Adjuvant platinum-based chemotherapy in patients with epithelial ovarian cancer: prognostic factors and final outcome.

PURPOSE: epithelial ovarian cancer (OVCA) prognosis depends on the clinical stage, histological grade and surgical cytoreduction. Our goal was to retrospectively analyze several prognostic factors in relation with the final outcome in patients with OVCA subjected to adjuvant platinum (PL)- based chemotherapy (CT). METHODS: three hundred OVCA patients were treated at the Department of Medical Oncology A', "Metaxa" Cancer Hospital, between 11/1989-3/2010. Of those, analyzed were patients with R0 debulking operation, treated with adjuvant PL-based CT. Their clinico/imaging/pathological findings and serum tumor marker CA 125 levels were analyzed and related to relapse rate (RR), progression-free survival (PFS) and overall survival (OS). RESULTS: out of 53 R0 OVCA patients 35 (66%) experienced long-term PFS (median follow up time 63 months, range 5-195(+)) and 18 (34%) relapsed after a median of 19 months. Fifteen of the 18 relapsing patients were treated with first-line CT. Twelve (80%) of them were PL-sensitive and 3 (20%) PL-resistant. Their median PFS was 9 and 3 months in PL-sensitive and PL-resistant cases, respectively (p=0.073). Statistical analysis of prognostic factors demonstrated FIGO stage and abnormal postoperative CA 125 values as significant. Patients with FIGO stage III had significantly shorter PFS (p=0.002) and OS (p=0.078) than those in earlier stages, and patients with abnormal postoperative CA 125 values had significantly worse PFS (p=0.017) but not OS (p=0.386) than those with normal values. Age, histological subtype and grade did not affect PFS and OS. CONCLUSION: FIGO stage and abnormal postoperative CA 125 have prognostic significance in OVCA patients after R0 surgical therapy and adjuvant PL-based CT. Patients with PL-sensitive disease achieved better results during therapy for relapse.

Sequential administration of docetaxel followed by maintenance gefitinib, as salvage treatment in patients with advanced NSCLC: a multicenter phase II trial.

PURPOSE: To evaluate the activity and toxicity of the sequential administration of docetaxel followed by gefitinib in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Forty-one patients pre-treated with at least one prior chemotherapy regimen (platinum- or taxane-based) for advanced/metastatic NSCLC received three cycles of docetaxel 30 mg/m2, administered as a 1-h IV infusion, on days 1, 8 and 15 of each 4-week cycle followed by gefitinib 250 mg daily po. Gefitinib treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of patients consent. RESULTS: Two (4.9%) patients achieved a partial response and 10 (24.4%) stable disease, for a disease control rate of 29.3% (95% CI: 15.3%-43.2%) while on weekly docetaxel treatment. Additionally, progressive disease (PD) was observed in 29 (70.7%). No objective responses were observed during the gefitinib maintenance therapy; however, 17 (41.5%) patients presented stable disease maintained for more than 2 months. Median time to progression was 3.0 months (range: 1-38.3 months; 95% CI: 2.4-3.6); median overall survival 6.9 months (range: 1.2-40.2 months; 95% CI: 5.34-8.52) while the 1-year survival was 28.8%. Therapy was generally well tolerated with diarrhea and rash being the most frequent toxicities. CONCLUSIONS: The sequential administration of docetaxel and gefitinib was well tolerated and moderately active against advanced pre-treated NSCLC.

Salvage chemotherapy with gemcitabine and oxaliplatin in heavily pretreated patients with metastatic breast cancer: a multicenter phase II study.

PURPOSE: It was the aim of this study to evaluate the activity and tolerance of gemcitabine and oxaliplatin in pretreated metastatic breast cancer patients. METHODS: Thirty-one patients who had disease relapse or progression after completion of an anthracycline- and/or taxane-based front-line regimen were treated with gemcitabine 1,500 mg/m(2) on days 1 and 8 as a 30-min intravenous infusion and oxaliplatin 130 mg/m(2) on day 8 as a 4-hour intravenous infusion, in cycles of 21 days. RESULTS: Complete response occurred in 1 patient (3%) and partial response in 4 patients (13%) (overall response rate 16%; 95% confidence interval 3.2-29.1). Nine patients (29%) had stable disease and 17 (55%) progressive disease. Three partial responses (13%) were achieved among 23 patients receiving the regimen as third-line treatment. The median duration of response was 6 months (range 3-44.8), the median time to tumor progression 4.6 months (range 0.8-43.8), and the median survival 14.4 months (range 2.1-44.8). Grade 3 and 4 neutropenia occurred in 14 patients (45%), grade 3 and 4 thrombocytopenia in 6 patients (20%), and grade 2 and 3 asthenia in 4 patients (13%). There was no episode of febrile neutropenia. CONCLUSION: The gemcitabine-oxaliplatin combination is a relatively active and well-tolerated salvage regimen in patients with heavily pretreated metastatic breast cancer.

Multicenter phase II study of gemcitabine and oxaliplatin (GEMOX) as second-line chemotherapy in colorectal cancer patients pretreated with 5-fluorouracil plus irinotecan.

