Weekly high-dose 5-fluorouracil (5-FU), leucovorin (LV) and bimonthly cisplatin in patients with advanced gastric cancer.

BACKGROUND: A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer. PATIENTS AND METHODS: From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break. RESULTS: There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively. CONCLUSIONS: This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

New annonaceous acetogenins from Rollinia mucosa.

Four new compounds, a mixture of 20,23-cis-2,4-trans-bullatalicinone (1) and 20,23-cis-2,4-cis-bullatalicinone (2), rollimusin (3), and rolliacocin (4), along with eight known acetogenins, were isolated from an ethyl acetate extract of the unripe fruits of Rollinia mucosa. The structures and stereochemistry of 1-4 were determined on the basis of spectral data and chemical evidence.

Correlation between computed tomographic density of lymph node metastases and response to cisplatin-based chemotherapy in patients with head and neck squamous cell carcinoma in an area in which betel quid chewing is prevalent.

BACKGROUND: Identifying the factors predicting response to chemotherapy is important for patients with head and neck squamous cell carcinoma (HNSCC). It allows more rational selection of subsets of patients who may benefit from multidisciplinary treatment. Correlation of lymph node density in contrast-enhanced computed tomographic (CT) scans of HNSCC with response to chemotherapy was observed in the recent literature. This prospective study was designed to validate this clinical issue. METHODS: From January 1992 to March 1995, 71 patients with untreated HNSCC were included in this study in which the following criteria were met: 1) a lymph node > 3 cm by physical examination or > or = 2 cm by scanographic examination; 2) clinically evaluable disease treated by cisplatin-based neoadjuvant chemotherapy; and 3) availability of a pretherapeutic contrast-enhanced CT scan showing the cross-sections of relevant lymph node metastases. The density of the largest lymph node was compared with that of the nuchal muscles by a radiologist blinded to the patient's therapeutic outcome. A lymph node was classified as hypodense if more than 33% of the lymph node surface area was comprised of a hypodense zone, and isodense if less than a third of the lymph node surface area was comprised of a hypodense zone. RESULTS: Fifty-one patients (72%) had the largest lymph node classified as hypodense, and 63 patients (89%) were found to have extranodal spread (ENS) in the relevant lymph nodes. Fifty-nine patients were betel quid chewers. Lymph node density was not related to T classification, primary site, or histologic differentiation of the primary tumor. There was also no correlation between lymph node density and lymph node N classification. The lymph node chemotherapy response rate was 35% (7 of 20) of the isodense group and 47.1% (24 of 51) of the hypodense group (P = 0.36). ENS was found to have no impact on the chemotherapy response. CONCLUSIONS: Computed tomographic density of lymph node metastases did predict chemotherapy response in the HNSCC patients in the current study from an area in which betel quid chewing is prevalent.

Cisplatin and 5-fluorouracil as neoadjuvant chemotherapy: predicting response in head and neck squamous cell cancer.

In order to prospectively evaluate the efficacy, toxicity and predictive factors of response to neoadjuvant chemotherapy, a total of 120 patients with head and neck squamous cell cancer diagnosed from January 1992 to November 1993 were enrolled in this study. There were 118 male and 2 female patients, with a median age of 51 years (range 30-74 years). The primary sites were the oral cavity (77), oropharynx (15), hypopharynx (25) and larynx (3). Betel quid chewing was habitual in 91% of patients. All patients were previously untreated, and 94% had stage III or IV disease. Chemotherapy was given in two or three courses to 96 patients who were then assessed for response rate and predictive factors. The chemotherapy regimen consisted of cisplatin 100 mg/m2/day on day 1 and 5-fluorouracil (5-FU) 1 g/m2/day intravenous infusion continuously for 4 to 5 days for 4 weeks. The overall chemotherapy response rate was 56%, with a 3% complete response. By univariate analysis, both the T-stage and tumor volume were significant for predicting the response of the primary site. The age, histologic differentiation, tumor location and N-stage were unpredictive for response. The nodal response (43%) was less than that of the primary site (68%). By multivariate analysis, only the tumor volume (> or = 50 cm3) and the presence of nodal metastases were predictive for the combined TN response. Based on the World Health Organization toxicity criteria, 49 patients experienced grade 3 to 4 mucositis, and 24 patients had grade 3 to 4 vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient neurological disturbances induced by the chemotherapy of high-dose methotrexate for osteogenic sarcoma.

Temporary neurologic abnormalities were observed in one out of 23 patients undergoing chemotherapy with high-dose methotrexate (HD-MTX) for osteogenic sarcoma. This patient developed sequential symptoms including alternative hemiparesis, dysarthria and altered consciousness 5 days after the second course of HD-MTX (8 gm/m2 by 6 h continuous infusion) with leucovorin rescue. Laboratory evaluations disclosed normal electrolytes, hemograms and non-toxic serum MTX levels at the onset of the symptoms. Computed tomography of the brain was normal but electroencephalography showed focal theta and delta slow waves over the right temporal-parietal-occipital area. The neurological symptoms resolved completely within 72 h.

Transient hyperammonemia related to chemotherapy with continuous infusion of high-dose 5-fluorouracil.

Hyperammonemic encephalopathy has been reported in patients receiving chemotherapy (CT). It is characterized by abrupt alteration in mental status with markedly elevated plasma ammonium levels in the absence of obvious liver disease. This paper reports seven patients who developed transient hyperammonemia during chemotherapy. The regimens all included continuous infusion of high-dose 5-fluorouracil (5-FU). The onset of hyperammonemic encephalopathy was 1.5-4 days after the start of CT. Five cases had infection and six had prerenal azotemia at the time of hyperammonemia. After management, plasma ammonium levels all returned to the normal range within 2 days. Except for one persistent coma, status of consciousness cleared completely. The true mechanism of transient hyperammonemia is unclear. The excess production of ammonium due to metabolites of 5-FU added to precipitating factors such as infection, hypovolemia or constipation may be the explanation for transient hyperammonemia in our study.