Abstract
The feasibility of combining cladribine with cyclophosphamide and prednisone in the management of indolent lymphoid malignancies was determined. Nineteen patients [nine chronic lymphocytic leukaemia (CLL), seven non-Hodgkin's lymphoma (NHL) and three macroglobulinaemia (M))] received cladribine 0.1 mg kg−1 per day as a subcutaneous bolus injection on days 1–3 (up to 5 injections) with intravenous cyclophosphamide 500 mg m−2 on day 1 and oral prednisone 40 mg m−2 on days 1–5 at 4-weekly intervals up to a maximum of six courses. A total of 80 courses were given. Overall response rate was 88%, with four patients achieving a complete clinical and haematological response and 12 achieving a partial response. Neutropenia WHO grade 4 in two patients and WHO grade 3 infection in one patient were the limiting toxicities on treatment. During the follow-up, WHO grade ≥3 haematological complications occurred in five patients and WHO grade ≥3 non-haematological complications in five patients. There were no treatment-related deaths. This study demonstrates the feasibility of the cladribine/cyclophosphamide/prednisone (CCP) combination that appears highly active and safe in the management of indolent lymphoid malignancies. © 1999 Cancer Research Campaign
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- Betticher D. C., Fey M. F., Rabaglio M., Cerny T., Hess U., Meier V., Stalder M., Zulian G. Cladribine and severe myelotoxicity. Lancet. 1993 Nov 27;342(8883):1369–1369. doi: 10.1016/0140-6736(93)92281-w. [DOI] [PubMed] [Google Scholar]
- Betticher D. C., Zucca E., von Rohr A., Egger T., Radford J. A., Ambrosetti A., Bürki K., Rufener B., Schmitz S. F., Cerny T. 2-chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients with follicular stage III-IV non-Hodgkin's lymphoma. Ann Oncol. 1996 Oct;7(8):793–799. doi: 10.1093/oxfordjournals.annonc.a010757. [DOI] [PubMed] [Google Scholar]
- Beutler E. Cladribine (2-chlorodeoxyadenosine) Lancet. 1992 Oct 17;340(8825):952–956. doi: 10.1016/0140-6736(92)92826-2. [DOI] [PubMed] [Google Scholar]
- Cheson B. D. Infectious and immunosuppressive complications of purine analog therapy. J Clin Oncol. 1995 Sep;13(9):2431–2448. doi: 10.1200/JCO.1995.13.9.2431. [DOI] [PubMed] [Google Scholar]
- Danhauser L., Plunkett W., Keating M., Cabanillas F. 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate pharmacokinetics in plasma and tumor cells of patients with relapsed leukemia and lymphoma. Cancer Chemother Pharmacol. 1986;18(2):145–152. doi: 10.1007/BF00262285. [DOI] [PubMed] [Google Scholar]
- Delannoy A., Martiat P., Gala J. L., Deneys V., Ferrant A., Bosly A., Schieff J. M., Michaux J. L. 2-Chlorodeoxyadenosine (CdA) for patients with previously untreated chronic lymphocytic leukemia (CLL). Leukemia. 1995 Jul;9(7):1130–1135. [PubMed] [Google Scholar]
- Dimopoulos M. A., Kantarjian H., Estey E., O'Brien S., Delasalle K., Keating M. J., Freireich E. J., Alexanian R. Treatment of Waldenstrom macroglobulinemia with 2-chlorodeoxyadenosine. Ann Intern Med. 1993 Feb 1;118(3):195–198. doi: 10.7326/0003-4819-118-3-199302010-00007. [DOI] [PubMed] [Google Scholar]
- Hickish T., Serafinowski P., Cunningham D., Oza A., Dorland E., Judson I., Millar B. C., Lister T. A., Roldan A. 2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies. Br J Cancer. 1993 Jan;67(1):139–143. doi: 10.1038/bjc.1993.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoffman M., Tallman M. S., Hakimian D., Janson D., Hogan D., Variakogis D., Kuzel T., Gordon L. I., Rai K. 2-Chlorodeoxyadenosine is an active salvage therapy in advanced indolent non-Hodgkin's lymphoma. J Clin Oncol. 1994 Apr;12(4):788–792. doi: 10.1200/JCO.1994.12.4.788. [DOI] [PubMed] [Google Scholar]
- Hosek B., Bohácek J., Sikulová J. The effect of cyclophosphamide and gamma irradiation on adenosine deaminase and purine nucleoside phosphorylase in mice. Life Sci. 1991;49(19):1403–1407. doi: 10.1016/0024-3205(91)90392-o. [DOI] [PubMed] [Google Scholar]
- Juliusson G., Christiansen I., Hansen M. M., Johnson S., Kimby E., Elmhorn-Rosenborg A., Liliemark J. Oral cladribine as primary therapy for patients with B-cell chronic lymphocytic leukemia. J Clin Oncol. 1996 Jul;14(7):2160–2166. doi: 10.1200/JCO.1996.14.7.2160. [DOI] [PubMed] [Google Scholar]
