Choichi Horiuchi

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/m2, day 4), 5-fluorouracil (5-FU) (600 mg/m2 given continuously for 120 h, days 1–5), methotrexate (MTX) (30 mg/m2, day 1), and leucovorin (LV) (20 mg/m2, 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.

Role of 18F-FDG PET in detecting primary site in the patient with primary unknown carcinoma

The aim of this study was to verify the effectiveness of positron emission tomography (PET) in detecting primary sites in carcinoma of unknown primary (CUP) patients. In this study, CUP represented a group of heterogeneous tumors that shared the clinical manifestation of metastatic carcinoma with no obvious primary site at the time of first diagnosis, which included clinical investigations, computed tomography, magnetic resonance imaging and panendoscopy. We reviewed the records of 24 patients with CUP between January 1995 and December 2009. The patients who demonstrated additional tracer uptake sites other than previously known metastatic lesions by PET scan were done direct biopsies for the sites of accumulation. Patients who had a negative PET scan or for whom the primary site could not be identified by direct biopsies underwent examination under anesthesia of the at-risk occult tumor sites. PET scan demonstrated focal accumulation suspicious for primary tumor in 12 (50.0%) of 24 patients: tonsil 5, nasopharynx 3, hypopharynx 1, tongue 1, larynx 1, and maxillary sinus 1. A subsequent biopsy of these sites revealed primary cancer in 9 (37.5%) of 24 patients: tonsil 5, nasopharynx 1, hypopharynx 1, tongue 1, and maxillary sinus 1. In the remaining three patients, no malignant cells were found by the biopsy of the accumulated area: nasopharynx 2, larynx 1. PET scans increase the yield of primary tumor by 37.5%. The sensitivity, specificity for PET scan were 80.8, 76.9%, respectively. PET scanning is useful in detecting primary cancer of CUP patients.

Correlation between FDG-PET findings and GLUT1 expression in salivary gland pleomorphic adenomas

ObjectiveOne reason for the difficulty in accurate preoperative pathological diagnosis of major salivary gland tumors with fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is the tendency of pleomorphic adenomas to have a high, standardized uptake value (SUV). The expression of glucose transporter 1 (GLUT1) and the quantity of GLUT1 messenger RNA (mRNA) were analyzed in specimens of pleomorphic adenoma to identify whether GLUT1 is responsible for the increased glucose uptake in FDG-PET examinations of these tumors.MethodsEighty salivary gland tumors resected at Yokohama City University Hospital were retrospectively investigated. FDG-PET was performed prior to surgery. PET images were evaluated by two experienced radiologists. GLUT1 was immunohistochemically stained, and GLUT1 mRNA density was quantified using real-time polymerase chain reaction in 10 of 40 pleomorphic adenomas.ResultsThe pleomorphic adenomas stained positively for GLUT1, and there was significant correlation between the GLUT1 index and the SUV in FDG-PET.ConclusionsGLUT1 is expressed in salivary gland pleomorphic adenomas. Furthermore, the GLUT1 index shows significant correlation with the SUV of FDGPET. This result suggests that GLUT1 plays an important role in increasing FDG uptake in salivary gland pleomorphic adenomas.

Phase I trial of combined chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for patients with locally advanced squamous cell carcinoma of the head and neck.

BackgroundThis phase I study was designed to determine the maximum tolerated dose (MTD) and toxicities of combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).MethodsPatients received two cycles of chemotherapy repeated every 4 weeks. Starting doses (dose level 0) were: docetaxel 60 mg/m2, cisplatin 60 mg/m2, and 5-day continuous infusion 5-FU 600 mg/m2 per day. At least three patients were examined at each dose level before advancing to the next level.ResultsNineteen male patients (median age, 59.5 years) were enrolled. Eighteen patients had previously untreated stage III or IV SCCHN and 1 had local relapse, rT4. In the 19 patients, the regimen was well tolerated, with neutropenia as the most common toxicity (grade 3; n = 11; grade 4; n = 1). Dose-limiting toxicity (DLT) was observed at the fifth dose level (docetaxel 70 mg/m2, cisplatin 70 mg/m2, 5-FU 750 mg/m2 per day), when 1 patient developed grade 2 renal toxicity during the first course; another 2 patients had persistent neutropenia. These doses were thus deemed the MTD for the regimen. In the 18 assessable patients, the overall clinical response rate was 94% (17/18 patients) and primary-site complete response (CR) occurred in 4 (22%) patients.ConclusionThe MTD of this regimen was docetaxel 70 mg/m2 on day 1, cisplatin 70 mg/m2 on day 4, and 5-FU 750 mg/m2 per day for 5 days. The regimen was safe and generally well-tolerated and demonstrated good efficacy in patients with locally advanced SCCHN.

