Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia

Cancer. 2007 Apr 1;109(7):1355-9. doi: 10.1002/cncr.22524.

Abstract

Background: From 20% to 30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) develop recurrent disease. Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL.

Methods: The authors investigated the efficacy of a combination of ATO, ATRA, and GO in 8 patients with APL in first recurrence (7 patients with hematologic recurrences and 1 patient with a molecular recurrence). All patients had received previous treatment with ATRA either alone or in combination with other agents. Patients received ATO 0.15 mg/kg intravenously until they achieved a bone marrow complete remission (CR). Once in CR, patients received consolidation with ATO, ATRA, and GO for 10 months. Patients then received maintenance with idarubicin, ATRA, 6-marcaptopurine, and oral methotrexate for 11 months.

Results: All 7 patients who had hematologic recurrences achieved CR after a median of 39 days (range, 21-56 days). After a median follow-up of >/=36 months (range, 4-55 months), 6 patients remained alive in CR, and 2 patients died in CR. Six of 8 patients remained in second CR that was longer than their first CR. All 7 evaluable patients achieved molecular remission. There were no grade 3 or 4 extramedullary toxicities. Two patients died, 1 secondary to a complication of metastatic lung adenocarcinoma, and the other of sepsis.

Conclusions: The combination of ATO, ATRA, and GO was effective and may achieve durable remissions in patients with APL in first recurrence. It should be considered as an effective alternative to allogeneic or autologous transplantation.

MeSH terms

  • Adult
  • Aged
  • Aminoglycosides / administration & dosage
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arsenic Trioxide
  • Arsenicals / administration & dosage
  • Gemtuzumab
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Oxides / administration & dosage
  • Remission Induction
  • Treatment Outcome
  • Tretinoin / administration & dosage

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Arsenicals
  • Oxides
  • Tretinoin
  • Gemtuzumab
  • Arsenic Trioxide