Chemoradiotherapy Regimen May Show Viability in Recurrent HNSCC

Combining radiation with cisplatin/paclitaxel appeared to improve survival over chemotherapy alone among patients with recurrent squamous cell carcinoma of the head and neck (HNSCC), although the regimen yielded a high incidence of grade 5 toxicity, according to data from the phase 2 NRG Oncology RTOG 9911 trial (NCT00005087) published in the International Journal of Radiation Oncology, Biology, and Physics.¹

Data revealed a median overall survival (OS) of 12 months with the experimental regimen vs 8.5 months among patients who received chemotherapy alone in a historical cohort (HR, 0.70; 95% CI, 0.51-0.95; P = .01). The 5-year OS rates in each respective group were 14.9% (95% CI, 7.9%-21.9%) and 3.8% (95% CI, 0.0%-8.0%). When adjusting for 2 factors that significantly correlated with improved outcomes—Zubrod performance status and prior surgery—the hazard ratio was 0.67 (95% CI, 0.49-0.92).

Investigators observed deaths in 64.9% of patients due to the incident cancer, 3.2% due to second primary tumors, and 22.3% due to noncancer (11.7%) or unknown causes (10.6%). Noncancer-related deaths were attributed to pulmonary etiology (n = 3), cardiac origin (n = 2), infection (n = 2), unknown illness (n = 1), suicide (n = 1), brainstem injury (n = 1), and carotid artery hemorrhage (n = 1).

“[R]eirradiation in locally recurrent or second primary [head and neck cancer], in the absence of distant metastases, remains a viable option for treatment and potential long-term survival,” lead study author Corey J. Langer, MD, from the Department of Hematology-Oncology at the University of Pennsylvania, wrote with coauthors in the publication.¹ “Optimization with modern systemic therapies and/or reirradiation techniques may further improve these outcomes.”

In this phase 2 trial of split-course radiation therapy plus concurrent paclitaxel and cisplatin, 100 evaluable patients were assigned to receive radiation at 1.5 Gy per fraction twice daily for 5 days every other week for 4 cycles, with a daily inter-fraction interval of 4 to 6 hours. Additionally, patients received cisplatin at 15 mg/m² plus paclitaxel at 20 mg/m², both given daily for 5 days then every other for 4 cycles.

The trial’s primary end point was OS relative to a historical control cohort of patients who received chemotherapy alone in the phase 2 NRG Oncology RTOG 9610 trial. Secondary end points included disease-free survival, grade 4/5 toxicity, and patterns of failure.²

Patients 18 years and older with histologically confirmed locally recurrent primary HNSCC or second primary HNSCC and disease confined to the head and neck were eligible for enrollment on the study. Other eligibility criteria included having measurable disease, ineligibility to undergo complete surgical resection, and no distant metastases.

The median follow-up was 9.1 years (range, 5.0-10.1). The median age was 60 years (range, 27-83), and most patients were male (76.0%) and White (90.0%). Additionally, a majority of the study population had a Zubrod performance status of 1 (66.0%), no feeding tubes (53.0%), recurrence of a prior head and neck tumor at study entry (77.0%), local disease only (58.0%), and stage T2 disease (35.0%).

Grade 5 toxicities within 3 months of completing treatment occurred in 5% of patients, and 21% had grade 3 or higher anemia. Additionally, 11% of patients needed red cell or platelet transfusions, while 15% experienced grade 3 or higher infections or febrile neutropenia.

Among 86 patients who were evaluable for late toxicities, 3.5% had grade 5 carotid hemorrhages, and 1.2% had deaths associated with oral-cutaneous fistula and soft tissue necrosis. Cumulatively, the estimated 5-year rate of grade 3 or higher toxicities was 44.2% (95% CI, 33.3%-54.5%) in the RTOG 9911 trial compared with 22.7% (95% CI, 13.4%-33.5%) in the historical cohort of patients in the RTOG 9610 trial (P = .01). The rates of late grade 4/5 toxicities among patients who survived for more than 1 year were 22.4% (95% CI, 11.8%-35.1%) and 3.2% (95% CI, 0.2%-14.5%) in each respective population (P = .02).

References

1. Langer CJ, Harris J, Horwitz EM, et al. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: long-term follow-up of NRG Oncology RTOG 9911. Int J Radiat Oncol Biol Phys. 2026;124(1):50-60. doi:10.1016/j.ijrobp.2025.07.1434
2. Paclitaxel, cisplatin, and filgrastim combined with radiation therapy in treating patients with locally recurrent head and neck cancer. ClinicalTrials.gov. Updated November 17, 2025. Accessed January 2, 2026. https://tinyurl.com/bdecht33