Phase I trial of lonidamine with whole body hyperthermia in advanced cancer

Lonidamine is a dechlorinated derivative of indazole-3-carboxylic acid which preclinically synergizes with hyperthermia. Clinically, this nonmyelosuppressive drug (given p.o. daily) is active as a single agent in a variety of malignancies. On this basis, a Phase I study which incorporates a drug esc...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1988-11, Vol.48 (22), p.6587-6592
Main Authors: ROBINS, H. I, LONGO, W. L, LAGONI, R. K, NEVILLE, A. J, HUGANDER, A, SCHMITT, C. L, RIGGS, C
Format: Article
Language:English
Subjects:
Adult
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Blood Cell Count
Chemotherapy
Combined Modality Therapy
Drug Evaluation
Female
Humans
Hyperthermia, Induced - adverse effects
Indazoles - adverse effects
Indazoles - blood
Indazoles - therapeutic use
Male
Medical sciences
Middle Aged
Neoplasms - therapy
Pharmacology. Drug treatments
Pyrazoles - therapeutic use
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lonidamine is a dechlorinated derivative of indazole-3-carboxylic acid which preclinically synergizes with hyperthermia. Clinically, this nonmyelosuppressive drug (given p.o. daily) is active as a single agent in a variety of malignancies. On this basis, a Phase I study which incorporates a drug escalation schema as well as an escalation in temperature, i.e., 41.0 degrees C for 85 min to 41.8 degrees C for 75 min, was executed. Induction therapy included seven whole-body hyperthermia treatments. Whole-body hyperthermia was delivered using a radiant heat system. Twenty-four patients were entered on study. Of these, 20 were evaluable for response. Group A (60 mg/m2) had three patients with three no responses. Group B (180 mg/m2) consisted of three patients: one lymphoma, partial response; two gastrointestinal adenocarcinomas, one partial response and one improvement, i.e., less than a partial response. Group C (360 mg/m2) had 17 patients: two lung cancers, one complete response and one improvement; one melanoma, improvement; one ovarian, disease stabilization (greater than 100 days); two adenocarcinomas of the gastrointestinal tract, two disease stabilizations; 11 patients, no responses; one patient entered at this level was ineligible for study and did not receive lonidamine. Therapy was well tolerated. Of 16 patients reporting myalgias, two required a lonidamine dose reduction; one patient required dose reduction for central nervous system toxicity. Results obtained encourage Phase II clinical trials.
ISSN:0008-5472
1538-7445