Phase II trial of the novel taxane BMS-184476 as second-line in non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the tolerability and efficacy of BMS-184476, an analog of paclitaxel, in patients with advanced non-small-cell lung cancer (NSCLC) progressing or relapsing following at least one prior chemotherapy regimen. PATIENTS AND METHODS: Fifty-six previously treated advanced NSCLC patients received BMS-184476 at a dose of 60 mg/m(2) administered intravenously over 1 h every 21 days. RESULTS: The median number of cycles delivered per patient was five (range one to 17). Dose reduction was required in only 3.8% of cycles. Grade 4 neutropenia occurred in 19.6% of patients, but no grade 4 thrombocytopenia or anemia was reported. Febrile neutropenia was observed in only two (3.6%) patients and there were no life-threatening events. Grade 3/4 peripheral sensory-motor neuropathy was reported in 9% of patients. Other non-hematological toxicities, such as nausea and vomiting, myalgia and arthralgia, diarrhea, and mucositis, were uncommon. Partial responses were observed in eight (14.3%) patients and stable disease in 33 (58.9%). Median progression-free survival was 3.7 months [95% confidence interval (CI) 2.7-5.4] and median overall survival was 10 months (95% CI 6-13.4). CONCLUSIONS: BMS-184476 was well tolerated at the dose of 60 mg/m(2) and showed evidence of antitumor activity in previously treated NSCLC.

Prostate-specific antigen density: a means to enhance detection of prostate cancer.

The ability of serum prostate-specific antigen (PSA) and PSA density (PSAD) to distinguish patients with prostate cancer from those with benign diseases of the prostate was assessed in 495 men. All men were evaluated with PSA determination, digital rectal examination (DRE), transrectal ultrasonography (TRUS) and ultrasound-guided prostatic biopsies. PSA was analysed by the polyclonal (Yang) assay. Prostate volume was estimated from TRUS. PSAD was determined by dividing the serum PSA by the volume of the prostate. Prostatic biopsies identified cancer in 246 of the 495 patients (49.7%). The entire group was divided into 6 subgroups according to PSA level at presentation. Cancer and noncancer patients were compared in each subgroup with respect to the values of PSA, prostate volume and PSAD. For the entire group of patients, there was no statistically significant advantage, for PSAD over serum PSA alone, in distinguishing between benign and malignant prostatic conditions. However, when patients were stratified according to PSA level, PSAD was statistically significantly superior to serum PSA alone in the detection of prostate cancer for PSA values in the intermediate range (2.6-30 ng/ml). This analysis with respect to the DRE and TRUS results showed PSAD to be superior to PSA when both examinations are normal. Our results demonstrate that the influence of PSAD level on cancer detection proportionally increases as the PSAD value increases. Curves constructed from the incidence of prostate cancer according to PSAD values may be useful to select patients with intermediate levels of serum PSA, and normal DRE and TRUS for prostatic biopsies.

[Computerization in private urologic practice with multiple practice locations: the use of medical software and a portable microcomputer]. / Informatisation en pratique urologique libérale avec lieux d'exercice multiples: utilisation d'un logiciel médical et d'un micro-ordinateur transportable.

The authors have used a medical programme, Medistory, since June 1990 to computerize a private urological practice. This programme allows personalization of data collection adapted to urology: interview sheets related to the disease, standard report forms, edition of letters, creation of a multi-entry file and entering of accounts. The consultation was always held without a paper support with real-time data acquisition and the accounting was performed at the end of the visit. Letters were printed separately at home, at the end of the day, so as not to delay the patient. A back-up was performed every second day on hard disk. We used a portable Macintosh with 20 mega octets of REM and a 40 mega octet internal hard disk as our practice is based at several sites. This computerisation benefited from the Macintosh interface which facilitated learning and use of the programme. No time loss and no patient discomfort were recorded in comparison with a conventional consultation. The possibility of opening several files at the same time allowed a simple reply to any demands for other information. Two files out of 700 were lost (0.3%) due to an error when saving data. No accounting errors were detected. The use of a medical programme is particularly well adapted to private urological practice with multiple offices. The advantages of a personal computer include the gain of place, rapidity, unlimited storage capacity and the possibility of recovering data with other standard programmes. Medistory, a programme created for general practitioners, is perfectly adapted to this use due to the ease of personalization allowing the creation of interview sheets related to the disease and the edition of reports and various letters.

Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer.

