Platinum levels and clinical responses of tumours treated by cisplatin with and without concurrent hyperthermia: a case study.
The heterogeneity of platinum distributed within tissue after clinical administration of cisplatin was evaluated for the first time. Platinum levels were correlated with the observed clinical responses of separate superficial histiocytic sarcomas located in the forearm of a 74-year-old male patient. One of four lesions received four weekly treatments with hyperthermia administered concurrently with 30 mg/m2 cisplatin, while three lesions were treated with cisplatin alone. The lesion receiving hyperthermia concurrently with cisplatin had a solid partial response during a 6-week period following this therapy, whereas two other tumours receiving cisplatin alone progressed. One lesion could not be clinically evaluated. Platinum levels were determined in multiple samplings from three of the four lesions and normal tissue in order to evaluate the validity of taking a single tumour sample of 100 mg or less for the analysis of platinum content. Such a small single sample might provide a value significantly different from the true average because of sampling error. The range in platinum distribution encompassed an average of three-fold difference within eight separate sample groups, with a factor of six being the greatest difference in a single sample group. This degree of heterogeneity is great enough to suggest that conclusions made from the analysis of small and single random tissue samples could be sufficiently in error to misdirect investigative or medical decisions.
Richmond
R C
RC
Radiation Oncology, Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
Stafford
J H
JH
Ryan
T P
TP
Mahtani
H K
HK
Memoli
V A
VA
Taylor
J H
JH
Coughlin
C T
CT
D000368:Aged; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005542:Forearm; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D010984:Platinum / Q000493:pharmacokinetics; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D014018:Tissue Distribution
D010984:Platinum; D002945:Cisplatin