Generic Name: Pentostatin
Class: Antineoplastic Agents
VA Class: AN200
Chemical Name: (R) - 3 - (2 - deoxy - β - D - erythro - pentofuranosyl) - 3,6,7,8 - tetrahydroimidazo[4,5 - d][1,3]diazepin - 8 - ol
Molecular Formula: C11H16N4O4
CAS Number: 53910-25-1
- Experience of Supervising Clinician
Use under supervision of a qualified clinician experienced in therapy with antineoplastic agents.1
- Dose-limiting Toxicity
Risk of dose-related toxicities; use of dosages higher than those specified not recommended.1 Possible dose-limiting severe renal, liver, pulmonary, and CNS toxicities with higher than recommended doses of pentostatin (e.g., dosages as high as 20–50 mg/m2 in divided doses over 5 days).1 (See Prescribing Limits under Dosage and Administration.)
Uses for Nipent
Hairy Cell Leukemia
Used alone as first-line therapy for active hairy cell leukemia (leukemic reticuloendotheliosis), defined as disease involving clinically relevant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.1 15 59
Used in patients with active hairy cell leukemia that responds inadequately to, or progresses during, interferon alfa therapy (i.e., disease that progresses despite ≥3 months of interferon alfa therapy or fails to respond to ≥6 months of therapy).1 15 59 97 110
Pentostatin or cladribine considered first-line therapy because of apparent greater efficacy (i.e., higher complete response rate) compared with interferon alfa;15 59 99 100 101 102 103 104 105 106 107 however, cladribine may be preferred.99 100 103 105 106 107
Chronic Lymphocytic Leukemia (CLL)
Cutaneous T-cell Lymphoma
Nipent Dosage and Administration
Consult specialized references for procedures for proper handling and disposal of antineoplastics.1
Hydrate with 500–1000 mL of 5% dextrose in 0.45% sodium chloride injection or a similar IV fluid prior to pentostatin administration; hydrate with an additional 500 mL of 5% dextrose or a similar IV fluid immediately after pentostatin administration to minimize risk of adverse renal effects.1 3 11 97 (See Renal Effects under Cautions.)
For solution and drug compatibility information, see Compatibility under Stability.
Administer by IV infusion or direct IV injection.1
Handle cautiously; use of protective clothing and polyethylene gloves recommended during preparation of IV solution.1 Treat spills and waste with 5% sodium hypochlorite solution prior to disposal.1 97
Reconstituted and diluted solutions contain no preservatives; use within 8 hours of preparation.1
Reconstitute vial containing 10 mg of lyophilized pentostatin by adding 5 mL of sterile water for injection to provide a solution containing 2 mg/mL.1 Shake thoroughly to ensure complete dissolution of the drug.1 97
Prior to administration by IV infusion, must be diluted in 5% dextrose injection or 0.9% sodium chloride injection.1 Dilute entire contents of reconstituted vial with 25 or 50 mL of 5% dextrose injection or 0.9% sodium chloride injection to provide solutions containing 0.33 or 0.18 mg/mL, respectively.1
Rate of Administration
Hairy Cell Leukemia
Optimum duration of therapy not determined.1 If clinical improvement is observed (in the absence of any major toxicity), continue therapy until a complete response is achieved.1 Clinical evidence suggests 2 additional doses following achievement of a complete response.1 97 98
If a complete or partial response is not achieved after 6 months of therapy, discontinue therapy.1 If a partial response is achieved, continue therapy until a complete response is achieved.1 If after 12 months of therapy only a partial response is achieved, discontinue therapy.1
Dosage Modification for Toxicity and Contraindications for Continued Therapy
Patients with initial ANC >500 cells/mm3: If ANC decreases during treatment to <200 cells/mm3, temporarily withhold therapy and resume when ANC returns to predose levels.1
No dosage adjustments necessary when starting therapy in patients with anemia, neutropenia, or thrombocytopenia.1
Dosage adjustments not necessary during treatment in patients with thrombocytopenia or anemia managed with appropriate hematologic monitoring and/or therapy.1
If patient exhibits evidence of nervous system toxicity (e.g., lethargy, seizures, coma), withhold or discontinue therapy.1
If patient experiences a severe rash, withhold therapy.1
Withhold individual doses and determine Clcr in patients with an increased predose Scr.1 (See Renal Impairment under Dosage and Administration.)
Hairy Cell Leukemia
Maximum 4 mg/m2 as a single dose every other week.1 3 4 Risk of severe toxicity (e.g., renal, hepatic, pulmonary, CNS) increases with higher dosages (e.g., 20–50 mg/m2 in divided doses over 5 days).1 2 97 98
Patients unable to achieve a complete or partial response to therapy: Maximum 6 months.1
Patients with only a partial response to therapy: Maximum 12 months.1
No specific dosage recommendations at this time.1
Hairy Cell Leukemia
Withhold individual doses and determine Clcr in patients with an elevated predose Scr.1
Insufficient data to recommend an initial or subsequent dose of pentostatin in patients with impaired renal function (i.e., Clcr<60 mL/minute); 2 patients with Clcr of 50–60 mL/minute achieved complete responses without unusual toxicity when treated with 2 mg/m2 of pentostatin.1
Select dosage with caution, usually starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1
Cautions for Nipent
Known hypersensitivity to pentostatin or any ingredient in the formulation.1
Risk of severe myelosuppression (e.g., anemia, thrombocytopenia, neutropenia) especially during initial courses of treatment.1
Neutropenia may be severe and may worsen during initial courses of therapy.1 Monitor hematologic function (e.g., CBC) frequently for neutropenia.1 If severe neutropenia continues beyond initial therapy cycles, evaluate patients for disease status (e.g., bone marrow examination).1 (See Adequate Patient Evaluation and Monitoring under Cautions.)
Frequency and severity of myelosuppression appear related to underlying disease type and tumor mass.2 10 46 85 97 98 105 107 Myelosuppression occurs more frequently and is more severe in patients with preexisting malignancy with bone marrow involvement than in those without such involvement (e.g., in mycosis fungoides); such toxicity also may occur at relatively low dosages.2 10 105 107
Risk of worsening and potentially fatal infections in patients with preexiting infections.1 Weigh risks and benefits of therapy in patients with preexisting or secondary infections.1 10 In patients with evidence of infection, temporarily withhold therapy and attempt to control infection before initiating or resuming therapy.1 9
Risk of severe pulmonary toxicity reported with high dosages (e.g., 20–50 mg/m2 in divided doses over 5 days).1
Risk of severe and/or fatal pulmonary toxicity when administered concomitantly with fludarabine; do not use fludarabine with pentostatin.1 (See Specific Drugs under Interactions and also see Boxed Warning.)
Potentially fatal acute pulmonary edema reported when pentostatin was administered concomitantly with carmustine, etoposide, and high-dose cyclophosphamide in an ablative regimen as preparation for a bone marrow transplant.1 (See Specific Drugs under Interactions.)
Severe dose-related renal toxicity reported, usually occurring with dosages higher than those recommended for hairy cell leukemia.1 9 98 105 Mild to moderate renal toxicity also reported in patients with normal renal function prior to pentostatin therapy.1 7 46 In patients treated with the recommended dosage and adequate hydration, increases in Scr generally are minor and reversible.1 9 98 107
Hemolytic-uremic syndrome, possibly fatal, reported in patients receiving high dosages of pentostatin for cutaneous T-cell lymphoma;120 121 syndrome resolved with plasma exchange and glucocorticoid therapy.120
Fetal/Neonatal Morbidity and Mortality
Risk of severe hepatic toxicity with higher than recommended doses.1
Potentially severe and rarely fatal neurologic effects (e.g., seizures, coma) reported.2 32 Effects may be dosage schedule-dependent;2 8 32 75 temporarily withhold or discontinue therapy in patients exhibiting evidence of nervous system toxicity.1 9 97 98
Adequate Patient Evaluation and Monitoring
Toxic drug with a low therapeutic index; therapeutic response unlikely without some evidence of toxicity.1 2 Administer only under supervision of qualified clinicians experienced in therapy with cytotoxic agents.1
Prior to and during therapy, monitor hematologic function; frequent monitoring recommended during the first several courses of therapy in patients at increased risk of myelosuppression (e.g., those with hairy cell leukemia).1 2 9 10 Bone marrow examination may be required to determine disease status when severe neutropenia continues beyond the initial cycles.1 (See Hematologic Effects under Cautions.)
If severe adverse effects occur during therapy, discontinue the drug or reduce dosage and institute appropriate measures.1 9 (See Dosage Modification for Toxicity and Contraindications for Continued Therapy under Dosage and Administration.)
Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Safety and efficacy not established.98 Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults;1 monitor renal function in geriatric patients because of possible age-related decreases in renal function that may increase their risk of pentostatin-induced toxicity.1
Common Adverse Effects
Nausea,1 2 3 4 5 9 11 12 59 75 80 107 vomiting,1 2 3 4 5 9 11 12 59 75 80 107 fever,1 2 4 9 rash,1 fatigue,1 cough,1 upper respiratory infection,1 herpes zoster,1 dyspnea,1 leukopenia,1 pruritus,1 chills,1 headache,1 diarrhea,1 myalgia,1 abdominal pain,1 asthenia,1 anorexia,1 rhinitis,1 stomatitis,1 anemia,1 pain,1 pharyngitis,1 sweating,1 thrombocytopenia,1 unspecified GU disorder.1 a
Interactions for Nipent
Possible abnormalities in renal or hepatic function8
Fatal hypersensitivity vasculitis reported; causal relationship not established1
Abnormalities usually resolve following discontinuance of allopurinol; some clinicians suggest that pentostatin and allopurinol not be used concurrently8
Potentially fatal acute pulmonary edema and hypotension reported with combination chemotherapy regimen of pentostatin, carmustine, etoposide, and high-dose cyclophosphamide prior to bone marrow transplant1
Potentially fatal acute pulmonary edema and hypotension reported with a combination chemotherapy regimen of pentostatin, carmustine, etoposide, and high-dose cyclophosphamide prior to bone marrow transplant1
Potentially fatal acute pulmonary edema and hypotension reported with a combination chemotherapy regimen of pentostatin, carmustine, etoposide, and high-dose cyclophosphamide prior to bone marrow transplant1
Inhibition of adenosine deaminase by a single dose may persist in some cells for ≥1 week.2
Not known whether distributed into milk.1
Plasma Protein Binding
Powder for Injection
Use reconstituted and diluted solutions within 8 hours when stored at room temperature in ambient light; discard unused portions.1
For information on systemic interactions resulting from concomitant use, see Interactions.
Dextrose 5% in water
Ringer’s injection, lactated
Sodium chloride 0.9%
Potent transition-state (tight-binding) inhibitor of adenosine deaminase (an enzyme involved in purine metabolism) 1 2 9 10 11 18 20 29 49 52 53 55 56 57 that appears to regulate intracellular adenosine concentrations via irreversible deamination of adenosine and deoxyadenosine.2 18 53 55 56 57
Inhibition of adenosine deaminase results in intracellular accumulation of toxic levels of adenine deoxynucleotides (e.g., deoxyadenosine triphosphate [dATP]) and in the presence of deoxyadenosine can lead to cell death.1 2 10 27 28 29 30 49 52 53 54 55 57 97 98
Cytotoxic effects do not appear to be attributable directly to the drug or its metabolites; appear to result indirectly from effects of the substrates for adenosine deaminase (adenosine and deoxyadenosine) and/or their metabolites.26 49 52 58 97 98
Inhibits RNA synthesis, causes DNA strand breaks, disrupts ATP-dependent cellular processes, and inhibits adenosylhomocysteinase (S-adenosylhomocysteine hydrolase); all of which also may contribute to lymphocytotoxic effects.1 2 5 27 29 49 52 53
Advice to Patients
Importance of immediately informing a clinician of any adverse reactions (e.g., fever, rash).1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or infections.1
Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed;1 necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Pentostatin for Injection
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.
Only references cited for selected revisions after 1984 are available electronically.
1. Bedford Laboratories. Pentostatin for injection prescribing information. Bedford, OH; 2006 Aug.
2. O’Dwyer PJ, Wagner B, Leyland-Jones B et al. 2′-Deoxycoformycin (pentostatin) for lymphoid malignancies: rational development of an active new drug. Ann Intern Med. 1988; 108:733-43. [IDIS 242862] [PubMed 3282467]
3. Blick M, Lepe-Zuniga JL, Doig R et al. Durable complete remissions after 2′-deoxycoformycin treatment in patients with hairy cell leukemia resistant to interferon alpha. Am J Hematol. 1990; 33:205-9. [PubMed 2301379]
4. Kraut EH, Bouroncle BA, Grever MR. Pentostatin in the treatment of advanced hairy cell leukemia. J Clin Oncol. 1989; 7:168-72. [PubMed 2783731]
5. Ho AD, Thaler J, Mandelli F et al. The European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. Response to pentostatin in hairy-cell leukemia refractory to interferon-alpha. J Clin Oncol. 1989; 7:1533-8. [PubMed 2789273]
6. Ho AD, Thaler J, Stryckmans P et al. Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer. J Natl Cancer Inst. 1990; 82:1416-20. [PubMed 2388293]
7. Lembersky BC, Ratain MJ, Westbrook C et al. Rapid response to 2′-deoxycoformycin in advanced hairy cell leukemia after failure of interferons alpha and gamma. Am J Hematol. 1988; 27:60-2. [PubMed 3128105]
8. Johnston JB, Glazer RI, Pugh L et al. The treatment of hairy-cell leukaemia with 2′-deoxycoformycin. Br J Haematol. 1986; 63:525-34. [PubMed 3488071]
9. Cancer Therapy Evaluation Program. Treatment protocol (group C): pentostatin in patients with active hairy cell leukemia previously treated with alpha interferon. NCI Protocol No. I88-15. Bethesda, MD: National Cancer Institute; August 15, 1988.
10. Spiers ASD, Moore D, Cassileth PA et al.Remissions in hairy-cell leukemia with pentostatin (2′-deoxycoformycin). N Engl J Med.1987; 316:825-30. [IDIS 227381] [PubMed 2434850]
11. Spiers ASD, Parekh SJ, Bishop MB.Hairy-cell leukemia: induction of complete remission with pentostatin (2′-deoxycoformycin). J Clin Oncol. 1984; 2:1336-42. [PubMed 6334721]
12. Cassileth PA, Cheuvart B, Spiers ASD et al. Pentostatin induces durable remissions in hairy cell leukemia. J Clin Oncol. 1991; 9:243-6. [PubMed 1988572]
13. Dutcher JP, Salva KM, Wiernik PH. Successful treatment of hairy cell leukemia with 2′-deoxycoformycin after failure of interferons alpha or beta. Am J Clin Oncol. 1990; 13:290-3. [PubMed 2198792]
14. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food Drug and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to November 30, 1991. Rockville, MD; 1991 Dec.
15. Hairy cell leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2007 Dec 5.
16. Major PP, Agarwal RP, Kufe DW. Deoxycoformycin: neurological toxicity. Cancer Chemother Pharmacol. 1981; 5:193-6. [PubMed 6975188]
17. Blatt J, Venner PM, Riccardi R et al. Cerebrospinal fluid levels of 2′-deoxycoformycin after systemic administration in monkeys. J Natl Cancer Inst. 1982; 68:391-3. [PubMed 6977672]
18. Agarwal RP. Inhibitors of adenosine deaminase. Pharmacol Ther. 1982; 17:399-429. [PubMed 6187032]
19. Weinrib AB. Clinical pharmacokinetics of 2′-deoxycoformycin in cancer patients. Diss Abstr Int (Sci). 1982; 43:103-B.
20. Smyth JF, Paine RM, Jackman AL et al. The clinical pharmacology of the adenosine deaminase inhibitor 2′-deoxycoformycin. Cancer Chemother Pharmacol. 1980; 5(2):93-101. [PubMed 6970630]
21. Venner PM, Glazer RI, Blatt J et al. Levels of 2′-deoxycoformycin, adenosine, and deoxyadenosine in patients with acute lymphoblastic leukemia. Cancer Res. 1981; 41(11 Part 1):4508-11. [IDIS 166759] [PubMed 6975654]
22. Chronic lymphocytic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 Feb 25.
23. Kantarjian HM, Schachner J. Fludarabine therapy in hairy cell leukemia. Cancer. 1991; 67:1291-3. [IDIS 277935] [PubMed 1991291]
24. Kraut EH, Chun HG. Fludarabine phosphate in refractory hairy cell leukemia. Am J Hematol. 1991; 37:59-60. [PubMed 1708945]
25. Pentostatin. In: NCI investigational drugs pharmaceutical data 1990. 1990:129-30.
26. Yu AL, Matsumoto S, Bleeker L et al. Biochemical basis for the differential effects of deoxycoformycin on human leukemias. Adv Exp Med Biol. 162(Part B):305-8. (IDIS 162484)
27. Matsumoto SS, Yu J, Yu AL. Inhibition of RNA synthesis by deoxyadenosine plus deoxycoformycin in resting lymphocytes. J Immunol. 1983; 131:2762-6. [PubMed 6196398]
28. Matsumoto SS, Yu AL, Yu J. Morphological changes in leukemic lymphoblasts and normal lymphocytes treated with deoxyadenosine and deoxycoformycin. Cancer Invest. 1985; 3:225-33. [PubMed 3873981]
29. Ho AD, Ganeshaguru K, Knauf W et al. Enzyme activities of leukemic cells and biochemical changes induced by deoxycoformycin in vitro—lack of correlation with clinical response. Leuk Res. 1989; 13:269-78. [PubMed 2785618]
30. Russell NH, Prentice HG, Lee N et al. Studies on the biochemical sequelae of therapy in Thy-acute lymphoblastic leukaemia with the adenosine deaminase inhibitor 2′-deoxycoformycin. Br J Haematol. 1981; 49:1-9. [PubMed 6974003]
31. Johnston JB, Glazer RI, Pugh L et al. The treatment of hairy-cell leukaemia with 2′-deoxycoformycin. Br J Haematol. 1986; 63:525-34. [PubMed 3488071]
32. Grever MR, Siaw MF, Jacob WF et al. The biochemical and clinical consequences of 2′-deoxycoformycin in refractory lymphoproliferative malignancy. Blood. 1981; 57:406-17. [IDIS 164480] [PubMed 6970050]
33. Koller CA, Mitchell BS. Alterations in erythrocyte adenine nucleotide pools resulting from 2′-deoxycoformycin therapy. Cancer Res. 1983; 43:1409-14. [IDIS 165657] [PubMed 6600652]
34. Ganeshaguru K, Lee N, Llewellin P et al. Adenosine deaminase concentrations in leukaemia and lymphoma: relation to cell phenotypes. Leuk Res. 1981; 5:215-22. [PubMed 6973675]
35. Smyth JF, Harrap KR. Adenosine deaminase activity in leukaemia. Br J Cancer. 1975; 31:544-9. [PubMed 1057444]
36. Adams A, Harkness RA. Adenosine deaminase activity in thymus and other human tissues. Clin Exp Immunol. 1976; 26:647-9. [PubMed 1009688]
37. Van der Weyden MB, Kelley WN. Human adenosine deaminase: distribution and properties. J Biol Chem. 1976; 251:5448-56. [PubMed 9388]
38. Grever MR, Siaw MF, Coleman MS et al. Inhibition of K and NK lymphocyte toxicity by an inhibitor of adenosine deaminase and deoxyadenosine. J Immunol. 1982; 129:365-9.
39. Lum CT, Schmidtke JR, Sutherland DE et al. Inhibition of human T-cell rosette formation by the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA). Clin Immunol Immunopathol. 1978; 10:258-61. [PubMed 307473]
40. Hirschhorn R, Sela E. Adenosine deaminase and immunodeficiency: an in vitro model. Cell Immunol. 1977; 32:350-60. [PubMed 902324]
41. Carson DA, Seegmiller JE. Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis. J Clin Invest. 1976; 57:274-82. [PubMed 176177]
42. Hovi T, Smyth JF, Allison AC. Role of adenosine deaminase in lymphocyte proliferation. Clin Exp Immunol. 1976; 23:395-403. [PubMed 133008]
43. Parks RE Jr, Dawicki DD, Agarwal KC et al. Role of nucleoside transport in drug action: the adenosine deaminase inhibitor, deoxycoformycin, and the antiplatelet drugs, dipyridamole and dilazep. Ann NY Acad Sci. 1985; 451:188-203. [PubMed 3878117]
44. Chen SF, Stoeckler JD, Parks RE Jr. Transport of deoxycoformycin in human erythrocytes: measurement by adenosine deaminase titration and radioisotope assays. Biochem Pharmacol. 1984; 33:4069-79. [PubMed 6334522]
45. Agarwal RP Recovery of 2′-deoxycoformycin-inhibited adenosine deaminase of mouse erythrocytes and leukemia L1210 in vivo. Cancer Res. 1979; 39:1425-7.
46. Prentice HG, Russell NH, Lee N et al. Therapeutic selectivity of and predication of response to 2′-deoxycoformycin in acute leukaemia. Lancet. 1981; 2:1250-4. [IDIS 141104] [PubMed 6118669]
47. Grever MR, Leiby JM, Kraut EH et al. Low-dose deoxycoformycin in lymphoid malignancy. J Clin Oncol. 1985; 3:1196-201. [PubMed 2993534]
48. Piga A, Ganeshaguru K, Green ES et al. Selective toxicity of purine nucleosides to human leukaemic cells. Adv Exp Med Biol. 1989; 253(Suppl B):291-8.
49. Wortmann RL, Holcenberg J, Poplack DG. Relationship of 5′-nucleosidase activity and antileukemic effect in 2′-deoxycoformycin therapy. Cancer Treat Rep. 1982; 66:387-90. [IDIS 145479] [PubMed 6275991]
50. Leung KL, Yu AL. Natural killing (NK) activity in T-cell chronic lymphocytic leukemia (T-CLL) treated with deoxycoformycin (DCF). Cancer Res. 1981; 22:277.
51. Aye MT, Dunne JV. Effect of 2′-deoxycoformycin on erythroid, granulocytic, and T-lymphocyte colony growth. Blood. 1981; 58:1043-6. [IDIS 143285] [PubMed 6975136]
52. Major PP, Agarwal RP, Kufe DW. Clinical pharmacology of deoxycoformycin. Blood. 1981; 58:91-6. [IDIS 136201] [PubMed 6263381]
53. Mitchell BS, Koller CA, Heyn R. Inhibition of adenosine deaminase activity results in cytotoxicity to T lymphoblasts in vivo. Blood. 1980; 56:556-9. [IDIS 126239] [PubMed 6967747]
54. Koller CA, Mitchell BS, Grever MR et al. Treatment of acute lymphoblastic leukemia with 2′-deoxycoformycin: clinical and biochemical consequences of adenosine deaminase inhibition. Cancer Treat Rep. 1979; 63:1949-52. [IDIS 110527] [PubMed 316725]
55. Sinkule JA, Mauer EC, Murphy S et al. Monitoring the biochemical sequelae after 2′-deoxycoformycin administration. Drug Intell Clin Pharm. 1982; 16:481.
