Population pharmacokinetics and pharmacodynamics of cisplatin in patients with cancer: analysis with the NONMEM program.

The population pharmacokinetics and pharmacodynamics of cisplatin (CDDP) were evaluated based on a mixed-effect model using the NONMEM program. Unchanged CDDP in plasma was measured as a biologically active platinum species during CDDP chemotherapy, using high-performance liquid chromatography. Plasma concentration measurements (157) of unchanged CDDP from 26 patients with cancer receiving 80 mg/m2 CDDP by infusion over 2 hours, 3.5 hours, or 4 hours were analyzed according to a one-compartment model. The influences of individual characteristics such as body weight, dose schedule, course, and clinical laboratory values (renal function markers, albumin) on total body clearance (Cl) and volume of distribution (Vd) were examined. In the final pharmacokinetic model, body surface area and dose schedule affected Cl of unchanged CDDP. The Cl of CDDP was increased by 27.3% after the 2-hour infusion schedule compared with Cl after the longer infusions. The Vd was estimated as 13.4 L/m2. The interindividual variability for Cl and Vd and residual variability were 22.9%, 30.9%, and 35.5%, respectively. The relationships between maximum concentration (Cmax) of unchanged CDDP and maximum blood urea nitrogen (BUNmax), or minimum creatinine clearance (ClCr,min) over a 1-month period after CDDP administration were evaluated according to linear, exponential, or maximum response (Emax) models. The linear or Emax model described pharmacodynamics most successfully, with relatively large interindividual variability for both slope and EC50 (more than 25%). Residual variability was 15.3% and 17.1% in BUNmax and Clcrmin, respectively. The population means and interindividual and residual variability of pharmacokinetics and pharmacodynamics of CDDP were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic and pharmacodynamic approach could be useful to manage CDDP nephrotoxicity using sparse data in a clinical setting.

[A case report of lung cancer with chest wall invasion arising from a bulla wall].

A 45-year-old man with a history of pulmonary bullae complained of back pain and chest pain while playing golf. His plain chest X-ray film revealed pulmonary bullae and an 8 cm tumorous mass. Although bronchoscopic biopsy was unsuccessful, adenocarcinoma was confirmed by transcutaneous lung biopsy. Because chest wall invasion was found by CT scanning, right upper lobectomy with chest wall resection and dissection of hilar and mediastinal lymph nodes was performed (p-T3N0M0, stage IIIA, relative curative resection). The postoperative course was uneventful and no sign of recurrence is evident eight months later. It was strongly suggested by histopathological study that the chest wall invasion of poorly differentiated adenocarcinoma arose from the bulla wall. Formerly, only two non-curatively resected cases with chest wall invasion of lung cancer arising from a bulla have been reported in Japanese literature.

[Cisplatin, adriamycin and VP-16 (CAV) in the treatment of small cell carcinoma of the lung].

Sixteen patients with small cell carcinoma of the lung were treated with a combination of cisplatin (25 mg X 5 or 80 mg/m2 X 1), adriamycin (30 mg/m2 X 1) and VP-16 (200 mg (p.o) X 5) every 3-4 weeks. Nine of these patients had received prior therapy. In 12 evaluable patients, there were 9 partial responses and 1 complete response, giving a total response rate of 83.3% (10/12). 6 of 10 responders received radiation therapy after induction chemotherapy, and 4 patients achieved complete response. The median survival time of responders was 52 weeks. The major toxic effects included nausea and vomiting (81%), leukocytopenia less than 2,000 (75%), and thrombocytopenia less than 10 X 10(4) (44%). Renal toxicity was mild and none of these patients developed renal insufficiency. These results demonstrate that CAV is an effective regimen for remission induction chemotherapy in patients with small cell carcinoma of the lung.

White uniformity measurements on color TV picture tubes.

A minicomputer controlled scanning colorimeter has been developed, which automatically measures the distribution of chromaticity coordinates over the phosphor screen of a color picture tube. After measurement, the distribution of chromaticity difference vectors is displayed immediately on a CRT screen. Mean color difference is calculated for all points measured. This difference is highly correlated to visual evaluations by inspectors. These experiments indicate that white uniformity can be evaluated instrumentally.