Phase I-II trial of oral cyclophosphamide, prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma

British Journal of Haematology

Volumn 168, Issue 1, 2015, Pages 46-54

  Reece, Donna E ^a   Masih Khan, Esther ^a   Atenafu, Eshetu G ^a   Jimenez Zepeda, Victor H ^b   Anglin, Peter ^c   Chen, Christine ^a   Kukreti, Vishal ^a   Mikhael, Joseph R ^d   Trudel, Suzanne ^a  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b TOM BAKER CANCER CENTRE   (Canada)

^c SOUTHLAKE REGIONAL HEALTH CENTRE   (Canada)

^d MAYO CLINIC   (United States)

Author keywords

Cyclophosphamide; Lenalidomide; Prednisone; Refractory multiple myeloma; Relapsed

Indexed keywords

ACETYLSALICYLIC ACID; BETA 2 MICROGLOBULIN; BORTEZOMIB; CALCIUM; CREATININE; CYCLOPHOSPHAMIDE; DEXAMETHASONE; GRANULOCYTE COLONY STIMULATING FACTOR; GROWTH FACTOR; HEMOGLOBIN; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN KAPPA CHAIN; IMMUNOGLOBULIN LAMBDA CHAIN; LENALIDOMIDE; LEVOFLOXACIN; LOW MOLECULAR WEIGHT HEPARIN; MELPHALAN; PREDNISONE; THALIDOMIDE; ANTINEOPLASTIC AGENT;

ACUTE GRANULOCYTIC LEUKEMIA; ADENOCARCINOMA; ADULT; ALLERGY; ANTICOAGULATION; ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; BACTERIAL ENDOCARDITIS; BLEEDING; BONE MARROW DISEASE; CANCER RECURRENCE; CAUSE OF DEATH; CLINICAL ARTICLE; COHORT ANALYSIS; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DIVERTICULITIS; DRUG CONTRAINDICATION; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; EAR DISEASE; ENDOCRINE DISEASE; EYE DISEASE; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; FOLLOW UP; GASTROINTESTINAL DISEASE; HEARING IMPAIRMENT; HEART ARRHYTHMIA; HEART DISEASE; HEART INFARCTION; HEMATOLOGIC DISEASE; HERPES ZOSTER; HIP PAIN; HOSPITALIZATION; HUMAN; INFECTION; INSOMNIA; KIDNEY DISEASE; LUNG DISEASE; LYMPHATIC SYSTEM DISEASE; MALE; METABOLIC DISORDER; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MUSCLE CRAMP; MUSCULOSKELETAL DISEASE; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUROLOGIC DISEASE; NEUTROPENIA; NEUTROPENIC TYPHLITIS; NEUTROPHIL COUNT; NEUTROPHILIA; NON SMALL CELL LUNG CANCER; OPEN STUDY; OVERALL SURVIVAL; PAIN; PANCYTOPENIA; PERFORATED DIVERTICULUM; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REFRACTORY MULTIPLE MYELOMA; REFRACTORY PERIOD; SALVAGE THERAPY; SEXUAL DYSFUNCTION; SICK SINUS SYNDROME; SKIN DISEASE; SOFT TISSUE DISEASE; THROMBOCYTE COUNT; THROMBOCYTOPENIA; THROMBOSIS; TREATMENT DURATION; TREATMENT RESPONSE; TREMOR; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; UROGENITAL TRACT DISEASE; VASCULAR DISEASE; VENOUS THROMBOEMBOLISM; VOMITING; AGED; ANALOGS AND DERIVATIVES; CANCER STAGING; CLINICAL TRIAL; MIDDLE AGED; MORTALITY; PATHOLOGY; TREATMENT OUTCOME; TUMOR RECURRENCE; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CYCLOPHOSPHAMIDE; FEMALE; HUMANS; MALE; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; PREDNISONE; THALIDOMIDE; TREATMENT OUTCOME;

EID: 84915781489     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.13100     Document Type: Article

