title: Phase I-II trial of oral cyclophosphamide, prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma.
abstract: This single institution, open label Phase I-II dose escalation trial evaluated the safety and efficacy of the combination of lenalidomide (Revlimid®), cyclophosphamide and prednisone (CPR) in patients with relapsed/refractory multiple myeloma. The maximal administered dose of CPR consisted of cyclophosphamide 300 mg/m(2) on day 1, 8, and 15, lenalidomide 25 mg on d 1-21 and prednisone 100 mg every other day in a 28-d cycle. Between November 2007 and June 2009, 32 patients were entered in cohorts of three at three dose levels. The median age was 64 years, 59% were male, with a median two prior regimens. Responding patients could stay on treatment until progression. The full-dose CPR regimen produced no dose-limiting toxicity and was delivered for a median of 16 months (3·5-65 months) with acceptable safety and tolerance. The overall response rate (≥ partial response) was 94% at a median follow up of 28 months. The median progression-free survival was 16·1 months [95% confidence interval (CI); 10·9-22·5 months], while the median overall survival was 27·6 months (95% CI; 16·8-36·6 months). Only the beta-2 microglobulin level at protocol entry correlated with a better survival (P = 0·047). These observations compare favourably with other 2- and 3- drug combinations for relapsed/refractory myeloma, and suggest that CPR should be evaluated further in the setting of relapsed/refractory disease, or in newly diagnosed patients.
authors.affiliation: Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Donna E
authors.initials: DE
authors.lastname: Reece
authors.forename: Esther
authors.initials: E
authors.lastname: Masih-Khan
authors.forename: Eshetu G
authors.initials: EG
authors.lastname: Atenafu
authors.forename: Victor H
authors.initials: VH
authors.lastname: Jimenez-Zepeda
authors.forename: Peter
authors.initials: P
authors.lastname: Anglin
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Mikhael
authors.forename: Suzanne
authors.initials: S
authors.lastname: Trudel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003520:Cyclophosphamide; D000077269:Lenalidomide; D011241:Prednisone
keywords: cyclophosphamide; lenalidomide; prednisone; refractory multiple myeloma; relapsed