Phase I and Clinical Pharmacologic Evaluation of Lonidamine in Patients with Advanced Cancer

Abstract

Lonidamine was studied in 31 patients with different types of advanced cancer. With one exception, patients were pretreated. Lonidamine was given at 6 dosage levels from 180 to 520 mg/m² for at least 28 days. No toxicity on hematopoietic function was observed. Side effects consisted mostly in musculoskeletal discomfort, testicular pain in males and a reversible ototoxicity. In 2 patients conjunctivitis and photophobia occurred. Plasma Lonidamine levels were measured in 14 patients. Peak concentrations were observed from 1 to 2 h after administration and ranged from 3 to 35 μg/ml. Objective antitumoral effects were observed in only 2 patients with mycosis fungoides; a 3rd patient with mycosis fungoides was considered to have stable disease.

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

“…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.…”

“…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.…”

The combined use of radiation therapy and lonidamine in the treatment of brain metastases

“…The mean nadir white blood cell count (WBC) was 8.3 x 103/ram 3 (range: 0. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].0 x 103/ram3). Three patients had WBC below 2.0 x 103/mm3; 1 had tumor in his bone marrow and 2 others received systemic chemotherapy, 1 of whom also received pelvic RT.…”

The potential role of lonidamine (LND) in the treatment of malignant glioma

“…Its main side effects are myalgia, testicular pain and gastric discomfort [11][12][13][14]. It does not interfere with neurological findings, such as focal deficit and/or intracranial hypertension [15].…”