© 2004 Foundation for Promotion of Cancer Research
A Multi-institutional Survey of the Effectiveness of Chemotherapy Combined with Radiotherapy for Patients with Nasopharyngeal Carcinoma
1 Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, 2 Department of Radiation Oncology, Aichi Cancer Center, Nagoya, 3 Department of Radiation Oncology, National Sapporo Hospital, Sapporo, 4 Department of Clinical Radiology, Kyushu University, Fukuoka, 5 Department of Radiation Oncology, University of the Ryukyus, Okinawa, 6 Department of Head and Neck Surgery, Miyagi Cancer Center, Sendai, 7 Department of Radiation Oncology, Nagasaki University, Nagasaki, 8 Department of Radiation Oncology, University of Yamanashi, Kofu, 9 Department of Radiology, Shinshu University, School of Medicine, Matsumoto, Nagano, 10 Department of Otolaryngology, Fukushima Medical University, Fukushima and 11 Department of Radiation Oncology, National Kure Medical Center, Kure, Hiroshima, Japan
For reprints and all correspondence: Mitsuhiko Kawashima, Division of Radiation Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. E-mail: mkawashi{at}east.ncc.go.jp
Received May 26, 2004; accepted August 16, 2004
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Abstract |
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 TOP Abstract INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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Background: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved.
Methods: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether 
2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone.
Results: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1–3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261).
Conclusion: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.
Key Words: nasopharyngeal cancer • radiotherapy • chemotherapy • survey
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INTRODUCTION |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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Although nasopharyngeal cancer often responds well to radiotherapy (RT), the cure rate in patients with advanced stage disease has not been satisfying (1,2). Local recurrence at the periphery of the irradiated area receiving an insufficient RT dose due to its proximity to critical organs and a high propensity for distant metastasis have been the two major causes of treatment failure (3). The addition of chemotherapy to RT for patients with advanced disease has been studied extensively during the last 2 decades (4–12). These results have indicated the followings: (i) in comparison with treatment with RT alone, concurrent chemoradiotherapy with or without adjuvant chemotherapy showed a significant survival benefit in two randomized studies (6,11); (ii) sequential (neoadjuvant and/or adjuvant) chemotherapy with RT failed to achieve survival advantage in seven randomized studies (4,5,7–10,12), although some showed a longer relapse-free survival when neoadjuvant chemotherapy was used (5,8).
Nasopharyngeal cancer is a relatively rare disease in Japan, compared with countries in which it is endemic, and, to our knowledge, no large-scale clinical reports have been published from our country. We therefore conducted a multi-institutional questionnaire survey to look at patterns of treatment and outcome of this disease, giving special attention to the effect of RT combined with chemotherapy on survival outcome. The principal purpose of this study was to evaluate the applicability of results of previously reported randomized trials conducted in the USA and endemic countries to the Japanese population with this disease.
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SUBJECTS AND METHODS |
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SURVEY
A questionnaire was sent in August 2002 to 17 institutions (seven universities, four affiliated hospitals and six national or regional cancer centers in Japan) participating in the study group of chemoradiotherapy for head and neck cancer supported by Grant-Aided Cancer Research 14-15, Ministry of Health, Labor and Welfare of Japan. It requested information about the treatment and outcome for all patients with biopsy-proven nasopharyngeal carcinoma. The data collected included age, gender, histology, clinical stage, RT dose, contents and timing (neoadjuvant, concurrent, alternating or adjuvant) of chemotherapy, patterns of failure and survival outcome. Collected data were analyzed in autumn 2003.
