Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan.
This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon alpha (IFN-alpha) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN-alpha as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3.6 years from registration. The survival of responders (CR + PR) was significantly better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7-year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD-IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non-responders.
Department of Haematology, Tokyo Women's Medical University, Tokyo, Japan. wada@dh.twmu.ac.jp
M
M
Wada
H
H
Mizoguchi
S I
SI
Kuriya
H
H
Taguchi
T
T
Kawamura
I
I
Maekawa
C
C
Shimazaki
Y
Y
Sato
Y
Y
Niho
T
T
Miyazaki
A
A
Shibata
T
T
Kitani
N
N
Hamajima
R
R
Ohno
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D064211:Connectin; D003907:Dexamethasone / Q000008:administration & dosage; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D016015:Logistic Models; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy*; D009124:Muscle Proteins; D009194:Myeloma Proteins; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D010865:Pilot Projects; D011446:Prospective Studies; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage
D064211:Connectin; D016898:Interferon-alpha; D009124:Muscle Proteins; D009194:Myeloma Proteins; D009607:Nitrosourea Compounds; C085016:multiple myeloma M-proteins; D014750:Vincristine; D003907:Dexamethasone; D008558:Melphalan; C020766:ranimustine