Whole-body hyperthermia and lonidamine as adjuvant therapy to treatment with cisplatin with or without local radiation in mouse bearing the Lewis lung carcinoma

Abstract

The Lewis lung carcinoma implanted subcutaneously in the hind leg of a C57BL mouse metastasizes avidly to the lungs of the host. This tumour model system thus allows assessment of both primary and metastatic disease to treatment. Lonidamine (50 mg/kg) administered once or twice daily produced approximately additive tumour growth delay with whole-body hyperthermia (60 min to 42°C and 60 min at 42°C). The addition of lonidamine to treatment with cisplatin (10 mg/kg) and whole-body hyperthermia continued to produce increased tumour growth delay of up to 14·7 days compared with 10·8 days for cisplatin/whole-body hyperthermia. The response of the metastatic disease paralleled that of the primary tumour with a reduction in the number and percent of large metastases (> 3 mm) on day 20 post-tumour implantation. The addition of local fractionated radiation therapy (3 Gy × 5) to the primary tumour produced a very effective treatment regimen resulting in 37·5 days of tumour growth delay along with twice daily lonidamine/cisplatin whole-body hyperthermia. With this treatment regimen there was also a reduction to 50% of control of the number of lung metastases as well as the percent of large metastases on day 20. Further investigation of these treatment combinations is warranted.

Key Words:

• Whole-body hyperthermia
• lonidamine
• lung metastases
• cis-diamminedichloroplatinum (II)