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Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients. J Clin Oncol 1993 Sep;11(9):1787-94

Date

09/01/1993

Pubmed ID

8355046

DOI

10.1200/JCO.1993.11.9.1787

Scopus ID

2-s2.0-0027171586 (requires institutional sign-in at Scopus site)   86 Citations

Abstract

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes in a phase I clinical trial.

PATIENTS AND METHODS: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m2. Carboplatin was administered at target temperature.

RESULTS: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung--minor response (200 mg/m2); gastrointestinal neuroendocrine--complete response (CR) (400 mg/m2); pancreatic--partial response (PR) (480 mg/m2); small bowel--PR (575 mg/m2); ovarian--CR, two patients (575 mg/m2), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2).

CONCLUSION: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.

Author List

Robins HI, Cohen JD, Schmitt CL, Tutsch KD, Feierabend C, Arzoomanian RZ, Alberti D, d'Oleire F, Longo W, Heiss 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
Aged
Carboplatin
Combined Modality Therapy
Female
Humans
Hyperthermia, Induced
Male
Middle Aged
Neoplasms
Time Factors
Treatment Outcome