Thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl transferase levels as predictive factors of chemotherapy in oral squamous cell carcinoma.

We conducted a clinicopathologic study on protein and mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) using biopsy tissue specimens before treatment. The mRNA levels have been measured in tumor cells microdissected from paraffin-embedded specimens (Danenberg Tumor Profile method: DTP method). We studied the mRNA and protein expression as effect predictive factors in chemotherapy. The subjects consisted of 20 cases of untreated oral squamous cell carcinoma who had undergone chemotherapy with TS-1 (16 males and 4 females, tongue in 8 cases, upper gingiva in 3 cases, lower gingiva in 3 cases, buccal mucosa in 5 cases and floor of the mouth in 1 case). TS gene expressions of the responders were lower than those for the nonresponders. Furthermore, regarding males who were less than 70 years of age, stage I and II, well differentiated type and tongue, TS mRNA expression of the responders were lower than that for the nonresponders. The mRNA expression of OPRT for the male responders was lower than that for the nonresponders. No remarkable difference was observed by immunohistochemistry. In this study, the measurement of the TS levels using the DTP method may potentially act as a predictive factor of antitumor effectiveness.

[Nedaplatin (NDP)-combination therapy (NDP/5-FU,NDP/S-1) for oral cancer].

PURPOSE: The present study evaluated the efficacy and safety of nedaplatin-combination therapy (NDP/5-FU [5-FU arm] or NDP/S-1 [S-1 arm] ) for the treatment of oral squamous cell carcinoma. PATIENTS AND METHOD: Previously non-treated oral squamous cell carcinoma patients were eligible. Patients received 5-FU 600 mg/m(2)iv, as a 24-hour infusion (day 1 to 5) followed by NDP 80 to 100 mg/m(2) iv (day 1), or S-1 60 to 80 mg/m(2) orally twice a day (day 1 to 14) followed by NDP 80 mg/m(2) iv (day 8) every 28 days for one or two cycles. RESULTS: In total, 32 patients (18 in the 5-FU arm, 14 in the S-1 arm) were enrolled. Twenty patients were male and 12 were female. Median age was 57 years (range 20 years to 87 years). Thirty-one patients had a performance status (PS) oF 0, and 1 patient had a PS 1. Three patients were stage I, 12 stage III, and 12 were stage IV. The overall response rate was 69% (5-FU arm,72%;S-1 arm,64%). Two patients achieved a complete response, 20 patients a partial response, and 10 patients had no change. Grade 3 leucopenia, grade 3 and 4 thrombocytopenia and liver injury occurred in 6% (one in the 5-FU arm, and one in the S-1 arm), 9% (two in the 5-FU arm, and one in the S-1 arm), and 3% (one in the 5-FU arm), respectively. No other severe toxicities were observed. RESULTS: Response rate and toxicities were similar in both arms. However, the psychosocial stress on patients in the S-1 arm was reduced compared to that in the 5-FU arm, which required hospitalization for a longer period. The outcome in the present study needs further investigation.

[Combination chemotherapy with nedaplatin (CDGP) and 5-FU for oral cancer].

Chemotherapy using CDGP plus 5-FU was evaluated in patients with oral cancer. The subjects were patients with squamous cell carcinoma of the oral cavity who had not received any therapy, comprising 7 patients with carcinoma of the tongue, 2 with buccal carcinoma, 2 with maxillary gingival carcinoma, and 1 with carcinoma of the oral floor. There were 4 patients in Stage II, 3 patients in Stage III and 5 patients in Stage IV. Patients with a PS < or = 1, WBC > or = 4,000/mm3, Hb > or = 10 g/dl, platelet count > or = 10 x 10/mm3, and normal liver, kidney, and heart function at baseline were selected for this study. In all patients, 5-FU was administered at a dose of 600 mg/m2/day for 5 days (day 1 to day 5) by continuous infusion, for a total dose of 3,000 mg/m2. CDGP was administered on day 1 at a dose of 80 mg/m2 in 8 patients and at 100 mg/m2 in 4 patients. This treatment was one course of therapy, and patients received 1 or 2 courses. Of 12 patients who were evaluable, there were 9 partial responses and 3 no changes, for a major response rate of 75%. Toxicities experienced by patients were mild (grade 2 or lower) gastrointestinal disorders (including nausea/vomiting) and renal impairment, while grade 3 leukopenia and thrombocytopenia developed in 1 patient each and grade 4 thrombocytopenia occurred in another patient. Thus, patients receiving CDGP + 5-FU therapy should be closely monitored for hematologic toxicity. Since CDGP + 5-FU therapy achieved a good response rate (75%) in the treatment of squamous cell carcinoma of the oral cavity, we plan to use this therapy in the future and assess its benefit in a larger number of patients.