Familial Nasopharyngeal Carcinoma 6

Nasopharyngeal Cancer in Pediatric and Adolescent Patients 301usually complicated with high heterogeneous patientpopulation and disease characteristics, staging methods,and treatment modalities. Therefore, it is usuallydifficult to interpret the historical and more recentresults within the same study or to compare themwith other studies.During the past three decades, studies on the treatmentof adults and children with NPC have identifiedseveral factors that can explain the rationale underlyingchemotherapy in the management of childhoodand young adolescence NPC:1. Undifferantiated histopathology associated withadvanced locoregional disease at presentation.2. Propensity to systemic metastasis.3. ltough highly sensitive to high dose radiotherapyinitially, high rate of distant and locoregionalrecurrences might be observed.4. Radiation volume and doses adopted from adultshave serious acute and late effects including secondmalignancies in young patients.5. Undifferantiated NPC is highly chemosensitive.6. Preradiation chemotherapy minimizes the riskof distant recurrence through eradication ofmicrometastases.7. Complete response or marked and rapid reductionin tumor volume can be achieved by preradiationchemotherapy resulting in improvementin locoregional disease control.8. Preradiation chemotherapy may render toreduce radiation dose and volume in children bydecreasing the tumor volume.9. Concurrent administration of chemotherapywith radiation as a radiosensitizer may have arole in improving DMFS, perhaps through betterloco-regional control.10. Better OS and DFS by the integration of chemotherapy.As with other malignancies, attempts on chemotherapyin NPC started in the mid-1960s. Single agents(mostly cyclophosphamide) or different chemotherapeuticcombinations of noncisplatin agents adoptedfrom the adult NPC trails have been employed as anadjuvant treatment, following 35–83 Gy radiotherapy,in patients with advanced diseases. The results ofthese early studies suggested that combined modalitytreatment may be of value (Deutsch et al. 1978;Jenkin et al. 1981). By the 1990s, several long-termand heterogeneous data from single or multiinstitutionalseries have provided valuable information andcontributed to our understanding of childhood andadolescence NPC regarding biological and clinicalcharacteristics, as well as the utilization of chemotherapyfollowing radiotherapy. Various combinationsof cyclophosphamide, vincristin, doxorubicin,actinomycin-D, 5-FU, methotrexate, and bleomycinhave been used in postradiation setting, and 5-yearOS rates of 30%–58% have been reported in thesestudies (Table 23.1).Unfortunately, the postradiation chemotherapystudies did not provide a standard chemotherapyregimen in terms of drug combination, doses, andtreatment duration. Furthermore, these studies didnot result in an improved outcome when comparedwith the trials used for radiotherapy alone in childrenwith NPC. It was suggested that the unsatisfactoryresults might be due to inadequate drug-dose intensity,ineffective chemotherapy combinations, insufficientcourses of treatment, delay in systemic diseasecontrol in the setting of postradiation, and/or the lackof randomized studies because of small sample sizes.One of the early studies on preradiation chemotherapyreported by Lobo-Sanahuja et al. (1986)demonstrated a 100% (12/12) clinical response rateto 6-week trail of preradiation cyclophosphamidealternated with adriamycine. The same chemotherapyregimen was continued following reduced doses(45–60 Gy) of radiotherapy for 30 more weeks, resultingin a 67% OS rate at 5 years. This limited experienceindicated that pre and postradiationchemotherapy was effective in prolonging DFS andmay allow a decrease in the radiation dose. Anotherimproved result in pediatric NPC patients werereported by Gasparini et al. (1988), who, in a smallseries of children, demonstrated a 2-year relapse-freesurvival of 75% with preradiation VAC followed byradiation therapy. Several retrospective studies havebeen published thereafter. In most of these series,cisplatin-based preradiation chemotherapy combinationswere used, and OS rates of 45%–91% havebeen reported (Table 23.1). Some of the chemotherapyregimens used in these studies are provided inTable 23.2.Excellent overall response rates were achieved withthese induction regimens. A single-institution experiencefrom Argentina demonstrated a 100% overallresponse rate in 11 children, 5 (45%) of whom had CRwith three courses of bleomycin, cisplatin, and 5-FU(Zubizarreta et al. 2000). In another single-institutionstudy from Turkey, we have reported 100% overallresponse rate (22% CR, 39% very good partial response(VGPR), and 39% partial response (PR) ) followingthree cycles of bleomycin, epirubicin, and cisplatin in