):2869; J Clin Oncol. 1998;16(11):3493 J Clin Oncol. 2008;26(34):5537

  4. Annals of Oncology 22: 257-267, 2011

  5. NPLD: Phase II Trials in MBC 1) monochemotherapy 60mg/m2well tolerated 2) monochemotherapy 75mg/m2well tolerated 3) 60mg/m2 + 5FU + CFwell tolerated 4) monochemioterapia 135 mg/m2 severe neutropenia LOWER CARDIAC TOXICITY RR PFS TTF = doxorubicin Dose for phase III trials: 75 mg/m2 in monotherapy, 60 mg /m2 in combination 1) Batist et al, 1992 - 2) Ervin data on file - 3) Valero et al, 1999 - 4) Shapiro et al, 1999 adapted

  6. NPLD: Phase III Trials in MBC Vs doxorubicin – naïve and pre-treated patients Vs epirubicin – naïve patients Vs doxorubicin – only pre-treated adapted

  7. FIRST LINE IN MBC HER2 - Author Pts Drugs %RR mOS (m) ------------------------------------------------------------------------- Schmid 51 My+DTX 50 25 Curtit 34 My+DTX 79 28.2 Del Barco 53 My+GEM 51 25.4 Livi 34 My+DTX/CYC 71 -- Rosati 56 wMy+DTX/TAX 73 23 Valero 51 My+CYC+FU 73 19.4

  8. M. S. Rosati et al Endpoint I: CB e toxicity Endpoint II: TTP e OS Combined weekly administration of taxane and NPLD is well tolerated and CB data encourage phase III study design

  9. E. Curtit et al

  10. L’associazione di antracicline e trastuzumab mostra attività clinica significativa… Pivotal phase III combination trial (H0648g), IHC 3+ H = Herceptin; AC = anthracycline/cyclophosphamide Slamon D, et al. N Engl J Med 2001; 344: 783 – 92 Smith I. Anticancer Drugs 2001; 12:S3 - 10

  11. . . . ma anche un tasso elevato di cardiotossicità 30 25 20 15 10 5 0 + AC + Other CT + Cisplatin +Paclitaxel Trastuzumab Modified from Seidman A et al J Clin Oncol 20(5):1215-1221, 2001

  12. FIRST LINE IN MBC HER2 + Author Pts Drugs %RR < LVEF ---------------------------------------------------------------- Theodoulou 40 My+T 50 13% Venturini 31 My+DTX+T 65 9.7% Amadori 52 My+DTX+T 55 8% Cortes 37 My+TAX+T 96 17%

  13. RECHALLENGE WITH ANTHRACYCLINE • rechallenge with anthracyclines remains an option for metastatic breast cancer patients, provided relapse-free survival is >1 year after the end of adjuvant anthracycline-containing chemotherapy • may be appropriate in symptomatic patients, requiring a rapid response • published data indicating that re-treatement with anthracyclines in the metastatic setting is active also in anthracycline-pretreated patients, but discouraged by the risk of cardiotoxicity associated with high cumulative doses • NPLD is associated with a significantly reduced risk of cardiotoxicity compared with conventional doxorubicin, even in patients with prior anthracycline exposure Airoldi el al, Tumori 2011; 97 (6): 690-692

  14. CLINICAL RECOMMENDATIONS • NPLD can be safely administered up to high cumulative doses and may represent an attractive drug for patients requiring anthracycline rechallenge • NPLD may be used in HER2-negative patients in combination with taxanes, as this is a viable option in clinical practice • NPLD in combination with cyclophosphamide may be used as a first-line metastatic option due to the low cardiotoxic potential, which allows higher cumulative anthracycline dosages • NPLD can be also considered in anthracycline-pretreated patients in subsequent lines of treatment if sequential monochemotherapy is the preferred choice Airoldi el al, Tumori 2011; 97 (6): 690-692

  15. CONCLUSIONS • NPLD is a viable option in breast cancer • NPLD use should be preferred to conventional anthracyclines, especially in those patients at risk of developing cardiotoxicity • Patients candidate to rechallenge with anthracyclines after adjuvant administration could be suitable for NPLD due to the possibility of a more prolonged treatment, not limited by cumulative dosages Airoldi el al, Tumori 2011; 97 (6): 690-692

  16. GRAZIE PER L’ATTENZIONE….

More Related