title: Single-institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: prognostic factors and unique toxicity profile.
abstract: We previously reported a pilot study of thalidomide monotherapy for Japanese patients with refractory or relapsed multiple myeloma. In the present work, we have extended this clinical trial to a single-institute phase 2 study with a larger number of patients and longer follow-up time. New information on the optimal dose and prognostic factors as well as the correlation of toxicities with treatment schedule was obtained. Fifteen of 56 (27%) patients achieved a partial response, including three cases with near-complete remission. Most patients suffered toxicities at a dose of 400 mg per day, but there was no clear dose-response relationship. Thus, a lower dose such as 200 mg per day or less is considered optimal. Multivariate analyses identified only lack of response to therapy as an adverse prognostic factor for progression-free survival. Chromosomal abnormality, C-reactive protein >10 mg/L, and more than six previous courses of chemotherapy were significantly associated with shorter overall survival. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 23 and 11% of patients, respectively. Grade 4 interstitial pneumonia and grade 5 pulmonary hypertension were observed; however, no patient suffered deep vein thrombosis, which has frequently been observed in other studies. Duration of therapy was closely related to the development of peripheral neuropathy. The efficacy and prognostic factors of this treatment were confirmed in long-term observation. However, special attention should be paid to toxicities such as hematological and pulmonary complications as well as peripheral neuropathy in long-term users.
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shimanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. yhattori@sc.itc.keio.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hattori
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimada
authors.forename: Tsunayuki
authors.initials: T
authors.lastname: Kakimoto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Morita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013792:Thalidomide / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide