s-1-(combination) and Deglutition-Disorders

To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272).. Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome.. With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose.. This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer.

Topics: Adult; Aged; Anemia; Chemoradiotherapy; Cisplatin; Deglutition Disorders; Drug Combinations; Female; Humans; Hypoalbuminemia; Male; Middle Aged; Nutritional Support; Oxonic Acid; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tegafur

We conducted a phase I study to determine a recommended dose (RD) of S-1 for chemo-radiotherapy consisting of S-1+ radiotherapy for T 2 N 0 larynx cancer. The method of administration used to assess the RD was irradiation with 2 Gy/day for 5 days a week until a total dose of 60 Gy, and concomitant administration of S-1 once a day for 2 weeks beginning on the day therapy was started followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body/day (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). 18 patients were enrolled. 4 patients developed an adverse event of grade 3 radiation dermatitis which became a dose-limiting toxicity (DLT) at level 3. We then concluded that 100 mg/body/day was the maximum tolerated dose (MTD) of S-1 and decided that the RD of S-1 was 80 mg/body/day.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Glottis; Humans; Laryngeal Neoplasms; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Stomatitis; Tegafur

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Tegafur

We administered TS-1 to a patient with advanced oropharyngeal carcinoma who underwent a gastrostomy because of swallowing difficulties. TS-1 was dissolved in 50 degrees C water and administered through a gastrostogavage tube. The pharmacokinetics of TS-1 were then investigated. The plasma 5-FU level was measured, and adverse events appearing after administration were monitored. The highest plasma 5-FU concentration on day 1 was 138.7 ng/ml; this level was obtained in a sample drawn 2 hours after the administration of TS-1. The highest plasma 5-FU concentration of TS-1 on day 8 (159.8 ng/ml) was also drawn 2 hours after the administration of TS-1. No major adverse events were observed in the patient. In particular, no toxic effects on the digestive systems were observed. Furthermore, the administration of TS-1 through a gastrostomy was safe. Such a procedure could also be used in patients with naso-gastric feeding tubes. We conclude that the administration of TS-1 through either a gastrostomy or a naso-gastric feeding tube may be a new administration method that can improve the quality of life (QOL) of patients with advanced and/or recurrent head and neck carcinoma.

Topics: Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Fluorouracil; Gas Chromatography-Mass Spectrometry; Gastrostomy; Humans; Informed Consent; Intubation, Gastrointestinal; Male; Middle Aged; Oropharyngeal Neoplasms; Oxonic Acid; Pyridines; Tegafur