晚期转移性头颈部腺样囊性癌治疗进展

晚期转移性腺样囊性癌目前无标准的治疗方案,各个指南现在对头颈部腺样囊性癌的治疗规范较少,关于晚期转移性腺样囊性癌的治疗以全身治疗为主,化疗方案多采用以蒽环类和环磷酰胺为主的联合治疗方案,紫杉类和吉西他滨治疗无效,部分靶向药物治疗有效,但是有效率均不超过20％.我们总结现有的数据,为晚期转移性腺样囊性癌的治疗提供循证医学...     

Prognostic factors affecting the clinical outcome of adenoid cystic carcinoma of the head and neck

BACKGROUND: Adenoid cystic carcinoma (ACC) is an uncommon tumor, constituting approximately 10% of all head and neck tumors. Classically, ACC has been described as a tumor with indolent, but persistent and recurrent, growth and late onset of metastases, leading eventually to death. This study assessed the prognostic factors affecting the clinical outcome in patients with ACC in the head and neck region. METHODS: We performed a retrospective study of 42 patients who underwent primary tumor resection or radiotherapy with curative intent and evaluated the clinical parameters, treatment and clinical outcomes. RESULTS: Forty-two patients (18 males and 24 females with a median age of 65 years) received curative treatment. The overall 3- and 5-year survival was 87.4% and 55.3%, respectively, whereas the 3- and 5-year disease-free survival was 64.3% and 36.1%, respectively. Of the 32 patients in whom recurrence could be evaluated, 18 (56.3%) developed distant metastases, with the lung (72.2%) being the most common site. Perivascular invasion influenced metastasis to the lung with borderline significance (P = 0.053). The recurrence rate was higher (P = 0.045) in patients with high-grade tumor. The status of lymph node metastasis was significantly associated with overall survival (P = 0.030). CONCLUSIONS: High tumor grade and lymph node involvement were predictive of recurrence and overall survival, respectively. Despite aggressive treatment, it seems to be impossible to prevent the development of distant metastasis. Therefore, more research is needed to identify molecular biomarkers that predict the clinical outcome and to develop effective treatment for patients with ACC.     

Adenoid cystic carcinoma of the head and neck: Incidence and survival trends based on 1973-2007 Surveillance, Epidemiology, and End Results data

BACKGROUND:

Adenoid cystic carcinoma (ACC) of the head and neck (ACCHN) is a rare tumor of minor salivary, parotid, and submandibular glands. The biologic behavior of the disease is poorly understood, and nonsurgical treatment strategies have yet to be standardized. The long‐term prognosis continues to be guarded, with an estimated 10‐year survival of <60%. Population‐based studies examining ACC are scarce. The authors aimed to analyze incidence rates and survival outcomes for patients diagnosed with ACCHN using national population‐based data.

METHODS:

Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Newly diagnosed ACCHN cases reported to SEER from 1973 through 2007 were categorized according to their sex, race, age, year of diagnosis, marital status, treatment interventions, primary tumor site, and disease stage. Incidence of ACCHN and postdiagnosis survival were examined over time and compared across different demographic and disease‐related categories.

RESULTS:

The authors identified 3026 patients with ACCHN. The mean age at diagnosis among those cases was 57.4 years (range, 11‐99 years). Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflexion points. The overall 5‐year, 10‐year, and 15‐year survival outcomes for ACCHN patients were 90.3%, 79.9%, and 69.2%, respectively. Females, patients with localized disease, and younger patients were found to have significantly better survival across all time periods (all comparison‐specific log‐rank P values <0.001). Multivariate analyses revealed better prognosis among women compared with men (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65‐0.82), among married compared with unmarried individuals (HR, 0.81; 95% CI, 0.71‐0.91), with certain sites of origin and stage of disease (HR, 2.788; 95% CI, 2.36‐3.29), and in those who had surgery of the primary tumor site (HR, 0.45; 95% CI, 0.37‐0.54).

