Antiemetic effects of granisetron and dexamethasone combination therapy during cisplatin-containing chemotherapy for head and neck cancer: dexamethasone dosage verification trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for patients and is associated with a substantial deterioration in quality of life; appropriate use of antiemetic drugs is crucial in maintaining the quality of life in patients undergoing chemotherapy. METHODS: This randomized, crossover trial evaluated the antiemetic efficacy and safety of 8 mg per day (low-dose) and 16 mg per day (standard-dose) dexamethasone, in combination with the 5-HT(3) receptor antagonist granisetron, in 36 patients receiving cisplatin (CDDP)-containing chemotherapy for head and neck cancer. Following chemotherapy, the antinausea/vomiting inhibition rate for each dexamethasone dose was measured. RESULTS: During the 24-h period following administration of chemotherapy (acute phase), the antinausea/vomiting inhibition rates (no nausea and no episodes of vomiting) for 8 mg and 16 mg dexamethasone were comparably high (58.3% and 63.8%, respectively; P = 0.8092). Similar results were seen on days 2-5 following chemotherapy. Efficacy during the acute phase, based on the number of instances of vomiting and degree of nausea, was also comparably high for the two dexamethasone doses (overall efficacy rates were 94.4% and 88.8%, respectively, for 8 mg and 16 mg dexamethasone; P = 0.7637). Both doses maintained an 80% or higher response rate until day 3, and neither dose produced severe side effects. CONCLUSION: The results suggest that granisetron and dexamethasone combination therapy is useful in controlling acute and delayed nausea and vomiting induced by CDDP-containing chemotherapy for head and neck cancer. Furthermore, 8 mg and 16 mg dexamethasone have equivalent antiemetic efficacy.

Comparison of hyperfractionation and conventional fractionation radiotherapy with concurrent docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

PURPOSE: Radiotherapy (RTx) has been considered as the treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN). However, with only conventional fractionation (Cfx), response rates are relatively low. In this study, we report the results of hyperfractionation (Hfx) RTx with concurrent docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CTx) in patients with locally advanced SCCHN and compare Hfx and Cfx RTx with concurrent TPF CTx. METHODS: Fifty patients with previously untreated stage III-IV SCCHN were entered into this study. Eligible patients received RTx delivered using arm 1: Hfx at 1.2 Gy/fraction, twice daily, 5 days/week to 76.8 Gy/64 fractions, and arm 2: Cfx at 2 Gy/fraction/day, 5 days/week to 70 Gy/35 fractions. Patients received 2 cycles CTx every 4 weeks. The doses were docetaxel 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 4), and 5-FU 600 mg/m2/day (days 1-5). RESULTS: The overall clinical response rate and the pathological CR were 100% (25/25) and 84% (21/25) in arm 1, and 100% (25/25) and 80% (20/25) in arm 2. Local-regional control was better significant in arm 1 than arm 2 (P = 0.048). There were also trend toward improved disease-free survival (P = 0.059) and overall survival (P = 0.078) in arm 1. Mucositis was significantly more frequent in arm 1 (P = 0.048). CONCLUSION: There were trend toward improved local-regional control, disease-free survival and overall survival in Hfx RTx with concurrent TPF CTx, compared to Cfx RTx with concurrent TPF CTx.

Analysis of efficacy and toxicity of chemotherapy with cisplatin, 5-fluorouracil, methotrexate and leucovorin (PFML) and radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck.

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) and leucovorin (LV) (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Seventy-seven patients with previously untreated stages III-IV SCCHN were included in this trial. Patients received two cycles of chemotherapy repeated every 4 weeks. The chemotherapy regimen consisted CDDP (60 mg/m2, day 4), 5-FU (600 mg/m2 given over 24 h for 5 days, days 1-5), MTX (30 mg/m2, day 1) and LV (20 mg/m2, days 1-5). Radiation was targeted to begin on the starting day of chemotherapy, day 1. The total radiation dose to the primary site and neck lymph nodes was 70.0 Gy. When grade>or=3 toxicities were observed frequently, radiotherapy and/or chemotherapy were delayed or reduced. RESULTS: The main toxicities were mucositis (grade>or=3, 39%), leukocytopenia (grade>or=3, 34%) and neutropenia (grade>or=3, 30%). The overall clinical response rate and the pathological complete response (CR) were 94% (72/77) and 71% (55/77). The primary site CR and neck lymph node CR were 79% (61/77) and 85% (44/52), and 3-year survival rate was 73%. CONCLUSIONS: This concurrent chemoradiotherapy with PFML was safe and well tolerated. The high CR rate justifies further evaluation of this chemoradiotherapy modality in locally advanced SCCHN patients.

