Search

Background: This single-center, phase II study assessed the safety/tolerability and initial efficacy of gefitinib in patients with nasopharyngeal carcinoma (NPC) pretreated with platinum-based chemotherapy., Methods: Patients with recurrent and metastatic NPC who had treatment failure with at least 2 lines of chemotherapy including platinum were given gefitinib at a fixed dose of 250 mg daily. Treatment was continued until the patient experienced unacceptable side effects or disease progression., Results: Nineteen patients were enrolled, having had treatment failure with a median of 2 chemotherapy regimens. Treatment was well tolerated, and only grades 1 to 2 adverse events were observed. None of the patients achieved partial or complete response. Median time-to-progression was 4 months, and median overall survival was 16 months., Conclusion: Gefitinib was well tolerated, but the response rate was poor in this heavily pretreated study population, and its use in NPC is not recommended outside the context of clinical trial.

Background: Capecitabine monotherapy had activity in recurrent/metastatic nasopharyngeal carcinoma (NPC) as demonstrated previously in a small pilot study. We conducted a retrospective review of patients who received capecitabine for recurrent and metastatic NPC to further evaluate its clinical benefits., Methods: Forty-nine patients with recurrent and metastatic NPC received capecitabine at a dose of 1-1.25 G/m(2) twice daily for 14 days in 3-week cycles. Disease sites were locoregional in 29%, distant in 45% and locoregional plus distant in 26%. All except one had prior platinum-based chemotherapy for relapse or as adjunctive treatment. Median follow-up was 10 months (range: 3-41)., Results: Treatment was generally well tolerated. Hand-foot syndrome was common and occurred in 86% (25% Grade 3). Grade 3 hematological toxicity occurred in 6%. Partial response rate was 31% (95% CI: 18%, 44%) and complete response rate was 6% (95% CI: 0%, 13%), for an overall response rate of 37% (95% CI: 23%, 50%). Median time-to-progression was 5 months and median survival was 14 months. One- and two-year survival rates were 54 and 26%, respectively. Significantly better survival was observed in patients treated for locoregional recurrence and those with severe hand-foot syndrome., Conclusions: Capecitabine has single agent activity in NPC and severe hand-foot syndrome predicts favorable outcome. Based on our experience, capecitabine monotherapy should be considered in patients with recurrent/metastatic NPC.

Purpose: Local recurrence remains one of the major causes of failure in nasopharyngeal carcinoma (NPC). Stereotactic radiosurgery and fractionated stereotactic radiation therapy (FSRT) have recently evolved as a salvage option of NPC. This study was conducted to review the treatment outcome after FSRT for NPC., Methods and Materials: Between September 1999 and December 2005, 90 patients with persistent (Group 1: n = 34, relapse within 6 months of RT) or recurrent (Group 2: n = 56, relapse beyond 6 months) NPC received FSRT using multiple noncoplanar arcs of 8-MV photon to the target. Median FSRT dose was 18 Gy in three fractions (Group 1) or 48 Gy in six fractions (Group 2). Median follow-up was 20.3 months., Results: Complete response rate after FSRT was 66% for Group 1 and 63% for Group 2. One-, 2-, and 3-year disease-specific survival (DSS) and progression-free survival (PFS) rates for all patients were 82.6%, 74.8%, 57.5%, and 72.9%, 60.4%, 54.5%, respectively. Three-year local failure-free survival, DSS, and PFS rates were 89.4%, 80.7%, and 72.3% for Group 1, and 75.1%, 45.9%, and 42.9% for Group 2, respectively. Multivariate analysis showed that recurrent disease and large tumor volume were independent factors that predicted poorer DSS and PFS. Seventeen patients developed late complications, including 2 with fatal hemorrhage., Conclusions: Our results indicate that FSRT is effective for patients with persistent and recurrent NPC. Compared with reported results of radiosurgery, FSRT provides satisfactory tumor control and survival with a lower risk of complications and it may be a better treatment for local failures of NPC.

Background and Purpose: To evaluate the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT)., Materials and Methods: Between October 2001 and May 2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT. The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14 for r T4. Median time from first course of radiotherapy to re-irradiation was 51 months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional treatments included cisplatin-based induction chemotherapy in 68% and radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%. Median follow-up time was 11 months., Results: After re irradiation, 58% of patients had complete regression of primary tumor. One-year loco-regional progression-free, distant metastasis-free and overall survival rates were 56, 90, and 63%, respectively. Significantly better 1-year local progression-free rate was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities, mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3., Conclusion: Our preliminary results showed that good control of rT1-3 NPC can be achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r T4 tumor remained poor. Late toxicities were common but incidence of severe toxicities was relatively low.