The following definitions were applied to the initial treatment given, with these definitions not changing even where salvage chemotherapy was ultimately used for failure of response to the initial treatment given: neoadjuvant therapy = chemotherapy followed by RT; adjuvant therapy = chemotherapy after completion of RT; concurrent therapy = simultaneous administration of chemotherapy and RT; and alternating therapy = repetitive sequential administration of chemotherapy and RT (e.g. chemo–RT–chemo–RT). To be included in the assessment, the patient must have had pre-treatment computed tomography (CT) and/or magnetic resonance imaging (MRI), and the diseases were restaged according to the 1997 UICC TNM staging system. Tumor histology was divided into two categories only (i.e. keratinizing or non-keratinizing), instead of the World Health Organization (WHO) types 1–3, because of the inter-institutional variation of the diagnostic criteria employed. Total RT dose/fractionation to the primary tumor, grossly involved cervical lymph nodes and other nodal areas were described separately. The dates of first detection of recurrence of the primary tumor, involvement of cervical lymph nodes and distant organ metastasis were surveyed to analyze patterns of failure. The date of patient death (or last follow-up for surviving patients) was also surveyed.
REPLIES
All of the 17 institutions replied to the questionnaire, and information on the treatment of 385 patients for whom treatments had started between January 1989 and July 2001 was received. The number of patients in each institution ranged from three to 90 (median 18 patients), and eight institutions had 20 or more patients during this study period. Thirty-three patients were excluded for the following reasons: 19 were lost to follow-up within 2 years without evidence of disease recurrence; eight did not allow distinction between keratinizing or non-keratinizing disease on histological examination; three had organ metastases at the time of first presentation; two had palliative treatment alone; and in one patient staging was not possible from the data provided. An additional 19 patients were excluded because they had been given intra-arterial infusion chemotherapy via the superficial temporal artery before commencement of RT (stage II, four; stage III, eight; stage IV, seven) according to their institutional policy. In this treatment, the cisplatin was neutralized with sodium thiosulfate immediately after entering the systemic circulation from the locoregional area, removing its systemic activity (13). The outcome in the remaining 333 patients is the basis for the subsequent analysis, the patient characteristics of which are shown in Table 1. The median follow-up period for surviving patients was 69 months (range 20–127).
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CLASSIFICATION OF CHEMOTHERAPY PROCEDURES
Based on the previous randomized trials which showed positive results for nasopharyngeal cancer (6,11) and a meta-analysis of the effect of adding chemotherapy to RT for non-nasopharyngeal cancer (14), two assumptions were made: (i) the key chemotherapeutic agents for nasopharyngeal cancer were platinum and 5-fluorouracil (5-FU; the FP regimen); and (ii) concurrent use of platinum might be more effective than sequential use. Consequently, the type of chemotherapy used was classified based on the following two items: (i) whether the FP regimen was administered for two or more cycles; and (ii) whether the platinum was administered concomitantly with RT. Patients were then classified into the following five groups regarding (i)/(ii) = YES/YES, YES/NO, NO/YES, NO/NO and RT alone. Because a multi-institutional phase II study of alternating chemoradiotherapy for advanced nasopharyngeal cancer had been conducted during this study period, 45 patients who participated in this study were included in our data set (15). In addition, 19 patients who had received alternating chemoradiotherapy because of their physician's discretion were also included. These 64 patients who received alternating chemoradiotherapy were regarded as concurrent chemoradiotherapy in the analysis.
STATISTICAL ANALYSIS
Overall (OAS) and progression-free (PFS) survival rates from the start of RT were calculated from the replies. To calculate OAS, death from any cause was considered as an event and censored at the time of last follow-up for a surviving patient; however, patients who were lost to follow-up after tumor recurrence (n = 17) were considered as dead at the date of last follow-up. Recurrence of the tumor at any sites or death from any cause were defined as events for calculation of PFS. Tumor recurrence at the primary site and/or cervical lymph nodes was considered as an event to calculate the locoregional control rate (LRC), and censored at the time of the lastfollow-up or patient death when there was no evidence of either of these events. Distant failure was considered as an event for calculation of distant metastasis-free rate (DMF), and censored at the time of locoregional failure, patient death or date of the last follow-up visit when there was no evidence of distant metastasis. Time to event was calculated using the Kaplan–Meier method (16), and the significance of any difference was estimated using the log-rank test. Multivariate analysis was done using Cox's proportional hazards model (17).
