Concomitant chemoirradiation for stage III-IV nasopharyngeal carcinoma in Chinese patients: results of a matched cohort analysis

PURPOSE: To evaluate the toxicity and efficacy of concomitant chemoirradiation (CRT) followed by adjuvant chemotherapy compared with radiotherapy (RT) alone in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between March 1997 and September 2000, 47 Chinese patients with Stage III (n = 9, 19%) and IV (n = 38, 81%) NPC were treated with by CRT using cisplatin 100 mg/m(2) on Days 1, 22, and 43 of RT, plus adjuvant chemotherapy using cisplatin 80 mg/m(2) for 1 day and 5-fluorouracil 1 g/m(2) for 4 days on Days 71, 99, and 127. These patients were then compared with a cohort of 47 patients treated between 1990 and 1993 with RT alone, who were matched with respect to T stage, N stage, nodal bilaterality, nodal level, and nodal size. The RT techniques were similar in the two groups but different dose and fractionation schemes were used. The median biologic equivalent dose to 2 Gy per fraction delivered to the nasopharynx was 68 Gy in the CRT group and 65.3 Gy in the RT-alone group. RESULTS: The compliance rates were 62% for concomitant chemotherapy and 40% for adjuvant chemotherapy. No treatment-related deaths occurred. At the end of treatment, 96% of the CRT group and 79% of the RT-alone group achieved a complete response (p = 0.013). With a median follow-up of 26 months, the 3-year relapse-free survival, disease-specific survival, overall survival, local relapse-free survival, nodal relapse-free survival, and distant metastasis-free survival rate for the CRT group and the RT-alone group was 62% vs. 44% (p = 0.048), 67% vs. 71% (p = 0.88), 65% vs. 69% (p = 0.93), 87% vs. 75% (p = 0.059), 95% vs. 80% (p = 0.026), and 75% vs. 70% (p = 0.84), respectively. CONCLUSION: Our experience indicates that concomitant CRT improves locoregional control in Chinese patients with locoregionally advanced NPC, but our analyses failed to detect any impact on distant failure and survival. The failure to reduce distant metastasis and improve survival may have related in part to the more advanced disease stage in our patients and the relatively low compliance rate of adjuvant chemotherapy. Our findings suggest caution should be exercised in extrapolating the findings of the Intergroup Study 0099 to Chinese patients, and confirmatory results from prospective randomized studies in the endemic population are needed.     

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin–gemcitabine (GC) regimen (800 mg/m² gemcitabine on Days 1 and 8 and 20 mg/m² cisplatin on Days 1–5, every 4 weeks) (sGC‐RT); sequential chemoradiotherapy with a cisplatin–fluorouracil (PF) regimen (20 mg/m² DDP and 500 mg/m² 5‐FU on Days 1–5, every 4 weeks) (sPF‐RT) and cisplatin‐based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con‐RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3‐year overall survival (OS), disease‐free survival (DFS) and distant metastasis‐free survival (DMFS) rates in the sGC‐RT group were significantly higher than those observed in the Con‐RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3‐year OS, DFS and MFS rates between the Con‐RT and the sPF‐RT groups. The GC‐RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC‐RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.     

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.     

Efficacy and feasibility of cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma

OBJECTIVE: To investigate the efficacy and feasibility of a cisplatin-based concurrent chemoradiotherapy (CRT) protocol based on Intergroup Study 0099 for nasopharyngeal carcinoma (NPC). METHODS: Sixteen patients with stage II-IVB NPC were treated with a protocol of cisplatin-based concurrent CRT and adjuvant chemotherapy from 1998 to 2002. Three courses of cisplatin (80 mg/m2) were scheduled during 70 Gy of radiotherapy (RT), and two agents of adjuvant chemotherapy (FP regimen: cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day by 4-day continuous infusion) were challenged. Overall survival (OS) and relapse-free survival (RFS) rates were calculated by the Kaplan-Meier method. RESULTS: Median follow-up duration was 45 months. Both 3-year OS and RFS rates were 81%. Proportions of patients who tolerated each scheduled treatment were 94% for RT, 63% for concurrent chemotherapy and 38% for adjuvant chemotherapy. CONCLUSIONS: Our protocol of the cisplatin-based concurrent CRT followed by adjuvant chemotherapy consisting of FP regimen was effective for Japanese patients with NPC. However, the doses and numbers of cycle of chemotherapy need to be modified because of the low compliance rate. Larger numbers of data accumulation and/or multi-institutional trials may be warranted to confirm the efficacy of this protocol.     