Cell proliferation, apoptosis, and apoptosis inhibition in malignant transformation of sinonasal inverted papilloma.

CONCLUSION: Increasing cell proliferation seems to be a very important factor in the development of inverted papilloma (IP). Apoptosis that was increased but weakly inhibited by Bcl-2 did not cause imbalance in the cell proliferation. Further increased cell proliferation in IP with dysplasia was an important mechanism of growth in dysplastic areas. OBJECTIVES: The purpose of this study was to compare cell proliferation, apoptosis, and apoptosis inhibition by Bcl-2 in IP. PATIENTS AND METHODS: Cell proliferation and apoptosis inhibition were detected by immunohistochemical staining with monoclonal antibodies to Ki-67 and Bcl-2. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling (TUNEL) method. RESULTS: As regards the Ki-67 index (KI), a significant increase was observed in IP with severe dysplasia, IP with carcinoma and invasive squamous cell carcinoma (SCC) compared with EP and IP with mild and moderate dysplasia. For the apoptosis index (AI), a significant increase was observed in IP with mild and moderate dysplasia compared with IP with carcinoma, invasive SCC and EP. For the Bcl-2 index (BI), a significant increase in expression was observed in IP with severe dysplasia and carcinoma and invasive SCC compared with control, EP and IP with mild dysplasia. Among IP, the KI (average 18.2%) was much higher than the AI (6.4%) and BI (4.1%).

Concurrent chemoradiotherapy with carboplatin and uracil-f tegafur (UFT) for patients with poor performance status with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

CONCLUSIONS: Concurrent chemoradiotherapy with carboplatin and uracil-f tegafur (UFT) seems to be a promising and appropriate regimen for patients with poor performance status (PS) with locally advanced squamous cell carcinoma of the head and neck (SCCHN). OBJECTIVE: We designed a regimen based on divided low-dose administration to reduce toxicity for patients with poor PS with locally advanced SCCHN. PATIENTS AND METHODS: Sixty-two patients with previously untreated stage III-IV SCCHN and PS of 2 or 3 were entered into this study. They received radiotherapy: 70 Gy/35 fractions. The chemotherapy consisted of a combination of carboplatin (Calvert's formula: (GFR+25) x AUC (=5)/4 mg/week; where AUC area under the curve and GFR = glomerular filtration rate) and UFT (300 mg/day, per os). RESULTS: The overall clinical response rate and the pathological complete response (CR) were 90% (56/62) and 61% (38/62), respectively. Grade > or =3 mucositis occurred in only 6% of patients (4/62) and grade 2 > or =3 leukocytopenia and neutropenia occurred in only 5% (3/62).

Expression of epidermal growth factor receptor, transforming growth factor-alpha and Ki-67 in relationship to malignant transformation of pleomorphic adenoma.

CONCLUSION: Quantitative assessment is more sensitive as a measure of cellular protein content as compared with standard optical density measurements. The data support the hypothesis that increased epidermal growth factor receptor (EGFR) and transforming growth factor (TGF)-alpha expression is associated with early events in malignant transformation of pleomorphic adenoma (PA). OBJECTIVE: In the present study, we attempted to identify EGFR and TGF-alpha expression and Ki-67 index in carcinoma ex-pleomorphic adenoma (Ca ex-PA) and PA. We also compared the presence of EGFR and TGF-alpha and Ki-67 index with clinical data. MATERIALS AND METHODS: The tissues were stained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The results were analysed using quantitative immunohistochemical analysis. We also analysed the association of patients' prognosis with clinical parameters and the histological classification of the carcinomatous component. RESULTS: As regards the association of patients' prognosis with EGFR staining and Ki-67 index, a significant increase was observed in patients who died or had residual disease compared with patients who were alive without disease. In the immunohistochemical analysis of EGFR and TGF-alpha and Ki67 index, a significant increase was observed in Ca ex-PA, especially with adenocarcinoma, compared with PA and sialadenitis.

