The results showed that adult patients with previously untreated acute promyelocytic leukaemia (APL) who had standard chemotherapy to induce remission of their disease, and then received the chemotherapy drug arsenic trioxide to maintain remission, had a significantly better event-free survival (more patients free of leukaemia) and better overall survival than those who received only standard chemotherapy.
The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and was led by one of its cooperative clinical trials groups -- the Cancer and Leukaemia Group B (CALGB).
"The positive result in a clinical trial of a common element holding an uncommon disease in remission for a significant period of time is very encouraging," said NIH Director Elias A Zerhouni, MD.
Acute promyelocytic leukaemia, an uncommon subtype of acute myeloid leukaemia (AML), accounts for approximately 10 per cent of AML cases, or about 1,500 cases per year, in the United States. It is most often diagnosed in young and middle aged adults, but it also occurs in children and older adults.
Standard chemotherapy regimens produce complete remission rates of approximately 70 per cent and show a five-year survival without the recurrence of disease in 35 to 45 per cent of patients.
"Achieving success in a clinical trial for a rare cancer is a difficult task due to the limited number of patients eligible to enrol in the trial, so this is very encouraging news for all patients with this form of leukaemia," said NCI director John Niederhuber, MD. "This positive outcome demonstrates, yet again, the benefits of clinical trials and will hopefully serve as encouragement for others to join such trials."
This particular type of leukaemia is often accompanied by life-threatening bleeding at diagnosis that typically worsens, even as initial treatment is administered. Treatment has improved dramatically in recent years with the addition of all-trans retinoic acid (ATRA, or tretinoin) to chemotherapy. More recently, arsenic trioxide (Trisenox ) was shown to be an effective drug for producing a second remission in patients who had a relapse or recurrence of their APL after initial treatment. Both ATRA and arsenic trioxide are approved by the US Food and Drug Administration for the treatment of APL.
The CALGB-coordinated study tested the effectiveness and side effects from adding two 25-day courses of intravenous arsenic trioxide to the combination of ATRA and chemotherapy. Patients with newly diagnosed APL were randomly assigned to receive either the standard remission treatment with ATRA twice daily, daunorubicin for four days, and cytarabine for seven days, both of which are standard chemotherapy drugs for this disease, followed by a standard post-remission regimen with two more courses of ATRA plus daunorubicin.
The experimental treatment where patients received the same standard treatment with the addition of two courses of arsenic trioxide given immediately after the patient entered a complete or partial remission and before the standard post-remission regimen. The arsenic trioxide course was a two-hour intravenous infusion, Monday through Friday, on an outpatient schedule for five weeks. Patients who remained free of visible leukaemia after completio!
The percentage of adult patients who remained alive and in remission -- free of relapse of their leukaemia -- three years after diagnosis was 77 per cent on the treatment arm that included arsenic trioxide compared to 59 per cent on the standard treatment arm. This difference was highly statistically significant. The greater effectiveness of the experimental combination also resulted in better overall survival after three years of 86 per cent for the patients who received the arsenic trioxide compared to 77 per cent for patients on the standard treatment arm.
Patients were followed for a median period of 29 months. After reviewing the study results, a data safety monitoring board notified the investigators and the NCI of the positive results, and the findings are being released so that all APL patients will have a chance to benefit from this therapy.
Bayard Powell, MD, Wake Forest University, Winston-Salem, NC, principal investigator of the study, said, "The willingness of patients with leukaemia and their physicians to participate in this important clinical trial has markedly improved the outcome for these and future patients with APL."
The side effects from treatment were reported at the annual meeting of the American Society of Hematology in Orlando. There was no difference in haematological (blood count) toxicities between the group who received arsenic and those who did not, but there was a slightly higher incidence of headache and infection in the group who received arsenic trioxide.
Richard Larson, MD, University of Chicago, a co-investigator of the study, noted, "These results indicate that arsenic trioxide should be considered as part of the initial treatment of patients with acute promyelocytic leukaemia."