56. Agarwal RP, Spector T, Parks RE Jr. Tight-binding inhibitors. IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977; 26:359-67. [PubMed 849330]
57. Mitchell BS, Edwards NL, Koller CA. Deoxyribonucleoside triphosphate accumulation by leukemic cells. Blood. 1983; 62:419-24. [IDIS 174862] [PubMed 6603241]
58. Hershfield MS, Kredich NM, Koller CA et al. S-adenosylhomocysteine catabolism and basis for acquired resistance during treatment of T-cell acute lymphoblastic leukemia with 2′-deoxycoformycin alone and in combination with 9-β-d-arabinofuranosyladenine. Cancer Res. 1983; 43:3451-8. [IDIS 172827] [PubMed 6601986]
59. Anon. Drugs of choice for cancer. Treat Guide Med Lett. 2003; 1:41-52.
60. Foon KA, Rai KR, Gale RP. Chronic lymphocytic leukemia: new insights into biology and therapy. Ann Intern Med. 1990; 113:525-9. [IDIS 271730] [PubMed 2203293]
61. Keating MJ. Fludarabine phosphate in the treatment of chronic lymphocytic leukemia. Semin Oncol. 1990; 17(Suppl 8):49-62. [PubMed 1699283]
62. Cheson BD, Bennett JM, Rai KR et al. Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored Working Group. Am J Hematol. 1988; 29:152-63. [PubMed 3189311]
63. Gray DP, Grever MR, Siaw MFE et al. 2′-Deoxycoformycin (CDE) and 9-β-D-arabinofuranosyladenine (Ara-A) in the treatment of refractory acute myelocytic leukemia. Cancer Treat Rep. 1982; 66:253-7. [IDIS 145464] [PubMed 6976833]
64. Catovsky D, Fooks J, Richards S. Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults. Br J Haematol. 1989; 72:141-9. [PubMed 2757960]
65. Cheson BD. Current approaches to the chemotherapy of B-cell chronic lymphocytic leukemia: a review. Am J Hematol. 1989; 32:72-7. [PubMed 2667343]
66. Cheson BD. Recent advances in the treatment of B-cell chronic lymphocytic leukemia. Oncology (Williston Park). 1990; 4:71-8,83-4,87-8,90. [PubMed 2145022]
67. The French Cooperative Group on Chronic Lymphocytic Leukemia. A randomized clinical trial of chlorambucil versus COP in stage B chronic lymphocytic leukemia. Blood. 1990; 75:1422-5. [IDIS 265060] [PubMed 2180493]
68. The French Cooperative Group on Chronic Lymphocytic Leukemia. Effects of chlorambucil and therapeutic decision in initial forms of chronic lymphocytic leukemia (stage A): results of a randomized clinical trial on 612 patients. Blood. 1990; 75:1414-21. [IDIS 265059] [PubMed 2180492]
69. French Cooperative Group on Chronic Lymphocytic Leukaemia. Natural history of stage A chronic lymphocytic leukaemia untreated patients. Br J Haematol. 1990; 76:45-57.
70. Keller JW, Knospe WH, Raney M et al. Treatment of chronic lymphocytic leukemia using chlorambucil and prednisone with or without cycle-active consolidation chemotherapy: a Southeastern Cancer Study Group Trial. Cancer. 1986; 1185-92.
71. Chronic lymphocytic leukemia. In: Wilson JD, Braunwald E, Isselbacher KJ et al, eds. Harrison’s principles of internal medicine. l2th ed. New York: McGraw-Hill Company; 1991:1559-61.
72. Rogler-Brown T, Agarwal RP, Parks RE. Tight binding inhibitors. IV. Interactions of deoxycoformycin and adenosine deaminase in intact human erythrocytes and sarcoma 180 cells. Biochem Pharmacol. 1978; 27:2289-96. [PubMed 569482]
73. McConnell WR, Suling WJ, Rice LS et al. Use of microbiologic and enzymatic assays in studies on the disposition of 2′-deoxycoformycin in the mouse. Cancer Treat Rep. 1978; 62:1153-9. [PubMed 99236]
74. Chassin MM, Adamson RH, Zaharevitz DW et al. Enzyme inhibition titration assay for 2′-deoxycoformycin and its application to the study of the relationship between drug concentration and tissue adenosine deaminase in dogs and rats. Biochem Pharmacol. 1979; 28:1849-55. [PubMed 454456]
75. Poplack DG, Sallan SE, Rivera G et al. Phase I study of 2′-deoxycoformycin in acute lymphoblastic leukemia. Cancer Res. 1981; 41(9 Part 1):3343-6. [IDIS 139878] [PubMed 6973390]
76. Dearden C, Matutes E, Catovsky D. Deoxycoformycin in the treatment of mature T-cell leukaemias. Br J Cancer. 1991; 64:903-6. [PubMed 1931613]
77. Foss FM, Ihde DC, Breneman DL et al. Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol. 1992; 10:1907-13. [PubMed 1453206]
78. O’Dwyer PJ, Cheson BD, Leyland-Jones B et al. Deoxycoformycin: an active new drug for indolent lymphomas and hairy cell leukemia. Oncology (Williston Park). 1988; 2:17-23. [PubMed 3079330]
79. Lill MC, Golde DW. Treatment of hairy-cell leukemia. Blood Rev. 1990; 4:238-44. [PubMed 1706207]
80. Ho AD, Thaler J, Willemze R et al. Pentostatin (2′-deoxycoformycin) for chronic lymphoid neoplasms. J Chemother Infect Dis Malignancies. 1989; (Suppl 1):A383.