CONCLUSIONS:

The overall incidence of ACC is declining. The noted differences in survival based on sex, marital status, site of origin, and treatment intervention require further investigation. Cancer 2012. © 2012 American Cancer Society     

Docetaxel and cisplatin in locally advanced or metastatic squamous-cell carcinoma of the head and neck: A phase II study of the Southern Italy Cooperative Oncology Group (SICOG)

Background:Docetaxel is one of the most promising new drugsagainst squamous-cell carcinoma of the head and neck (SCCHN), while cisplatinis one of the most active single agents. A phase I study has shown thefeasibility of the combination of the two drugs, and activity in SCCHN hasbeen seen. Patients and methods:Patients with locally advanced, inoperable,or metastatic SCCHN, never pretreated with radiotherapy or chemotherapy,received three courses of docetaxel 75 mg/m² and cisplatin 100mg/m², every three weeks. Thereafter, responsive metastaticpatients received additional chemotherapy, while patients with locallyadvanced disease underwent radiation therapy. Results:Forty-six patients (forty-five with locally advanced, onewith metastatic disease) were entered into the study. Ten patients did notcomplete three courses of chemotherapy because of early death; one patientdiscontinued treatment after one course. Twenty-one objective responses wereobserved (46%, 95% confidence interval (CI):31%–60%), including five complete responses (11%)and sixteen partial responses (35%). Following induction chemotherapyplus radiation therapy, 9 of 21 evaluable patients were rendered disease free,while 8 additional patients had a partial response. After a median follow-upof 18 months, the median duration of response was 12 months, (range3–25+), and the median overall survival was 11 months. Six early deathswere considered possibly treatment-related (sepsis following grade 4neutropenia in two cases, hypovolemic shock following severe diarrhea in fourcases). Neutropenia was the most severe toxicity (grade 3–4 in 28patients, median duration 4 days); diarrhea and vomiting were the mosttroublesome non-haematologic toxicities (grade 4 in 4 and 3 patients,respectively). Conclusions:The combination of docetaxel and cisplatin is activein SCCHN, but toxicity is substantial. This schedule does not appear to offerany advantage compared with conventional regimens.     

头颈部腺样囊性癌的磁共振成像特点

背景与目的：腺样囊性癌（adenoid cystic carcinoma,ACC）是起源于涎腺组织的一种少见恶性肿瘤,该研究旨在探讨磁共振成像（magnetic resonance imaging,MRI）在头颈部ACC中的应用价值。方法：回顾性分析上海市质子重离子医院2015年5月—2017年9月收治的26例（19例原发,7例复发）经手术病理证实的头颈部ACC患者的临床和MRI资料。结果：26例肿瘤中,位于鼻咽8例,腭6例,鼻腔4例,上颌窦3例,颌下腺和舌各2例,喉1例。23例肿瘤形态不规则,边界不清;其余3例呈类圆形,边界较清。所有病灶与肌肉相比在T1WI上呈等信号,在T2WI上呈高或稍高信号,增强后可见明显强化。17例侵犯神经中,累及翼腭窝16例,累及海绵窦10例,卵圆孔8例,圆孔4例,眶上裂2例,视神经管2例,舌下神经管2例,翼管1例。21例侵犯骨质,11例侵犯颅内。结论：MRI能够清晰显示ACC的肿瘤范围及神经受累情况,可为临床治疗提供更多信息。     

