title: Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01-21.
abstract: Thalidomide has direct antimyeloma and immunomodulatory effects. In addition, both thalidomide and metronomic chemotherapy inhibit angiogenesis. The synergy of such a combination may decrease toxicity while maintaining efficacy. The Hoosier Oncology Group conducted a phase II trial of oral cyclophosphamide (50 mg b.i.d. for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per 28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients enrolled, 16 had prior stem cell transplantation. The median follow-up time was 25.3 months (95% confidence interval [CI] 23.2-27.7). Of 35 patients treated, 22 patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable disease, and three (8.6%) had disease progression. Two patients withdrew from the study early due to reasons unrelated to progression or toxicity and were treated as nonresponders. The median time to best response and time to progression were 3.6 months (95% CI 2.8-10.9) and 13.2 months (95% CI 9.4-21.0), respectively. The median number of treatment cycles was seven (range 1-12 cycles). Grade III to IV toxicities included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia (20%), sensory neuropathy (11.4%), thromboses (8%), and motor neuropathy (5.7%). No patient withdrew from the study due to toxicity. The efficacy and low toxicity of the CTP regimen support the future development of such an approach in MM.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, Indiana 46202, USA.
authors.forename: Attaya
authors.initials: A
authors.lastname: Suvannasankha
authors.forename: Christopher
authors.initials: C
authors.lastname: Fausel
authors.forename: Beth E
authors.initials: BE
authors.lastname: Juliar
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: William B
authors.initials: WB
authors.lastname: Fisher
authors.forename: Rafat H
authors.initials: RH
authors.lastname: Ansari
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Wood
authors.forename: Gina G
authors.initials: GG
authors.lastname: Smith
authors.forename: Larry D
authors.initials: LD
authors.lastname: Cripe
authors.forename: Rafat
authors.initials: R
authors.lastname: Abonour
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects*; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003520:Cyclophosphamide; D011241:Prednisone