Phase III study of ranimustine, cyclophosphamide, vincristine, melphalan, and prednisolone (MCNU-COP/MP) versus modified COP/MP in multiple myeloma: a Japan clinical oncology group study, JCOG 9301.
To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%-53.8%] and to MCNU-COP/MP was 56.1% (95% CI, 46.1%-65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9-25.8] versus 15.8 months [95% CI, 14.1-19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95%, CI, 32.8-59.8]) (P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.
Takenaka
Takeaki
T
Hematology Division, National Cancer Center Hospital, Tokyo, Japan.
Itoh
Kuniaki
K
Suzuki
Takayo
T
Utsunomiya
Atae
A
Matsuda
Shin
S
Chou
Takaaki
T
Sai
Toshiaki
T
Sano
Masayuki
M
Konda
Susumu
S
Ohno
Tatsuji
T
Mikuni
Chikara
C
Deura
Kijoh
K
Yamada
Takashi
T
Mizorogi
Fumi
F
Nagoshi
Haruhisa
H
Tomonaga
Masao
M
Hotta
Tomomitsu
T
Kawano
Kohichi
K
Tsushita
Keitaro
K
Hirano
Masami
M
Shimoyama
Masanori
M
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009607:Nitrosourea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D009607:Nitrosourea Compounds; D014750:Vincristine; D003520:Cyclophosphamide; D008558:Melphalan; C020766:ranimustine; D011241:Prednisone