Long-Term Outcomes and Toxicity of Concurrent Paclitaxel and Radiotherapy for Locally Advanced Head-and-Neck Cancer

Abstract

Purpose-To report the long-term outcomes and toxicity of a regimen of infusional paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). 1995 and 1999, 35 patients with non-metastatic stage III or IV SCCHN were treated with 3 cycles of paclitaxel as a 120-hour continuous infusion beginning days 1, 21, and 42 concurrent with radiation. The initial 16 patients received 105 mg/m 2 /cycle, and the subsequent 19 patients received 120 mg/m 2 /cycle. External beam radiation was delivered to 70.2-72 Gy in 5 fractions per week. Patients were followed to evaluate disease outcomes and the late toxicity of this regimen. Methods-BetweenResults-Median follow-up for all patients is 56.5 months. The median survival was 56.5 months and the median time to local recurrence was not reached. Fifteen patients (43%) developed hypothyroidism. Eleven of the 33 patients who underwent percutaneous endoscopic gastrostomy tube (PEG) placement were PEG-dependent until death or last follow-up. Five patients (14%) required a tracheostomy until death, while 3 patients (9%) suffered from severe esophageal stricture. *corresponding author: 10 CRC, B2-3500, NCI, NIH, Bethesda, MD 20892, (301) 496-5457, E-mail: citrind@mail.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of Interest:The authors report no conflicts of interest.This work was presented in part at the American Society of Therapeutic Radiology and Oncology in 2007. All evaluated long term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). NIH Public AccessConclusion-Concurrent chemo-radiation therapy with a 120-hour infusion of paclitaxel provides long-term local control and survival in patients with SCCHN.Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel

“…The MACH-NC meta-analysis did not reveal a survival advantage of additional 5-FU to platinum-based concurrent radiochemotherapy [17]. Paclitaxel -as "second generation" chemotherapy agent -has shown antitumor efficacy when used in phase I and II concomitant radiochemotherapy protocols with acceptable toxicity [7,11,16,24]. The combination of platinum and paclitaxel has been tested by several groups in phase II studies.…”

“…Paclitaxel -representative of the second generation chemotherapy -has been used in SCCHN single-agent [7,14] or platinum-based radiochemotherapy protocols [2,6,8,15,22,25]. Current treatment strategies often use hyperfractionated or hyperfractionated-accelerated radiotherapy protocols to enhance efficacy.…”

Trismus and reduced quality of life in patients with oral squamous cell carcinoma, who received post-operative radiotherapy alone or combined with chemotherapy

“…Xerostomia was the most common long-term toxicity reported in the literature. The prevalence can be high as 93% [2,26,27].…”

Re-irradiation with 36 Gy (1.5 Gy Twice Daily) Plus Paclitaxel for Advanced Recurrent and Previously Irradiated SCCHN is Feasible

“…Cisplatin, the most common agent, may lead to significant side effects and cannot be used in many patients with recurrent SCCHN (7). Beside other systemic treatments, paclitaxel may be an alternative option for these patients, which has been reported to be effective and associated with favorable toxicity profiles (8)(9)(10). For example, in a prospective study of 35 patients with locally advanced SCCHN, 70.2-72 Gy of radiotherapy plus three courses of paclitaxel resulted in a median survival of 56.5 months, and most toxicities were grade 2 or less (9).…”

“…However, many patients, particularly in recurrent disease after chemoradiation, may not be able to receive platin-based chemotherapy again due to expected toxicity such as nausea, vomiting and renal failure (7). For these patients, taxanes may be an alternative option, since these agents have been proved effective as a monotherapy in patients with SCCHN (8)(9)(10). In addition to concurrent chemotherapy, twice-daily administration of radiotherapy with lower doses per fraction (e.g.…”