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The addition of induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma, according to multicenter, randomized, controlled phase 3 trial results published in TheLancet Oncology.
Perspective from
Concurrent chemoradiotherapy is the standard treatment for locoregionally advanced nasopharyngeal carcinoma; however, distant metastasis is the main source of treatment failure.
The addition of induction chemotherapy demonstrated early eradication of micrometastases in previous studies; however, it did not reduce distant metastases or prolong survival.
“One explanation is that a truly effective induction chemotherapy regimen has not yet been identified,” Ying Sun, MD, from the department of radiation oncology at Sun Yat-sen University Cancer Center, and colleagues wrote.
The combination of docetaxel, cisplatin and fluorouracil (TPF) has shown promising results with manageable toxicity as induction chemotherapy for nasopharyngeal carcinoma, however survival data are lacking.
Therefore, Sun and colleagues evaluated the addition of TPF induction chemotherapy to chemoradiotherapy in 480 patients with previously untreated, stage III to IVB nasopharyngeal carcinoma aged 18 to 59 years. Researchers randomly assigned patients to receive concurrent chemoradiotherapy alone (n = 241) or with TPF induction chemotherapy (n = 239).
Induction chemotherapy consisted of three cycles of IV docetaxel (60 mg/m² on day 1), IV cisplatin (60 mg/m² on day 1) and continuous IV fluorouracil (600 mg/m² per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy, which included three cycles of 100 mg/m² cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy.
After a median follow-up of 45 months, more patients treated with TPF induction chemotherapy plus concurrent chemoradiotherapy were failure free at 3 years (80% vs. 72%; HR = 0.68; 95% CI, 0.48-0.97) and alive at 3 years (92% vs. 86%; HR = 0.59; 95% CI, 0.36-0.95). Further, more patients in the induction chemotherapy arm did not experience distant failure at 3 years (90% vs. 83%; HR = 0.59; 95 CI, 0.37-0.96) and were alive without locoregional failure at 3 years (92% vs. 89%; HR = 0.64; 95% CI, 0.36-1.13).
More patients treated with induction chemotherapy experienced grade 3 or grade 4 neutropenia (42% vs. 7%), leucopenia (41% vs. 17%) and stomatitis (41% vs. 35%).
Additional follow-up is needed to assess long-term efficacy and toxicity of TPF induction chemotherapy, Sun and colleagues wrote.
Future trials designed to evaluate TPF plus cisplatin-based concurrent chemoradiotherapy compared with concurrent chemoradiotherapy followed by adjuvant chemotherapy also are necessary, Michael T. Spiotto, MD, PhD, assistant professor of radiation and cellular oncology at University of Chicago Medical Center, wrote an accompanying editorial.
Such a study could validate induction chemotherapy or reaffirm the use of adjuvant chemotherapy; however, the addition of cisplatin-based concurrent chemotherapy may be limited for other head and neck squamous cell cancers.
“Nevertheless, this study is an important step for redefining treatment guidelines in nasopharyngeal cancers,” Spiotto wrote. – by Kristie L. Kahl
Disclosures: The researchers and Spiotto report no relevant financial disclosures.
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