Yasukazu Mikami

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.

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.

Concurrent chemoradiotherapy with carboplatin and uracil-ftegafur in patients with stage two (T2 N0 M0) squamous cell carcinoma of the glottic larynx.

This study aimed to evaluate the efficacy and toxicity of concurrent chemoradiotherapy as a primary treatment modality for larynx preservation in patients with stage two squamous cell carcinoma (SCC) of the glottic larynx. Between February 2000 and August 2003, a total of 20 patients received concurrent chemoradiotherapy. Carboplatin was given intravenously once a week during the period of radiotherapy. The weekly carboplatin dose was based on the area under the curve 1 to 1.25. Uracil-ftegafur (UFT) was given in a daily oral dose of 300 mg as tegafur. Radiotherapy was delivered five days a week using a once-daily fractionation of 2.0 Gray (Gy), to a total dose of 66-72 Gy. The three-year overall survival rate with larynx preservation was 100 per cent. Concurrent chemoradiotherapy with carboplatin and UFT for stage two SCC of the glottic larynx was safe and effective in improving local control with larynx preservation.

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.

The synergistic effects of interleukin 2 and interleukin 7 on the proliferation and autologous tumor cell lysis of tumor-associated lymphocytes

Interleukin-7 (IL-7) has an ability to stimulate the proliferation of pre-B cells. It has been shown that IL-7 can also activate T lymphocytes. We here demonstrate that IL-7 in combination with interleukin-2 (IL-2) can drive cell proliferation and enhance the autologous tumor cell lysis by peripheral blood mononuclear cells (PBMC) and autologous mixed lymphocyte tumor cell culture (MLTC)-derived effector cells (MLTC cells). These synergistic effects of IL-2 and IL-7 on the proliferation and the augmentation of autologous tumor cell lysis were found for both effector cells. These effects were inhibited by neutralizing antibodies to IL-2 or IL-7, and by a combination of both antibodies, significantly. In terms of phenotypical expression, CD3 positive cells comprised the vast majority of MLTC cells after culture in medium containing IL-2 and IL-7 with an increase of IL-2 receptor positive cells.

A case of metastatic colon adenocarcinoma in the larynx

Metastatic carcinomas in the larynx are uncommon, and laryngeal tumors originating from the colon are extremely rare. We report a case of metastatic laryngeal tumor originating from a colon adenocarcinoma in an 81-year-old female. Only a tracheostomy was performed because the patient presented with multiple metastases in other regions. The diagnosis, route of metastasis, treatment and prognosis of metastatic laryngeal tumors are discussed.

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.

Pleomorphic adenoma of the lateral side of the tongue.

Pleomorphic adenoma is histopathologically the commonest tumor found in the major salivary glands. Pleomorphic adenoma originating from the tongue is very rare: only 26 cases have been reported in the world literature since 1960, only 2 of which originated from Ebners gland. Herein we report the case of a 54-year-old female with pleomorphic adenoma of the tongue. The tumor was in contact with the molars. A partial glossectomy was performed with a surgical margin, as the preoperative pathological finding in the tissue specimen taken from the tumor was epithelial hyperplasia. The postoperative pathological diagnosis was pleomorphic adenoma with hyperplasia. It is unclear whether the teeth being in contact with the tumor caused tumorigenesis in this case. This case suggests that pleomorphic adenoma of the tongue originating from Ebners gland should be considered in the differential diagnosis of lesions of the tongue.