- Juliusson G., Liliemark J. High complete remission rate from 2-chloro-2'-deoxyadenosine in previously treated patients with B-cell chronic lymphocytic leukemia: response predicted by rapid decrease of blood lymphocyte count. J Clin Oncol. 1993 Apr;11(4):679–689. doi: 10.1200/JCO.1993.11.4.679. [DOI] [PubMed] [Google Scholar]
- Juliusson G., Liliemark J. Long-term survival following cladribine (2-chlorodeoxyadenosine) therapy in previously treated patients with chronic lymphocytic leukemia. Ann Oncol. 1996 Apr;7(4):373–379. doi: 10.1093/oxfordjournals.annonc.a010604. [DOI] [PubMed] [Google Scholar]
- Kawasaki H., Carrera C. J., Piro L. D., Saven A., Kipps T. J., Carson D. A. Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Blood. 1993 Feb 1;81(3):597–601. [PubMed] [Google Scholar]
- Kay A. C., Saven A., Carrera C. J., Carson D. A., Thurston D., Beutler E., Piro L. D. 2-Chlorodeoxyadenosine treatment of low-grade lymphomas. J Clin Oncol. 1992 Mar;10(3):371–377. doi: 10.1200/JCO.1992.10.3.371. [DOI] [PubMed] [Google Scholar]
- Liliemark J., Albertioni F., Hassan M., Juliusson G. On the bioavailability of oral and subcutaneous 2-chloro-2'-deoxyadenosine in humans: alternative routes of administration. J Clin Oncol. 1992 Oct;10(10):1514–1518. doi: 10.1200/JCO.1992.10.10.1514. [DOI] [PubMed] [Google Scholar]
- Lister T. A., Cullen M. H., Beard M. E., Brearley R. L., Whitehouse J. M., Wrigley P. F., Stansfeld A. G., Sutcliffe S. B., Malpas J. S., Crowther D. Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type. Br Med J. 1978 Mar 4;1(6112):533–537. doi: 10.1136/bmj.1.6112.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Brien S., Kantarjian H., Estey E., Koller C., Robertson B., Beran M., Andreeff M., Pierce S., Keating M. Lack of effect of 2-chlorodeoxyadenosine therapy in patients with chronic lymphocytic leukemia refractory to fludarabine therapy. N Engl J Med. 1994 Feb 3;330(5):319–322. doi: 10.1056/NEJM199402033300504. [DOI] [PubMed] [Google Scholar]
- Piro L. D., Carrera C. J., Carson D. A., Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med. 1990 Apr 19;322(16):1117–1121. doi: 10.1056/NEJM199004193221605. [DOI] [PubMed] [Google Scholar]
- Robertson L. E., Chubb S., Meyn R. E., Story M., Ford R., Hittelman W. N., Plunkett W. Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2'-deoxyadenosine and 9-beta-D-arabinosyl-2-fluoroadenine. Blood. 1993 Jan 1;81(1):143–150. [PubMed] [Google Scholar]
- Rosenberg S. A. Karnofsky memorial lecture. The low-grade non-Hodgkin's lymphomas: challenges and opportunities. J Clin Oncol. 1985 Mar;3(3):299–310. doi: 10.1200/JCO.1985.3.3.299. [DOI] [PubMed] [Google Scholar]
- Saven A., Carrera C. J., Carson D. A., Beutler E., Piro L. D. 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood. 1992 Aug 1;80(3):587–592. [PubMed] [Google Scholar]
- Saven A., Emanuele S., Kosty M., Koziol J., Ellison D., Piro L. 2-Chlorodeoxyadenosine activity in patients with untreated, indolent non-Hodgkin's lymphoma. Blood. 1995 Sep 1;86(5):1710–1716. [PubMed] [Google Scholar]
- Saven A., Lee T., Kosty M., Piro L. Cladribine and mitoxantrone dose escalation in indolent non-Hodgkin's lymphoma. J Clin Oncol. 1996 Jul;14(7):2139–2144. doi: 10.1200/JCO.1996.14.7.2139. [DOI] [PubMed] [Google Scholar]
- Saven A., Piro L. D. 2-Chlorodeoxyadenosine: a newer purine analog active in the treatment of indolent lymphoid malignancies. Ann Intern Med. 1994 May 1;120(9):784–791. doi: 10.7326/0003-4819-120-9-199405010-00010. [DOI] [PubMed] [Google Scholar]
- Seymour J. F., Kurzrock R., Freireich E. J., Estey E. H. 2-chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia. Blood. 1994 May 15;83(10):2906–2911. [PubMed] [Google Scholar]
- Tefferi A., Witzig T. E., Reid J. M., Li C. Y., Ames M. M. Phase I study of combined 2-chlorodeoxyadenosine and chlorambucil in chronic lymphoid leukemia and low-grade lymphoma. J Clin Oncol. 1994 Mar;12(3):569–574. doi: 10.1200/JCO.1994.12.3.569. [DOI] [PubMed] [Google Scholar]
- Velasquez W. S., Cabanillas F., Salvador P., McLaughlin P., Fridrik M., Tucker S., Jagannath S., Hagemeister F. B., Redman J. R., Swan F. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117–122. [PubMed] [Google Scholar]