Al-Sarraf, M et al.
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001
Reviewers: John Han-Chih Chang, MD and Kenneth Blank, MD
Source: Journal of Clinical Oncology, Volume 16 Number 4, pg. 1310-1317
Histological classification is done by the World Health Organization (WHO) grading system. Type 1 is a well to moderately differentiated carcinoma with keratin production. Type 2 is a non-keratinizing carcinoma. Type 3 is an undifferentiated carcinoma (also includes lymphoepithelioma).
The standard treatment has been radiation therapy. The results for locally advanced disease (stages III and IV) have been fair. From many single institutional studies, 5 year survival rates range from 30 - 45%, but drops off to 25% by 10 years and 12% by 20 years. Many have explored other avenues of therapy such as chemotherapy. Trials with cisplatin (CDDP) have shown some promising results, but no positive randomized trial on survival has been published until now.
The current article details some of the initial results of the Southwest Oncology Group?s's (SWOG) cooperative intergroup trial 0099 involving the RatiationTherapy Oncology Group (RTOG) and the Eastern Cooperative Oncology Group (ECOG). This phase III randomized trial compared chemoradiotherapy (CTX/XRT) treatment to radiotherapy alone (XRT) for stage III and IV nasopharynx cancer.
Median follow-up was 2.7 years. Interim analysis had stopped the trial in 1995, because of the overwhelming data in support of improved outcome in the combined modality arm. The hazard ratio between the XRT and CTX/XRT arms was 3.28. This corresponded to median progression free and overall survivals of 15 and 34 months for the XRT arm, respectively, and neither having been reached in the CTX/XRT arm. The actuarial 3 year PFS and OS rates for XRT were 24% and 47%, respectively. For the CTX/XRT arm, they were 69% and 78%, respectively. These were statistically significant with p values of < 0.001 and 0.005.
One hundred and forty-six were evaluated for toxicity. No fatal or grade 5 toxicity were reported. The most severe toxicities seen in the CTX/XRT relative to the XRT alone arm were leukopenia (lowering of white blood cell count), nausea, vomiting, ototoxicity (hearing impairment) and stomatitis (breakdown of mucosa of the oral cavity).
Complete response rates were not statistically significant, but had a difference of 13% (36% versus 49%) favoring CTX/XRT. Failure was seen only locoregionally in 26% of the XRT alone arm and 10% in the CTX/XRT arm. Distant as any component of failure was 35% in the XRT alone arm and 13% in the CTX/XRT arm.
Compliance to chemotherapy was slightly over 50% in this trial. This troublesome figure holds true other combined modality trials involving the head and neck.
Lacking were data on compliance to chemotherapy and outcome. This maybe useful in tailoring the chemotherapy. Data on outcome and WHO grade/type was also missing. Despite similar survivals stage for stage, there is an inherent difference in how these patients fail (type 1 and 2 have more locoregional failure while distant disease predominates type 3). The effects of chemotherapy on these patterns of failure may have been useful.