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PubMed1990

Vomiting associated with pentostatin and pentostatin plus alpha-interferon: unique pattern and potential mechanisms.

Pentostatin (2'-deoxycoformycin) is a unique antineoplastic agent that has proven valuable in the treatment of a number of lymphoid malignancies. Dose-limiting toxicities observed in clinical trials include central nervous system (CNS) effects and acute renal failure. Information regarding the incidence, duration, and severity of nausea and vomiting from published reports is conflicting and insufficient to provide recommendations for optimal supportive measures. We report the results of a phase I study where pentostatin was associated with a 20% incidence of vomiting following courses one and two (pentostatin alone). The third course of pentostatin administered concurrently with alpha interferon resulted in a 29% incidence of vomiting and by course four had increased to 50%. Grade of severity was similarly increased, and nausea and vomiting was the dose-limiting toxicity in 6 of 15 patients. Forty-two percent of all episodes of vomiting were delayed in onset (onset 24 hr after drug administration) and in over 80% of cases persisted for greater than 48 hr in duration. Potential mechanisms that may account for these findings, as well as recommendations regarding antiemetic therapy are provided.

Adult↗

PubMed1990

Chemical stability of pentostatin (NSC-218321), a cytotoxic and immunosuppressant agent.

Pentostatin, an unusual nucleoside of natural origin, has been used for the treatment of hairy cell leukemia, as an immunosuppressant agent, and as an inhibitor of adenosine deaminase. The studies of the physicochemical properties and solution stability of pentostatin are important to the development of a parenteral formulation for extensive preclinical and clinical testing. Pentostatin displayed apparent pKa values at 25 +/- 0.1 degree C and ionic strength of 0.15 M of 2.03 +/- 0.03 and 5.57 +/- 0.14 (spectrophotometric) and 5.50 +/- 0.02 (potentiometric) for N1 and the amidine nitrogen in the seven-membered ring, respectively, which are the most likely protonation sites. The rates of degradation of pentostatin were determined as a function of pH, buffer concentration, and temperature. In the pH range 1.0-4.0, pentostatin undergoes acid-catalyzed glycosidic cleavage leading to the formation of the base compound, and 2-deoxyribose. A carbonium ion mechanism in which C-N bond cleavage was the rate-determining step was consistent with the data. In the pH range 6.5-10.5, the imine bond at C5 position in pentostatin is hydrolyzed to form the corresponding formamide. Pentostatin hydrolysis in this pH range was independent of pH. At pH greater than 11, pentostatin decomposes to nonchromophoric products probably through multiple-step base-catalyzed hydrolytic mechanisms. Pentostatin appears to be quite stable after reconstitution of a lyophilized experimental dosage form. Care must be taken if pentostatin is extensively diluted with 5% dextrose in water, as pentostatin stability is compromised at pH values less than 5.

Buffers↗

PubMed1996

Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases.

Pentostatin (2'-deoxycoformycin, dCF) is a purine nucleoside analog and a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in the cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was hypothesized that pentostatin would be lymphocytotoxic and this proved to be true; this finding prompted its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA, e.g. acute lymphocytic leukemia (ALL), particularly of the T-cell variety. Although pentostatin proved to be active in ALL, large doses were required and major toxic effects outweighed therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B-cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T-cell lymphomas, adult T-cell lymphoma-leukemia, and low grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppresion, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppressive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia. Clinical studies with pentostatin are ongoing, and its roles in the management of neoplastic and non-neoplastic diseases have yet to be fully defined.

Adenosine Deaminase Inhibitors↗

PubMed1995

Pentostatin (2prime prime or minute-Deoxycoformycin): Clinical Pharmacology, Role In Cancer Chemotherapy, and Future Prospects.

Pentostatin (2prime prime or minute-deoxycoformycin, dCF) is a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was speculated that pentostatin would be lymphocytotoxic, and this proved to be the case, promoting its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA---e.g., acute lymphocytic leukemia (ALL), particularly its T cell variety. Although pentostatin proved to be active in ALL, large doses were required and toxic effects outweighted therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T cell lymphomas, adult T cell lymphoma-leukemia, and low-grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppression, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppresive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia.

Journal Article↗

PubMed1999

Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine.