Objectives: Patients with advanced local recurrence of nasopharyngeal carcinoma (NPC) have a poor prognosis. Retreatment by external radiotherapy is frequently the only option but results are usually poor. This study was conducted to evaluate the benefits of adding induction chemotherapy with cisplatin and gemcitabine before reirradiation for locally recurrent NPC., Methods: Twenty patients with locally recurrent NPC not amenable to brachytherapy or surgery were enrolled between September 2001 and October 2003. The T stage distribution at recurrence was 5% rT2, 30% rT3, and 65% rT4. Induction chemotherapy consisted of cisplatin 40 mg/m2 and gemcitabine 1.25 g/m days 1 and 8 for 3 times per week for 3 cycles, followed by reirradiation using intensity-modulated radiotherapy., Results: A total of 58 chemotherapy cycles were administered to patients and most received 3 cycles. Hematological toxicities were mild, with grade 3 and 4 neutropenia in 55% and 5% of patients, respectively, and grade 3 thrombocytopenia in 5%. After chemotherapy, 15 patients achieved partial response (75%). Seventeen patients received external reirradiation and one had radiosurgery after chemotherapy. Severe acute radiation toxicities were uncommon. After a median follow-up of 14.5 months, 55% of patients had locoregional progression and 45% had died. The 1-year locoregional progression-free, local progression-free, and overall survival rates were 63%, 68%, and 80%, respectively. In patients with external reirradiation, the 1-year local progression-free and overall survival rates were 75% and 88%. Patients with rT2-3 stage had significantly better 1-year local control rates than those with rT4 stage (100% versus 52%)., Conclusions: The combination cisplatin and gemcitabine is active and well-tolerated in locally recurrent NPC. The current approach of using induction chemotherapy before reirradiation may improve the outcome of patients with advanced local recurrence and merits further investigation.

Background: The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS., Methods: Between January 1996 and December 2000, 2915 patients received primary radiotherapy (RT) with or without chemotherapy for nonmetastatic NPC. At a median follow-up of 3.1 years, 319 patients had developed local failure as the first failure, with or without synchronous regional/distant failure. OS was calculated from the start of primary RT. Univariate and multivariate analyses were performed to identify prognostic factors for OS in patients with isolated local failure., Results: The T classification distribution of the local failure (rT classification) was as follows: 68 (21%) rT1 to T2a, 92 (29%) rT2b, 82 (26%) rT3, and 77 (24%) rT4. The rT classification was the same as the initial T classification in 82% of patients. Two hundred seventy-five patients (86%) had isolated local failure, and 232 (84%) of them did not have any distant metastasis or regional failure develop during follow-up. Salvage treatment was given to 200 patients (73%) with isolated local failure. One hundred fifty-nine patients (80%) received reirradiation (108 external beam RT [EBRT], 44 brachytherapy, and seven EBRT plus brachytherapy), 22 patients (11%) underwent nasopharyngectomy with or without postoperative RT, and 19 patients (9%) were treated with chemotherapy alone. Four patients died of RT complications, and one died of chemotherapy toxicity in the absence of active NPC. The 3-year actuarial OS for patients with isolated local failure was 74%. On multivariate analysis, advanced initial T classification (hazard ratio [HR], 1.44; p = .0006) and the use of salvage treatment (HR, 0.54; p = .0038) were independent prognostic factors. For the subgroups of patients who had the same recurrent and initial T classification, salvage treatment was associated with improved OS only in the subgroup with T1 to T2 local failure (n = 127; p = 0.0446), but not in the subgroups with T3 (n = 48) or T4 (n = 54) disease., Conclusions: Most patients with first local failure have localized disease. Salvage treatment is feasible in most of the patients with clinically isolated local failure. Patients who had early initial T classification have a more favorable prognosis. Subgroup analysis suggests that salvage treatment only prolongs survival in patients with T1 to T2 recurrent disease., (2005 Wiley Periodicals, Inc.)

Background: The quantity of circulating cell-free Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) managed by radiotherapy has prognostic relevance. We measured the copy number of EBV DNA in patients with early recurrent NPC before and after salvage nasopharyngectomy., Methods: Nasopharyngectomy with the maxillary swing approach was performed for 28 patients. Serum blood samples were taken prospectively before nasopharyngectomy and on postoperative day 7. Plasma cell-free EBV DNA copies were measured with a real-time quantitative polymerase chain reaction for the BamHI-W fragment of the EBV genome., Results: Cell-free EBV DNA was detected in 17 patients before nasopharyngectomy. Surgical resection reduced the copy number of EBV DNA significantly (p = .016). Negative surgical margins achieved during nasopharyngectomy is associated with a zero EBV DNA copy postoperatively (p = .022)., Conclusion: Cell-free EBV DNA was detected in 61% of patients with recurrent NPC, and its quantity postoperatively reflects whether the salvage nasopharyngectomy has achieved a negative surgical margin.

