QOL for Advanced Squamous Cell Carcinoma of the Head and Neck: Results of a Phase III Randomized Trial of Tirapazamine, Cisplatin, and Radiation vs. Cisplatin and Radiation (TROG 02.02)

Quality of life (QOL) was measured prospectively in a Phase III randomized trial (HeadSTART) assessing the addition of the hypoxic cell sensitizer tirapazamine to a standard cisplatin and radiation regimen. Patients with previously untreated Stage III or IV (excluding T1-2N1 and M1) SCC of the oral cavity, oropharynx, hypopharynx, or larynx, were randomized to receive definitive radiotherapy (70 Gy/7 weeks) concurrently with either cisplatin (100 mg/m2) on Day 1 Weeks 1, 4, and 7 (CIS) or cisplatin (75 mg/m2) plus tirapazamine (290 mg/m2/day) on Day 1 of Weeks 1, 4, and 7 and tirapazamine alone (160 mg/m2/day) on Days 1, 3, and 5 of Weeks 2 and 3 (CIS/TPZ). The QOL was measured using the FACT-H&N at baseline, 2, 6, 12, 23, and 38 months post-treatment, with change from baseline to 6 months prespecified as the primary QOL comparison. Changes of >5–10% of instrument score are clinically significant. Median follow-up in 861 patients is 2.3 years. The OS at 2 years did not differ by arm (65.7% CIS; 66.2% CIS/TPZ; p = 0.65). QOL compliance (98% at baseline; 87% at 6 months) did not differ between arms, and no significant difference in baseline scores was seen for patients who did vs. did not complete the 6 month questionnaire. The FACT-H&N score was statistically but not clinically significantly higher in the CIS group at baseline (109.6 vs. 105.9 [2.5% difference]; p = 0.03). No significant difference was seen between arms in change from baseline to 6 months for FACT-H&N total score (-9.7 vs. -8.9; p = 0.72), or for any subscale. The QOL response assessment at 6 months showed a clinically significant FACT-H&N score worsening in 54% of patients, stability in 21%, and improvement in 25%, with no difference by arm (p = 0.25). A significant 6% (-9.3/144) decline in FACT-H&N score was seen for both groups from baseline to 6 months (p < 0.001); the head-and-neck cancer subscale also showed significant worsening (11.8%; p < 0.001), while the emotional subscale showed improvement (8.5%; p < 0.001). By 12 months, the overall FACT-head and neck score showed a nonsignificant 3% decline from baseline, with no statistical difference by arm (p = 0.78); clinically significant differences from baseline were still seen for the head-and-neck cancer (7% worsening) and emotional (11% improvement) subscales. As predicted, head-and-neck cancer-specific QOL declined following aggressive treatment with concurrent chemoradiotherapy, with persistent deficits observed overall at 6, but not 12, months post-treatment. This study represents the first available data on the QOL effects of concurrent chemoradiotherapy from a large randomized trial. No QOL differences were observed with the addition of tirapazamine as compared to standard cisplatin and radiotherapy.