References (35)

1. Anderson, K.C. (2007) Multiple myeloma. Preface. Hematology/Oncology Clinics of North America, 21, xiii-xiv.
2. Attal, M., Lauwers-Cances, V., Marit, G., Caillot, D., Moreau, P., Facon, T., Stoppa, A.M., Hulin, C., Benboubker, L., Garderet, L., Decaux, O., Leyvraz, S., Vekemans, M.C., Voillat, L., Michallet, M., Pegourie, B., Dumontet, C., Roussel, M., Leleu, X., Mathiot, C., Payen, C., Avet-Loiseau, H. & Harousseau, J.L. (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. New England Journal of Medicine, 366, 1782-1791.
3. Bahlis, N.J. (2012) Darwinian evolution and tiding clones in multiple myeloma. Blood, 120, 927-928.
4. Brandes, L.J. & Israels, L.G. (1987) Weekly low-dose cyclophosphamide and alternate-day prednisone: an effective low toxicity regimen for advanced myeloma. European Journal of Haematology, 39, 362-368.
5. Celesti, L., Clavio, M., Poggi, A., Casciaro, S., Vallebella, E. & Gobbi, M. (1997) The association of cyclophosphamide and dexamethasone in advanced refractory multiple myeloma patients. Haematologica, 82, 351-353.
6. Davies, F.E., Wu, P., Jenner, M., Srikanth, M., Saso, R. & Morgan, G.J. (2007) The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Haematologica, 92, 1149-1150.
7. Dimopoulos, M.A., Hamilos, G., Zomas, A., Gika, D., Efstathiou, E., Grigoraki, V., Poziopoulos, C., Xilouri, I., Zorzou, M.P., Anagnostopoulos, N. & Anagnostopoulos, A. (2004) Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. The Hematology Journal, 5, 112-117.
8. Dimopoulos, M., Spencer, A., Attal, M., Prince, H.M., Harousseau, J.L., Dmoszynska, A., San Miguel, J., Hellmann, A., Facon, T., Foa, R., Corso, A., Masliak, Z., Olesnyckyj, M., Yu, Z., Patin, J., Zeldis, J.B. & Knight, R.D. (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. New England Journal of Medicine, 357, 2123-2132.
9. Durie, B.G., Harousseau, J.L., Miguel, J.S., Blade, J., Barlogie, B., Anderson, K., Gertz, M., Dimopoulos, M., Westin, J., Sonneveld, P., Ludwig, H., Gahrton, G., Beksac, M., Crowley, J., Belch, A., Boccadaro, M., Cavo, M., Turesson, I., Joshua, D., Vesole, D., Kyle, R., Alexanian, R., Tricot, G., Attal, M., Merlini, G., Powles, R., Richardson, P., Shimizu, K., Tosi, P., Morgan, G. & Rajkumar, S.V. (2006) International uniform response criteria for multiple myeloma. Leukemia, 20, 1467-1473.
10. Egan, J.B., Shi, C.X., Tembe, W., Christoforides, A., Kurdoglu, A., Sinari, S., Middha, S., Asmann, Y., Schmidt, J., Braggio, E., Keats, J.J., Fonseca, R., Bergsagel, P.L., Craig, D.W., Carpten, J.D. & Stewart, A.K. (2012) Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood, 120, 1060-1066.
11. Ghiringhelli, F., Menard, C., Puig, P.E., Ladoire, S., Roux, S., Martin, F., Solary, E., Le Cesne, A., Zitvogel, L. & Chauffert, B. (2007) Metronomic cyclophosphamide regimen selectively depletes CD4 + CD25 + regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunology, Immunotherapy, 56, 641-648.
12. Hanahan, D., Bergers, G. & Bergsland, E. (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. The Journal of Clinical Investigation, 105, 1045-1047.
13. Kerbel, R.S. & Kamen, B.A. (2004) The anti-angiogenic basis of metronomic chemotherapy. Nature Reviews Cancer, 4, 423-436.