We report the long-term follow-up results on two groups of patients with hairy cell leukaemia (HCL) treated with either pentostatin (deoxycoformycin) or cladribine (2-chlorodeoxyadenosine). 165 HCL patients received treatment with pentostatin (between 1986 and 1994), and 45 were treated with cladribine (between 1992 and 1997). Age and sex characteristics were similar in the two groups. 38 patients in the pentostatin group and 12 in the cladribine group were previously untreated. 22 patients in the cladribine group had received prior treatment with pentostatin; four were resistant, 17 had relapsed following partial (four) or complete (13) responses, and one was not evaluable for response. The response rates were the same in the two groups: 82% complete response (CR), 15% partial response (PR) for pentostatin and 84% CR, 16% PR for cladribine. Relapse rates were 24% for pentostatin and 29% for cladribine after median follow-up of 71 and 45 months respectively. At 45 months, however, the relapse rate for pentostatin was only 9.7%. We found a statistically significant difference in the disease-free interval (DFI) between the two groups suggesting that patients may relapse more quickly after cladribine. The majority of relapsed patients achieved second remissions following further therapy with either pentostatin or cladribine, with no evidence of cross resistance between the two agents. The 5-year survival for all patients was 97% and treatment- related toxicity was low. We conclude that both pentostatin and cladribine induce durable remissions in the majority of HCL patients. Longer follow-up is required to establish whether some patients are cured as there is no plateau in DFI, and which of these two agents may be the treatment of choice.

Adult↗

PubMedDate not supplied

Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia.

OBJECTIVE: To review the pharmacology, pharmacokinetics, adverse effects, and various dosage regimens of pentostatin, and to evaluate the role of pentostatin in the treatment of hairy cell leukemia (HCL). DATA IDENTIFICATION: Articles were identified via an English-language literature search of MEDLINE (1966-91) and an extensive search of bibliographies from identified articles. STUDY SELECTION: Human clinical trials and case reports were selected for evaluation. DATA EXTRACTION: The literature was assessed for quality, methodology, and outcome information. DATA SYNTHESIS: At dosages of 4 mg/m2 administered every other week for 6-9 months, pentostatin has been shown to successfully induce a complete response in 58-90 percent of patients and to produce a partial response in up to 30 percent of patients with HCL. The median time to achieve a response is 4.7 months. Long-term remissions of at least 14 months' duration have occurred in some patients. Compared with interferon alfa alone, total response rates are not significantly different when pentostatin and interferon alfa are used in combination. When dosed appropriately, pentostatin is generally well tolerated. Common adverse effects include nausea, vomiting, myelosuppression, fever, and infection. CONCLUSIONS: Pentostatin is a purine analog that inhibits adenosine deaminase, a key enzyme necessary for purine salvage. Pentostatin has received labeling approval for the treatment of HCL refractory to a minimum of three to six months of treatment with interferon alfa. Based on current data, pentostatin will be a useful addition to the therapeutic agents presently available to patients with HCL. Ongoing trials are evaluating the effectiveness of pentostatin as first-line therapy for patients with HCL.

Adenosine Deaminase Inhibitors↗

PubMed1995

Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study.

PURPOSE: Therapy of hairy cell leukemia has markedly improved. Interferon alfa-2a and pentostatin are active agents. The National Cancer Institute organized an intergroup trial to compare these agents prospectively in untreated patients. METHODS: Patients were randomized to receive either interferon alfa-2a (3 x 10(6) U subcutaneously three times per week) or pentostatin (4 mg/m2 intravenously every 2 weeks). Patients who did not respond to initial treatment were crossed over. RESULTS: Of 356 patients on study, 313 were eligible. Among interferon patients, 17 of 159 (11%) achieved a confirmed complete remission and 60 of 159 (38%) had a confirmed complete or partial remission. Among pentostatin patients, 117 of 154 (76%) achieved a confirmed complete remission and 121 of 154 (79%) had a confirmed complete or partial remission. Additional patients achieved criteria for complete remission, but lacked confirmatory follow-up evaluation. Response rates were significantly higher (P < .0001) and relapse-free survival was significantly longer with pentostatin than interferon (P < .0001). The median follow-up duration is 57 months (range, 19 to 82). Myelosuppression was more frequent with pentostatin (P = .013). A multivariate logistic regression analysis of the confirmed complete remissions on pentostatin showed the following factors to be important for achieving a complete remission: high hemoglobin level (two-tailed P = .024), young age (P = .0085), and no or little splenomegaly (P = .0029). CONCLUSION: Both agents were well tolerated. Pentostatin produced higher response rates, and the responses were durable. Patient age and clinical status had an impact on outcome with pentostatin. Pentostatin is effective therapy for hairy cell leukemia.

Adult↗

PubMedDate not supplied

Effect of adenosine deaminase inhibition with pentostatin on myocardial stunning in dogs.

Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and has been demonstrated to augment endogenous adenosine levels during regional and global myocardial ischemia. Based on the rationale that increasing endogenous adenosine during ischemia may be cardioprotective, the objective of this study was to determine if adenosine deaminase inhibition with pentostatin could improve postischemic contractile dysfunction (stunning) in open-chest anesthetized dogs. All animals underwent 15 min of coronary occlusion followed by 3 h of reperfusion preceded by an intravenous bolus of either 0.2 mg/kg of pentostatin (n = 8) or saline (n = 7). Sonomicrometers were placed in the ischemic area and were used to measure systolic wall thickening before, during, and after occlusion of the left anterior descending artery. Myocardial blood flow was measured with tracer labeled microspheres at baseline, 10 min of occlusion and at 1 h of reperfusion. Both groups were equally dyskinetic during occlusion (-21 +/- 5% of baseline thickening in the controls and -28 +/- 8% in the pentostatin group). The pentostatin group, however, demonstrated better contractile function at all time points during reperfusion, which was significantly different from the control group at 3 h of reperfusion. The improvement in regional function in the pentostatin group was not due to significant disparities in hemodynamic variables, size of the region at risk, or in collateral blood flow. These results indicate that pentostatin can ameliorate the severity of myocardial stunning, an effect we propose is due to increasing endogenous levels of adenosine during the ischemic interval. Although significant improvement was detected with pentostatin, the improvement was modest compared to controls, suggesting that the utility of inhibiting adenosine deaminase to modify regional mechanical stunning is limited.

Adenosine Deaminase Inhibitors↗

PubMed2002

Pentostatin pharmacokinetics and dosing recommendations in patients with mild renal impairment.

PURPOSE: The purpose of this study was to determine the pharmacokinetic parameters of pentostatin in renally impaired patients in order to establish dosing guidelines for this population. METHODS: Pentostatin doses were administered as 15-min intravenous infusions to patients based on their measured creatinine clearance (CLcr) as follows. Patients with normal renal function (NRF), defined as CLcr >60 ml/min, received 4 mg/m(2) repeated every14 days. Patients with impaired renal function (IRF) included those with CLcr 41-60 ml/min who received 3 mg/m(2) and those with CLcr 21-40 ml/min who received 2 mg/m(2), also repeated every 14 days. Heparinized plasma samples were collected during drug infusion and out through 96 h after dosing, except in two patients in whom sampling was extended to 144 h after dosing. Urine sampling extended to 96 h after dosing, and all samples were analyzed by a validated enzyme immunoassay for pentostatin concentrations. RESULTS: Enrolled in the study were 13 patients (7 IRF and 6 NRF), of whom 12 contributed samples for pharmacokinetic analysis. Median baseline CLcr values were 71.5 ml/min for NRF patients and 44 ml/min for IRF patients. Following the end of intravenous infusion, pentostatin plasma concentrations declined biexponentially with time. In some patients there was a transient increase in pentostatin equivalents 2 to 4 h after dosing. There was a good correlation between measured CLcr and pentostatin total plasma clearance. The AUC(0- infinity ) values seen in IRF patients, at lower doses, were within the range of the AUC(0- infinity ) values seen in patients with normal CLcr. Toxicities observed in the two groups of patients were similar. CONCLUSIONS: The pentostatin doses used in the study appear to be appropriate for administration to cancer patients with varying degrees of renal impairment.

Aged↗

PubMed2004

Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia: a phase I/II study by the Eastern Cooperative Oncology Group study E1488.

Pentostatin is a purine nucleoside analog with demonstrated activity in low-grade lymphoid malignancies. The purpose of this study was to determine the dose of pentostatin (dCF) that could be combined with chlorambucil and prednisone to treat chronic lymphocytic leukemia (CLL), evaluate the toxicity of the resulting regimen and to estimate its efficacy. This was a multi-institutional Eastern Cooperative Oncology Group (ECOG) phase I-II study. Individuals with active B-CLL were eligible if they had no prior treatment or were in sensitive first relapse, provided they had normal renal and hepatic function. Pentostatin was evaluated in combination with orally administered chlorambucil 30 mg/m2 and prednisone 80 mg/day, 1-5 of each 14-day cycle. The pentostatin dose was 2 mg/m2 IV, day 1 for the first 6 patients; 3 mg/m2 IV, day 1 for the next 6 patients; and 4 mg/m2 IV, day 1 for the last set of 6 patients. Fifty-five patients were entered. Because of increasing toxicity with no apparent improvement in clinical efficacy on escalation of the pentostatin dose, 2 mg/m2 was chosen as the phase II dose, and 43 patients were treated at this level. Thirty-nine of these patients were eligible, of which 38 were evaluable for response, 36 of these 38 had no prior treatment. Complete response (CR) manifested by normal bone marrow morphology, peripheral blood counts and resolution of any lymphadenopathy or hepatosplenomegaly occurred in 17 patients (45%). The overall objective response rate was 87%. The median response duration was 33 months and the median survival 5 years. The median time to treatment failure is 32 months. Severe (Grade 3+) infections were seen in 31% of patients and included bacterial pneumonia (n = 4), Pneumocystis pneumonia (n = 1), fungal pneumonia (n = 2), urinary tract infection with sepsis (n = 1) and Herpes Zoster (n = 5). Overall, 11 patients had H. Zoster while on study. Due to toxicity, 33% of patients stopped therapy. Pentostatin, chlorambucil and prednisone is a highly active regimen in CLL but cannot be recommended in present form because of an unacceptable incidence of opportunistic infections. These findings add to other recent reports which suggest combination therapy with pentostatin and alkylators are active in B-CLL. However, these combination chemotherapies will need to be combined with appropriate addition of anti-bacterial and anti-viral prophylaxis to reduce infection risk for B-CLL patients.

