Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Phase I trial of lonidamine with whole body hyperthermia in advanced cancer. Cancer Res 1988 Nov 15;48(22):6587-92

Date

11/15/1988

Pubmed ID

3180069

Scopus ID

2-s2.0-0023701036 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

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.

Author List

Robins HI, Longo WL, Lagoni RK, Neville AJ, Hugander A, Schmitt CL, Riggs C

Author

Walter L. Longo MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Antineoplastic Agents
Blood Cell Count
Combined Modality Therapy
Drug Evaluation
Female
Humans
Hyperthermia, Induced
Indazoles
Male
Middle Aged
Neoplasms
Pyrazoles