Info

Regimen

Drugs

Doses

Frequency

Doxorubicin

Dexamethasone

(alternatively, DEX on days

1-4 and 14-18 every cycle, using a q 28 day schedule)

q 28-35 d

Bolus VAD16

4 Vincristine Doxorubicin Dexamethasone

0.4 mg/day, CIV, days 1-4 9 mg/m2/day, CIV, days 1-4 40 mg/day, days 1-4, 9-12, 17-20 (odd cycles) days 1-4, 14-18 (even cycles)

q 28-35 d

DVd49

Liposomal Doxorubicin (Doxil)

Vincristine

Dexamethasone

40 mg/m2, IVPB, day 1 2 mg IVP, day 1 40 mg/day, PO/IV, days 1-4

q 28 days

VAMP42 (C-VAMP)

Vincristine Doxorubicin Methylprednisolone (add Cyclophosphamide)

0.4 mg/day, CIV, days 1-4 9 mg/m2/day, CIV, days 1-4 1 g, IV/PO, days 1-5 (500 mg/m2 IVPB, days 1, 8, 15)

q 28 days

Vincristine

Dexamethasone

9 mg/m2/day, CIV, days 1-4 0.4 mg/day, CIV, days 1-4 40 mg/day, days 1-4, 9-12, 17-20

q 35 days

Mitoxantrone

Dexamethasone

0.4 mg/day, CIV, days 1-4 3 mg/m2/day, CIV, days 1-4 40 mg/day, days 1-4

q 28 days

VECD50

Vincristine Epirubicin Cyclophosphamide Dexamethasone

1.5 mg IVP, day 1 20 mg/m2 IVP, days 2, 3 200 mg/m2 IVPB, days 1-3 20 mg/m2 PO/IV, days 1-5

q 28 days

VID54

Vincristine Idarubicin (oral) Dexamethasone

40 mg/d PO/IV, days 1-4, 9-12, 17-20

q 28 days

Z-Dex53 Idarubicin (oral) 10 mg/m2 PO, days 1-4 q 28 days

Dexamethasone 40 mg/d PO/IV, d 1-4

Z-Dex53 Idarubicin (oral) 10 mg/m2 PO, days 1-4 q 28 days

Dexamethasone 40 mg/d PO/IV, d 1-4

elderly patients and other patients not going on to HDC/ASCS (see discussion below).

Oral cyclophosphamide (Cytoxan), with or without steroids, has been shown to be equally effective as oral melphalan.21' 22 Intravenous (IV) cyclophosphamide, 600-1200 mg/m2 every 3-6 weeks, is effective therapy and is also a viable alternative to oral melphalan.23, 24 More intensive IV cyclophosphamide dosing, such as 600 mg/m2/day for four consecutive days, is feasible25 but not typically considered because of the effectiveness of less-toxic lower doses. Very high-dose IV cyclophosphamide (i.e., 4-7 g/m2 followed by G-CSF or GM-CSF) is often used after induction to mobilize stem cells for collection prior to HDC/ASCS.26-28 It is likely that high-dose cyclophosphamide priming provides additional antimyeloma effect beyond that achieved by prior induction therapy,29 though there is no evidence that this results in any benefit over priming with growth factors alone in terms of transplant outcome.30

Many alkylator-based combination chemotherapy regimens have been evaluated and compared to MP. A meta-analysis showed no difference in response duration or OS in more than 6600 patients participating in 27 randomized trials,20 but two particular regimens warrant comment. The M2 regimen (see Table 83.1) generated interest in the United States after an Eastern Cooperative Oncology Group (ECOG) randomized trial demonstrated modest superiority over MP.31 Objective responses occurred in more than 70% of patients receiving M2, but 5-year OS was an unimpressive 26%. In contrast, a European study comparing VAD and M2 did not demonstrate superior response rate or OS for the 46 patients treated with M2.32 Interest in this regimen may be revived somewhat by the recent report of the US Intergroup study comparing VAD followed by two cycles of M2 versus VAD followed by HDC/ASCS in more than 800 patients, discussed in detail below, in which patients treated with

M2, had equivalent overall outcomes to those getting HDC/ASCS.33 VMCP alternating with VBAP (VMCP/ VBAP, Table 83.1) was used in the positive IFM 90 HDC/ASCS study.34 All patients received VMCP/VBAP induction, and then patients randomized to conventional therapy received additional cycles of the same regimen. In a SWOG study comparing VMCP/VBAP to MP, the alternating regimen demonstrated a superior response rate (53% vs 32%) and median OS (43 months vs 23 months).35 Another randomized study comparing these regimens, however, did not demonstrate either a response rate or survival advantage for VMCP/VBAP.36

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