Pharmacokinetics of Lonidamine after Oral Administration in Cancer Patients

Besner, Jean‐Guy; Leclaire, Robert; Band, Pierre R.; Deschamps, Michel; Sanctis, A.J. De; Catanese, B

doi:10.1159/000225885

Cited by 17 publications

(8 citation statements)

References 4 publications

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“…Thus the present study does not confirm the suggestion of Besner et al (1984) that the trough level of Lonidamine is lower (< 3 1tg ml-') in unresponsive patients than in responding individuals. In agreement with the present results, De Angelis et al (1989) failed to detect any difference in Lonidamine plasma levels in patients with brain metastases who did or did not respond to the drug when given with radiotherapy.…”

Section: Discussioncontrasting

confidence: 99%

“…The peak and trough concentrations together with the halflife are in general agreement with previous investigations (Young et al, 1981;Besner et al, 1984). Attempts to relate Lonidamine pharmacokinetics to either patient characteristics at the time of treatment or to side-effects revealed only one weak correlation.…”

Section: Discussionsupporting

confidence: 90%

“…The pharmacokinetics of Lonidamine have been studied in preclinical models (Segre & Catanese, 1981) but there is relatively little pharmacokinetic data from patients (Young et al, 1981;Besner et al, 1984). We have therefore measured Lonidamine levels using a high performance liquid chromatography assay (HPLC) with fluorescence detection in 17 patients after 1 month of therapy.…”

mentioning

confidence: 99%

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A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

Mansi

A²,

Dr³

et al. 1991

Br J Cancer

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Summary Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity.In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24 + months) and three (11%) a minor response. Two patients have stable disease (> 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required.Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity.Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

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A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

Mansi

A²,

Dr³

et al. 1991

Br J Cancer

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“…3(B)]. That is in agreement with the variable serum levels of the drug in cancer patients (Besner et al, 1984). However, the correlation between the concentrations in the two matrices was very good, suggesting that in rat, and most probably in humans, the testicular levels of the drug could be estimated based on the serum levels.…”

Section: Discussionsupporting

confidence: 76%

Analysis of lonidamine in rat serum and testis by high performance liquid chromatography

Grippa

Gatto

Leone

et al. 2001

Biomedical Chromatography

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A HPLC method for the determination of lonidamine in serum and testis, suitable for pharmacological studies in the rat and other mammals, has been developed. Briefly, 0.5 mL of serum or about 0.2 g of testicular tissue were extracted with ethyl acetate and evaporated to dryness under nitrogen. The residue was redissolved in methanol and an aliquot was injected onto a C18 column eluted with a mobile phase consisting of acetonitrile:water (51:49, v/v), containing 0.1% trifluoroacetic acid. The eluate was monitored at 230 nm with a sensitivity of 0.05 AUFS. By this method, the pharmacokinetics and the serum and testicular levels of the drug up to 120 h after the administration of one single dose (100 mg/kg body weight) of lonidamine to Sprague-Dawley rats have been studied. Results were highly variable, as previously reported, but a very good linear correlation was found between the serum and the testicular levels, suggesting that, in the rat, and possibly in the human, testicular levels could be estimated based on the serum concentrations.

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“…The antitumor action of the drug is thought to be mediated through its inhibitory effect on cellular oxygen consumption and aerobic glycolysis [1][2][3]. Further to our reports on the toxicity and pharmacology of LDM [4,5], we wish to present the preliminary results of a phase II study of this new anticancer agent. …”

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confidence: 99%

Phase II Study of Lonidamine in Cancer Patients

Band

Deschamps²,

Besner

et al. 1984

Oncology

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12 patients with metastatic cancer were treated with the substituted indazole carboxylic acid Lonidamine at oral daily doses of 270 mg/m². Toxicity, consisting mainly of myalgias, somnolence, hyperesthesia, anorexia and vomiting, generally decreased or disappeared over time despite continuing drug administration at unmodified dosage. Myalgias and hyperesthesias were markedly relieved with prednisone 5 mg twice daily. No laboratory abnormalities were seen. Partial responses were observed in a patient with hypernephroma and in a patient with breast cancer. Disease-oriented phase II studies with this new anticancer agent are warranted.

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Pharmacokinetics of Lonidamine after Oral Administration in Cancer Patients

Cited by 17 publications

References 4 publications

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

Analysis of lonidamine in rat serum and testis by high performance liquid chromatography

Phase II Study of Lonidamine in Cancer Patients

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