81. Agarwal RP. Deoxycoformycin toxicity in mice after long-term treatment. Cancer Chemother Pharmacol. 1980; 5:83-7. [PubMed 6970629]
82. Smyth JF, Prentice HG, Proctor S et al. Deoxycoformycin in the treatment of leukemias and lymphomas. Ann NY Acad Sci. 1985; 451:123-8. [PubMed 3878113]
83. Kanofsky JR, Roth DG, Smyth JF et al. Treatment of lymphoid malignancies with 2′-deoxycoformycin: a pilot study. J Clin Oncol. 1982; 5:179-82.
84. Food and Drug Administration. Specific requirements on content and format of labeling for human prescription drugs; proposed addition of “geriatric use” subsection in the labeling (Docket No. 89N-0474). Fed Regist. 1990; 55:46134-7.
85. Grever MR, Bisaccia E, Scarborough DA et al. An investigation of 2′-deoxycoformycin in the treatment of cutaneous T-cell lymphoma. Blood. 1985; 66:279-82.
86. Cass CE, Au-Yeung TH. Enhancement of 9-β-d-arabinofuranosyladenine cytotoxicity to mouse leukemia L1210 in vitro by 2′-deoxycoformycin. Cancer Res. 1976; 36:1486-91. [PubMed 944095]
87. Kuroki Y, Shimoyama M, Inaba S et al. Potentiation of growth-inhibitory activity of 9-β-d-arabinofuranosyladenine by 2′-deoxycoformycin in human cultured cell lines derived from leukemias and lymphomas. Jpn J Cancer Res. 1989; 80:482-9. [PubMed 2502523]
88. LePage GA, Worth LS, Kimball AP. Enhancement of the antitumor activity of arabinofuranosyladenine of 2′-deoxycoformycin. Cancer Res. 1976; 36:1481-5. [PubMed 946595]
89. Lee SH, Caron N, Kimball AP. Therapeutic effects of 9-β-d-arabinofuranosyladenine and 2′-deoxycoformycin combinations on intracerebral leukemia. Cancer Res. 1977; 37(7 Part 1):1953-5. [PubMed 861931]
90. Caron N, Lee SH, Kimball AP. Effects of 2′-deoxycoformycin, 9-β-d-arabinofuranosyladenine 5′-phosphate, and 1-β-d-arabinofuranosylcytosine triple combination therapy on intracerebral leukemia 1210. Cancer Res. 1977; 37:3274-9. [PubMed 884674]
91. Agarwal RP, Blatt J, Miser J et al. Clinical pharmacology of 9-β-d-arabinofuranosyladenine in combination with 2′-deoxycoformycin. Cancer Res. 1982; 42:3884-6. [IDIS 156284] [PubMed 6980706]
92. Yu AL, Mendelsohn J, Matsumoto SS. Induction of complete remission in T-cell acute lymphoblastic leukemia with deoxycoformycin (dcf) and 9-β-d-arabinofuranosyladenine (ara-A). Adv Exp Med Biol. 1986; 195(Pt A):491-6. [PubMed 3487920]
93. Asoh K, Saburi Y, Sato S et al. Potentiation of some anticancer agents by dipyridamole against drug-sensitive and drug-resistant cancer cell lines. Jpn J Cancer Res. 1989; 80:475-81. [PubMed 2568984]
94. Farmer JL, Prager MD. Inhibition of lymphoproliferation by dipyridamole. Biochem Pharmacol. 1982; 31:1381-6. [PubMed 7092928]
95. King ME, Naporn A, Young B et al. Modulation of cytarabine uptake and toxicity by dipyridamole. Cancer Treat Rep. 1984; 68:361-6. [IDIS 183938] [PubMed 6697325]
96. Chan TC, Young B, King ME et al. Modulation of the activity of PALA by dipyridamole. Cancer Treat Rep. 1985; 69:425-30. [PubMed 3857969]