Increased expression of cyclooxygenase-2 and Ki-67 are associated with malignant transformation of pleomorphic adenoma.

OBJECTIVES: In the present study, we attempted to identify cyclooxygenase-2 (COX-2) expression and Ki-67 index in carcinoma ex-pleomorphic adenoma (Ca ex-PA) using quantitative immunohistochemical analysis and to compare the benign component of the neoplasia. We also aimed to relate the overexpression of COX-2 with the pathways of malignant transformation of Ca ex-PA as evidenced by distinct morphological features. MATERIALS AND METHODS: Forty Ca ex-PA from patients treated at Department of Otolaryngology, Yokohama City University Medical Center, Yokohama, Japan, from 1999 to 2005, were selected. All Ca ex-PA showed only one malignant histological component: adenocarcinoma (23 cases), adenoid-cystic carcinoma (10), epithelial-myoepithelial carcinoma (7). The tissues were stained with monoclonal antibodies to COX-2 and Ki-67. The results were analyzed using quantitative immunohistochemical analysis. We also analyzed the association of the histological classification of the carcinomatous component. RESULTS: In the immunohistochemical analysis of COX-2 and Ki-67 index, significant increase was observed in Ca ex-PA, especially with adenocarcinoma, compared to pleomorphic adenoma and sialadenitis. Quantitative assessment is more sensitive as a measure of cellular protein content as compared to standard optical density measurement. CONCLUSIONS: The data support the hypothesis that increased COX-2 expression is associated with early events in malignant transformation of pleomorphic adenoma.

Concurrent chemoradiotherapy with cyclophosphamide, pirarubicin, and cisplatin for patients with locally advanced salivary gland carcinoma.

CONCLUSION: This concurrent chemoradiotherapy with CPA, THP, and CDDP showed major antitumor activity with manageable toxicity as treatment of advanced salivary gland carcinoma patients. The high response rate (RR) justifies further evaluation of this chemoradiotherapy combination. OBJECTIVES: The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using cyclophosphamide (CPA), pirarubicin (THP), and cisplatin (CDDP) in patients with locally advanced salivary gland carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated stage III-IV salivary gland carcinoma were entered in this trial between January 2000 and September 2005. Chemotherapy consisted of CPA 400 mg/m2 on day 1, THP 40 mg/m2 by 6-h infusion on day 1, and CDDP 60 mg/m2 by 2-h infusion on day 1. Radiotherapy (2.0 Gy/fraction/day, mean total dose: 67.2 Gy (64.0-72.0 Gy)) administered 5 days per week, was targeted to begin on day 1. RESULTS: The RR was 76% (13/17) and the pathological complete response (CR) was 24% (4/17). The primary site CR was 29% (5/17) and metastatic lymph node CR was 33% (4/12). The 5-year survival rate was 70%. Neutropenia, leukocytopenia and mucositis were common adverse effects, but all 17 patients were assessable for toxicity.

Histopathological parameters of recurrence and malignant transformation in sinonasal inverted papilloma.

CONCLUSIONS: A combination of parameters may be useful in predicting the clinical course of squamous cell carcinoma in inverted papilloma (IP). In particular, the parameters hyperkeratosis, squamous epithelial hyperplasia and high mitotic index were negative prognostic indicators. OBJECTIVE: To define histopathological parameters which could predict the recurrence and development of squamous cell carcinoma in IP. MATERIAL AND METHODS: We analyzed the histopathological characteristics of 39 cases of IP using the following parameters: site of origin of tumor; presence of bone invasion; presence of inflammatory polyp; ratio of endophytic to exophytic lesions; ratio of neoplastic epithelium to stroma; presence of hyperkeratosis; presence of squamous epithelial hyperplasia; mitotic index; number of mucin globules; and number of eosinophils. RESULTS: Malignancy was related to the presence of bone invasion (p=0.039), the absence of inflammatory polyp (p=0.033), increase in the ratio neoplastic epithelium:stroma (p=0.037), increase in hyperkeratosis (p=0.030), the presence of squamous epithelial hyperplasia (p=0.044), increase in the mitotic index (p=0.029) and a decrease in the number of eosinophils (p=0.037). Multiple recurrences (without malignancy) were related to frontal sinus origin (p=0.042), increase in hyperkeratosis (p=0.041), the presence of squamous epithelial hyperplasia (p=0.044) and increase in the mitotic index (p=0.031). Clinically benign behavior was related to the presence of inflammatory polyp (p=0.010) and the absence of hyperkeratosis (p=0.008).

