Familial Nasopharyngeal Carcinoma 6

194 B. C. Gohthe similarly favorable results of concurrent chemoradiotherapyover single modality radiation therapy,suggests that the main benefit of multimodality therapyderives mainly from the concomitant use of chemotherapywith radiation. Subsequent studies withconcomitant chemotherapy and radiotherapy withoutadjuvant chemotherapy compared with radiotherapyalone have shown similar survival benefit forconcurrent chemoradiotherapy, further questioningthe impact of adjuvant chemotherapy (Chan et al.2005; Zhang et al. 2005). The advantage of the utilizationof adjuvant chemotherapy after definitiveradiation therapy or chemoradiation therapy is notclear. The aim of this chapter is to discuss the availableclinical evidences and interpret their results,with an attempt to provide insight for future researchdirection.15.2Prospective Randomized StudiesTwo prospective studies have examined the role ofadjuvant chemotherapy after radiation therapy, specificallyin the treatment of NPC (Rossi et al. 1988;Chi et al. 2002). The results of both trials did notdemonstrate improved clinical outcome with theaddition of chemotherapy in this treatment strategy.The first study was an Italian study conductedbetween 1979 and1983. A total of 229 patients withNPC were randomized between radiotherapy aloneand radiotherapy followed by 6–12 cycles of adriamycin,vincristine, and cyclophosphamide chemotherapy(Rossi et al. 1988). Seventy percent ofpatients presented with undifferentiated histologicalsubtype, and stage of patients ranged from T2N0 toT4N3 using Ho’s staging classification. The relapsefreesurvival and overall survival were similar in bothstudy arms, as were the patterns of relapse of disease.In the light of currently known efficacy of platinumcontainingregimens when compared with the regimenstudied, and more proper selection of high-riskpatients for additional therapy, as well as the applicationof concomitant chemoradiotherapy, the resultsof this study are certainly not applicable to currentpractice. In addition, there was significant delaybetween the end of radiation therapy and start ofadjuvant chemotherapy of 65 days.The second study conducted by the TaiwaneseCooperative Oncology Group (TCOG) accruedpatients with T4 or N2-3 using AJCC 1992 NPC(Chi et al. 2002). The randomized clinical trial comparedradiotherapy alone with radiotherapy followedby 9 weekly cycles of cisplatin, 5-fluorouracil, andleucovorin. Despite this relatively well-tolerated chemotherapyregimen, only 22% of the patients scheduledto receive chemotherapy completed nine cyclesof treatment. Furthermore, 34% of patients randomizedto receive adjuvant chemotherapy changed theirminds after completion of radiotherapy. These reflectthe difficulty in achieving compliance with adjuvantchemotherapy after radiotherapy. There was no differencein 5-year overall survival, which were 54.5%and 60.5% (p = 0.5) for adjuvant chemotherapy andno adjuvant chemotherapy, respectively. Similarly,median relapse-free survival was no differentbetween the two groups (39 months for radiotherapyalone and 40 months for radiotherapy with adjuvantchemotherapy).In a 2 × 2 factorial design study conducted inHong Kong, patients with Ho’s stage T3 or N2/3 orpatients with cervical lymph nodes equal or largerthan 4 cm without distant metastases were randomizedto receive radiotherapy alone or with adjuvantchemotherapy, chemoradiotherapy alone or withchemotherapy. Adjuvant chemotherapy consisted ofalternating cisplatin/5-FU with vincristine, bleomycin,methotrexate (VBM) for a total of six cycles(Kwong et al. 2004). Comparison of 111 with adjuvantchemotherapy with 108 without adjuvant chemotherapyshowed no difference in the 3-year overallsurvival (80.4% adjuvant chemotherapy vs. 83.1% noadjuvant chemotherapy, p = 0.69), failure-free survival(62.5% adjuvant chemotherapy vs. 65% noadjuvant chemotherapy, p = 0.83), 3-year local relapse(19.1% for adjuvant chemotherapy vs. 28.6% for noadjuvant chemotherapy, p = 0.15), or 3-year distantrelapse (24.7% for adjuvant chemotherapy vs. 19.1%for no adjuvant chemotherapy, p = 0.34) rates betweenboth arms. The nonconventional use of VBM chemotherapyadds to the difficulty in interpretation of thisstudy.15.3Meta-Analysis and Ongoing StudiesA meta-analysis examining the role of chemotherapyon improving event-free survival and overall survivalwhen combined with radiotherapy for NPCincluded eight studies with updated individual datafor 1,753 patients. Chemotherapy was found to lead to