The clinical pharmacology of chlorambucil and prednimustine [letter]

Newell,; Calvert, Ah; Harrap, K. R.; McElwain, T. J.

doi:10.1111/j.1365-2125.1983.tb02264.x

Cited by 4 publications

(1 citation statement)

References 11 publications

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“…There is little information relating to the pharmacokinetics of chlorambucil, but the information that exists demonstrates that it has good oral bioavailability (Newell et al , 1983). The Scotland and Newcastle Lymphoma Group (SNLG) has used high‐dose/short‐course chlorambucil in a number of studies of all‐oral chemotherapy combinations for low‐grade non‐Hodgkin's lymphoma (Taylor et al , 2000) and relapsed Hodgkin's disease (Lennard et al , 1990) with good efficacy and minimal toxicity.…”

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confidence: 99%

High‐dose chlorambucil for the treatment of chronic lymphocytic leukaemia and low‐grade non‐Hodgkin's lymphoma

et al. 2002

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Summary. Chlorambucil has been used for many years for the treatment of low-grade B-cell lymphoproliferative disorders, including chronic lymphocytic leukaemia and lowgrade non-Hodgkin's lymphoma. There is evidence in the literature that increasing the dose of chlorambucil produces better results than ÔstandardÕ doses in terms of response rates and overall survival. There is also evidence that this approach may be at least as effective as the use of fludarabine, as well as being very much less expensive. We describe a high-dose chlorambucil (HDC) regimen, which involves a sustained but intermittent dose of chlorambucil, i.e. 30 mg/d for 4 d per week for 4 weeks, followed by a further four courses at fortnightly intervals for 8 weeks (a total of eight 4-d courses) given as a single drug over an initial 12-week period. The outcome of treatment in previously treated and untreated patients was excellent, with a median time to treatment failure of 33 months for the patient cohort overall and for previously treated and chemotherapy-naive patients of 13 and 104 months respectively. In patients previously treated with fludarabine, 78% had a response. Autoimmune haemolytic anaemia was reversed in one patient. Toxicity, both haematological and other, was minimal. We propose that escalated-dose chlorambucil regimens should be compared with fludarabine in randomized controlled trials, rather than ÔstandardÕ lower dose protocols.

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High‐dose chlorambucil for the treatment of chronic lymphocytic leukaemia and low‐grade non‐Hodgkin's lymphoma

et al. 2002

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Alkylating Agents

Wilman¹,

Farmer²

1989

Cancer Management in Man

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Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Musch¹,

Malek

Peter‐Katalinić

et al. 1992

Cancer Chemother. Pharmacol.

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Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB + P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB + P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB + P.

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The clinical pharmacology of chlorambucil and prednimustine [letter]

Cited by 4 publications

References 11 publications

High‐dose chlorambucil for the treatment of chronic lymphocytic leukaemia and low‐grade non‐Hodgkin's lymphoma

High‐dose chlorambucil for the treatment of chronic lymphocytic leukaemia and low‐grade non‐Hodgkin's lymphoma

Alkylating Agents

Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

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