14. Knop, S., Gerecke, C., Liebisch, P., Topp, M.S., Platzbecker, U., Sezer, O., Vollmuth, C., Falk, K., Glasmacher, A., Maeder, U., Einsele, H. & Bargou, R.C. (2009) Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom). Blood, 113, 4137-4143.
15. Koontz, M.Z., Horning, S.J., Balise, R., Greenberg, P.L., Rosenberg, S.A., Hoppe, R.T. & Advani, R.H. (2013) Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials. Journal of Clinical Oncology, 31, 592-598.
16. Kropff, M., Bisping, G., Schuck, E., Liebisch, P., Lang, N., Hentrich, M., Dechow, T., Kroger, N., Salwender, H., Metzner, B., Sezer, O., Engelhardt, M., Wolf, H.H., Einsele, H., Volpert, S., Heinecke, A., Berdel, W.E. & Kienast, J. (2007) Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. British Journal of Haematology, 138, 330-337.
17. Kyriakou, C., Thomson, K., D'Sa, S., Flory, A., Hanslip, J., Goldstone, A.H. & Yong, K.L. (2005) Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. British Journal of Haematology, 129, 763-770.
18. Loeffler, M., Brosteanu, O., Hasenclever, D., Sextro, M., Assouline, D., Bartolucci, A.A., Cassileth, P.A., Crowther, D., Diehl, V., Fisher, R.I., Hoppe, R.T., Jacobs, P., Pater, J.L., Pavlovsky, S., Thompson, E. & Wiernik, P. (1998) Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. Journal of Clinical Oncology, 16, 818-829.
19. McCarthy, P.L., Owzar, K., Hofmeister, C.C., Hurd, D.D., Hassoun, H., Richardson, P.G., Giralt, S., Stadtmauer, E.A., Weisdorf, D.J., Vij, R., Moreb, J.S., Callander, N.S., Van Besien, K., Gentile, T., Isola, L., Maziarz, R.T., Gabriel, D.A., Bashey, A., Landau, H., Martin, T., Qazilbash, M.H., Levitan, D., McClune, B., Schlossman, R., Hars, V., Postiglione, J., Jiang, C., Bennett, E., Barry, S., Bressler, L., Kelly, M., Seiler, M., Rosenbaum, C., Hari, P., Pasquini, M.C., Horowitz, M.M., Shea, T.C., Devine, S.M., Anderson, K.C. & Linker, C. (2012) Lenalidomide after stem-cell transplantation for multiple myeloma. New England Journal of Medicine, 366, 1770-1781.
20. Morgan, G.J., Schey, S.A., Wu, P., Srikanth, M., Phekoo, K.J., Jenner, M. & Davies, F.E. (2007) Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients. British Journal of Haematology, 137, 268-269.
21. Noronha, V., Krishna, M.V., Patil, V., Joshi, A., Banavali, S.D. & Prabhash, K. (2013) Metronomic therapy: chemotherapy revisited. Indian Journal of Cancer, 50, 142-148.
22. Omer, B., Kadan-Lottick, N.S., Roberts, K.B., Wang, R., Demsky, C., Kupfer, G.M., Cooper, D., Seropian, S. & Ma, X. (2012) Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults. British Journal of Haematology, 158, 615-625.
23. Palumbo, A., Falco, P., Falcone, A., Benevolo, G., Canepa, L., Gay, F., Larocca, A., Magarotto, V., Gozzetti, A., Luraschi, A., Morabito, F., Nozza, A., Knight, R.D., Zeldis, J.B., Boccadoro, M. & Petrucci, M.T. (2009) Melphalan, prednisone, and lenalidomide for newly diagnosed myeloma: kinetics of neutropenia and thrombocytopenia and time-to-event results. Clinical Lymphoma and Myeloma, 9, 145-150.