Adult↗

PubMed2000

Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin.

The nucleoside analogue, pentostatin, has demonstrated high complete response rates and long relapse-free survival times in patients with hairy cell leukemia, a disease that historically had been unresponsive to treatment. Long-term data on duration of overall survival and relapse-free survival and incidence of subsequent malignancies with this agent are lacking. Patients completing the treatment phase of a randomized, intergroup study who received pentostatin as an initial treatment or who crossed over after failure of interferon alpha were followed for survival, relapse, and diagnosis of subsequent malignancies. Two hundred forty-one patients treated with pentostatin as initial therapy (n = 154) or who crossed over after failure of interferon alpha (n = 87) were followed for a median duration of 9.3 years. Estimated 5- and 10-year survival rates (95% confidence interval) for all patients combined were 90% (87%-94%) and 81% (75%-86%), respectively. In the 173 patients with a confirmed complete response to pentostatin treatment, 5- and 10-year relapse-free survival rates were 85% (80%-91%) and 67% (58%-76%), respectively. Survival curves for patients initially treated with pentostatin and those crossed over were similar. Only 2 of 40 deaths were attributed to hairy cell leukemia. The mortality rate and incidence of subsequent malignancies were not higher than expected in the general population. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses. Subsequent malignancies do not appear to be increased with pentostatin treatment.

Adult↗

PubMed2000

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.

Adenosine Deaminase Inhibitors↗

PubMedDate not supplied

Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes.

Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. CD26 is a surface glycoprotein with a key role in T cell function as the ADA binding protein. We conducted a phase II study to evaluate pentostatin efficacy in relapsed T-non-Hodgkin's lymphoma (T-NHL) and to correlate response with tumor CD26 expression. We also examined the lymphopenic effect of pentostatin on CD26+ T lymphocytes. Eighteen patients were registered for the study. Pentostatin was administered as intravenous bolus daily over 3 days at an initial dose of 5 mg/m(2)/day, repeated every 4 weeks. CD26 surface expression on tumor cells and T lymphocytes was determined by flow cytometry. Out of 14 patients evaluable for response, there was 1 (7%) complete response (CR) and 6 (43%) partial responses (PR). Median progression-free survival for responders was 6 months (range: 2-15 months); median number of courses was 4 (range: 1-6). Responders included 1 of 2 CD26+ and 5 of 9 CD26- cases. Pentostatin also specifically depleted CD26+ rather than CD26- T lymphocytes, potentially associated with immunosuppression. We therefore conclude that while pentostatin is a safe and active agent for T-NHL regardless of CD26 expression, it may selectively deplete CD26+ T lymphocytes, with potentially significant clinical implications.

Adult↗

PubMed2005

[Pentostatin treatment for a patient with chronic type adult T-cell leukemia undergoing hemodialysis].

This is a preliminary feasibility study to assess the pharmacokinetics and efficacy of pentostatin in a patient undergoing dialysis. Pentostatin is a safe and well-tolerated medication, but a dose reduction is required for patients with renal insufficiency. We present a patient with chronic adult T-cell leukemia, whose white blood cell count exceeded 100 X 10(9)/l, and end-stage renal disease, receiving long-term thrice-weekly dialysis. The initial treatment with oral cyclophosphamide or with oral etoposide resulted in no response. After informed consent was obtained, pentostatin (1, 2, or 3mg/m2) was administered. 1 or 2 hours after injection, the patient received hemodialysis over 4 hours to remove any of the drug remaining in his system. Plasma concentrations of pentostatin were calculated with the known pharmacokinetics parameters. The differential equations describing a 2-compartment open-infusion pharmacokinetic model were fitted to the measured concentration-time data. Tumor lysis syndrome occurred 4 days after the course of the highest dose (3mg/m2), and the patient achieved complete remission. Anorexia, graded as 2 according to the NCI-CTC classification system, occurred and continued for four weeks. Pentostatin therapy consisting of the decreased dose (2mg/m2) was then administered every other week and provided a transient partial response with mild anorexia. Consequently, pentostatin can be considered as one of the chemotherapeutic regimens available for a patient undergoing dialysis.

