Pentostatin

• Pentostatin (2-deoxy-coformycin or DCF) is a purine nucleoside analogue (PNA).
• It is a cytotoxic agent with high activity in a variety of lymphoid and myeloid malignancies, exerting cytotoxic effect in both proliferating and quiescent cells.
• It has a well established place in treatment of hairy cell leukaemia.^1,2
• In recent years lower dose combination regimens with pentostatin have been developed which may have profound effects on complete remission rates and, ultimately, cure in some chronic lymphocytic leukaemias (CLL).^3,4
• Low dose combination regimens with pentostatin appear to be active and very promising in other lymphoproliferative diseases.^5,6

• The PNAs share similar chemical structure and mode of action.
• The cytotoxic effect is exerted through a variety of mechanisms (inhibition of DNA synthesis and repair, mitochondrial pathways etc) culminating in apoptosis.⁷
• It is a strong inhibitor of adenosine deaminase, an important degradative enzyme in purine metabolism which is present in all human tissues but in higher concentration in lymphoid tissue.⁵
• Synergistic actions have been demonstrated between PNAs and other cytotoxic agents (such as the alkylating agents, anthracycline antitumour antibiotics, cytacarbine and monoclonal antibodies) which explain the enhanced benefits of combination regimens.⁷

• Pentostatin and fludarabine is the treatment of choice in hairy cell leukaemia, but other combinations with pentostatin have been used. ^1,2,7,8 A report from the Marsden of 219 patients treated with PNAs showed that with pentostatin 96% of patents showed a complete response with relapse rates of 24% at 5 years and 42% at 10 years. Survival at 10 years was 96%.²
• Pentostatin is highly effective in:
  • Chronic lymphatic leukaemia (CLL)^{4,9,10,11,12,13,14}
  • Low grade B and T cell non Hodgkin's lymphomas, including Waldenstrom's macroglobulinemia^{6,15,16,17,18}
  • T-cell cutaneous lymphomas^17,19
• Controlled trials have shown pentostatin to be effective in:
  • Acute myeloid leukaemia⁷
  • Myelodysplastic syndromes⁷
• Pentostatin has an important role in non-myeloablative regimens in allogenic stem cell transplantation^7,20

When introduced pentostatin was given in high doses for acute lymphoblastic leukaemias. New regimens have been developed and are being developed for a wider range of disease. In general it is being given in lower dosages and in combination regimens:

• It is given intravenously. 10mg vials of powder for reconstitution costs over £800
• It is usually given every 2-3 weeks in cycles (e.g. 6 cycles¹⁰).
• Dosages are low (e.g. 4mg/ sq metre in previously treated CLL¹⁰).
• It is given most appropriately in specialist centres.
  Patients are likely to be involved in trials which are needed to further improve regimens and define relative benefits. For example in CLL,⁴ in relapsed CLL and non-Hodgkin's lymphoma^10,11,21 for indolent lymphoproliferative disorders,⁶ peripheral T-cell lymphomas.^16,17
• It is likely to be used in combination regimens to take advantage of the synergism with other agents (e.g. alkylating agents and monoclonal antibodies).

• The low dose regimens appear to be well tolerated.^6,10,20 It is even well tolerated in elderly patients.²²
• It is less myelosuppressive than other PNAs and not toxic to myeloid progenitors (hence use in autologous stem cell transplant patients²⁰).
• The main problems arise from the prolonged immunosuppression. Opportunistic infections are a problem and there should be awareness of this amongst all involved in the care of treated patients. This has implications for shared care protocols and communication between specialist centres, patients and the primary health care team.

• Confirm that for patients on chemotherapy there is a record (preferably shared) of the regimen being used.
• Confirm that patients on chemotherapy are aware of possible complications and what to do if such complications arise (contact details etc).
• Encourage the specialist centre to produce a shared care protocol so that the primary health care team and patient are appropriately and consistently informed.