24. Palumbo, A., Bringhen, S., Kumar, S.K., Lupparelli, G., Usmani, S., Waage, A., Larocca, A., van der Holt, B., Musto, P., Offidani, M., Petrucci, M.T., Evangelista, A., Zweegman, S., Nooka, A.K., Spencer, A., Dimopoulos, M.A., Hajek, R., Cavo, M., Richardson, P., Lonial, S., Ciccone, G., Boccadoro, M., Anderson, K., Barlogie, B., Sonneveld, P. & McCarthy, P.L. (2014) Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. The Lancet Oncology, 15, 333-342.
25. Pasquier, E., Kavallaris, M. & Andre, N. (2010) Metronomic chemotherapy: new rationale for new directions. Nature Reviews Clinical Oncology, 7, 455-465.
26. Rajkumar, S.V., Jacobus, S., Callander, N.S., Fonseca, R., Vesole, D.H., Williams, M.E., Abonour, R., Siegel, D.S., Katz, M. & Greipp, P.R. (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. The Lancet Oncology, 11, 29-37.
27. Reece, D.E. (2007) Management of multiple myeloma: the changing landscape. Blood Reviews, 21, 301-314.
28. Reece, D.E., Rodriguez, G.P., Chen, C., Trudel, S., Kukreti, V., Mikhael, J., Pantoja, M., Xu, W. & Stewart, A.K. (2008) Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. Journal of Clinical Oncology, 26, 4777-4783.
29. Richardson, P.G., Xie, W., Jagannath, S., Jakubowiak, A., Lonial, S., Raje, N.S., Alsina, M., Ghobrial, I.M., Schlossman, R.L., Munshi, N.C., Mazumder, A., Vesole, D.H., Kaufman J.l., Colson, K., McKenney, M., Lunde, L.E., Feather, J., Maglio, M.E., Warren, D., Francis, D., Hideshima, T., Knight, R., Esseltine, E.L., Mitsiades, C.S., Weller, E. & Anderson, K.C. (2014) A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood, 123, 1461-1469.
30. San Miguel, J., Weisel, K., Moreau, P., Lacy, M., Song, K., Delforge, M., Karlin, L., Goldschmidt, H., Banos, A., Oriol, A., Alegre, A., Chen, C., Cavo, M., Garderet, L., Ivanova, V., Martinez-Lopez, J., Belch, A., Palumbo, A., Schey, S., Sonneveld, P., Yu, X., Sternas, L., Jacques, C., Zaki, M. & Dimopoulos, M. (2013) Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. The Lancet Oncology, 14, 1055-1066.
31. Schey, S.A., Morgan, G.J., Ramasamy, K., Hazel, B., Ladon, D., Corderoy, S., Jenner, M., Phekoo, K., Boyd, K. & Davies, F.E. (2010) The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study. British Journal of Haematology, 150, 326-333.
32. Sidra, G., Williams, C.D., Russell, N.H., Zaman, S., Myers, B. & Byrne, J.L. (2006) Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma. Haematologica, 91, 862-863.
33. Trieu, Y., Trudel, S., Pond, G.R., Mikhael, J., Jaksic, W., Reece, D.E., Chen, C.I. & Stewart, A.K. (2005) Weekly cyclophosphamide and alternate-day prednisone: an effective, convenient, and well-tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantation. Mayo Clinic Proceedings, 80, 1578-1582.
34. Weber, D.M., Chen, C., Niesvizky, R., Wang, M., Belch, A., Stadtmauer, E.A., Siegel, D., Borrello, I., Rajkumar, S.V., Chanan-Khan, A.A., Lonial, S., Yu, Z., Patin, J., Olesnyckyj, M., Zeldis, J.B. & Knight, R.D. (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. New England Journal of Medicine, 357, 2133-2142.
35. de Weerdt, O., van de Donk, N.W., Veth, G., Bloem, A.C., Hagenbeek, A. & Lokhorst, H.M. (2001) Continuous low-dose cyclophosphamide-prednisone is effective and well tolerated in patients with advanced multiple myeloma. Netherlands Journal of Medicine, 59, 50-56.