More than half of patients with squamous cell carcinoma of the head and neck will experience disease relapse. Locoregional recurrence is most common, but there is increasing evidence that metastases and distant metastases can occur. On initial presentation, 10% of cases will show metastases, but that figure can triple to 30% upon subsequent evaluation.
"What are the primary challenges in this patient population?" asked Athanassios "Ethan" Argiris, MD, a professor of medicine and medical director of the aerodigestive cancers program at the University of Pittsburgh. First, almost all patients with recurrent disease have already received radiotherapy, which can lead to chronic toxicities from prior therapy and functional impairment. It's not simply a matter of re-treating, Dr. Argiris pointed out. Issues that need to be addressed are:
| • | The time interval between therapies |
| • | The resectability of the tumor |
| • | The patient's overall condition and comorbidities |
| • | The potential for curative treatment |
"We should individualize care, and a multimodality approach is needed," Dr. Argiris said. "Salvage may play a role, and the best example of that is salvage laryngectomy. Re-irradiation may play a role in the form of intensity-modulated radiotherapy (IMRT) or stereotactic radiosurgery. There's certainly a role for systemic therapy, including traditional chemotherapy and novel agents, mainly EGFR inhibitors, and one can combine those modalities."
At the 2010 ASTRO Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Dr. Argiris moderated a session on the therapeutic challenges of recurrent squamous cell carcinoma of the head and neck (SCCHN). A trio of experts offered the pros and cons of three treatment modalities: systemic therapy, re-irradiation with or without systemic therapy, and surgery.
Presented by DR. JAN VERMORKEN
| • | Outcome of patients with recurrent metastatic squamous cell carcinoma of the head and neck remains unchanged over the last 30 years despite improvement in cytotoxic therapies. |
| • | Combination therapy leads to more toxicity than single-agent therapy. However, treatment with taxanes seems to result in lower toxicity, compared with methotrexate(Drug information on methotrexate). |
| • | Addition of cetuximab(Drug information on cetuximab) to standard platinum-based chemotherapy improves OS and PFS vs platinum-based chemotherapy alone without adversely affecting quality of life. Cetuximab also has shown promise as second-line therapy. |
Pros and cons of systemic therapy
Conventional agents for recurrent metastatic disease include methotrexate, cisplatin(Drug information on cisplatin), fluorouracil(Drug information on fluorouracil) (5-FU), vinblastine(Drug information on vinblastine), and doxorubicin(Drug information on doxorubicin). Used as single agents, conventional chemotherapy induces a response rate of around 25% based on data culled from multiple studies, said Jan Vermorken, MD, PhD, professor of oncology and head of the medical oncology department at University Hospital Antwerp in Belgium. Newer agents include gemcitabine(Drug information on gemcitabine) (Gemzar), vinorelbine (Navelbine), irinotecan(Drug information on irinotecan) (Camptosar), paclitaxel(Drug information on paclitaxel), and docetaxel(Drug information on docetaxel) (Taxotere).
Unfortunately, neither conventional nor new agents have done much to boost overall survival (OS) rates. In Europe, methotrexate has been the standard of care for recurrent metastatic disease, but global randomized trials that have compared single-agent methotrexate with single-agent cisplatin have not shown a difference in OS, Dr. Vermorken said (Eur J Cancer 40:2071-2076, 2004; Ann Oncol 10:693-700, 1999; Cancer 52:206-210, 1983; Cancer Treat Rep 69:577-581, 1985).
This lack of impact on OS also holds true for studies that have compared methotrexate with taxanes. In the European trial that Dr. Vermorken was involved in, weekly methotrexate was compared with two schedules of paclitaxel. The response rate varied from 11% to 23%, but there was still no impact on OS.
"Going a little bit into the details of this study, patients were treated for first-line recurrent metastatic disease, and methotrexate [was used] in the way that we think of as standard: 40 mg/m2 per week, which could be escalated up to 60 mg/m2 per week. Paclitaxel was given by three-hour infusion or by 24-hour infusion, but at the same dose, 175 mg/m2, which is rather high for 24-hour infusion," he said (Ann Oncol 10:693-700, 1999).
But what the trial clearly demonstrated was the value of paclitaxel in the recurrent metastatic disease setting because of a lower toxicity rate with the three-hour infusion. Specifically, stomatitis was seen less frequently with the taxanes than with methotrexate, Dr. Vermorken said.
In terms of managing toxicity, physicians must decide whether to use single-agent therapy or combination therapy. The trend in cancer care is to rely on increasingly aggressive treatment and that's especially true when dealing with recurrent metastatic disease. Studies that have evaluated a combination of cisplatin and 5-FU have noted that toxicity was moderate and that patients with a good performance status (≥ 70%) responded well to treatment (Cancer Treat Rep 70:461-464, 1986; Cancer 53:1819-1824, 1984).