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RESULTS |
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RADIOTHERAPY
Of 333 patients, 23 (7%) received twice daily fractionation RT and 12 (4%) underwent a brachytherapy boost. Otherwise all patients underwent external beam RT with once daily fractionation administering 1.5–2.4 Gy (median 2.0 Gy) per fraction. Differences in fractionation and the use of brachytherapy were not taken into account in the following analysis because of the small number of patients having such variations. One patient could not receive any RT because of the toxicity due to neoadjuvant chemotherapy; however, this patient was included in the survival analysis because of the radical intent of the treatment. The total dose of RT to the primary tumor ranged from 0 to 84.6 Gy (median 69.4 Gy). Metastatic cervical lymph nodes and elective nodal areas received 35.0–82.0 Gy (median 66.0 Gy) and 0–65.0 Gy (40.0 Gy), respectively. All but two patients received a total dose of
50 Gy, and 325 (98%) patients received 60 Gy to the primary tumor and metastatic cervical lymph nodes.
CHEMOTHERAPY
A total of 259 (78%) patients received chemotherapy as a part of their initial treatment. Of 24 patients with stage I disease, 15 (63%) underwent RT alone. On the other hand, 74 out of 100 (74%), 86 out of 100 (86%) and 90 out of 109 (83%) patients with stage II, III and IV, respectively, received chemotherapy combined with RT. Of these 259 patients, 248 (96%) received platinum-based regimens and 161 (62%) received two or more cycles of systemic infusions of the FP regimen, mostly by means of bolus infusions of platinum on day 1 and 4–5 days of continuous infusion of 5-FU. Otherwise pepleomycin (n = 33), vitamin A (n = 27), adriamycin (n = 11), methotrexate (n = 5) or vinca alkaloids (n = 2) were used with or without platinum and/or 5-FU according to institutional protocols or physicians' discretion.
According to the treatment classification described above, 67 patients corresponded to the YES/YES, 94 to the YES/NO, 56 to the NO/YES, 42 to the NO/NO and 74 to the RT alone group.
For patients in YES/YES or YES/NO groups (n = 161), the total dose of cisplatin given ranged from 75 to 100mg/m2, with the dose of 5-FU being 3200–5000mg/m2 in each cycle of the FP regimen, with individual dose modification as necessary. Carboplatin (400mg/m2) was used instead of cisplatin in the FP regimen for 10 patients. Thirteen patients in these groups received other chemotherapeutic agents in addition to FP.
In the YES/YES group, two or more cycles of FP were administered concurrent or alternated with RT in 59 patients (four followed by additional FP in the adjuvant setting). Six patients received one cycle of FP concurrent with RT, followed by 1–2 cycles of adjuvant FP in three or preceded by 2–3 cycles of neoadjuvant FP in three. Two patients received concurrent single agent cisplatin, followed by three cycles of adjuvant FP.
In the YES/NO group, 53 received 2–4 cycles (median, two cycles) of FP in the adjuvant setting, and 37 received 2–3 cycles (median, two cycles) in the neoadjuvant setting. The other four patients received both neoadjuvant and adjuvant FP.
For 56 patients in the NO/YES group, 28 patients received single agent platinum at various doses concurrent with RT (four received additional adjuvant chemotherapy using one course of FP regimen) and six received platinum with drugs other than 5-FU concurrent with RT (three received adjuvant chemotherapy using oral FU derivatives). Fifteen received FU-based concurrent chemotherapy with split-course RT in combination with alternating chemotherapy using platinum and pepleomycin based on institutional policy. Seven received a single cycle of FP concurrent with RT without further chemotherapy.
The NO/NO group (42 patients) included 17 patients who underwent miscellaneous platinum-based neoadjuvant (n = 17) or adjuvant (n = 9) chemotherapy other than the FP regimen. The remaining 16 patients received FU-based chemotherapy without platinum concurrent with RT in 12, and sequentially in four.
There were no statistically significant differences in total RT dose to the primary tumor, grossly involved nodes and elective nodal areas among these five groups (data not shown).
