A randomized trial of cytarabine with high-dose mitoxantrone compared to a standard vincristine/prednisone-based regimen as induction therapy for adult patients with ALL

Reviewer: Ryan Smith , MD
OncoLink
Ultima Vez Modificado: 16 de mayo del 2005

Share article


Presenter: M.A. Weiss
Presenter's Affiliation: Memorial Sloan-Kettering Cancer Center
Type of Session: Scientific

Background

  • Induction therapy for adult ALL is similar across most regimens
  • The most commonly used regimens employ vincristine, a corticosteroid, an anthracycline, with either cyclophosphamide or aspariginase or both added
  • There are known adverse prognostic factors in ALL, including a high white blood cell count, older age, Philadelphia chromosome positivity (Ph+), and slow response to therapy defined as time to complete response (CR) of > 5 weeks
  • The time to CR is the only prognostic factor that can be controlled by therapy
  • The authors had previously tried cytarabine and mitoxantrone as an induction regimen, which seemed to be superior in terms of CR rates, failure with resistant disease, and activity in Ph+ patients
  • This study reports on a randomized trial comparing this novel induction therapy to a more widely accepted startegy

Materials and Methods

  • 154 patients were randomized to one of two arms
  • The experimental arm (ALL-2) consited of an induction regimen using cytarabine (3 mg/m2) IV over 3 hours days 1-5 and mitoxantrone (80 mg/m2) on day 3 along with intrathecal methotrexate and GM-CSF
  • The accepted arm (L-20) consisted of vincristine, prednisone, cyclophosphamide, and doxorubicin
  • Both arms then underwent a consolidation phase, maintenance phase and CNS prophylaxis
  • Patients had a median age of 43 and were well-balanced in age, WBC count, Ph + patients, and T cell disease

Results

For all results, the ALL-2 arm, with cytarabine and mitoxantrone, is listed first

  • CR rate was 83% vs. 71%
  • Deaths during the induction phase was 9% vs. 8%
  • Recurrence with resistant disease was 8% vs. 21%
  • Time to CR was 32 days vs 55 days
  • 5 year OS was 34% vs. 21%
  • CR in Ph+ patients was 85% vs. 47%
  • 6 year Ph + survival 26% vs 0
  • Patients with serious adverse events were 56% vs 45%
  • All were statistically significant except deaths during induction phase and 5 year OS

Author's Conclusions

  • This induction therapy of cytarabine and mitoxantrone was superior in terms of frequency of CR, failure with resistant disease, efficacy in Ph + patients, and with a trend toward improved 5 year survival
  • It was well-tolerated, with similar treatment death rate and serious adverse events
  • More follow up is needed to determine survival

Clinical/Scientific Implications
Many induction therapies have been tried, with similar results.  In these studies, there is much more of an effect of patient characteristics, most notably patient age, than treatment effects.  This study had a much older median age of patients (43 years) compared to prior studies with excellent results.  Perhaps the best data is that of a short time to CR, as this is prognostic for these patients.  Obviously more follow up is needed, as it appeared that the survival curves continue to separate despite the current nonsignificant overall survival results. Confirmation trials are needed, but this induction regimen seems to have promise, especially in patients with + Philadelphia chromosome.  Notably, this trial took 7 years to accrue 154 patients, which speaks to the fact that more collaboration needs to be done to complete important studies such as this.



I Wish You Knew

How cancer patients have changed my life

View More



Blogs and Web Chats

OncoLink Blogs give our readers a chance to react to and comment on key cancer news topics and provides a forum for OncoLink Experts and readers to share opinions and learn from each other.




OncoLink OncoPilot

Frente a un nuevo diagnóstico de cáncer o de cambiar el curso de su tratamiento actual? Deje que nuestro personal de enfermería cáncer que ayudan a pasar!

Más información