Two hundred and sixteen patients, presenting with a suspicious digital examination (stage T3 excluded) or a level of prostate-specific antigen (PSA) greater than or equal to 2.5 ng/ml, assessed by radioimmunoassay, underwent a transrectal ultrasound examination. Prostate volume was systematically calculated and correlated to PSA level. Biopsies were performed: (1) on suspicious peripheral hypoechoic areas; ultrasound-guided biopsies; (2) systematically on the 2 prostate lobes, whatever the result of transrectal ultrasound imaging:random systematic ultrasound-guided biopsies. In the 186 patients who had never undergone prostate surgery, ultrasound-guided biopsies showed 42 prostate cancers and random systematic ultrasound-guided biopsies showed 75; 14 of the 76 patients with normal digital rectal examination and transrectal ultrasound imaging had a prostate cancer. In the 30 patients who had previously undergone surgery for benign prostatic hypertrophy, random systematic ultrasound-guided biopsies showed 18 prostate cancers, 13% more than ultrasound-guided biopsies; 75% of patients with a serum PSA greater than 5 ng/ml had a prostate cancer. A very significant correlation was found between PSA level and prostatic volume (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[The correlation between the level of prostate-specific antigen and prostate gland volume in the early diagnosis of prostatic cancer]. / La corrélation entre le taux d'antigène prostatique spécifique et le volume prostatique dans le diagnostic précoce du cancer prostatique.

One hundred and eighty six patients (Pts) presenting with either an abnormal per rectum examination (P.R. suggestive of prostatic cancer (P.Ca) (excluding stage T3) or a prostatic specific antigen (P.S.A.) level greater than or equal to 2.5 ng/ml (radioimmunoassay) were submitted to transrectal ultrasonography (T.R.U.) using a 7 MHz transducer. The prostatic volume (Vol.P) was systematically calculated during T.R.U. and correlated with the P.S.A. level. Six systematic multiple ultrasound-guided biopsies (S.M.U.B.) were performed in the 2 prostatic lobes (3 per lobe) regardless of the result of T.R.U. In the 111 patients in whom the S.M.U.B. were negative, a highly significant correlation (p < 0.001) was observed between the serum P.S.A. level (y) and the prostatic volume (Vol.P): y = (4.13 +/- 0.15 Vol.P) +/- 8.43. In the 75 Pts with P.Ca, the P.S.A./Vol.P correlation was significantly different (p < 0.05) from the straight line of regression with the previous standard deviation. A similar difference in correlation (p < 0.05) was observed in the sub-group of 14 Pts with P.Ca despite normal P.R. and T.R.U. These results suggest: 1) that there is a correlation between the Vol.P measured by T.R.U. and the P.S.A. level in patients with negative S.M.U.B. 2) that the absence of correlation is highly suspicious of P.Ca and requires S.M.U.B. 3) that there is a 15% incidence of P.Ca in the sub-group of Pts with normal P.R. and T.R.U. which are only detected by the raised P.S.A. not correlated with the volume of the prostate.

[A pharmacokinetic study of diffusion in adenomatous prostatic tissue of an intravenous bolus of cefamandole]. / Etude pharmacocinétique de la diffusion dans le tissu prostatique adénomateux d'un bolus intra-veineux de céfamandole.

Twenty-three patients undergoing transurethral resection of the prostate for benign prostatic hypertrophy received antibiotic prophylaxis with a second generation cephalosporin, cefamandole, administered by a single IV bolus of 2.5 g. A pharmacokinetic study was performed on blood and resection chips collected at regular intervals. Cefamandole penetrates rapidly into the prostate without any saturation threshold. It diffuses less extensively and persists for a shorter period in elderly subjects, but penetrates to an identical degree regardless of the volume of the adenoma. The prostatic concentration was always higher than the minimal inhibitory concentration for the bacteria generally encountered, except for pseudomonas. The pharmacokinetic study of cefamandole therefore demonstrated that an IV bolus of 2.5 g is perfectly suitable for antibiotic prophylaxis prior to prostatic resection.

[Arthropathies following the administration of pefloxacin to an adolescent with mucoviscidosis]. / Arthropathies consécutives à l'administration de péfloxacine chez un adolescent atteint de mucoviscidose.

We report the occurrence of knee joint effusion with prolonged functional impairment in a 17-year old boy with cystic fibrosis treated with pefloxacin for recurrent lower respiratory tract infections caused by Pseudomonas aeruginosa. Because the quinolone pefloxacin fairly often induces joint disease in pediatric age groups, we advocate restricting its use to those patients whose growth is completed. In growing individuals, it seems reasonable to use second generation quinolones only in infections caused by resistant organisms and to avoid exerting the joints during treatment.