Response of peritoneal solid tumours after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin

Abstract

The combination of heat and chemotherapy was studied in an intraperitoneal tumour model. Rats bearing peritoneal CC531 tumours (2-6 mm) were treated i.p. with cDDP or CBDCA [maximal tolerated dose (MTD)] in combination with regional hyperthermia (41.5 degrees C, 1 h) of the peritoneal cavity. The addition of hyperthermia to the i.p. treatment led to a decrease in the MTD of cDDP by 33.3% at 41.5 degrees C. This was due to increased nephrotoxicity. The MTD of CBDCA did not change as a result of hyperthermia treatment. The chemo-hyperthermia treatment resulted in more cDDP or CBDCA DNA adducts in peritoneal tumours after the combined treatment than after chemotherapy alone. The increased tumour platinum concentrations, rising from 1.3 micrograms Pt g-1 tumour at 37 degrees C to 5.4 micrograms Pt g-1 tumour at 41.5 degrees C for cDDP and from 0.2 microgram Pt g-1 tumor to 0.7 microgram Pt g-1 tumour at 41.5 degrees C for CBDCA, contributed considerably to the enhanced numbers of cDDP or CBDCA DNA adducts. As a result of the latter, i.p. chemotherapy combined with regional hyperthermia led to an increase in tumour growth delay (TGD) after increasing the temperature to 41.5 degrees C for cDDP and CBDCA (by 40 days for cDDP, 22 days for CBDCA). These data were in agreement with the in vitro findings, i.e. that higher temperatures led to increased cytotoxicity.

Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

“…These results seem to confirm that an increase in platinum-DNA adduct formation is involved in the in vitro thermal enhancement of cytotoxicity of these drugs, as has been shown by Los et al (1993Los et al ( , 1994 for cisplatin. Whether the measured increase in adducts is responsible for the thermal enhancement of the cytotoxicity of oxaliplatin and lobaplatin cannot be adequately answered.…”

“…Cisplatin was used as the basis for comparison, because the cytotoxicity of cisplatin and platinum-DNA adduct formation are clearly enhanced by hyperthermia (Dahl and Mella 1990;Los et al 1993Los et al , 1994. Los et al (1993Los et al ( , 1994 found that hyperthermia not only increased the killing effect but also led to a doubling in cisplatin-DNA adduct formation at 41.5~ compared to 37~ In an intraperitoneal rat tumour model there was also a clear thermal enhancement of cisplatin cytotoxicity, as well as an increase in adduct formation. The adduct increase ratio was 2.7 (Los et al 1994).…”

“…Los et al (1993Los et al ( , 1994 found that hyperthermia not only increased the killing effect but also led to a doubling in cisplatin-DNA adduct formation at 41.5~ compared to 37~ In an intraperitoneal rat tumour model there was also a clear thermal enhancement of cisplatin cytotoxicity, as well as an increase in adduct formation. The adduct increase ratio was 2.7 (Los et al 1994).…”

“…Recently, Los et al (1993Los et al ( , 1994 found that hyperthermia primarily affected the cellular uptake of cisplatin. As a result of this increase in cellular uptake, cisplatin-DNA adduct formation was also increased.…”

Hyperthermic intraperitoneal perfusion chemotherapy and response evaluation in patients with gastric cancer and malignant ascites

“…Although IP chemotherapy may deliver high-dose intensity treatment to the peritoneal cavity, drug penetration deep into the peritoneal surface is limited (28). Hyperthermia treatment may augment the penetration distance of anticancer drugs by up to 2,000 µm, as well as altering the permeability of tumor cell membranes to enhance uptake of chemotherapeutic drugs (28).…”