SURVIVAL OUTCOMES
The OAS and PFS rates at 5 years for all patients were 59% (95% confidence interval 53–65%) and 50% (44–56%), respectively. The OAS for patients with stage I (n = 24), II (n = 100), III (n = 100) and IV (n = 109) disease was 87% (73–100%), 75% (66–84%), 56% (46–67%) and 41% (30–51%), respectively, whereas the PFS was 79% (63–96%), 61% (51–71%), 48% (37–58%) and 37% (28–47%) at 5 years.
Table 2 shows LRC, DMF, PFS and OAS according to the stage and histology of the disease. T4 and/or N2–3 were statistically significant factors associated with a poor prognosis. Cumulative total RT dose to the primary tumor (66 Gy versus <66 Gy) did not have a significant influence on OAS (58 versus 60% at 5 years, P = 0.746). The results of univariate and multivariate analyses to evaluate the prognostic significance of the patient's age (<60 versus 60 years), T-stage (T1–3 versus T4), N-stage (N0/1 versus N2/3), histology (keratinizing versus non-keratinizing), gender, numbers of administered cycles of FP chemotherapy (
1 cycle versus 2 cycles) and concurrent platinum-based chemotherapy (yes versus no) for OAS and PFS are shown in Table 3. Although the receipt of 2 cycles of FP did have prognostic significance, concurrent or alternating use of platinum did not. Multivariate analyses revealed that age, T and N stage, histology, and numbers of cycles of FP were independent prognostic factors for both OAS and PFS (P < 0.05).
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DEFINITION OF STAGE SUBGROUPS AND PATTERNS OF TREATMENTS
Based on the results of the multivariate analyses, it seemed reasonable to divide the patients into two risk groups according to the T and N classification: favorable risk group (T1–3 and N0–1) and unfavorable risk group (T4 or N2–3). In addition, the principal target populations for the previously reported randomized trials approximately corresponded to patients with node-positive stage II or stage III/IV disease in terms of the 1997 AJCC staging system. Therefore, patients with T1–2 and N0 were analyzed separately in order to facilitate an estimation of the applicability of the data originating from previous randomized trials to the Japanese population. Consequently, we tentatively classified patients into the following three stage subgroups: early stage, T1–2 and N0; intermediate stage, T1–3 and N0–1 excluding the early stage; and advanced stage, T4 or N2–3. The distribution of the chemotherapy given in cancer centers and universities according to the stage subgroups is shown in Table 4. It was significantly different between cancer centers and universities, i.e. the cancer centers selected RT alone for more patients with early stage disease, and the combined FP and RT regime for patients with intermediate and advanced stage disease, than were used in the universities (P < 0.020,
2 test).
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PATTERNS OF FAILURE
The LRC rate for patients with early, intermediate and advanced stage disease were 72, 72 and 61% at 5 years, respectively, with no significant difference of LRC according to the stage subgroups being observed (P > 0.100). However, there was a considerable difference in the LRC rate between non-keratinizing and keratinizing tumors as shown in Table 2. On the other hand, the DMF rates were 97, 88 and 68% at 5 years, respectively, and statistically significant differences in DMF rates were observed between patients with intermediate and advanced stage disease (P < 0.001).
DIFFERENCE IN SURVIVAL ACCORDING TO THE CHEMOTHERAPY GIVEN
Detailed comparisons of OAS and PFS at 5 years according to types of chemotherapy given are shown in Tables 5 and 6, respectively. For patients with early stage disease, no significant survival advantage of combining chemotherapy with RT was observed without taking notice of patient selection, which was not thoroughly surveyed. Since none of the comparisons of OAS and PFS between the two groups from among the YES/NO, NO/YES and NO/NO groups showed statistically significant differences (P > 0.05), these three groups were combined into a MISC group (patients who received miscellaneous chemotherapy) in the following analyses.