Concurrent chemoradiotherapy with cisplatin, 5-fluorouracil, methotrexate, and leucovorin in patients with advanced resectable squamous cell carcinoma of the larynx and hypopharynx.

CONCLUSIONS: This regimen of concurrent chemoradiotherapy was safe and well tolerated. In terms of larynx preservation, the present regimen appears to be useful for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and hypopharynx. OBJECTIVES: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy in patients with advanced resectable SCC of the larynx and hypopharynx, and to demonstrate the feasibility of larynx preservation. PATIENTS AND METHODS: Forty-six eligible patients were treated. The chemotherapy regimen consisted of a combination of four drugs: cisplatin (60 mg/m(2), day 4), 5-fluorouracil (5-FU) (600 mg/m(2) given continuously for 120 h, days 1-5), methotrexate (MTX) (30 mg/m(2), day 1), and leucovorin (LV) (20 mg/m(2), days 1-5). Two cycles of this regimen were given every 4 weeks during radiotherapy. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8-2.0 Gray, to a total dose of 66.6-70.2 Gray. RESULTS: The 3-year disease-specific survival rates of patients with laryngeal or hypopharyngeal SCC were 81.3% and 78%, respectively. The 3-year disease-specific survival rates with larynx preservation of patients with laryngeal or hypopharyngeal SCC were 46.7% and 59%, respectively. The main toxicities were neutropenia, dermatitis, mucositis, and infection.

[Clinical efficacy of administration with S-1 alone for head and neck carcinoma].

Most head and neck carcinomas are squamous cell carcinomas (HNSCCs). The combination of cisplatin with a continuous infusion of 5-fluorouracil (5-FU) has been a standard chemotherapy regimen for HNSCC. Based on basic and clinical studies, the critical plasma concentration of 5-FU is suspected to be about 0.1 microg/ml. The administration of the conventional dose of S-1 including dihydropyrimidine dehydrogenase (DPD), an metabolic inhibitor of 5-FU, results in exceeding the critical plasma concentration of 5-FU, and the long-term administration with high plasma concentration of 5-FU is considered to show clinical effectiveness in head and neck cancer. The results of early and late phase II studies on head and neck carcinoma were also described in the present paper.

[Adjuvant chemotherapy with S-1 for advanced head and neck carcinoma].

Most cases of head and neck squamous cell carcinoma (HNSCC) are in the advanced stages, resulting in a poor prognosis. To improve the poor outcome, adjuvant chemotherapy is indispensable for advanced cases with a high relapse risk after standard definitive treatments including surgery and/or radiotherapy. To define an adequate administration schedule in adjuvant chemotherapy with S-1, a controlled randomized study in multi-institutes was done. The results showed the 2-week administration followed by 1-week rest was superior to the 4-week administration followed by the 2-week rest in terms of safety and efficacy. In the present paper, some problems of adjuvant chemotherapy were discussed, and the protocol was described in terms of a multi-institutional controlled randomized comparison study of S-1 versus UFT in an adjuvant chemotherapy setting for locally advanced HNSCC.

Four cases of simultaneous triple primary cancers of the hypopharynx, esophagus, and stomach.