Clinical Observation of Concurrent Radio-Chemotherapy Combined with Adjuvant Chemotherapy in Treating Locoregionally Advanced Nasopharyngeal Carcinoma

OBJECTIVE To investigate the efficacy and side effects of concurrent radiochemotherapy using the TP regimen (paclitaxel and cisplatin) combined with adjuvant treatment in treating patients with locoregionally advanced nasopharyngeal carcinoma (NPC).METHODS A total of 82 patients with a confirmed diagnosis of locoregionally advanced stage-Ⅲ and Ⅳa NPC were randomly divided into 2 groups: the treatment group (TG) with concurrent radiochemotherapy combined with adjuvant chemotherapy (n =44) and the control group (CG) with simple radiotherapy (RT)(n=38). A total dose of 68-74 Gy of conformal radiation (X-ray,4 MV or 8 MV) was given to patients in both groups. In the TG,a regimen of paxlitaxel and cisplatin was given via intravenous infusion in the 1st and 6th week concurrently with RT. After a 2-week intermission following RT, these patients received 2 cycles of the same chemotherapeutic regimen triweekly.RESULTS The effective rates of the treatment were, respectively,71.1% and 76.3% in the CG, and 88.6% and 95.5% in the TG, at the end of treatment and 3 months thereafter. The differences in the therapeutic efficacy between the 2 groups were statistically significant (P<0.05). The 1-and 2-year survival rates were 81.1% and 73%, and 95.2% and 90.5%, respectively in the CG and the TG, and the differences between the 2 groups were statistically significant (P<0.05). The grade Ⅰ-Ⅱ reactions in the gastrointestinal tract, skin and oral mucosa were higher in patients receiving concurrent radiochemotherapy combined with adjuvant chemotherapy than in patients receiving simple radiotherapy(P< 0.05). The differences in the occurrence of grade Ⅲ-Ⅳ side effects including gastrointestinal, dermal and oral mucosal discomfort,other side effects, and late radioactive damage between the 2 groups were not statistically significant.CONCLUSION Concurrent radiochemotherapy combined with adjuvant chemotherapy in treating patients with locoregionally advanced NPC can further improve short-term therapeutic effects and the overall survival. However, there is an increased trend in toxicity secondary to treatment.     

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial

Aim of the studyPrevious results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC).MethodsPatients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m² weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m² and fluorouracil 800 mg/m²/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival.ResultsTwo hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14).ConclusionAdjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities.Registration numberNCT00677118.     

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.     

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

PURPOSE: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). RESULTS: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). CONCLUSIONS: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.     

Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: impact of chemotherapy schemes

PURPOSE: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. METHODS AND MATERIALS: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. RESULTS: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). CONCLUSIONS: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.     

Concurrent weekly docetaxel chemotherapy in combination with radiotherapy for stage III and IVA-B nasopharyngeal carcinoma

Background and Purpose: Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Methods and Materials: Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Results: Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Conclusions: Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.     

中晚期鼻咽癌新辅助化疗联合放疗前瞻性 临床试验的长期结果

目的：评价新辅助化疗联合放疗在中晚期鼻咽癌治疗的价值。方法：前瞻性临床试验采用化疗方案：Cisplatin20mg/m^2,1-5天,5－FU500mg/m^2,1-5 天,BLM7mg/m^2,第1、5天,化疗2－3个疗程。放射治疗鼻咽剂量：66－74Gy/33-37次,共7－9周;预部淋巴结剂量：60－70Gy/30-35次,共7－8.5周;颈部预防量：48－50Gy。结果：1992－1993年457例鼻咽癌病人进入研究,17例因各种原因退出队列,440例进入分析（化疗＋放疗组219例、单纯放疗组221例）。5年生存率及无瘤生存率实验组及对照组分别为62％vs55％（P＝0.1335)及55％vs48%(P=0.0539)。5年无局部复发生率及无远处转移生存率两组分别为82％vs74%（P＝0.0412)及79％vs75%(P=0.4177)。亚组分析显示新辅助化疗能明显提高T3－4期的局控率;对N2－3病人的远处转移率无影响。结论：新辅助化疗未能提高中晚期鼻咽癌病人的总生存率,亦未能降低远处转移率,有提高无瘤生存率的趋势。新辅助化疗的指征：T3－4期病人。     

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC.

Between November 1994 and March 1999, 157 patients with Stage IV, M₀ (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35–40 fractions, 1.8–2.0 Gy/fraction/day, 5 days/week, to a total dose 70–72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m² cisplatin, 2,200 mg/m² 5-fluorouracil, and 120 mg/m² leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis.

With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p VALUE = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3).

We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.     

Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m² d1), cisplatin (60 mg/m² d1), and fluorouracil (600 mg/m²/d civ d1–5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m² cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.     

Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group.

PURPOSE: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS: Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS: From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION: Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.     

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.     

