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

• Published in: International journal of hematology Vol. 79; no. 2; pp. 165 - 173
• Main Authors: TAKENAKA, Takeaki, ITOH, Kuniaki, MIKUNI, Chikara, DEURA, Kijoh, YAMADA, Takashi, MIZOROGI, Fumi, NAGOSHI, Haruhisa, TOMONAGA, Masao, HOTTA, Tomomitsu, KAWANO, Kohichi, TSUSHITA, Keitaro, HIRANO, Masami, SUZUKI, Takayo, SHIMOYAMA, Masanori, UTSUNOMIYA, Atae, MATSUDA, Shin, CHOU, Takaaki, SAI, Toshiaki, SANO, Masayuki, KONDA, Susumu, OHNO, Tatsuji
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01.02.2004; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Chemotherapy; Confidence intervals; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Disease-Free Survival; Female; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Japan; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - adverse effects; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Nitrosourea Compounds - administration & dosage; Nitrosourea Compounds - adverse effects; Prednisone - administration & dosage; Prednisone - adverse effects; Treatment Outcome; Vincristine - administration & dosage; Vincristine - adverse effects; Asia; Japan; Antineoplastic agent; Phase III trial; Nitrosoureas; Multiple myeloma; Myeloma; Alkaloid; Randomization; Immunoglobulinopathy; Lymphoproliferative syndrome; Melphalan; Antimitotic; Prednisolone; Corticosteroid; Immunopathology; MP; Hematology; Antiinflammatory agent; Malignant hemopathy; Vincristine; Symptomatology; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Combination chemotherapy; Nitrogen mustard; Adrenal hormone; Combined treatment; Randomized study; Immunosuppressive agent; Ranimustine; Comparative study
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1532/ijh97.03115

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.