Familial Nasopharyngeal Carcinoma 6

170 J. Weethey also took the opportunity to study the role ofaccelerated radiation therapy in improving local controlin patients with T3–4 disease, but with early or noneck disease (N0–1), where local control was expectedto be the major problem. Thus two parallel trials wereconducted, the HK 99-01 trial for patients withT1-4N2-3M0 disease, and HK 99-02 for patients withT3-4N0-1M0 disease. This group also used the 1997version of TNM (AJCC 1997) as their basis of stagingand eligibility. The dose of radiation therapy dose wasin general higher, as it was routine in Hong Kong toadd a “parapharyngeal boost” when there was tumorextension laterally into the parapharyngeal space.HK 99-01 (Lee et al. 2005a) accrued 348 patientsfrom March 1999 to January 2004, 176 in the radiationtherapy arm and 172 in the chemoradiation arm.About 40% of patients on both arms received a boostradiotherapy dose, and about half the patients onboth arms were treated using 3D radiation techniques.Fifty-two percent of patients on the chemoradiationtherapy arm received all three cycles of concurrentcisplatin and 76% received all three cycles of adjuvantchemotherapy. Patients on the chemoradiation armsuffered more severe acute toxicities (84% vs. 53%;p < 0.001) as well as late toxicities (28% vs. 13%;p = 0.024). The chemoradiation arm achieved significantlyhigher failure-free survival (FFS) (72% vs. 62%at 3-year, p = 0.027), mostly as a result of an improvementin locoregional control (92% vs. 82%, p = 0.005).However, distant control did not improve significantly(76% vs. 73%, p = 0.47), and the overall survival rateswere almost identical (78% vs. 78%, p = 0.97).The HKNPCSG subsequently published the resultsof over 2,500 consecutive patients (Lee et al. 2005b)treated with radiation therapy alone at all public oncologycenters in Hong Kong during the period 1996–2000and found similar 3-year overall survival rate (74%) tothat achieved in the radiation therapy alone arm of theHK 99-01 trial (78%). The group concluded by questioningif the difference in the result of the HK 99-01trial, compared with the results from both theIntergroup and Singapore trials, could be explained byimproved radiation technology, which could havenegated any potential benefit of chemotherapy.HK 99-02 (Lee et al. 2006) the sister trial to HK99-01 was a four arm study comparing radiation therapyvs. chemoradiation therapy and standard 5-fractionsper week radiation vs. accelerated 6-fractionsper week for patients who had T3-4N0-1M0 disease. Ablocked randomization scheme was used to allocatepatients in equal proportions to the four treatmentarms. The accelerated fractionation scheme of 6-fractionsper week was based on the Danish Head andNeck Cancer Study Group (DAHANCA) 6–7 Trials(Overgaard et al. 2003). One hundred and eightyninepatients were accrued to this trial between 1999and 2004 and the trial was terminated early becauseof slower than expected accrual. Prolongation ofoverall treatment time by more than 7 days occurredin 2% of the accelerated 6-fraction/week radiationalone arm and 5% of the accelerated 6-fraction/weekchemoradiation arm. There was no difference in theproportion of patients who received all six cycles ofchemotherapy (55% vs. 57%) in both the conventionaland accelerated fractionation chemoradiation arms.Late toxicity, which just reached statistical significance,was greater in the accelerated fractionationchemo-RT arm when compared with the conventionalfractionation RT alone arm (34% vs. 14%;p = 0.05). The majority of the toxicities were of Grade3 severity and only 2% of late toxicities in the acceleratedfractionation chemoradiation therapy arm wereGrade 4.At a median follow-up period was 2.9 years, significantimprovement in FFS was achieved by the accelerated6-fraction/week chemoradiation threapy regimenwhen compared with the conventional 5-fraction/weekRT alone regimen (94% vs. 70% at 3 years, p = 0.008).Accelerated radiation therapy alone and conventionalfractionation chemoradiation therapy did not produceany improvement in FFS when compared with theconventional fractionation radiation alone arm.13.4.3The Guangzhou TrialThe Guangzhou Trial was the fourth trial to test theAl-Sarraf regimen in an endemic NPC population. Itaccrued 316 patients between 2002 and 2005 (Chen et al.2008). Similar to the other three trials, patients werestaged according to the 1997 AJCC/TNM staging system(AJCC 1997), and only patients with the endemic formof NPC (WHO Type II and III) were eligible. Like theHong Kong cohort, selected patients in this study werealso routinely treated with a parapharyngeal boost.Unlike the other trials, cisplatin was given weekly at adose of 40 mg/m 2 for 7 weeks during the radiotherapyphase and the adjuvant chemotherapy consisted of acombination of cisplatin (80 mg/m 2 intravenously) onDay 1 and 5-FU (800 mg/m 2 intravenously) on Days 1–5by a 120-h infusion. Although the chemoradiotherapygroup experienced significantly more acute toxicity(62.6% vs. 32%, p = 0.000), most patients completed