The efficacy and safety of concurrent chemoradiotherapy for maxillary sinus squamous cell carcinoma patients

OBJECTIVE Combined treatment modality, e.g., definitive surgery followed by radiotherapy (RT) and definitive RT with concurrent chemotherapy, has been applied for advanced maxillary sinus squamous cell carcinoma (MSSCC) patients to obtain a better survival with organ preservation in Japan. METHODS The outcome of 40 patients with MSSCC between 1991 and 2007 in our institute was analyzed retrospectively. There were 36 males and 4 females, the average age being 59.5 years (ranging from 34 to 81 years). The median follow-up time was 66.1 months. All the patients had received a combined treatment consisting of definitive surgery, RT, and intra-arterial or systemic chemotherapy. The chemotherapeutic regimen was different depending on the performance status and/or complications of the patients. Since 1998, concurrent chemoradiotherapy with cisplatin, 5-fluorouracil, methotrexate and leucovorin regimen (CCRT-PFML) instead of neo-adjuvant chemotherapy has been applied. RESULTS The overall 5-year survival rate was 59.2%, the 5-year disease-specific survival rate was 71.7%, and the 5-year organ preservation survival rate was 42.4%. In the group receiving CCRT-PFML, the overall 5-year survival rate was 60.0%, the 5-year disease-specific survival rate was 76.0%, and the 5-year organ preservation survival rate was 60.3%. CONCLUSION CCRT-PFML for advanced MSSCC patients is feasible to preserve the organs without reducing the survival rate.

Decrease of creatinine clearance rate with aging in patients with head and neck cancer in Japan

BackgroundWe aimed to clarify the reason for the lower dosage of cis-platinum (CDDP) in patients with head and neck cancer in Japan compared with that in other countries, by evaluating renal function.MethodsWe studied 375 patients with head and neck cancer who had been hospitalized from January 1998 to October 2005, to evaluate and treat the disease. The creatinine clearance rate (Ccr) was calculated at least three times before beginning the treatments, and the average Ccr was estimated to evaluate the renal function.ResultsThe Ccr decreased with aging, and the percentages of patients with Ccr lower than 65 ml/min per 1.73 m2 were 27.1% of patients in their fifties, 36.8% in their sixties, 62.3% in their seventies, and 87.5% in their eighties. There was no correlation between renal function and the Japanese lifestyle (i.e., diet. water consumption).ConclusionThe renal function of Japanese decreases rapidly with aging, whereas that of Americans is maintained for longer periods. The poor renal function of Japanese is one of the causes of the need to reduce the dosage of or avoid the administration of CDDP in cancer patients.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy

OBJECTIVE To review our experience in the treatment of concurrent chemoradiotherapy (CCR) for patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and to evaluate the different factors affecting survival and primary organ preservation. METHODS We reviewed the records of 101 patients with SCCHN treated with CCR between February 1998 and April 2004. Of 101 patients, 76 were treated with a cisplatin, 5-fluorouracil, methotrexate, and leucovorin (PFML) regimen and 25 were treated with a carboplatin and uracil-tegafur (CBDCA-UFT) regimen. Overall survival (OS), disease-specific survival (DSS) and DSS with primary organ preservation were estimated using Kaplan-Meier methods. The log-rank test and Cox proportional hazards regression were employed to identify significant prognostic factors for OS, DSS, and DSS with primary organ preservation. RESULTS The 5-year OS and DSS for all patients were 51.6 and 67.4%, respectively. On multivariate analysis, resectability of the tumor and degree of histological differentiation were significant predictors of survival for patients undergoing CCR; T stage and differentiation were significant prognostic factors for primary organ preservation. CONCLUSION In the treatment of CCR for advanced SCCHN, the survival rate of the patients with resectable tumors was excellent and significantly greater compared with the patients with unresectable tumors. T1 to T3 disease in patients with advanced resectable SCCHN is a good predictor of organ preservation. CCR may improve not only primary organ preservation (local control) but also survival in patients with poorly differentiated tumors.

Efficacy of fluoro-2-deoxy-d-glucose positron emission tomography to evaluate responses to concurrent chemoradiotherapy for head and neck squamous cell carcinoma

OBJECTIVE This study evaluates the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with head and neck squamous cell carcinoma (HNSCC) who received concurrent chemoradiotherapy (CCRT). METHODS Sixty-five patients were recruited for this study between November 2002 and April 2007. The FDG-PET scan was performed before treatment and 4-6 weeks after treatment. RESULTS The mean of maximum standardized uptake value (SUVmax) before treatment at the primary tumor site was 8.1 (range, 2-22). The sensitivity of FDG-PET for the diagnosis of primary tumor site was 98%. The mean of SUVmax after treatment was 2.6 (range, 2-5). The sensitivity, specificity, and accuracy of FDG-PET for the diagnosis of primary tumor site after treatment were 100%, 40%, and 46%, respectively. The mean of SUVmax before treatment at the nodal site was 4.7 (range, 2-16). The mean of SUVmax after treatment was 2.0 (range, 2-6.7). The pre-treatment SUVmax of T2, T3, and T4 stages were significantly higher than that of the T1 stage. The N stage had no correlation in terms of the pre-treatment nodal site SUVmax. CONCLUSION Our results indicate that FDG-PET is a useful imaging method for evaluating the response of CCRT in patients with HNSCC. However, performing FDG-PET 4-6 weeks after treatment may be too early as it may give false-positive results due to fibrosis and scarring.

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

BackgroundChemotherapy-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.MethodsThis 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-HT3 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.ResultsDuring 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.ConclusionThe 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.

Biodistribution and radiation dosimetry of [18F]-5-fluorouracil

PURPOSE To estimate the radiation dose and biodistribution of (18)F-5-fluorouracil ([(18)F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. METHODS Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2h after intravenous administration of [(18)F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [(18)F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. RESULTS In human subjects, high [(18)F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [(18)F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [(18)F]-5-FU dose was higher in humans (0.0124mSv/MBq) than in mice (0.0058mSv/MBq). CONCLUSION Biodistribution and radiation dosimetry of [(18)F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [(18)F]-5-FU PET/CT for human studies.