OBJECTIVE: To study the efficacy of intensive chemotherapy for simultaneous triple primary cancers of the hypopharynx, esophagus, and stomach. STUDY DESIGN: Retrospective case study. METHODS: From April 2000 to March 2002, we treated 4 patients who had simultaneous triple primary cancers, including hypopharyngeal, esophageal, and gastric carcinomas. These 4 patients were designated as the objects for analysis, and the treatment modality for simultaneous multiple primary cancer cases was examined. RESULTS: In 3 of 4 patients, all 3 primary cancers could be controlled by intensive induction chemotherapy and concurrent chemoradiotherapy for hypopharyngeal cancer and by endoscopic mucosal resection or argon plasma coagulation for esophageal and gastric carcinomas. CONCLUSIONS: In the treatment modality for simultaneous multiple primary cancers, including head and neck cancer, it is important to select intensive systemic chemotherapy and decide the order for treating each primary lesion in consideration of each patient's curability and prognosis.

Staging of surgical approach of sinonasal inverted papilloma.

OBJECTIVE: In this study, we tried to make the staging of surgical approach of inverted papilloma (IP) and investigated the recurrence rate of IP. PATIENTS AND METHODS: Operating staging was as follows: When the IP was limited to the middle meatus, anterior and posterior ethmoid, or sphenoethmoid recess, standard endoscopic sinus surgery (SESS) was performed. When the lesion extended from the middle meatus into the maxillary sinus or originated from the medial wall of the maxillary sinus, radical endoscopic sinus surgery (RESS) was performed. And, when the IP originated from or involved the posterolateral, anterior, inferior wall of the maxillary sinus, intraorbital involvement, extensive growth of the lesion into the frontal or sphenoid sinus, or intradural invasion, external approach with endoscope assistance (Ex+E) was performed. RESULTS: 14 (36%) patients underwent SESS, 9 (23%) patients underwent RESS, and 16 (41%) patients underwent Ex+E. Malignancy occurred in no patient, and recurrences developed in four patients (10%). One of these recurrences happened after SESS, one after RESS and two after Ex+E. CONCLUSION: In this study, there was no significance of recurrence rate in each group. Better visualization can be obtained by combining the endonasal operation with an external procedure.

Lobular capillary hemangioma of the nasal cavity in child.

Although the head and neck is not an uncommon region, the nasal cavity is extremely rare sites for lobular capillary hemangioma (LCH) in children. The authors report a case of an 11-year-old boy with LCH of the nasal cavity presenting with nasal obstruction and epistaxis. To our knowledge, on searching the English literature, only nine cases of hemangioma of nasal cavities have been reported in children since 1985. The authors feel that it should be considered in the differential diagnosis of lesion of the nasal cavity.

Acute epiglottitis: analysis of factors associated with airway intervention.

We reviewed acute epiglottitis (AE) and identified factors associated with airway intervention. This report was a retrospective review of patients with AE and compared with factors associated with airway intervention. We reviewed 96 patients who were diagnosed with AE in our hospitals in Japan. Ninety-two (96 per cent) patients were adults, and no seasonal variation in the incidence of AE was encountered. Eight (8 per cent) patients had tracheostomy and endotracheal intubation had not been done. We found that symptoms of stridor and muffled voice, a rapid clinical course, and diabetes mellitus were the factors associated with airway intervention. Extremely severe swelling of the epiglottis such that only less than half of the posterior vocal fold (scope classification (SC): III) could be seen, and extension of the swelling to the arytenoids (SC: B) were the two factors that were strongly associated with airway intervention.

Post-operative adjuvant chemoradiotherapy with carboplatin and 5-fluorouracil for primary branchiogenic carcinoma.

BACKGROUND: Branchiogenic carcinoma occurs only rarely. A pathologic description and post-operative adjuvant therapy with carboplatin (CBDCA) and daily oral 5-fluorouracil (UFT) are analysed. CASE REPORT: We present the case of a 52-year-old man with a lateral neck mass lesion. A fine-needle aspiration was performed and cytological examination showed class IV disease. The patient underwent excision of the mass and an intra-operative rapid pathological diagnosis of squamous cell carcinoma was made; we then went on to perform neck dissection. The patient received post-operative radiation therapy (total 64 Gy) and chemotherapy (CBDCA 100 mg/week and UFT 300 mg/day). He was followed up for 62 months after surgery without any evidence of recurrence of cancer. CONCLUSION: This case satisfies the histological criteria established by Martin and Khafif for a primary branchiogenic carcinoma. The management would be wide surgical excision of the tumour, including neck dissection, followed by adjuvant therapy, such as chemoradiation. As post-operative adjuvant therapy for primary branchiogenic carcinoma, chemoradiotherapy with carboplatin and UFT was a safe and well tolerated regimen.

