Oxaliplatin (Eloxatin®) Plus Radiation Superior in Advanced Nasopharyngeal CancerKey Words
Nasopharyngeal cancer, oxaliplatin (Eloxatin®), chemoradiotherapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Patients with locally advanced nasopharyngeal cancer who received oxaliplatin (Eloxatin®) during their initial treatment with radiotherapy did significantly better than those receiving radiation alone. Side effects expected from oxaliplatin occurred, but were low grade and reversible.
Source
Journal of Clinical Oncology, published online October 17, 2005, and in print Nov. 20, 2005 (see the journal abstract).
Background
Nasopharyngeal cancer that begins at the top of the throat behind the nose is a relatively uncommon type of head and neck cancer in the United States but more common worldwide. If detected early, more than four in five of these cancers can be cured with radiation.
However, by the time most cases of nasopharyngeal cancer have been diagnosed, the cancer has spread to nearby tissues and lymph nodes (stage III or stage IV). For these patients, the odds of living five years fall to 50 percent or less.
Nasopharyngeal tumors are not easily reached by surgery; historically, most were initially treated with radiotherapy. A phase III clinical trial in 1998 (called the Intergroup 0099 trial) showed that giving these two treatments at the same time (chemoradiotherapy) was better than radiotherapy alone.
The 1998 trial used cisplatin with radiotherapy. Oxaliplatin is a newer platinum-based drug that has fewer side effects than cisplatin or another commonly used platinum drug, carboplatin.
Results of this trial were first presented at the American Society of Clinical Oncology meeting in 2003, but have now been published with a longer follow-up.
The Study
In this phase III study, 115 patients with advanced nasopharyngeal cancer that had not yet spread (metastasized) received radiation treatments for about seven weeks. During that time, 56 of them also got oxaliplatin intravenously for two hours a week. Patients were enrolled between January 2001 and January 2003.
Researchers followed the patients for a median of 24 months after treatment to see how the cancer responded and whether any side effects occurred. Patients were seen weekly until the immediate effects of treatment went away, and then less frequently, every two, three, then six months. A few patients who did not respond well were treated with surgery or more radiation.
The study was led by Dr. Li Zhang and colleagues from the Cancer Center at Sun Yat-Sen University in Guangzhou, People’s Republic of China. Patients with Asian ancestry are at much higher risk for nasopharyngeal cancer.
Results
Patients who were treated with radiation plus oxaliplatin did significantly better than those receiving radiation alone. None of the patients getting chemoradiotherapy had died after two years, compared to a survival rate of 77 percent for those getting radiation alone.
Patients receiving radiation alone were more likely to relapse after two years: 17 percent, compared to only four percent who also got oxaliplatin. Cancer had spread outside the original area (metastasized) in 20 percent of radiation-only patients, compared to eight percent who also got oxaliplatin.
The chemoradiotherapy patients experienced more side effects of treatment––all of which are common to oxaliplatin––but these were not severe, and diminished or disappeared over time. They had more nausea and vomiting, and their blood count was more likely to drop. They also experienced more numbness and tingling in their hands and feet.
Comments
“This study was very well done,” said C. Norman Coleman, M.D., a senior principal investigator in the Radiation Oncology Branch of National Cancer Institute’s Center for Cancer Research. “Although [the 1998 Intergroup 0099 trial] changed the standard practice in this country, it was so effective they stopped it early. Therefore, this confirmatory trial adds important additional information as to the efficacy of chemoradiotherapy as well as the drugs that might be used.”
The findings show that “chemoradiotherapy is clearly the way to go for the more advanced stages, as most [of these] tumors are,” Coleman added. “Both of the trials used platinum-based chemotherapy. This trial demonstrates that oxaliplatin is an excellent choice to complement radiation, as is cisplatin from the initial Intergroup Trial.”
Coleman noted that the advantage in metastasis-free survival was particularly interesting, but needs more follow-up time. “We know chemoradiotherapy with a platinum drug improves cancer control locally. The improvement in local control does not always result in an improvement in metastasis-free survival and overall survival. These data suggest that persistent tumor leads to additional metastases, so that improving local control has multiple benefits.”
Thus, he said, the chemoradiotherapy approach may be impacting both the distant cancer cells that were too small to detect at the time of original treatment, and also the secondary metastases that can occur as the result of persistent local tumor. “Longer follow-up will be important, of course.”
Finally, said Coleman, “There is no reason to believe results in these Chinese subjects would not reflect on the experience of patients in the United States.”
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