A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85.

Abstract

PURPOSE:

A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx.

PATIENTS AND TREATMENT:

Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months.

RESULTS:

Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P = 0.0008), neck-nodes (N- 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P = 0.02) and sex (females 51% versus males 38%, P = 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P = 0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P = 0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P = 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications.

CONCLUSION:

Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.

• Authors: J Overgaard, H S Hansen, M Overgaard, L Bastholt, A Berthelsen, L Specht, B Lindeløv, K Jørgensen
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 46 Issue 2 Pg. 135-46 (Feb 1998) ISSN: 0167-8140 [Print] Ireland
• PMID: 9510041 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Radiation-Sensitizing Agents
• Nimorazole

Topics

• Adult
• Aged
• Aged, 80 and over
• Cell Hypoxia
• Combined Modality Therapy
• Double-Blind Method
• Female
• Humans
• Laryngeal Neoplasms (drug therapy, radiotherapy, surgery)
• Male
• Middle Aged
• Nimorazole (therapeutic use)
• Pharyngeal Neoplasms (drug therapy, radiotherapy, surgery)
• Placebos
• Radiation-Sensitizing Agents (therapeutic use)
• Salvage Therapy
• Treatment Outcome