局部晚期鼻咽癌化疗和放射综合治疗--随机临床研究

目的：研究局部晚期鼻咽癌化疗和放射综合治疗的疗效及毒副反应。方法：1995年9月—1997年7月，86例病理确诊为鼻咽癌、根据福州九二新分期为N2-3的初治患者随机分组，综合治疗组41例，其中2例拒绝接受放疗后的辅助化疗，即综合治疗组可评估39例，单纯放疗组45例。综合治疗组接受2程诱导化疗[每天顺铂(DDP)20mg／m^2，第1～3天，每天氟尿嘧啶(5-FU)500mg／m^2，第1—3天，第二程化疗在第14天进行，放疗在第27天开始)及放疗后3程的辅助化疗。放疗为常规分割放疗。原发灶用^60Co治疗，每次1．85—1．9Gy，一周5次，7—7．5周总剂量65．1—70．3Gy／35—37次。颈部行双侧全颈根治性照射7—7．5周共56．6—65．5Gy／35—38次。如有残留，则局部缩野加量。两组鼻咽加量及颈淋巴结加量无显著差异。结果：中位随访期5．04年，综合治疗组和单纯放疗组五年生存率为72．3％，58．4％，(P=0．154)；无瘤生存率为59．9％，47．7％，(P=0．207)；鼻咽局控率为89．5％，81．4％，(P=0．151)；颈部局控率为88．3％，75．2％，(P=0．134)；无远处转移生存率为76．3％，60．3％，(P=0．181)，发生转移的中位时间分别为1．08年和0．88年。虽未达统计学意义，但综合治疗组有较单纯放疗组提高疗效的趋势。综合治疗组的主要毒性反应为白细胞降低、血小板降低及胃肠道反应。两组急性粘膜反应的严重程度差异无显著性。无与治疗有关的死亡发生。两组后期反应差异无显著性。结论：经5年观察，综合治疗有提高局控、降低远处转移、延迟远处转移的发生、提高无瘤生存率的可能，但均未达统计学意义，综合治疗未明显增加放疗反应。     

Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma

This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.     

Expression of ERCC1 predicts clinical outcome in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy

The aim of the present study was to evaluate the correlation between excision repair cross-complementation group 1 (ERCC1) protein with the clinical outcome of nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based induction chemotherapy. One hundred one Stage III-IVB nonkeratinizing NPC patients who were treated with cisplatin (DDP)+fluorouracil (5-Fu) induction chemotherapy were recruited. Pre-treatment tumor biopsy specimens were analyzed for ERCC1 by immunohistochemistry. The relationship of ERCC1 expression and chemotherapy response and survival of these NPC patients was analyzed. The objective response to induction chemotherapy of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 88.2% vs. 72% (P=0.041). The 5-year distant failure-free survival (D-FFS) of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 73.5% vs. 51.3% (P=0.037). ERCC1 expression was a significant prognostic factor for overall survival and D-FFS using Cox regression analysis. High tumor ERCC1 expression predicts low chemotherapy response and poor survival mainly caused by more metastasis in locoregionally advanced NPC treated with cisplatin-based induction chemotherapy.     

调强放疗联合化疗在T1-2N1M0期鼻咽癌患者中的作用回顾性研究

目的 探索调强放疗(IMRT)联合化疗在治疗T1-2N1M0期鼻咽癌患者中的作用。方法 收集2008—2016年间浙江省肿瘤医院和中山大学肿瘤防治中心接受根治性治疗的T1-2N1M0期鼻咽癌患者343例。所有患者均接受IMRT,分为单纯放疗组(RT组)和放化疗组(CRT组),后者又分为同步放化疗组(CCRT组)、诱导化疗+同步放化疗组(IC+CCRT组)和同步放化疗+辅助化疗组(CCRT+AC组)。采用Kaplan-Meier法评价局部区域无复发生存率(LRFFS)、远处无转移生存率(DMFS)、无进展生存率(PFS)、肿瘤特异生存率(CSS)和总生存率(OS)。Cox模型多因素预后分析。结果 303例存活患者的中位随访时间为91个月(49~138个月)。CRT组∶RT组的5年OS、CSS、PFS、LRFFS、DMFS均相近(93.7%∶93.9%、93.7%∶93.9%、89.0%∶87.7%、93.8%∶92.8%、93.8%∶91.2%,均P>0.05)。T1N1期和T2N1期亚组分析也显示CRT组与RT组的治疗结果均相近(均P>0.05)。多因素分析显示只有年龄是OS、PFS、CSS和DMFS的独立预后因素,随年龄增长与上述结局呈负相关。CCRT组、IC+CCRT组、CCRT+AC组与RT组的治疗结局均未给患者带来生存获益,且上述3种联合治疗方式之间的疗效也相近(均P>0.05)。结论 T1-2N1M0期鼻咽癌患者接受单纯IMRT获得了满意的治疗效果,预后与联合化疗相当。但未来是否可在T1-2N1M0期人群中取消化疗仍需要前瞻性随机对照临床试验的进一步证实。