An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

Background: Vinorelbine is an active drug in the treatment of lung and breast cancers and has a favorable toxicity profile. Many clinical trials have demonstrated its antitumor activity in other tumor types including squamous cell carcinoma of the head and neck (SCCHN). We investigated the efficacy and tolerability of vinorelbine in patients with recurrent and/or metastatic SCCHN, previously untreated by chemotherapy.Patients and methods: Seventy-one patients with locoregional recurrent and/or metastatic SCCHN were treated with vinorelbine at a dose of 30 mg/m2/week i.v. by short-duration infusion on an out-patient basis. Doses were adjusted according to tolerance.Results: Two complete and seven partial responses were observed among 56 evaluable patients, yielding a response rate of 16% (95% confidence interval (CI): 8%–28%). The overall response rate of all eligible patients (63) was 14%. The responses were seen in recurrent tumors, lymph nodes and in lung metastases, and their median duration was 19 weeks (12–63). The main toxicity, severe and reversible neutropenia (grade 3–4) occurred in 53% of the 69 evaluable (for toxicity) patients. Twelve patients developed severe bronchopulmonary infections, which caused two early deaths. Constipation was observed in 31 patients (45%). Other gastrointestinal toxicities, asthenia, acute pain syndrome and peripheral sensory neuropathy, were mild to moderate. The median number of treatments was seven cycles and the median relative dose intensity of vinorelbine was 85% (25.5 mg/m2/week).Conclusions: Vinorelbine is an active drug, with acceptable toxicity, in recurrent and/or metastatic SCCHN, at the dose and schedule administered in the present study. Further evaluation in association with other agents and/or radiotherapy is warranted.     

Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial

Background:

Epidermal growth factor receptor (EGFR) is highly expressed in adenoid cystic carcinoma (ACC). The efficacy and toxicity of cetuximab with concomitant platinum-based chemoradio- or chemotherapy in patients with locally advanced or metastatic ACC, respectively, was evaluated.

Methods:

Eligible patients (9 with locally advanced tumour and 12 with metastases) had positive tumour EGFR expression. The cetuximab loading dose (400 mg m⁻²) was followed by 250 mg m⁻² per week. Locally advanced tumours were irradiated (mean dose 65 Gy) and treated with concomitant cisplatin (75 mg m⁻², intravenously). Patients with metastases received concomitant cisplatin and 5-fluorouracil (4 × 1000 mg m⁻²).

Results:

For patients with locally advanced disease (median follow-up: 52 months), the median progression-free survival (PFS) was 64 months and the 2-year overall survival (OS) rate was 100%. For patients with metastases (median follow-up: 72 months), the median PFS and OS were 13 and 24 months, respectively. In both groups the objective response rate was >40%. Skin rash, in-field dermatitis, mucositis and vomiting were the most frequent grade 3/4 adverse events.

Conclusion:

In this single-arm study, the efficacy of cetuximab plus chemoradio- or chemotherapy appeared favourable as compared with historical controls. All side effects were manageable and did not hamper the treatment.     

Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced non-nasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: The prognosis of patients with recurrent and/or metastatic head and neck cancer (HNC) is poor. Median survival of these patients following chemotherapy is in the range of 6 to 9 months. In the present randomized phase III trial we compared two new combinations containing new drugs with proven activity in phase II studies with patients with HNC. PATIENTS AND METHODS: From November 1999 until November 2004, 166 eligible patients with HNC were enrolled in the study. They were treated with paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8 every 3 weeks (group A, 85 patients) or with paclitaxel, as in group A, and pegylated liposomal doxorubicin 40 mg/m(2) on day 1 every 4 weeks (group B, 81 patients). RESULTS: There was no significant difference in response rate (20% versus 29%, P = 0.21), time to disease progression (median; 4.4 months versus 6.0 months, P = 0.09) and survival (median; 8.6 months versus 11.05 months, P = 0.25). Both regimens were generally well tolerated. The most frequently reported side effect, apart from alopecia, was neutropenia. Overall, there was no significant difference in severe toxicity between the two treatment arms. CONCLUSIONS: The present study could not demonstrate a survival benefit with either regimen. Both treatments were well tolerated. Randomized studies comparing each of the two regimens with standard chemotherapy are warranted.     

Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck

BACKGROUND: Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC. METHODS: Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty-three additional patients were treated with this dose. RESULTS: Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted. CONCLUSIONS: The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial.     

Cisplatin, raltitrexed, levofolinic acid and 5-fluorouracil in locally advanced or metastatic squamous cell carcinoma of the head and neck: a phase I-II trial of the Southern Italy Cooperative Oncology Group (SICOG).

