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 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.
Robins
H I
HI
University of Wisconsin Clinical Cancer Center, Madison 53792.
Longo
W L
WL
Lagoni
R K
RK
Neville
A J
AJ
Hugander
A
A
Schmitt
C L
CL
Riggs
C
C
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001772:Blood Cell Count; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007191:Indazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D011720:Pyrazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D007191:Indazoles; D011720:Pyrazoles; C016371:lonidamine