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OAS and PFS for 287 patients with intermediate or advanced disease given chemotherapy/RT are shown in Figs 1 and 2. The YES/YES group achieved significantly better OAS and PFS rates than the RT alone group, whereas the MISC group showed intermediate results between the other two groups. The OAS and PFS rates for patients with intermediate and advanced stage disease given chemotherapy/RT are shown in Figs 3
–6. The YES/YES group achieved significantly better OAS rates and/or PFS rates than the RT alone group for both intermediate and advanced stage disease. The OAS and PFS rates in the MISC group were almost identical to those in the YES/YES group in the intermediate stage, while there were no significant differences of OAS and PFS between the MISC and the RT alone group in advanced stage disease. When the patients with non-keratinizing disease only were analyzed, these comparative results according to the stage subgroups were unchanged.
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EFFECTS OF CHEMOTHERAPY ON LOCOREGIONAL AND SYSTEMIC TUMOR CONTROL
The LRC and DMF rates according to the chemotherapy used in patients with intermediate stage disease are shown in Figs 7 and 8, and those in patients with advanced stage disease are shown in Figs 9 and 10. Differences in LRC and DMF rates in the YES/YES, MISC and RT alone group were not statistically significant in the intermediate stage, as shown in Figs 7 and 8, while the differences became more distinct in the advanced stage disease favoring the YES/YES group, as shown in Figs 9 and 10, although the differences in DMF rates in advanced stage disease was marginally significant as noted in Fig. 10. When the patients with non-keratinizing disease only were analyzed, these comparative results of LRC and DMF according to the stage subgroups were unchanged.
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SURVIVAL AFTER DISEASE RECURRENCE
Of 105 patients who experienced locoregional recurrence without distant failure, 43 received salvage treatment that resulted in 24 months of median survival time and 43% of OAS at 3 years after detection of first failure. Otherwise median survival time and 3year OAS were 10 months and 14%, respectively. Of 47 patients who experienced distant metastasis as the first site of failure, three patients who had a solitary lung metastasis received salvage surgery. Two of them were treated successfully with 57 months and 48 months of failure-free period thereafter, but one developed a bone metastasis 1 year after salvage surgery. Otherwise median survival was 7 months and the 3 year OAS rate was 8% after detection of distant failure.
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DISCUSSION |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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Although some single institutional studies employing sequential chemoradiotherapy or RT alone showed comparable, or even better, results of OAS compared with that in both arms in the intergroup study (18,19), RT with concurrent use of platinum-based chemotherapy is becoming accepted as a standard treatment for patients with advanced nasopharyngeal cancer (20–22). However, compliance with this treatment had been a problem mainly due to its invariably severe acute mucosal and hematological toxicity (6,11). Because of their broad eligibility criteria with limited sample size precluding subgroup analysis with sufficient statistical power, the currently available data have not answered the question as to whether further adjustment of the chemotherapy procedures is required for patients with intermediate stage disease, although their actual definition had not been clearly established. Differences in distribution of histological subtypes between trials further confuses their interpretation, because these have a considerable influence on LRC and survival (Table 2) (23).
According to the assumptions regarding chemotherapy that we made in this study, concurrent platinum-based chemoradiotherapy combined with 2 courses of FP, which was classified as the YES/YES group, was expected to be the most efficacious treatment for this disease. However, for patients with intermediate or advanced disease, only 63 (27%) out of 236 patients who received chemotherapy were in the YES/YES group. Since significant differences in treatment strategy were observed between cancer centers and universities as shown in Table 4, the differences are probably due to differences in institutional policies rather than the result of individual modification of therapeutic programs. On the other hand, only 51 out of 287 (17.8%) patients with intermediate or advanced stage disease received RT alone. This suggests that the principal approach for this disease had been combining chemotherapy and RT in the institutions we surveyed, and that there had been a relatively unfavorable background for patients receiving RT alone. Although our study was undoubtedly affected by these inherent drawbacks of a retrospective survey of this kind, it should be noted that the MISC group, which was considered as a less intensive treatment, had an identical OAS to that in the YES/YES group for patients with intermediate stage disease, whereas this was identical to that of the RT alone group for those who had advanced stage disease. Prolonged survival after salvage treatment for tumor recurrence is not unusual in nasopharyngeal cancer and, therefore, differences of OAS according to the chemotherapy used might be obscured compared with the difference of PFS (8).