Background:The combination of cisplatin (CDDP) and 5-fluorouracil(5-FU) can be regarded as a reference regimen in squamous cell carcinoma ofthe head and neck (SCCHN). Raltitrexed (Tomudex) is a direct and specificthymidilate synthase (TS) inhibitor, which has shown clinical activity againstSCCHN in a previous phase I study, when combined with 5-FU and levo-folinicacid (LFA). Preclinical data support the combination of CDDP and raltitrexed.The aim of the present study was to evaluate the combination of cisplatin,raltitrexed, LFA and 5-FU in a phase I–II study. Patients and methods:Patients with locally advanced or metastaticSCCHN were treated with a combination of cisplatin at the starting dose of 40mg/m², followed by raltitrexed at the starting dose of 2.5mg/m² on day 1; levo-folinic acid at fixed dose of 250mg/m², followed by 5-fluorouracil at the starting dose of 750mg/m² on day 2. Doses of the three cytotoxic agents werealternately escalated up to dose-limiting toxicity (DLT). Treatment wasrecycled every two weeks and given up to a maximum of eight courses; afterchemotherapy, patients with locally advanced disease received a locoregionaltreatment. Results:Forty-five patients were entered into the study. Six doselevels were tested. At CDDP 50 mg/m², raltitrexed 3mg/m², 5-FU 900 mg/m², four out of six patients showedDLT, which was in all cases grade 4 neutropenia. Therefore, this dose levelwas defined as maximum tolerated dose (MTD). CDDP 60 mg/m²,raltitrexed 2.5 mg/m², LFA 250 mg/m², 5-FU 900mg/m² was the dose level recommended for phase II. CDDP,Raltitrexed and 5-FU mean actually delivered dose intensities at the selecteddose level were 26, 1.05, and 378 mg/m²/week, respectively.Neutropenia was the main side effect and was observed even at the lowest doselevels. Non-hematologic side effects were mild. Nine complete responses(20%) and twenty-one partial responses (47%) were observed, foran overall response rate of 67% (95% confidence interval(95% CI): 51%–80%), according to intention to treatanalysis. Fifteen of fifteen patients (100%) treated at the dose levelselected for phase II had an objective response (5 complete responses, 10partial responses). Conclusions:The results of our dose escalation clearlydemonstrate that it is possible to combine CDDP, raltitrexed, and modulated5-FU at effective doses, without unexpected toxicities. The response datapoint to an impressive clinical activity, which will be better defined by anongoing large phase II study.     

Single-agent docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN)

BACKGROUND: The objective of this retrospective study was to investigate the efficacy and tolerability of single-agent docetaxel in patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS: Platinum-refractory disease was defined as cancer with documented tumor progression during platinum-based treatment or recurrence within 6 months after platinum-based chemoradiotherapy. Patients fulfilling the following criteria were enrolled: histologically confirmed SCCHN, excluding nasopharyngeal cancer; measurable metastatic lesions as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST); and platinum-refractory disease. Docetaxel (60 mg/m2) was administered every 3-4 weeks and continued unless there was evidence of disease progression or unacceptable toxicity. RESULTS: Twenty patients were recruited. Overall response rate was 10% (2/20) and tumor control rate was 25% (5/20). Median progression-free and median overall survival times were 1.7 and 4.6 months, respectively. The most common hematological toxicities were leucopenia (grade 4: 35%) and neutropenia (grade 4: 30%). Grade 3 febrile neutropenia and grade 3 mucositis (functional/symptomatic) each occurred in two patients (10%). One fatal bleeding occurred during this treatment, however, the relation between this event and docetaxel was unlikely. Median inpatient period during treatment was 5.4 days (range, 0-50 days). CONCLUSION: A single-agent docetaxel regimen appeared to offer an acceptable clinical profile in patients with platinum-refractory SCCHN.     

