Marked potentiation of the antitumour activity of chemotherapeutic drugs by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).

PURPOSE: To determine whether there is a therapeutic interaction between the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and nine chemotherapy drugs against an early-passage mouse mammary tumour (MDAH-MCa-4), and to investigate the mechanism of any such interaction. METHODS AND RESULTS: Female C3H/HeN mice bearing intramuscular MDAH-MCa-4 tumours were injected intraperitoneally with DMXAA (80 micro mol/kg) or chemotherapy drug (at a range up to the maximum tolerated dose) alone, or coadministered. A small reduction in the dose of the chemotherapy drug was required in most cases, but the increase in antitumour effect was much greater than the increase in host toxicity (body weight loss). The therapeutic gain increased in the order 5-fluorouracil (no gain)<(etoposide, carboplatin, cyclophosphamide, doxorubicin, cisplatin)<(docetaxel, vincristine)