Treatment registry in focal epilepsy (TRIP): multicenter observational study in Lebanon.

PURPOSE: Treatment of newly diagnosed epilepsy with a single antiepileptic drug (AED) is the favored approach for seizure management. This observational study aimed to assess, under daily practice conditions, remission and retention rates with the first AED prescribed as monotherapy in patients newly or recently diagnosed with focal epilepsy. METHODS: The treatment registry in focal epilepsy (TRIP) study was conducted on 234 Lebanese patients with newly or recently diagnosed focal epilepsy, requiring treatment with an AED. Demographics, baseline focal seizure characteristics and results of the Clinical Global Impression (CGI) scale at the 12-month visit were reported. The primary objective of this study was to assess the percentage of patients who achieved a 6-month terminal seizure remission at the 12-month visit following treatment with a first AED administered as monotherapy. Secondary outcome variables included the calculation of the 6-month terminal seizure remission according to the baseline seizure types and patient retention at the 12 and 18 month visits. In addition, bivariate and multivariate analyses were conducted to identify independent predictors of 6-month terminal seizure remission at the 12-month visit. RESULTS: The mean age of the 234 eligible patients was 31.6 years and the majority were males (62%). At baseline, the most common type of focal seizures was focal seizures with impairment of consciousness (45%), and the most frequent topographical localization was in the temporal lobe (47%). In total, 77.6% of the patients achieved a 6-month terminal seizure remission at the 12-month visit. Patients with an epileptogenic lesion on neuroimaging were significantly less likely to achieve a 6-month remission compared to those with no identifiable pathological substrate. Patients with focal motor seizures without impairment of consciousness at baseline had significantly lower odds of achieving a 6-month terminal seizure remission compared to patients with a combination of seizure types. There was no significant association between age or gender and 6-month terminal seizure remission. The retention rates were 95.7% and 88.5% at months 12 and 18 respectively with the great majority of patients (90.7%) reporting marked improvement on the CGI scale. CONCLUSIONS: A substantial proportion of patients with newly diagnosed epilepsy achieved a 6-month terminal seizure remission following treatment with a first AED administered as monotherapy. Patients with an epileptogenic lesion on neuroimaging and those with focal motor seizures without impairment of consciousness at baseline were significantly less likely to achieve a 6-month terminal seizure remission. This study demonstrated the feasibility of conducting long-term multicenter studies in Lebanon and will hopefully serve as an impetus to conduct randomized studies in the field of epilepsy.

Identifying predictors of blood pressure control in the Lebanese population - a national, multicentric survey -- I-PREDICT.

BACKGROUND: Blood Pressure (BP) is not well controlled and factors that predict BP control are not well identified in Lebanon. Improvement of hypertension management requires an understanding of patients' characteristics and factors associated with uncontrolled BP. This national, multicentric, observational prospective study was designed to determine the predictors of BP control in patients followed up to 6 months. METHODS: I-PREDICT study was conducted on 988 patients with newly diagnosed or uncontrolled hypertension. Socio-demographic and clinical characteristics were analyzed. The level of agreement between doctors' perceptions on BP control status and JNC VII guidelines was analyzed. RESULTS: The predictor associated with poor BP control was diabetes (OR = 0.17, CI = 0.10-0.28 at month-1; OR = 0.15, CI = 0.10-0.24 at month-6). The predictors associated with better BP control at month-6 were the early control of BP at month-1 (OR = 10.39, CI = 6.18-17.47) and combination therapy prescribed at baseline and month-1 (OR = 15.14, CI = 1.09-208.46, P = 0.04). In the sub-group of diabetes, the predictors that were associated with better BP control at 6 months were following diet at V1 (OR = 2.27, CI = 1.01 to 5.12) and BP control at V2 (OR = 7.34, CT = 3.83 to 14.07). The predictors that were associated with poor BP control at 6 months were middle economic class (OR = 0.036, CI = 0.16-0.94) and upper economic class (OR = 0.036; CI = 0.13-0.93).The rate of BP control was significantly higher at month 6 versus month 1 (67.52% vs 44.08%, P = 0.001). Additional analysis showed poor agreement between the doctors' perceptions on BP control status and the guidelines. CONCLUSIONS: Reaching an early BP control and combination therapy were significant predictors of better BP control, whereas diabetes was a significant predictor of poor BP control. A poor agreement between JNC VII guidelines and clinical practice was observed. I-PREDICT study identified factors that can be targeted for improving BP control.

Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS).

BACKGROUND: The IDMPS is a study to identify changes in diabetes treatment practice in several developing countries. This paper focuses on diabetes management and compliance with guidelines in a Middle Eastern country like Lebanon. METHODS: The cross-sectional data from the 2006 wave of two weeks duration on the Lebanese population along with the longitudinal data of a 9-month follow-up study were collected. RESULTS: A large proportion of Lebanese patients were not adequately controlled or followed up. A slight proportion was managed by diet and exercise alone while most patients were on two or more oral anti-hyperglycemics. Metformin was the most common monotherapy followed by sulfonylureas. 22.6% of Lebanese patients were on insulin, most commonly basal insulin alone followed by premix insulin alone. Blood glucose self-monitoring was more frequently done by insulinized patients and was associated with better glycemic control. Glycemic control was reached in 29.6% of type 2 patients (HbA1c < 7%) with poorest outcome for patients on insulin and was more frequently achieved in patients who had more frequent monitoring of HbA1c levels. CONCLUSION: For a proper assessment of diabetic control, maintaining adherence to international guidelines needs to be evaluated. Promoting patient education, improving physician knowledge with better implementation of guidelines is recommended.

Role of low dose capecitabine combined to irinotecan in advanced and metastatic gastric cancer.

