Successful second-line therapy for relapsed or refractory APL
Clinical studies have demonstrated the important role arsenic trioxide may have in the treatment
of patients with relapsed or refractory acute promyelocytic leukemia (APL). When initial
therapies fail, TRISENOX
® (arsenic trioxide) injection has shown to be a successful second-line
therapy.
Current first-line therapy for APL
In the past, APL was associated with a high risk of early mortality, but with the introduction of
all-trans retinoic acid (ATRA), APL has become the most curable subtype of acute myeloid leukemia
(AML).
1
Multiple studies have established that the combination of ATRA and chemotherapy in newly
diagnosed patients has increased the cure rate to 70% from 35% in patients treated with
chemotherapy alone.
2 Additionally, the incorporation of ATRA into the treatment regimen has
more than doubled the survival rate of newly diagnosed patients over that achieved with
chemotherapy alone.
3,4-7 Given this success, the current first-line standard
treatment given to patients with newly diagnosed APL consists of ATRA and anthracycline-based
cytotoxic chemotherapy.
8 Daunorubicin and idarubicin are two commonly used anthracyclines
shown to induce complete remission in 60% to 80% of APL patients.
9-11 Patients may
also undergo combination therapy consisting of cytarabine in combination with an anthracycline.
9,12
Relapse and resistance
Despite improvements in remission and survival rates, 20% to 30% of patients relapse and are
often resistant to further treatment with ATRA.
1,2,8
Approximately 50% of the patients in first relapse presently have the chance to achieve
long-lasting second remissions and probably cure with salvage regimens.
1 Salvage
therapy often involves high doses of cytotoxic chemotherapy, followed by either autologous
or allogeneic transplantation. With this approach, these patients are exposed to, and a
certain proportion die from, the toxic effects of chemotherapy, an important consideration
in treating young or elderly patients. Clearly, there remains a critical need for new
therapeutic options in treating relapsed APL.
3
The role of arsenic trioxide
Studies of arsenic trioxide have demonstrated a high rate of complete remission, suggesting that
TRISENOX is an important treatment option for patients who have relapsed from, or did not
respond to, initial therapy.
3,13 According to the National Comprehensive Cancer
Network (NCCN) guidelines for oncology, arsenic trioxide is the standard of care for patients
who have relapsed from, or did not respond to, their initial treatment.
14
>> Click here to view the efficacy data for TRISENOX.
TRISENOX is indicated for induction of remission and consolidation in patients with APL who are
refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is
characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
1. Lengfelder E, Saussele S, Weisser A, et al. Treatment concepts of acute promyelocytic leukemia. Crit Rev Oncol Hematol. 2005;56:2:261-274.
2. Douer D. Advances in the treatment of relapsed acute promyelocytic leukemia. Acta Haematol. 2002;107:1-17.
3. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852-3860.
4. Soignet S, Fleishauer A, Polyak T, et al. All-trans retinoic acid significantly increases 5-year survival in patients with acute promyelocytic leukemia: long-term follow-up of the New York study. Cancer Chemother Pharmacol. 1997;40 Suppl:S25-S29.
5. Tallman MS, Anderson JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337:1021-1028.
6. Fenaux P, Chastang C, Chevret S, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192-1200.
7. Warrell RP Jr, de The H, Wang ZY, et al. Acute promyelocytic leukemia. N Engl J Med. 1993;329:177-189.
8. Soignet SL. Clinical experience of arsenic trioxide in relapsed acute promyelocytic leukemia. Oncologist. 2001;6 Suppl 2:11-16.
9. Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2003:82-101.
10. Bernard J, Weil M, Boiron M, et al. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood. 1973;41:489-496.
11. Avvisati G, Mandelli F, Petti MC, et al. Idarubicin (4-demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: a pilot study of the Italian cooperate group GIMEMA. Eur J Haematol. 1990;44:257-260.
12. Petti MC, Avvisati G, Amadori S, et al. Acute promyelocytic leukemia: clinical aspects and results of treatment in 62 patients. Haematologica. 1987;72:151-155.
13. Soignet SL, Maslak P, Wang Z-G, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341-1348.
14. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia — v.2.2007.