To compare irinotecan (CPT-11) þ gemcitabine vs CPT-11 alone as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) progressing after docetaxel -cisplatinum-based therapy. A total of 147 evaluable, pretreated patients, with NSCLC, received either gemcitabine (1000 mg m À2 , days 1 and 8) þ CPT-11 (300 mg m À2, day 8) (Group A, n ¼ 76) or CPT-11 (300 mg m À2 , day 1) (Group B, n ¼ 71), every 3 weeks. All patients were evaluable for response and toxicity. The objective response rate was 18.4% (95% CI: 9.71 -27.14%) and 4.2% (95% CI: 0 -8.90%) (P ¼ 0.009) for groups A and B, respectively. No significant differences between the two groups in terms of the median duration of response, time to tumour progression, overall survival and 1-year survival were observed. The CPT-11/gemcitabine regimen significantly improved the patients' quality of life ('general mood today' (P ¼ 0.014), 'coughing' (P ¼ 0.003) and 'intensity of symptoms' (P ¼ 0.034)) compared with CPT-11. More cycles had to be delayed (P ¼ 0.001) and required prophylactic growth factor support (P ¼ 0.001) in Group A than B. Three (3.9%) patients in Group A and eight (11.3%) in Group B developed febrile neutropenia (P ¼ 0.09); one patient died of sepsis in each group. Three additional (Group A, n ¼ 1; Group B, n ¼ 2) treatment-related deaths were observed. Grade 3 -4 haematologic toxicity was comparable in the two groups except anaemia (P ¼ 0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and similar in the two groups. CPT-11 þ gemcitabine resulted in a higher response rate and better control of disease-related symptoms than CPT-11 alone, but without any improvement in the overall survival.

Purpose: To evaluate the efficacy and tolerance of the docetaxel/gefitinib combination as second-line treatment in patients with advanced pancreatic cancer. Patients and Methods: Twenty-six patients pretreated with gemcitabine-based chemotherapy were enrolled in the study. Docetaxel (75 mg/m², i.v.) was administered every 3 weeks for a maximum of 6 cycles and gefitinib (250 mg/day, p.o.) was given continuously. Results: Five (19.2%) patients achieved stable disease. The median duration of disease control was 4.8 months (range 1–13.2), the median time to disease progression 2.1 months (range 1–7.3) and the median survival time 2.9 months (range 1–13.9). Grade 3/4 neutropenia was recorded in 9 (34.6%) patients, although only 1 (3.8%) developed grade 2 febrile neutropenia. One (3.8%) patient experienced grade 3 fatigue and 2 (7.7%) grade 3 diarrhea. Grade 1/2 rash was observed in 13 (50%) patients. There were no treatment-related deaths. Conclusion: The docetaxel/gefitinib combination, although safe, has no activity as salvage treatment for advanced pancreatic cancer after failure of gemcitabine-based chemotherapy.

In order to investigate the effect of atrial pressure on the propensity of the atria to fibrillate and the mechanism of this association, the right atrial pressure was changed acutely by transfusion-bleeding in 12 anaesthetized open-chest dogs. Under various atrial pressures the conduction time was measured between two pairs of hook electrodes positioned on the two atrial appendages respectively. The effective refractory period was measured by continuous pacing of the right atrium at a 250 ms cycle length at double threshold intensity and interpolating a progressively earlier stimulus after each eighth paced beat. The propensity of fibrillation was studied by rapid (450 min-1) pacing of the atria at double threshold intensity for 10 s at different atrial pressures. At a high (> or = 14 mmHg) atrial pressure the conduction time (45.7 +/- 14.2 ms) was significantly (P < 0.01) longer, the effective refractory period (157.9 +/- 15.2 ms) significantly (P < 0.01) longer and the atrial fibrillation (11/19 or 57.9%) significantly (chi 2 = 9.95, P < 0.001) more common than at a low (< or = 10 mmHg) pressure (35.2 +/- 11.6, 146.2 +/- 12.4, 3/24 or 12.5%, respectively). Analysis of variance showed that the probability of atrial fibrillation was significantly affected by the atrial pressure but not by either the conduction time or the effective refractory period. The findings suggest that an increase in right atrial pressure by acute volume overload prolongs the inter-atrial conduction time and right atrial refractoriness and increases the propensity of the atria to fibrillate by rapid atrial stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to compare the irinotecan/cisplatin regimen with cisplatin as second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) pretreated with a taxane/gemcitabine regimen. Patients (n ¼ 147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m À2 , day 1 and 100 mg m À2 , day 8) and cisplatin (80 mg m À2 , day 8) (IC; n ¼ 74) or CDDP (80 mg m À2 , day 1) (C; n ¼ 73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P ¼ 0.933). The 1-year survival rate was 34.3% for IC-treated patients and 31.7% for C-treated patients. Cox's regression analysis revealed that response to treatment (hazard ratio (HR) ¼ 2.787; 95% confidence interval (CI): 1.1578 -4.922) and performance status (HR ¼ 1.865; 95% CI: 1.199 -2.872) was independent prognostic factors for survival. Overall response rate was 22.5% (95% CI: 12.8 -32.2%) for IC-treated patients and 7.0% (95% CI: 1.15 -13.6%) for C-treated patients (P ¼ 0.012); tumour growth control (partial remission (PR) þ stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P ¼ 0.878). There was no difference in terms of quality of life between the two chemotherapy arms. The incidence of febrile neutropenia, grade 3 and 4 neutropenia and grade 3 and 4 diarrhoea was significantly higher in the IC-than the C-treated patients. Other toxicities were mild. There were no treatment-related deaths in either arm. The IC regimen did not confer a survival benefit compared with C as second-line treatment of patients with advanced NSCLC pretreated with a taxane/gemcitabine regimen, despite its better efficacy in terms of response rate.

Background: A multicenter phase II study was conducted in order to evaluate the efficacy and safety of oxaliplatin as first-line treatment of patients with locally advanced or metastatic carcinoma of the biliary tract. Patients and Methods: Twenty-nine chemo-naïve patients with locally advanced or metastatic biliary tract carcinoma received oxaliplatin 130 mg/m² i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity. Results: An objective response (3 complete responses, 3 partial responses) was achieved in 6 patients (20.6%, 95% CI 5.95–35.4). Disease control (complete response, partial response and stable disease) was observed in 14 patients (48.2%). The median time to tumor progression was 3 months (range 0.7–39) and the median overall survival was 7 months (range 1–39). The 1-year survival rate was 32%. Toxicity was mild. Conclusion: Oxaliplatin is an active agent against biliary tract carcinoma and therefore should be further investigated in combination with other cytotoxic drugs.