Multiple daily fractionation (MDF) radiotherapy in association with hyperthermia and/or misonidazole: Experimental and clinical results

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Abstract
Several modalities involving a Multiple Daily Fractionation (MDF) course in combination with hyperthermia and/or the hypoxic sensitizer misonidazole have been tested on a mouse tumor system and then applied, with the proper sequencing, to a group of patients with multiple (N2–N3) neck node metastases from H&N cancers. Different lesions of the same patients underwent different modalities. The clinical results indicate the effectiveness, in respect to a historical series of patients treated with conventional fractionation (200 rads/day, five days/week), of either MDF alone (200 + 150 + 150 rads/day, five days/week) or MDF + hyperthermia (500 MHz, 42–43 C, 45 min., after 2nd daily fraction, on day 1, 3, and 5 of each week) or MDF + misonidazole (1.2 g/m2 daily, 2 hours before 1st fraction, up to a maximum dose of 12 g/m2), or MDF + hyperthermia + misonidazole. The latter modality appears to be possibly the most effective at inducing a complete local tumor response lasting longer in time (follow-up to a minimum of four months). The pharmacology of misonidazole has been monitored in the patients to avoid undesired excessive drug plasma level. No neurological symptoms have been observed. Oropharyngeal mucositis has been observed only in patients treated with misonidazole and radiation through two cross-firing portals. The problem of selecting individual patients for a particular modality is discussed.