Overall survival in this study and previous trials is compared in Table 7. Although caution must be exercised when accepting the results of a retrospective study, there were no remarkable differences in the OAS rate between our results and those in previous randomized trials, even when the differences of distribution of histological subtypes were taken into account. In other words, there is a possibility that the difference in chemotherapy effect between the intermediate and advanced stage disease might have indeed existed in the previous randomized trials, which should be confirmed in future trials. Chua et al. reported negative results in their randomized study testing the efficacy of neoadjuvant chemotherapy employing cisplatin and epirubicin in addition to RT alone; however, they showed a non-significant trend of OAS in favor of the neoadjuvant chemotherapy arm for patients with nodal metastasis of 6 cm in size (73 versus 37% at 3 years, P = 0.057) (7). Chan et al. also reported results of a subgroup analysis demonstrating significant differences in PFS in favor of a concurrent cisplatin and RT arm compared with RT alone for patients with Ho's T3 disease, although the entire study showed a negative result (10). Considering our results as shown in Figs 7
–10, tumor control above the clavicle might be the principal goal for intermediate stage disease, whereas minimizing both locoregional and distant failure using intensive radiosensitizing and systemic chemotherapy is mandatory for the advanced stage disease. The novel RT technique, intensity-modulated RT (24), is one of the promising tools to resolve the former issue, and the efficacy of less toxic approaches compared with that employed in the previous trials (6,11) should be tested in future prospective studies in patients with intermediate stage disease.
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In conclusion, the superiority of a treatment approach using concurrent platinum-based chemoradiotherapy combined with
2 cycles of FP over RT alone was shown in this group of patients with node-positive or T3/4 disease in terms of overall and progression-free survival. These results are consistent with the data obtained in previous randomized studies, although the feasibility of this intensive approach for Japanese patients remains to be investigated. In addition, three important clues arose from this survey which should influence the future direction of clinical trials for nasopharyngeal cancer: (i) this intensive approach seems more important for patients in the advanced stage disease than for those who have intermediate stage disease; (ii) a less toxic approach using adjunctive chemotherapy combined with RT aiming at improvement of LRC should be tested for patients with intermediate stage disease; and (iii) different treatment approaches in order to improve LRC should be planned for patients with keratinizing disease considering their remarkably poor LRC. |
Acknowledgments |
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The authors are most appreciative of the kind cooperation they received from the following doctors: Akiko Egawa MD, Department of Radiology, Nagasaki University, Nagasaki; Takashi Matsuzuka MD, Department of Head and Neck Surgery, Fukushima Medical University, Fukushima; Natsuo Tomita MD and Professor Yuta Shibamoto MD, Department of Quantum Radiology, Nagoya City University, Nagoya; Shunichi Ishihara MD, Department of Radiation Oncology, Toyohashi Municipal Hospital, Toyohashi; Hiroshi Onishi MD, Department of Radiation Oncology, Narita Red Cross Hospital, Narita; Kazukiyo Arakawa MD, Department of Radiology, Iida Municipal Hospital, Iida and Nagano Red Cross Hospital, Nagano; and Yoshikazu Kagami MD, Division of Radiation Oncology, National Cancer Center Hospital, Tokyo. This study was supported by Grant-Aided Cancer Research 14-15, Ministry of Health, Labor and Welfare of Japan.
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References |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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1 Lee AWM, Poon YF, Foo W, Law SCK, Cheung FK, Chan DKK et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys 1992;23:261–70.[Web of Science][Medline]
2 Sanguinetti G, Geara FB, Garden AS, Tucker SL, Ang KK, Morrison WH et al. Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local control and regional control. Int J Radiat Oncol Biol Phys 1997;37:985–96.[CrossRef][Web of Science][Medline]
3 Fu KK. Combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Semin Radiat Oncol 1998;8:247–53.[CrossRef][Web of Science][Medline]
4 Rossi A, Molinari R, Boracchi P, Del Vecchio M, Marubini E, Nava M et al. Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local–regional nasopharyngeal cancer: Results of a 4-year multicenter randomized study. J Clin Oncol 1988;6:1401–10.
