PENTOSTATIN 
Pronounciation
- (PEN-toh-stah-tin)
Trade Name(s)
- 2-Deoxycoformycin, Nipent
Baseline studies and prehydration are required before administration; see Monitor.
4 mg/M2 every other week. Do not exceed recommended dose; see Precautions. If there is no major toxicity and improvement is continuous, treat until a complete response is achieved, then administer two additional doses. Do not treat beyond 12 months.
Reduced dose and benefit-versus-risk assessment may be required with impaired renal function (CrCl below 60 mL/min); insufficient data available. Two patients with impaired renal function (CrCl 50 to 60 mL/min) achieved complete response without unusual adverse events when treated with 2 mg/M2. ■ Withhold dose if SCr elevated; obtain CrCl. ■ Withhold dose if the absolute neutrophil count falls from a baseline of greater than 500 cells/mm3 before therapy to less than 200 cells/mm3 during treatment. Resume treatment when count returns to predose levels.
Specific techniques required; seePrecautions. Diluent (5 mL SWFI) provided; dissolve completely; will yield 2 mg/mL. May be given by IV injection or further diluted in 25 to 50 mL NS or D5W; 25 mL yields 0.33 mg/mL, 50 mL yields 0.18 mg/mL. Treat spills or waste with a 5% sodium hypochlorite solution before disposal.
Refrigerate before initial reconstitution. Store at room temperature and use within 8 hours after initial reconstitution or dilution for infusion.
Does not interact with PVC infusion containers or administration sets at concentrations specified for dilution.
Other sources suggest a few specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Follow each dose with an additional 500 mL of prehydration infusion fluids.
A single dose over 1 minute.
A single dose over 20 to 30 minutes.
Mechanism of action is not known, but it is cytotoxic as a result of its potent inhibition of the enzyme adenosine deaminase (ADA). Blocks DNA and RNA synthesis and causes DNA damage. Average terminal half-life of 6 hours is extended to 18 hours in patients with impaired renal function (CrCl less than 50 mL/min). Inhibits ADA for up to 1 week; actual response may not occur for months. Primarily excreted in urine.
Single-agent treatment of both untreated patients and alpha-interferon–refractory hairy cell leukemia (HCL) patients with active disease as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.
Treatment of chronic lymphocytic leukemia, prolymphocytic leukemia, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and peripheral T-cell lymphomas.
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Assess drug profile before administration. ■ Severe renal, liver, pulmonary, and CNS toxicities have occurred at higher doses; do not exceed recommended dose.■ Usually administered by or under the supervision of a physician specialist.■ Myelosuppression, especially neutropenia, is most severe during the first few courses of treatment. ■ Must consider risk/benefit in patients with some bone marrow suppression, the possibility of chickenpox or herpes zoster, a history of gout or urate renal stones, renal function impairment, or previous cytotoxic drug or radiation therapy. Use extreme caution. ■ After 6 months of treatment, assess for response; if partial or complete response is not evident, discontinue treatment. If partial response is evident, re-evaluate as indicated but do not treat beyond 12 months.
Monitor CBC (including differential and platelet count) and SCr before each dose and as indicated. Blood chemistries, including serum uric acid, and a CrCl assay are required before and during treatment. ■ Prehydration with 500 to 1,000 mL D5/½NS or an equivalent is required. An additional 500 mL is required postadministration. ■ Treatment of patients with infection may exacerbate symptoms and cause death. Control infection before treatment is initiated. Withhold treatment if an active infection occurs; resume when infection is controlled. ■ Prophylactic antiemetics recommended (e.g., prochlorperazine [Compazine], ondansetron [Zofran]); continue for 48 to 72 hours. ■ Observe closely for severe rashes, nervous system toxicity, and myelosuppression (especially after initial cycles); pentostatin may have to be withheld or discontinued. ■ For severe neutropenia beyond the initial cycles, evaluate for disease status, including a bone marrow examination. ■ Assess response to treatment with periodic monitoring of peripheral blood for hairy cells. Bone marrow aspirates and biopsies may be required at 2- to 3-month intervals. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood).
Consider birth control options; effective birth control recommended. ■ Report rashes, symptoms of infection, or bruising and bleeding immediately. ■ See Appendix D.
Category D: avoid pregnancy; can cause fetal harm. ■ Discontinue breast-feeding. ■ Safety for use in pediatric patients under 18 years of age not established.
Consider decreased renal function.
Assess drug profile before administration. ■ Do not use with fludarabine; may increase risk of fatal pulmonary toxicity.■ Combination therapy with carmustine, etoposide, and high-dose cyclophosphamide as part of the ablative regimen for bone marrow transplant has caused acute pulmonary edema and hypotension. Deaths have occurred. ■ Pentostatin enhances the effects of vidarabine. Combined use of these agents may result in an increase in adverse reactions associated with each drug. The therapeutic benefit of this drug combination has not been established. ■ May cause skin rash with allopurinol.■ Elevates liver function tests; usually reversible. ■ Do not administer live virus vaccines to patients receiving antineoplastic drugs. ■ Uric acid levels may increase; increased dose of gout agents (e.g., colchicine, probenecid, sulfinpyrazone) may be indicated. ■ Leukopenia and thrombocytopenia increased by agents causing blood dyscrasias (e.g., anticonvulsants [phenytoin], penicillins, phenothiazines, and many others).
Anemia, anorexia, chills, cough, diarrhea, fatigue, fever, GU disorders, headache, hepatic disorders/elevated liver function tests, hypersensitivity reactions, infection, leukopenia, lung disorders, myalgia, nausea, neurologic disorders/CNS, pain, rashes, skin disorders, thrombocytopenia, upper respiratory infections, and vomiting occur in 10% of patients and may require discontinuation of treatment. Abdominal pain; abnormal ECG; abnormal thinking; abnormal vision; anxiety; arthralgia; asthenia; back pain; bronchitis; cardiac arrhythmias; chest pain; confusion; conjunctivitis; constipation; depression; dizziness; dry skin; dyspnea; dysuria; ear pain; ecchymosis; eczema; elevated BUN, creatinine, and LDH; epistaxis; eye pain; flatulence; flu syndrome; hematuria; hemorrhage; herpes simplex; herpes zoster; insomnia; lung edema; lymphadenopathy; maculopapular rash; malaise; neoplasm; nervousness; paresthesia; peripheral edema; petechiae; pharyngitis; pneumonia; pruritus; rhinitis; seborrhea; sinusitis; skin discoloration; somnolence; stomatitis; sweating; thrombophlebitis; vesiculobullous rash; weight loss; and death have occurred in 3% to 10% or more of patients.
Keep physician informed of all side effects; most will be treated symptomatically if indicated. Withhold dose and notify physician for elevated SCr, absolute neutrophil count below 200 cells/mm3, myelosuppression, infection, CNS toxicity, or severe rash. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes) and/or blood modifiers (e.g., darbepoetin alfa, epoetin alfa, filgrastim, pegfilgrastim, sargramostim) may be indicated to treat bone marrow toxicity. Overdose may cause death due to severe renal, hepatic, pulmonary, or CNS toxicity. There is no specific antidote. Supportive therapy as indicated will help sustain the patient.