Chemotherapy has a proven role in advanced and metastatic gastric cancer (AMGC) significantly improving quality of life and prolonging survival compared with best supportive care alone. Multiple regimens have been explored. The choice of treatment should be individualized and tailored to the patient's overall conditions and preference. This manuscript is divided into two sections. The first section illustrates the results of a phase II trial combining weekly irinotecan and low dose capecitabine in the management of untreated AMGC patients. The second section aims to identify the current optimal place of this combination in the management of AMGC in the light of the latest advances. In this manuscript we detail our phase II trial which showed objective response rate of 47% (15 patients), disease stabilization of 28% (9 patients), and overall tumor control rate of 75% (24 patients). Median time to progression and overall survival were 5.8 and 8 months, respectively. Grades III-IV toxicities were reported in 7 cases. Low-dose capecitabine plus irinotecan is effective in the treatment of AMGC with an acceptable toxicity profile. Compared to the recent published data, this combination is indicated in the second-line treatment of AMGC and in the first-line treatment where a contraindication for docetaxel- and/or oxaliplatin-based regimen is present.

Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC).

Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.

Sequential vinorelbine-capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial.

PURPOSE: To evaluate the response rate of the combination of capecitabine (C) and vinorelbine (V) followed by Docetaxel (D) in the 1st line treatment of advanced and metastatic breast cancer patients. PATIENTS AND METHODS: Patients with measurable disease and no prior chemotherapy in advanced disease were eligible. Pts received V 25 mg/m(2) on day 1 and 8 in combination with C 825 mg/m(2) twice a day from day 1 to 14 every 3 weeks for four cycles followed by 12 consecutive weeks of D 25 mg/m(2)/w. RESULTS: Between March 2002 and November 2003, 40 patients were enrolled. Median age was 57 years. Of patients, 77.5% of pts had visceral involvement and 32.5% had more than two metastatic sites. In the adjuvant setting, 62.5% received anthracycline and 10% Taxanes. In the intent-to-treat population, an overall objective response was observed in 25 patients (62.5, 95% CI, 45.8-77.27) and stable disease in 5 (12.5%). Median time till progression (TTP) was 12.3 months (range 1.5-48; 95% CI, 10.05-14.54). The median survival was 35.7 months (range 2-47). Reported grade 3-4 toxicities under Navcap were neutropenia (4 pts), anemia (1 pt), thrombopenia (1 pt) and febrile neutropenia (3 pts). Reported grade 3-4 toxicities under weekly Docetaxel were neutropenia (1 pt), thrombopenia (2 pts), leucopenia (1 pt) and anemia (1 pt). CONCLUSION: The sequential use of Navcap followed by weekly Docetaxel demonstrated an interesting efficacy with a prolonged TTP and OS and warrants further evaluation.

FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer.

OBJECTIVE: Advanced pancreatic carcinoma (APC) has a poor prognosis and chemotherapy remains the most common approach. Gemcitabine was the only drug recently approved for use as single agent therapy in APC. However, the combination of oxaliplatin and 5-fluorouracil (5-FU) has shown some promising results. This phase II trial was conducted to investigate the efficacy of oxaliplatin, 5-FU, and folinic acid (FOLFOX-6) in previously untreated APC patients. METHODS: We studied response rate, time to progression, and toxicity profile. Treatment included oxaliplatin 100 mg/m2 and folinic acid 400 mg/m2 on day 1 followed by a 5-FU bolus 400 mg/m2 and a 46-hour infusion of 3000 mg/m2 every 2 weeks. RESULTS: From January 2003 through December 2004, 30 eligible patients were included. Median age was 65 (range, 38-75). There were 22 patients who had metastatic disease and 29 had an adenocarcinoma. A total of 181 cycles were delivered with a mean of 6 cycles per patient. There were 23 patients evaluable for response. There were 8 patients with partial response (27.6% response rate) and 10 with stable disease status (34.5%), while tumor growth control was found in 62% of the patients. Recorded toxicities of grade 3/4 were: neutropenia (26.67%), thrombocytopenia and anemia (10% each), diarrhea (6.67%), and mucositis (3.33%). Neurosensory toxicity was mild. The median time to progression and the median survival were 4 and 7.5 months, respectively. CONCLUSION: In patients with APC, FOLFOX-6 regimen achieved an interesting response rate within a tolerable level of toxicity. This regimen seems to warrant further controlled investigation to confirm its efficacy.

Phase II trial of capecitabine and vinorelbine as first-line chemotherapy for metastatic breast cancer patients.

BACKGROUND: Vinorelbine is one of the most active cytotoxic agents in metastatic breast cancer. Its association with 5-Fluorouracil generates objective responses, varying between 44 and 55%, and improves the tolerance profile. The aim of this multicenter phase II trial was to assess the combination of capecitabine and vinorelbine as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty patients with MBC received a 3-week cycle combining capecitabine 825 mg/m2 twice a day on days 1 through 14, with 25 mg/m2 of vinorelbine on days 1 and 8. Treatment continued until progression, unacceptable toxicity or patient refusal to continue. The median age was 54 years (30-77) and the median WHO-PS was 1. Twenty patients (67%) received adjuvant chemotherapy including anthracycline and taxanes. RESULTS: Objective responses occurred in 21 patients (70%). Stable disease lasting more than 6 months was observed in six patients (20%). The clinical benefit rate was 90%. The median progression-free survival and overall survival were 10 months and 30.4 months, respectively. The most frequent treatment-related toxicities were: WHO grades 3 and 4 neutropenia (two patients), febrile neutropenia (two patients), grade 3 asthenia (two patients) and grade 3 nausea/vomiting (one patient). No grade 3 hand-foot syndrome was observed. CONCLUSION: The combination of capecitabine and vinorelbine is an active and safe regimen for first-line treatment of MBC.