[A randomized crossover study of ramosetron plus dexamethasone for the prevention of nausea and vomiting induced by chemotherapy including cisplatin-comparison of ramosetron combined with 8 mg and 12 mg of dexamethasone].

A randomized crossover study between 0.3 mg of ramosetron (RAM) combined with 8 mg of dexamethasone (DEX) and 0.3 mg of RAM combined with 12 mg of DEX was performed to investigate the prevention of nausea and vomiting due to chemotherapy including 60 mg/m2 or 70 mg/m2 of cisplatin (CDDP) in patients with advanced head and neck squamous cell carcinoma (HNSCC). Twenty-five patients the study consisted of who received chemotherapy with CDDP were enrolled in the present study between January 2001 and December 2002 at the Yokohama City University School of Medicine or Yokohama City University Medical Center. The antiemetic effectiveness in the group receiving 12 mg of DEX was not significantly superior to the group receiving 8 mg of DEX. It was suggested that the antiemetic therapy of RAM 0.3 mg plus DEX 8 mg was effective for the prevention of nausea and vomiting induced by CDDP in patients with advanced HNSCC.

[Combined chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF), and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)].

We evaluated the recommend dose and efficacy of chemotherapy (CTx) and concurrent chemoradiotherapy (ConcCRTx) with docetaxel (DOC), cisplatin (CDDP) and 5-FU (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients underwent 2 cycles of chemotherapy with TPF. In ConcCRTx, radiation was targeted to begin on Day 1. We compared the efficacy of ConcCRTx and induction chemotherapy followed by radiation (CTx followed by RTx) with TPF. In CTx followed by RTx, radiation was targeted to begin 21 days after the end of CTx. The recommend dose of CTx with TPF was DOC 60 (Day 1), CDDP 70 (Day 4) and 5 FU 750 (Day 1-5) mg/ m2/ day and overall response rate of CTx with TPF was 95%. The recommended dose of ConcCRTx was DOC 50 (Day 1), CDDP 60 (Day 4) and 5-FU 600 (Day 1-5) mg/ m2/ day. Overall response rate of ConcCRTx and CTx followed by RTx with TPF were both 100%, and CR rate of them were 87% and 84% (p > 0.05). One-year survival rate of them were 69% and 95% (p < 0.05). More patients had distant metastasis in CTx followed by RTx than in ConcCRTx. Toxicity, such as mucositis, leukocytopenia and neutropenia, was higher in ConcCRTx than in CTx followed by RTx.

Reduction of in vivo tumor growth by MMI-166, a selective matrix metalloproteinase inhibitor, through inhibition of tumor angiogenesis in squamous cell carcinoma cell lines of head and neck.

Matrix metalloproteinases (MMPs) have been implicated in tumor invasion, metastasis, and angiogenesis. We have recently shown that MMI-166, a new orally active MMP inhibitor specific for MMP-2 and -9, suppressed experimental metastasis of Lewis lung cancer, C-H1 human colon cancer, and pancreatic cancer without affecting tumor growth in vitro. In the present study, we determined whether oral administration of MMI-166 reduces tumor growth not only in such tumors but also in squamous cell carcinoma of head and neck (SCCHN). MMI-166 inhibited both activity of MMP-2 and -9 without affecting steady state levels of their mRNAs in SCCHN. Interestingly, protein levels of MMP-2 and -9 from the cultures were drastically diminished by culturing with MMI-166. This was also observed in xenografts of MMI-166-administered mice. In addition, daily oral administration of MMI-166 (100mg/kg) inhibited local tumor growth accompanied by the reduction of blood vessel density and Ki-67-positivity and increase in terminal deoxynucleotidyl transferase-mediated cUDP nick-end labeling (TUNEL)-positivity. These results suggested that orally administered MMI-166 reduced in vivo tumor growth of SCCHN through inhibition of angiogenesis and induction of apoptosis accompanied by the reduction of MMP productions and activities. Therefore, MMI-166 seems to be useful for tumor dormancy therapy of SCCHN.