pentostatin and Vomiting

Pentostatin (Nipent; SuperGen, San Ramon, CA) is a safe and well-tolerated medication but, like all chemotherapeutic agents, it may be associated with some toxicity. The toxicity seen with pentostatin is dose and schedule dependent and can be minimized by appropriate dosing. The dose of pentostatin should never exceed 4 mg/m2. A dose reduction is required for patients with renal insufficiency. Renal and neurological toxicities may occur, yet are uncommon with appropriate dosing. Nausea and vomiting also occur; however, they are usually controlled with antiemetic therapy. Like the other purine nucleoside analogs, pentostatin is an immunosuppressive drug that may increase the risk of infection, especially with opportunistic organisms. Prophylactic antibiotics should be considered when treating patients with pentostatin.

Topics: Antibiotic Prophylaxis; Antibiotics, Antineoplastic; Antiemetics; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunosuppressive Agents; Kidney; Nausea; Nervous System; Opportunistic Infections; Pentostatin; Vomiting

YK-176 is a newly isolated 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, produced by Aspergillus nidulans. In a cooperative phase I study, YK-176 was administered to 22 patients, comprising 18 with adult T-cell leukemia-lymphoma (ATL), two with cutaneous T-cell lymphoma (CTCL), one with lymphoblastic lymphoma of T-cell type and one with carcinoma of the uterine cervix. Doses of YK-176 ranged from 3.0 to 9.0 mg/m2 and were given intravenously for three consecutive days. General malaise, anorexia, nausea, vomiting and low grade fever were frequently encountered, but were transient and not dose-related. At all dose levels hematological toxicities were mild. Two of seven patients receiving 7.0 mg/m2 for three consecutive days developed hepatocellular enzyme elevations (grade 2) and one patient, proteinuria (grade 2). One of two patients given 9.0 mg/m2 for three consecutive days manifested a life-threatening (grade 4) disturbance of consciousness and dyspnea, presumably ascribable to the drug-related toxicity of YK-176. The results suggest that 7.0 mg/m2 i.v. for three consecutive days is the maximum acceptable dose of YK-176. Central nervous system, pulmonary and possibly renal toxicities appeared to be dose-limiting. Out of the 20 patients evaluable for therapeutic response, partial remissions were observed in four, three with ATL and one with CTCL, who received less than 7.0 mg/m2 for three consecutive days. We conclude that YK-176 is an active agent against ATL at doses that may not be associated with prohibitive toxicity. A starting dose of 5.0 mg/m2 for three consecutive days is recommended for further phase II studies on ATL.

Topics: Adult; Aged; Appetite; Drug Evaluation; Female; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Nausea; Pentostatin; Remission Induction; Vomiting

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.

Topics: Adult; Aged; Drug Therapy, Combination; Humans; Incidence; Interferon Type I; Lymphoma; Middle Aged; Pentostatin; Vomiting

2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.

Topics: Adenosine Deaminase Inhibitors; Adolescent; Adult; Child; Child, Preschool; Coformycin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia, Lymphoid; Liver; Lymphopenia; Male; Nausea; Pentostatin; Prognosis; Ribonucleosides; Vomiting