Clinical phase II evaluation of paclitaxel in combination with cisplatin in metastatic or recurrent squamous cell carcinoma of the head and neck

Background: Paclitaxel as single agent has shown marked activity in several malignancies. The aim of the present phase II trial was to determine the activity of paclitaxel/cisplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck.Patients and methods: 200 mg/m² paclitaxel was administered over three hours followed by cisplatin (100 mg/m²), repeated every 22 days. Twenty-eight patients were entered and received a total of 99 cycles (median 2, range 1–6). All patients were evaluable for toxicity, and 25 for response.Results: Hematologic toxicities included leukopenia CTC grade 3 in 13 patients, and grade 4 in five patients, neutropenia grade 3 in nine patients, and grade 4 in eigth patients, grade 3 anemia and grade 2 thrombocytopenia in one patient each. Non-hematologic toxicities included hypotension grade 2 (six patients), grade 3 (four patients), and grade 4 (two patients). A decline in renal function was observed in 15 courses and 10 patients, leading to a median delay of 2.5 days. Neurosensory and neuromotor toxicity grade 1 were observed in 13 patients (grade 2: 12 patients; grade 3: one patient), myalgia grade 3 in one patient, asthenia grade 3 in two and grade 4 in one patient. Partial responses were observed in 12 patients for an overall response rate of 48% (95% CI: 28%–68%) with a median response duration of 6.5 months (range 1-10 months). Stable disease was observed in seven patients, of who two also had clinical benefit.Conclusions: Paclitaxel 200 mg/m² administered over three hours combined with cisplatin 100 mg/m² is an active regimen warranting further evaluation.     

Docetaxel and irinotecan in recurrent or metastatic head and neck cancer

BACKGROUND:

Docetaxel and irinotecan have single‐agent antitumor activity in squamous cell carcinoma of the head and neck (SCCHN). The authors sought to evaluate their combination in the treatment of patients with recurrent or metastatic SCCHN.

METHODS:

Eligibility criteria included recurrent or metastatic SCCHN with measurable disease, good performance status, and adequate laboratory parameters. Patients received docetaxel 35 mg/m² and irinotecan 60 mg/m², intravenously, on Days 1 and 8, every 21 days, until disease progression. The authors assessed UGT1A1 genotype, vascular endothelial growth factor (VEGF) in serum, and cyclooxygenase‐2 and VEGF in baseline tumor tissue.

RESULTS:

Fifty‐two patients were analyzable: 20 chemotherapy naive (Group A) and 32 previously treated with 1 chemotherapy regimen (Group B); 73% of patients had distant metastasis, and 60% were paclitaxel‐exposed. In Group A, 3 (15%) patients achieved a partial response; in Group B, 1 (3%) patient achieved a partial response. Median progression‐free survival (PFS) and overall survival were 3.3 and 8.2 months in Group A and 1.9 and 5.0 months in Group B, respectively. Common serious toxicities were diarrhea, fatigue, and anorexia. Patients with high serum VEGF had a median PFS of 2.8 months versus 1.7 months for patients with low VEGF (P = .085).

CONCLUSIONS:

Docetaxel and irinotecan had acceptable toxicities, but efficacy results in unselected patients with recurrent or metastatic SCCHN did not suggest an advantage over docetaxel alone or platinum‐based regimens. Cancer 2009. © 2009 American Cancer Society.     

Management and palliative chemotherapy for metastatic or recurrent squamous cell carcinoma of the head and neck

Squamous cell carcinoma of the head and neck with distant metastases or locoregional relapse not amenable to radical surgery or radiation therapy are incurable. Median overall survival is approximately 10 months and the site of relapse, frequently in the head and neck area, is responsible for important local and regional complications that significantly impact quality of life. This article will focus on the general management and treatment of these recurrent and/or metastatic patients. We will discuss the challenges faced by the clinician when diagnosing tumor recurrence, as well as the indications and the limitations of the locoregional and systemic treatments available to treat this population.     

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck.

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m(-2) by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1-9) per patient. The median cumulative dose was 449 mg m(-2). Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1-50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4-52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h(-1) m(-2) and an area under the curve of 6.00 microg ml(-1) h(-1) was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance.     

Adenoid cystic carcinoma: a retrospective clinical review.

