Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: a phase I trial.

BACKGROUND: We conducted a phase I trial of gemcitabine (gem) with concurrent radiotherapy in patients with muscle-invasive bladder cancer (BC) ineligible for surgery or cisplatin or refusing organ loss. PATIENTS AND METHODS: Patients with urothelial cancer, cT2-T4, cN0-1, M0, ineligible for surgery due to local tumor extension, PS, age or co-morbidities or who refused surgery were included. After maximal transurethral resection, the treatment schedule included: twice-weekly i.v. infusion of gem [dose levels (DL) 1-6: 20, 27, 30, 33, 50 and 40 mg/m(2), respectively] for 30 min and concurrent radiotherapy (RT) to the bladder with 55.5 Gy. The primary end point was to determine the maximum-tolerated dose (MTD) and the dose recommended (RD) for further studies of this gem schedule. The secondary end point was late toxicity. The MTD was defined by dose-limiting toxicity (DLT) in 2 or more of 6 patients, discontinuation of RT and/or gem for >1 week in 2 or more of 6 patients due to grade (G) 3/4 acute and/or late toxicity in more than 2 of 18 patients. RESULTS: Thirty-five of 44 patients were assessable for toxicity and thus the primary end point. DLTs occurred in two of five patients at dose level 5: one G3 alanine aminotransferase elevation and one G3 fatigue. The MTD, therefore, was 50 mg/m(2) gem twice weekly. At DL 6 with 40 mg/m(2), the RD was established: only one of six patients developed G3 fatigue and diarrhea. Late toxicity was rare and of low grade (only G1-2). The 2-year locoregional failure rate was 32% (9/28); 10 of 28 patients (38%) were alive with an intact bladder and no evidence of recurrent disease, 9 patients developed distant metastases and 6 died of their disease. CONCLUSIONS: Gemcitabine in combination with RT is well tolerated in BC patients ineligible for surgery and/or cisplatin. The RD of gemcitabine for subsequent trials is 40 mg/m(2) twice weekly with concurrent radiation.

Spirometric values in obese individuals. Effects of body position.

Obesity is increasingly prevalent. Earlier studies indicated that there was a significant but small difference in spirometric values between sitting and standing position in the normal population. It is not known if this is true for obese individuals. The recommendations of the American Thoracic Society (ATS) are to document if a spirometry is done in a sitting or standing position. We performed a study in which we compared sitting and standing spirometric values in obese individuals. Patients with a body mass index (BMI) > or = 30 kg/m2 who were referred for spirometry were invited to participate. All tests were done according to American Thoracic Society recommendations. We studied 50 subjects (32 females and 18 males; mean age 45 yr [SD +/- 14.4]). Age range was 20-71 years. Average BMI was 39 (SD +/- 7, range 30 to 65). Twenty-two did the first testing in the sitting position and 28 standing. There was a small but statistically significant difference between forced vital capacity (FVC) in the standing versus sitting position (Wilcoxen test, p < or = 0.05). There was no significant difference in FEV1 between sitting and standing. Our conclusion is that body position is not important when performing spirometry in persons with BMI > or = 30 kg/m2.

Short-time splenic irradiation for splenomegaly.

BACKGROUND: Splenic irradiation is routinely used in the supportive treatment of lymphoepithelial and hemopoietic diseases associated with splenomegaly. A new short-time irradiation schedule with conventional dosage (Group A: 2 Gy/fract.) was compared retrospectively with low-dose prolonged treatment schedules (Group B: < or = 1 Gy/fract.) to establish its tolerance and its efficacy in terms of relieving splenomegaly-associated symptoms. PATIENTS AND METHOD: Between 12/1996 and 3/2002 49 patients (6 with CLL, 14 with CML, 6 with NHL, 16 with MPD, 6 with OMF and 1 with AML) underwent 85 treatment courses (13 courses low-dose prolonged treatment and 72 courses short-time treatment).The spleens had been exposed to pretreatment doses of 3-70 Gy (mean 20.75 Gy). Splenic size was 12-35 cm (mean 22.76 cm). One treatment was done with 60Co. 9-20 MeV electron beams were used in 23 treatments and 6 MV photons in 61 treatments. Blood counts were monitored daily. Clinical improvement (pain relief, improvement of splenomegaly-associated symptoms), spleen volume reduction and effects on blood counts were evaluated and documented at the end of the treatment. RESULTS: Of the 85 treated patients, 55 (Group A: 47/72, Group B: 8/13) showed a > 10% reduction of spleen volume and 62 (Group A: 57/72, Group B: 5/13) clinical improvement. 15 of 49 patients underwent multiple irradiation (2-8 courses) without clinical or hematologic complications. The intervals between the courses were 2-19 months. Rapid response in terms of reduction in splenic size in 23 patients permitted field reduction during treatment. Significant hematologic abnormalities were absent throughout. CONCLUSION: The short-time treatment schedule ensured a rapid response with relief of pain and improvement of gastrointestinal and pulmonary symptoms at an overall treatment time shorter than that of low-dose prolonged treatment schedules. No differences in terms of hematologic abnormalities were found between single doses of 2 Gy and < or = 1 Gy.