Haematologica 2003 - Supplements

9. Chemotherapy, maintenance,
treatment and supportive care
9.1 Chemotherapy
225
The value of anthracycline sparing by the use of weekly
cyclophosphamide after induction with the ABCM
regimen: the results of the VIIIth MRC Myeloma trial
Mark T.Drayson*, Janet A.Dunn , Ian C.M.MacLennan*,
Nicola Barth, Gulnaz Begum
On behalf of the Medical Research Council Working Party for
Leukaemia in adults; *Department of Immunity and Infection,
Cancer Research UK Clinical Trials Unit
This trial compared the efficacy of two cytotoxic chemotherapy
regimens in patients presenting with multiple myeloma, at the age
of 65yrs and over, or patients presenting under the age of 65yrs in
whom intensive chemotherapy was contraindicated. The
treatment options were ABCM to plateau vs 3 courses ABCM
then C-weekly to plateau.
ABCM cycle-time 6weeks – adriamycin 30mg/m2 plus BiCNU
30mg/m2 iv on day one; cyclophosphamide 100mg/m2 plus
melphalan 6mg/m2 orally days 22, 23, 24 & 25.
C-weekly – cyclophosphamide 400mg/m2 orally on first day of
each week; prednisolone 40mg/m2 orally on alternate days for
first 6 weeks.
Observations in the Vth MRC myelomatosis trial and subsequent
pilot studies indicate that changing to weekly cyclophosphamide after
starting treatment with ABCM may be as effective as continuing to
give ABCM until plateau is reached (Lancet, 1992 339: 200-205).
The modified treatment: 1) Causes less marrow toxicity than either
conventional melphalan regimens or ABCM. 2) Uses less adriamycin
than continued ABCM and so is less cardiotoxic. 3) Improves
treatment options after relapse from plateau. 4) The management of
treatment is easier and less expensive than when ABCM is used until
plateau. Given these advantages a result showing either equal or
improved efficacy of ABCM followed by C weekly would be taken
as an indication for using this modified regimen.
The trial opened for entry on 1 November 1993 and 600 patients
were registered into the study, the last in July 2002. Patients were
randomised after successfully completing three courses of ABCM at
a time that is between 18 and 36 weeks post diagnosis. Of the 600
patients registered, 55% of patients were randomised (163 - C-
weekly and 165 – ABCM). The main reasons for non-randomisation
were early deaths and disease progression or early conversion to C-
weekly because of myelotoxicity in the first 3 courses of ABCM.
Patient characteristics were well balanced between the two treatment
arms of the trial. Of the 328 randomised patients, the median age was
68 years (IQR 65–71 years), 27% were under 65 years, 34%
presented with a Serum β2 microglobulin