Background: Lung carcinoma is a leading cause of cancer deaths worldwide. To better understand this disease, the authors studied genetic alterations in nonsmall cell lung carcinoma (NSCLC) and the association between genetic changes and clinical features., Methods: Genetic alterations in 30 patients with adenocarcinoma (AC) and 39 patients with squamous cell carcinoma (SCC) were analyzed by comparative genomic hybridization. The genetic changes in patients with AC and SCC were compared and the associations of these changes with clinical features were studied., Results: A gain of 3q with a minimal amplified region at 3q25.3-qter was significantly higher in patients with SCC compared with patients with AC (72% vs. 27%; P < 0.001). A gain of 20q and loss of chromosome 9 were detected more frequently in patients with AC compared with patients with SCC (P < 0.05). Gains of 5p and 20q and loss of 5q were significantly correlated with an advanced stage of NSCLC (P < 0.05). Amplification of 1q was significantly associated with NSCLC recurrence (P = 0.04)., Conclusions: The results of the current study suggested that different chromosomal aberrations may contribute to the types and pathologic stages of NSCLC., (Copyright 2004 American Cancer Society.)

Background: To review the outcome and evaluate the prognostic factors in the treatment of synchronous locoregional failures of nasopharyngeal carcinoma (NPC)., Methods: We reviewed the records of 43 patients with synchronous locoregional failures of NPC who received salvage treatment or chemotherapy between November 1986 and January 2001. The recurrent disease was stage II in 61%, stage III in 30%, and stage IV in 9%. The local disease was rT1-2 in 67% and rT3-4 in 33%, and the regional disease was rN1 in 91% and rN2 in 9%. Persistent disease, defined as failures within 4 months of completion of primary radiotherapy, occurred in 53.5% and recurrent disease in 46.5%. Seventeen patients received surgery for regional and/or local failures with or without combined radiotherapy (ST group), 14 patients received reirradiation to both local and regional disease (RT group), and 12 patients received palliative chemotherapy only (CT group). The median follow-up was 18 months (range, 4-153) and for the surviving patients it was 29 months (range, 6-153)., Results: The 3-year relapse-free survival (RFS) rate and disease-specific survival (DSS) rate after salvage treatment or chemotherapy were 17% and 38%, respectively. The 3-year RFS rates in stage II, III, and IV disease were 25%, 8%, and 0%, respectively. The corresponding 3-year DSS rates were 43%, 28%, and 38%. The 3-year RFS rates in the ST, RT, and CT group were 39%, 7%, and 0%, respectively. The corresponding 3-year DSS rates were 55%, 25%, and 25%. Patients whose local disease was treated by surgical resection had a 3-year local control rate of 71% compared with 38% by reirradiation using brachytherapy or external radiotherapy. For regional disease, the 3-year nodal control rate after radical neck dissection was 65% compared with 24% by reirradiation. Further locoregional failure represents the major failure pattern, and the proportion of patients who had further local, regional, and both locoregional failures were 16%, 9%, and 53%, respectively. Distant metastasis occurred in 30% of patients, and only 5% had isolated distant metastasis in the absence of locoregional failures. On multivariate analysis, treatment by reirradiation or chemotherapy alone and rN2 disease were independent factors that predicted poor survival, whereas treatment by reirradiation or chemotherapy alone was the only independent factor that predicted further relapse or failure., Conclusions: Proper selection of patients for aggressive salvage treatment and individualization of treatment are important in managing patients with synchronous locoregional failures of NPC. A significant proportion of patients with early stage locoregional failures can still achieve long-term disease control and survival after aggressive salvage treatment using surgery with or without combined radiotherapy. In patients with more advanced disease, treatment by reirradiation alone or palliative chemotherapy is largely ineffective and is associated with a poor outcome., (Copyright 2003 Wiley Periodicals, Inc. Head Neck 25: 585-594, 2003)

To evaluate the efficacy and toxicity of capecitabine as a salvage chemotherapy regimen in Chinese patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy, 17 patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments received oral capecitabine at a dose of 1.25 G/m(2) twice daily in 3-week cycles consisting of 2 weeks of treatment followed by rest period of 1 week. Seven patients had local recurrence, seven had distant metastases, one had loco-regional recurrence, and two had both local/regional recurrence and distant metastases. Patients received a median number of three cycles of capecitabine (range: 1-6). The median follow-up was 7.5 months (range: 3-25.3). All patients were included in the efficacy and adverse events analysis. Three patients (17.6%) achieved partial response and one patient (5.9%) achieved complete response, with an overall response rate of 23.5% (95% confidence interval, 7-50%). The duration of response's were 4.2, 5, 6+, and 23.1+ months. Nine patients (52.9%) had stable disease whereas four (23.5%) had progressive disease. The median time to progression was 4.9 months. The median survival was 7.6 months. Five patients are still alive with an estimated 1-year survival rate of 35%. Treatment-related adverse events were generally mild except hand-foot syndrome which occurred in 58.8% of patients. Capecitabine is an effective salvage regimen in patients with recurrent and metastatic NPC. Capecitabine as a single agent or in combination with other chemotherapeutic agents or treatment modalities should be further studied in NPC., (Copyright 2003 Elsevier Science Ltd.)