Value of adjuvant misonidazole in the definitive irradiation of advanced head and neck squamous cancer: an RTOG pilot study (78-02)

Journal Article · Mon Nov 30 23:00:00 EST 1981 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(81)90196-6· OSTI ID:6851537

Fazekas, J T ^[1]; Goodman, R L; McLean, C J

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1. Thomas Jefferson Univ. Hospital, Philadelphia, PA

This RTOG Phase II trial was instituted to determine the toxicity and potential value of the electron-affinic agent, Misonidazole, adjunctive to definitive radiotherapy of T3 and T4 squamous cancers of the oral cavity, oropharynx, or hypopharynx. The fractionation schema was altered to deliver two separate treatments (250 rad and 210 rad) on each day when Misonidazole was administered, while maintaining relatively ''standard'' fractionation (5 fractions and 1000 rad per week). In order to achieve effective enhancement while minimizing toxicity, Misonidazole doses were limited to 2.5 gm/m/sup 2/ once per week, not to exceed 24 gm total cumulative in 6 weeks. The dosage was reduced to 2.0 gm/m/sup 2//wk after the first 30 patients were entered. Among the 50 patients entered, toxicity was confined to the nervous system, with one-third of the patients experiencing mild or moderate peripheral neuropathies and an equal number developing nausea and/or vomiting following p.o. drug administration. Encephalopathy occurred in 10% of the 30 patients receiving 2.5 mg/m/sup 2/ dosage. Serum drug levels and cumulative Misonidazole doses did not correlate well with toxicity or response except in comparison of the ''no response'' to the ''complete response'' categories. Immediate mucosal and skin reactions were not enhanced and unusual late normal tissue effects were not encountered. Complete disappearance of all visible and palpable primary tumor was noted in 67% of the 36 patients who completed the adjuvant sensitizer program. Tumor response and survival did not generally correlate with measured (serum) Misonidazole concentration; recurrence was also independent of these measured levels. These preliminary results seemed sufficiently encouraging to warrant a Phase III (randomized) study, now underway by the RTOG.

• OSTI ID: 6851537
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 7:12; ISSN IOBPD
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
BODY AREAS
DIGESTIVE SYSTEM
DRUGS
FRACTIONATED IRRADIATION
HEAD
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IRRADIATION
MEDICINE
MEMBRANES
MISONIDAZOLE
MUCOUS MEMBRANES
NAUSEA
NECK
NERVOUS SYSTEM
NUCLEAR MEDICINE
ORAL CAVITY
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATIENTS
PHARYNX
RADIATION EFFECTS
RADIOINDUCTION
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RADIOTHERAPY
RESPIRATORY SYSTEM
SIDE EFFECTS
SKIN
SYMPTOMS
THERAPY
TOXICITY
VOMITING