97. Parke-Davis, Morris Plains, NJ: Personal communication.
98. Reviewers’ comments (personal observations).
99. Beutler E. Cladribine (2-chlorodeoxyadenosine). Lancet. 1992; 340:952-6. [IDIS 304138] [PubMed 1357355]
100. Jaiyesimi IA, Kantarjian HM, Estey EH. Advances in therapy for hairy cell leukemia. A review. Cancer. 1993; 72:5-16. [IDIS 316257] [PubMed 7685243]
101. Spielberger RT, Golomb HM. Hairy cell leukemia 1992. Leukemia. 1992; 6(Suppl 4):142-6. [PubMed 1279327]
102. Tallman MS, Hakimian D, Variakojis D et al. A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood. 1992; 80:2203-9. [IDIS 304962] [PubMed 1358262]
103. Golomb HM, Ratain MJ, Mick R et al. The treatment of hairy cell leukemia: an update. Leukemia. 1992; 6(Suppl 2):24-7. [PubMed 1349662]
104. Baltz JK, Montello MJ. Cladribine for the treatment of hematologic malignancies. Clin Pharm. 1993; 12:805-13. [IDIS 321039] [PubMed 7903917]
105. Saven A, Piro L. Newer purine analogues for the treatment of hairy-cell leukemia. N Engl J Med. 1994; 333:691-7.
106. Saven A, Piro LD. Treatment of hairy cell leukemia. Blood. 1992; 79:1111-20. [IDIS 293082] [PubMed 1371410]
107. Bryson HM, Sorkin EM. Cladribine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in haematological malignancies. Drugs. 1993; 46:872-94. [PubMed 7507037]
108. Habermann TM, Andersen JW, Cassileth PA et al. Sequential administration of recombinant interferon alpha and deoxycoformycin in the treatment of hairy cell leukaemia. Br J Haematol. 1992; 80:466-71. [PubMed 1581231]
109. Grever M, Kopecky K, Foucar MK et al. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol. 1995; 13:974-82. [PubMed 7707126]
110. Parke-Davis. Nipent (pentostatin for injection) prescribing information. Morris Plains, NJ; 1991 Oct.
111. Urba WJ, Baseler MW, Kopp WC et al. Deoxycoformycin-induced immunosuppression in patients with hairy cell leukemia. Blood. 1989; 73:38-46. [IDIS 307942] [PubMed 2783373]
112. Flinn IW, Kopecky KJ, Foucar MK et al. Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood. 2000; 96:2981-6. [PubMed 11049974]
113. Dillman RO, Mick R, McIntyre OR. Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia Group B. J Clin Oncol. 1989; 7:433-8. [PubMed 2784491]
114. Döhner H, Ho AD, Thaler J et al. Pentostatin in prolymphocytic leukemia: phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group. J Natl Cancer Inst. 1993; 85:658-62.
115. Weiss MA, Maslak PG, Jurcic JG et al. Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia. J Clin Oncol. 2003; 21:1278-84. [PubMed 12663715]
116. Lamanna N, Kalaycio M, Maslak P et al. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol. 2006; 24:1575-81. [PubMed 16520464]
117. Kay NE, Geyer SM, Call TG et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood. 2007; 109:405-11. [PubMed 17008537]
118. Shanafelt TD, Lin T, Geyer SM et al. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer. 2007; 109:2291-8. [PubMed 17514743]
119. Ho AD, Suciu S, Stryckmans P et al. Pentostatin in T-cell malignancies—a phase II trial of the EORTC. Leukemia Cooperative Group. Ann Oncol. 1999; 10:1493-8. [PubMed 10643542]
120. Leach JW, Pham T, Diamandidis D et al. Thrombotic thrombocytopenic purpura–hemolytic uremic syndrome (TTP-HUS) following treatment with deoxycoformycin in a patient with cutaneous T-cell lymphoma (Sezary syndrome): a case report. Am J Hematol. 1999; 61:268-70. [PubMed 10440915]
121. Antunes I, Magina S, Granjo E et al. Hemolytic-uremic syndrome induced by pentostatin in a patient with cutaneous T-cell lymphoma. Dermatology. 1999; 198:179-80. [PubMed 10325474]
122. Else M, Ruchlemer R, Osuji N et al. Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years. Cancer. 2005; 104:2442-8. [PubMed 16245328]
123. Ghura HS, Carmichael AJ, Bairstow D et al. Fatal erythroderma associated with pentostatin. BMJ. 1999; 319:549. [PubMed 10463896]
a. AHFS Drug Information 2009. McEvoy GK, ed. Pentostatin. Bethesda, MD: American Society of Health-System Pharmacists; 2009.
HID. Trissel LA. Handbook on injectable drugs. 15th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2009:1282-3.