5 International Nasopharynx Cancer Study Group: Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in syage IV (>or=N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. VUMCA I trial. Int J Radiat Oncol Biol Phys 1996;35:463–9.[CrossRef][Web of Science][Medline]
6 Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T et al. Chemo-radiotherapy vs. radiotherapy in patients with locally advanced nasopharyngeal cancer: phase III randomized Intergroup study (0099) (SWOG 8892, RTOG 8817, ECOG 2388). J Clin Oncol 1998;16:1310–7.
7 Chua DT, Sham JS, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S et al. Preliminary report of the Asian–Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian–Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group. Cancer 1998;83:2270–83.[CrossRef][Web of Science][Medline]
8 Ma J, Mai HQ, Hong MH, Min HQ, Mao ZD, Cui NJ et al. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2001;19:1350–7.
9 Chi KH, Chang YC, Guo WY, Leung MJ, Shiau CY, Chen SY et al. A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys 2002;52:1238–44.[CrossRef][Web of Science][Medline]
10 Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B et al. Concurrent chemotherapy–radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 2002;20:2038–44.
11 Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol 2003;21:631–7.
12 Hareyama M, Sakata K, Shirato H, Nishioka T, Nishio M, Suzuki K et al. A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma. Cancer 2002;94:2217–23.[CrossRef][Web of Science][Medline]
13 Samant S, Robbins KT, Kumar P, Ma JZ, Vieira F, Hanchett C. Bone or cartilage invasion by advanced head and neck cancer: intra-arterial supradose cisplatin chemotherapy and concurrent radiotherapy for organ preservation. Arch Otolaryngol Head Neck Surg 2001;127:1451–6.
14 Pignon JP, Bourhis J, Domenge C, Designé L, the MACH-NC Collaborative Group. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. Lancet 2000;355:949–55.[Web of Science][Medline]
15 Fuwa N, Kano M, Toita T, Shikama N, Kodaira T, Matsumoto A et al. Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: a preliminary report of phase II study. Radiother Oncol 2001;61:257–60.[CrossRef][Web of Science][Medline]
16 Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457–81.[CrossRef][Web of Science]
17 Cox DR. Regression models and life-tables. J R Stat Soc 1972;34:187–220.
18 Prasad U, Wahid MI, Jalaludin MA, Abdullah BJ, Paramsothy M, Abdul-Kareem S. Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy. Int J Radiat Oncol Biol Phys 2002;53:648–55.[CrossRef][Web of Science][Medline]
19 Chow E, Payne D, O'Sullivan B, Pintilie M, Liu FF, Waldron J et al. Radiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study: is combined modality treatment really necessary? Radiother Oncol 2002;63:269–74.[CrossRef][Web of Science][Medline]
20 Cooper JS, Lee H, Torrey M, Hochster H. Improved outcome secondary to concurrent chemoradiotherapy for advanced carcinoma of the nasopharynx: preliminary corroboration of the intergroup experience. Int J Radiat Oncol Biol Phys 2000;47:861–66.[CrossRef][Web of Science][Medline]
21 Rischin D, Corry J, Smith J, Stewart J, Hughes P, Peters L. Excellent disease control and survival in patients with advanced nasopharyngeal cancer treated with chemoradiation. J Clin Oncol 2002;20:1845–52.
22 Cooper JS. Concurrent chemotherapy and radiation therapy for advanced stage carcinoma of the nasopharynx. Int J Radiat Oncol Biol Phys 2000;48:1277–9.[CrossRef][Web of Science][Medline]
23 Al-Sarraf M, LeBranc M, Giri PG, Fu K, Cooper J, Vuong T et al. Superiority of five year survival with chemo-radiotherapy vs radiotherapy in patients with locally advanced nasopharyngeal cancer. Intergroup 0099 Phase III study: final report. Proc Am Soc Clin Oncol 2001;20:227a (abstract).
24 Lee N, Xia P, Quivey JM, Sultanem K, Poon I, Akazawa C et al. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys 2002;53:12–22.[CrossRef][Web of Science][Medline]
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