Adenoid cystic carcinoma (ACC) are uncommon tumors, representing about 10% to 15% of head and neck tumors. We compare the survival and control rates at our institution with those reported in the literature, and examine putative predictors of outcome. All patients registered with the tumor registry as having had ACC were identified. Demographic and survival variables were retrieved from the database. Additionally, a chart review of all patients was done to obtain specific information. Minor gland tumors were staged using the American Joint Committee on Cancer's criteria for squamous cell carcinomas in identical sites. Histopathologic variables retrieved included grade of the tumor, margins, and perineural invasion. Treatment modalities, field sizes, and radiation doses were recorded in applicable cases. An effort to retrieve archival tumor specimens for immunohistochemical analysis was undertaken. A total of 69 patients were treated for ACC from 1955 to 1999. One patient, who presented with fatal brain metastasis, was excluded from further analysis. Of the remaining 68 patients, 30 were men and 38 were women. The average age at diagnosis was 52 years, and mean follow-up was 13.2 years. Mean survival was 7.7 years. Overall survival (OS) rates at 5, 10, and 15 years were 72%, 44%, and 34%, and cause-specific survival was 83%, 71%, and 55%, respectively. Recurrence-free survival rates were 65%, 52%, and 30% at 5, 10, and 15 years, with a total of 29 of 68 (43%) eventually suffering a recurrence. Overall survival was adversely affected by advancing T and AJCC stage. Higher tumor grades were also associated with decreased OS, although the numbers compared were small. Primaries of the nasosinal region fared poorly when compared with other locations. Total recurrence-free survival, local and distant recurrence rates were distinctly better in primaries of the oral cavity/oropharynx when compared with those in other locations. Reduced distant recurrence-free survival was significantly associated with increasing stage. No other variables were predictive for recurrence. Additionally, we found that nasosinal tumors were more likely to display higher stage at presentation, and were more often associated with perineural invasion. Also of interest was the association of perineural invasion with margin status, with 15 of 20 patients with positive margins displaying perineural invasion, while only 5 of 17 with negative margins showed nerve invasion (P = 0.02). On immunohistochemistry, 2 cases of the 29 (7%) tumor specimens found displayed HER-2/neu positivity. No correlation between clinical behavior and positive staining could be demonstrated. Our data concur with previous reports on ACC in terms of survival and recurrence statistics. Stage and site of primary were important determinants of outcome. Grade may still serve a role in decision making. We could not demonstrate any differences attributable to primary modality of therapy, perhaps due to the nonrandomization of patients into the various treatment tracks and the inclusion of palliative cases. Similarly, perineural invasion, radiation dose and field size, and HER-2/neu positivity did not prove to be important factors in our experience.     

Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies

BACKGROUND: The epidermal growth factor receptor (EGFR) inhibitor cetuximab is active in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). The activity of cetuximab was compared with that of commonly used treatments in this setting. METHODS: All patients had recurrent and/or metastatic SCCHN and had progressed on cisplatin- or carboplatin-based chemotherapy. Efficacy data from 3 prospective studies (n=278 patients) that administered cetuximab as a single agent (n=103 patients) or combined with either cisplatin/carboplatin (n=96 patients) or cisplatin (n=79 patients) were compared with the results from a retrospective study of patients who received various second-line treatments (all treatments including best supportive care only, n=151 patients; chemotherapy, n=43 patients). Safety data considered were only those from the cetuximab studies. RESULTS: Over the 3 cetuximab trials, overall response rates from 10% to 13% and disease control rates from 46% to 56% were observed. The median time to disease progression ranged between 2.2 months and 2.8 months, and the median overall survival ranged between 5.2 months and 6.1 months. No patients who progressed on cetuximab alone responded to additional platinum. These survival data compared favorably with those from the retrospective study (median survival, 3.4 months [n=151 patients] and 3.6 months [n=43 patients]). Cetuximab-based treatments generally were tolerated well, and cetuximab did not increase the side effects associated with platinum therapy. CONCLUSIONS: Cetuximab has the potential to prolong survival in patients with recurrent and/or metastatic SCCHN who fail on platinum therapy compared with various second-line therapies. Cetuximab did not increase the toxicities associated with chemotherapy. The results obtained by treatment with cetuximab alone after platinum failure did not appear to differ from the results obtained by reintroducing platinum in combination with cetuximab.