[Determination of the Appropriate Timing of Aprepitant Administration for Nausea in Patients with Head and Neck Cancer Receiving Combination Chemotherapy with Docetaxel, Nedaplatin（Divided Doses for 5 Days), and 5-fluorouracil].

The objective of this study was to determine the appropriate timing of aprepitant administration in patients with oral cancer by comparing the antiemetic effect of aprepitant administered on the first day (first-day group) and third day (third-day group) of combination chemotherapy with docetaxel, nedaplatin (divided doses for 5 days), and 5-fluorouracil. 1. In both groups, very few cases of vomiting were observed. Therefore, we could not compare the incidence of vomiting. 2. The mean highest grade of nausea in the third-day group was significantly higher than that in the first-day group (2.33±0.71 vs 0.78±0.22, p=0.002; U-test). 3. In addition, the mean area under the curve of the chronological changes in the grade of nausea in the third-day group was significantly higher than that in the first-day group (13.44±9.58 vs 3.11±3.59, p=0.019; U-test). 4. The incidence of nausea of grade 2 or higher in the first-day group was significantly lower than that in the third-day group (11.1% [1/9] vs 88.9% [8/9], p<0.001; c 2 test). These results indicate that initiation of aprepitant administration on the first day of combination chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil successfully prevented the development of nausea in patients with oral cancer.

[Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy).

Digestive symptoms as side effects of combination chemotherapy of docetaxel, nedaplatin and 5-fluorouracil for head and neck cancer.

BACKGROUND: The study was performed to determine the frequency of digestive symptoms in combination therapy of docetaxel, nedaplatin and 5-fluorouracil for head and neck cancer. METHODS: Frequencies of digestive symptoms were retrospectively investigated in 91 patients. Data for 203 treatment courses were evaluated using the JCOG/JSCO National Cancer Institute-Common Terminology Criteria for Adverse Events(v 4.0 in Japanese). RESULTS: The percentages of patients with nausea, vomiting, stomatitis, constipation, and diarrhea in the first course were 74%, 16%, 42%, 42%, and 13%, respectively. Nausea, vomiting and constipation started mostly on day 2 or 3 and peaked between day 5 and 7. Diarrhea and stomatitis began later and peaked between day 8 and 11. Nausea showed the highest frequencies, and in the late phase(day 6 to 14)of chemotherapy rather than the acute phase(day 1 to 5). Stratified analysis based on the occurrence of nausea and vomiting in previous course showed no significant influence in the frequency of nausea.And then, another stratified analyses showed higher frequency of vomiting and diarrhea in females, nausea in patients aged B65 years old. CONCLUSION: Nausea occurred at an unexpectedly high frequency in the late phase of chemotherapy with docetaxel, nedaplatin and 5-fluorouracil.

Anti-hypoalbuminemic effect of branched-chain amino acid granules in patients with liver cirrhosis is independent of dietary energy and protein intake.

AIM: A multicenter prospective intervention study was conducted in 204 patients with uncompensated liver cirrhosis to explore the influence of dietary intake and patient clinical characteristics on improvement of hypoalbuminemia at weeks 12 and 24 of treatment with branched-chain amino acid (BCAA) granules. METHODS: The primary endpoint set in this study was improvement of hypoalbuminemia in patients with liver cirrhosis. The dietary energy and protein intake per day were estimated based on the results of a survey on diet during a 3-day period preceding the start of the study. RESULTS: As for the primary endpoint, the mean serum albumin level increased significantly at weeks 12 and 24 of BCAA treatment, compared with the baseline level. The mean Child-Pugh score decreased significantly at weeks 12 and 24 of treatment as compared to the mean baseline score. There was a significant increase in the serum albumin level following treatment with BCAA granules regardless of energy intake and of protein intake. The incidence of ascites and edema significantly decreased in the overall patient population both at weeks 12 and 24 of treatment, compared with the baseline incidence. A subgroup analysis conducted in patients stratified according to changes in the serum albumin level at week 12 of treatment as against baseline showed that the incidence of ascites/edema was significantly reduced not only in the increased albumin group but in the unchanged albumin group. CONCLUSION: The present data suggest that the anti-hypoalbuminemic effect of BCAA treatment in patients with liver cirrhosis is independent of dietary intake.

[Phase I/II clinical trial of induction chemotherapy with nedaplatin (CDGP), docetaxel (DOC) and 5-fluorouracil (5-FU) for squamous cell carcinoma of head and neck].

In a phase I study, we determined the maximum tolerated dose (MTD) and the recommended dose (RD) of nedaplatin (CDGP) in combination chemotherapy with Docetaxel (DOC) and 5-fluorouracil (5-FU) for treatment of carcinoma of the head and neck. Then, in a phase II study, we examined the efficacy and safety of the RD of chemotherapy. Fresh patients with squamous cell carcinoma of the head and neck were enrolled in the study. The dosage of chemotherapy was as follows: DOC 60 mg/m(2) on day 1 by infusion over 2 hours; CDGP 20-30 mg/m(2)/day on day 1 to 5 by infusion over 1 hour, and 5-FU 600 mg/m(2)/day on day 1 to 5 by 5 days continuous infusion. For CDGP, an initial dose level was set at 20 mg/m(2), and 3 patients were enrolled for each level of dose escalation. The DLT was defined here as grade 4 neutropenia or grade> or =3 non-hematotoxic reactions. The dose at which DLT was observed in overall 33% cases was taken as MTD. The RD for phase II study was estimated to be DOC 60 mg/m(2), CDGP 20 mg/m(2)/day, 5-FU 600 mg/m(2)/day. Forty patients were enrolled in the phase II study. DLT of neutropenia was noted in 2 of 38 cases. DLT of non-hematotoxic reactions was found in less than 33% of the cases; 17 cases showed CR, and 12 cases showed PR. The response rate was 76.3%. The overall response rate in histological assessment was 55.3%. The combination chemotherapy with Low-Divided Dose of CDGP, DOC and 5-FU was suggested to be safe and effective.