Antibiotics, Antineoplastic↗

PubMed1999

Long term outcome of patients with hairy cell leukemia treated with pentostatin.

BACKGROUND: With the introduction of new drugs such as interferon-alpha (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, pentostatin has been found to produce higher complete remission rates than IFN. The current study was undertaken to investigate response and long term follow-up in HCL patients treated with pentostatin. METHODS: Between March 1989 and October 1996, 49 patients with HCL and 1 patient with a HCL variant were treated with pentostatin. Eighteen patients had received no prior therapy, 31 patients had received prior treatment with IFN, and 1 patient had received prior treatment with 2'-chlorodeoxyadenosine (2'CdA) and IFN. All patients except 1 were treated with a dose of 4 mg/m2 every 2 weeks. The median number of cycles was 12. RESULTS: The overall response rate was 96% (48 of 50 patients); 22 patients (44%) achieved a complete response, 18 patients (36%) achieved a good partial response (defined as residual bone marrow infiltration < 5%), 8 patients (16%) achieved a partial response, and 2 patients died. For a median follow-up of 33 months off therapy, there were 5 recurrences between 12-66 months; 3 of these patients were treated further with and responded to 2'CdA and 2 died of disease progression at 12 and 40 months, respectively. In addition, 3 patients died of unrelated causes (1 of very early infection, 1 of toxic death and another of cardiac arrest) comprising an overall death rate of 14% (7 of 50 patients). The overall survival rate was 86% for a median follow-up of 38 months (range, 8-105 months). Major side effects were febrile episodes, herpes zoster, nausea/emesis, and pancytopenia. CONCLUSIONS: This analysis confirms both the high remission rate and durable responses that may be achieved with pentostatin treatment in HCL patients. Although pentostatin is active, the risk of cytopenia and immunosuppression must be evaluated carefully.

Adult↗

PubMed1991

A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies.

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.

Adult↗

PubMed2003

Pentostatin for the treatment of chronic graft-versus-host disease in children.

Chronic graft-versus-host disease (cGVHD) is a major barrier to successful allogeneic stem cell transplantation. Pentostatin has been used to treat cGVHD in a small series of pediatric patients. The authors report the results of the first five pediatric patients receiving pentostatin for refractory cGVHD at Johns Hopkins Hospital. In this early experience, the authors saw considerable symptom response in their patients. Every patient in this series demonstrated a significant improvement in skin and oral symptoms. An increased incidence of infection secondary to pentostatin was not observed. No patient was permanently discontinued from pentostatin subsequent to side effects. If these promising results continue, a trial of pentostatin as a first-line therapy for cGVHD should be considered to potentially reduce our dependence on high-dose steroids for its treatment.

Bone Marrow Transplantation↗

PubMed1999

Pentostatin therapy of T-cell lymphomas with cutaneous manifestations.

PURPOSE: To determine the side effects of and response to pentostatin in patients with T-cell lymphomas with cutaneous manifestations. PATIENTS AND METHODS: Pentostatin was administered to 28 patients who had relapsed cutaneous T-cell lymphoma or peripheral T-cell lymphoma with prominent cutaneous disease. The starting dose was between 3.75 to 5.0 mg/m(2)/d intravenous for 3 days every 3 weeks. RESULTS: Of the 24 patients assessable for response, 17 (71%) achieved a partial remission (46%) or complete remission (25%). The patients had a median number of three (range, one to 12) prior therapies. Of the 86 courses of pentostatin given, 39 were administered at doses of 5.0 mg/m(2)/d and 30 at doses of 3. 75 mg/m(2)/d. Dose escalation to 6.25 mg/m(2)/d was possible in only five courses, and toxicity necessitated dose reduction to 2.8 mg/m(2)/d in 12 courses. The most common side effects were granulocytopenia, nausea, and nonneutropenic fever. Most patients developed significant lowering of CD4 counts. Herpes zoster was seen within 1 year after pentostatin in five patients (19%). CONCLUSION: Pentostatin is an active agent in heavily pretreated T-cell lymphomas with cutaneous manifestations.

Adult↗