Activity of pentostatin (Nipent) in cutaneous T-cell lymphoma: single-agent and combination studies.
Cutaneous T-cell lymphoma (CTCL) comprises a constellation of diseases of malignant clonal T lymphocytes that present initially in the skin. Since biochemical studies of pentostatin suggested that T cells are more sensitive to the effects of inhibition of adenosine deaminase by purine analogs, early studies with pentostatin were conducted in patients with refractory T-cell neoplasms. Durable responses were reported in several patients on phase I studies. Of 94 CTCL patients treated on five phase II studies with single-agent pentostatin, the overall response rate was 40%, with a 7% complete response rate; the median time to progression ranged from 1.3 to 8.3 months. There was a trend toward improved response in patients with diffuse erythroderma or plaque disease. A phase II study combining pentostatin with intermittent high-dose interferon-alpha demonstrated a 41% overall response rate, with two complete responses, both in patients with Sézary syndrome and diffuse erythroderma Toxicities have been tolerable at doses of 4 to 5 mg/m2 administered weekly or for 3 consecutive days, with grade 3-4 hematologic toxicity in 31 patients, renal insufficiency in seven, nausea in 17, and conjunctivitis in three. In summary, pentostatin has demonstrated impressive activity in patients with advanced and refractory CTCL. Additional studies using pentostatin in earlier-stage CTCL or in combination with other active agents in advanced disease are warranted.
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Hematology/Oncology Department, Tufts New England Medical Center, Boston, MA 02111, USA.
D058892:Adenosine Deaminase Inhibitors; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012751:Sezary Syndrome / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000187:drug effects
D058892:Adenosine Deaminase Inhibitors; D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D015649:Pentostatin