PURPOSE: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. PATIENTS AND METHODS: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m(2) days 1 and 8) and oxaliplatin (100 mg/m(2) day 1) were administered every 3 weeks. RESULTS: Partial responses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8-30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. CONCLUSION: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients.

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study.

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 = 147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m(-2), day 1 and 100 mg m(-2), day 8) and cisplatin (80 mg m(-2), day 8) (IC; n = 74) or CDDP (80 mg m(-2), day 1) (C; n = 73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P = 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) = 2.787; 95% confidence interval (CI): 1.1578-4.922) and performance status (HR = 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 = 0.012); tumour growth control (partial remission (PR) + stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P = 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.

Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study.

To compare irinotecan (CPT-11)+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(-2), days 1 and 8)+CPT-11 (300 mg m(-2), day 8) (Group A, n=76) or CPT-11 (300 mg m(-2), day 1) (Group B, n=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=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=0.014), 'coughing' (P=0.003) and 'intensity of symptoms' (P=0.034)) compared with CPT-11. More cycles had to be delayed (P=0.001) and required prophylactic growth factor support (P=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=0.09); one patient died of sepsis in each group. Three additional (Group A, n=1; Group B, n=2) treatment-related deaths were observed. Grade 3-4 haematologic toxicity was comparable in the two groups except anaemia (P=0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and similar in the two groups. CPT-11+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.

A case of Opisthorchis felineus infestation in a pilot from Greece.

We describe the case of a 28-year-old man from Greece with Opistorchis felineus infestation. The patient presented with intense abdominal pain, bilious emesis and eosinophilia. He probably acquired the infection overseas, since he was a commercial airline pilot who used to fly to endemic areas and to consume raw or undercooked fish. He was successfully treated with praziquantel administered in divided doses over a single day. Opisthorchiasis is common to eastern Europe and areas of the former Soviet Union, but extremely rare in Greece. Medical personnel should be cognizant of this parasitic infection, since world travel can spread it to areas of the world unaccustomed to it.

Cisplatin-etoposide alternating with topotecan in patients with extensive stage small cell lung cancer (SCLC). A multicenter phase II study.

PURPOSE: In order to investigate the feasibility of a potentially non-cross resistant drug regimen, we alternated cycles of cisplatin-etoposide with topotecan as front-line treatment in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-six previously untreated patients with extensive stage SCLC received cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 on cycles one, three, five and seven and topotecan 1.5 mg/m(2) IV on days 1-5 on cycles two, four, six and eight. Cycles were repeated every 21 days. Patients' median age was 60 years and performance status (WHO) was 0 for 13, 1 for 20 and 2 for three patients. All patients were evaluable for response and toxicity. RESULTS: Five (14%) patients achieved a complete response and 18 (50%) a partial response for an overall response rate of 64% (95% confidence interval: 48.2-79.6%). After a median follow up of 10 months, the median duration of response was 5.5 months, the time to tumor progression 8 months and the probability of 1-year survival 48.9%. A total of 126 cycles of cisplatin-etoposide and 117 cycles of topotecan were administered with a median number of 4 cycles/patient for each regimen. There were no toxic deaths. Treatment delays due to toxicity occurred in 13 (10%) cycles after cisplatin-etoposide and 16 (14%) cycles after topotecan while doses were reduced in seven (6%) and five (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia complicated 13, 1 and 3% of cisplatin-etoposide cycles and 28, 6 and 1% of topotecan, respectively. Non-hematologic toxicity was mild. The delivered dose intensity was 96% for cisplatin and etoposide and 98% for topotecan. CONCLUSIONS: The alternating administration of cisplatin-etoposide and topotecan is a feasible, active and well-tolerated regimen in patients with extensive stage SCLC.

Atrial pressure and experimental atrial fibrillation.

A possible profibrillatory effect on the atria of an elevated atrial pressure and the site of atrial stimulation was examined. In 15 anesthetized dogs, right or left atrial or biatrial pacing was applied at a high rate (300-600/min) for 5 seconds at double threshold intensity under a wide range of atrial pressures achieved by venous or arterial transfusion or bleeding. Induction of atrial fibrillation in 236 of 1,971 pacing runs was associated with a significantly higher (P < 0.001) atrial pressure (21.6 +/- 12.2 mmHg, mean +/- SD) than maintenance of sinus rhythm (16.8 +/- 11.1 mmHg in 1,735 of 1,971 pacing runs). Stimulation of the right atrium resulted in atrial fibrillation more frequently than left atrial or biatrial stimulation, with biatrial stimulation less frequent than right or left atrial stimulation. The induction of atrial fibrillation was related to the atrial pressure and to the site of stimulation but not to the pacing rate or the prepacing heart rate. The prepacing heart rate, associated with failure to induce sustained atrial fibrillation, was higher than that associated with atrial fibrillation in 12 of 15 experiments (significantly in 6) and not significantly lower in 3 of 15. Atrial fibrillation lasting 1 minute or more was more frequently associated with simultaneous stimulation of both atria than of either atrium alone. Thus, an elevated atrial pressure may facilitate the induction of atrial fibrillation. The site of stimulation also plays an important role for both the induction and maintenance of atrial fibrillation in this model.

Some observations on the mechanism of pressure related atrial fibrillation.

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)