Intratumoral injection of boiling carboplatin (BCBP) solution for treatment of liver cancer in the animal model.
OBJECTIVE
To develop a new modality of local hyperthermal chemotherapy for liver cancer.


METHODS
Carboplatin solutions of various concentrations were heated at 60 degrees C, 80 degrees C and 100 degrees C, and carboplatin content, pH value and ultraviolet absorption spectrum were assayed before and after heating. By establishing BALB/c murine model of subcutaneous transplant liver cancer, intratumoral injection of boiling carboplatin solution (group A), 45 degrees C carboplatin solution (group B), room-temperature carboplatin solution (group C), boiling distilled-water (group D) and room-temperature distilled-water (control group) was carried out, and tumor growth curve, tumor regression rate and pathohistological features following treatment were evaluated.


RESULTS
Carboplatin content remained stable, ultraviolet absorption spectrum presented no remarkable changes and pH value showed a slight decline after being heated for up to 20 min. Following treatment, all 16 tumors in group A were completely regressed up to day 21. In groups B, C and control group, no tumors became fully regressed and a size of 1.98 +/- 1.11 cm2, 1.50 +/- 0.58 cm2 and 4.83 +/- 0.37 cm2 was presented on day 21, respectively. In group D, though all tumors grossly disappeared during the early post-treatment days, 12 out of 16 recurred on day 21. The tumor regression rate in group A was significantly lower as compared with that of groups B, C, D and control group (all P < 0.01). Histological examination revealed massive necrosis with some degenerated tumor cells at the tumor margin in groups A and D, and only focal necrosis with more viable tumor cells at the center and margin in groups B and C on post-treatment day 1 and 3. Twenty-one days after injection, all tumors in group A presented complete necrosis and were partly replaced by fibrotic tissue. Except for 4 regressed tumors in group D which had the same histological features as those in group A, all other tumors in groups B, C, D and control group presented the same histological features as those untreated.


CONCLUSIONS
Carboplatin solution remained stable at boiling status. Intratumoral injection of boiling carboplatin solution could completely devitalize liver cancer tissue via synergistic effects of direct tumoricidal role of heat and the heat-enhanced tumoricidal role of carboplatin.
Lu
M
M
Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou, 510080, PR China. gylumd@public.guangzhou.gd.cn
Yin
X
X
Shen
Q
Q
Lu
J
J
D000818:Animals; D016190:Carboplatin / Q000494:pharmacology*; D005260:Female; D006979:Hyperthermia, Induced; D015552:Injections, Intralesional; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis
D016190:Carboplatin