Abstract: BACKGROUND AND OBJECTIVE: In the recent X-ACT (Xeloda in Adjuvant Colon cancer Therapy) trial, oral capecitabine (Xeloda) demonstrated superior efficacy and an improved safety profile compared with infused fluorouracil + leucovorin (folinic acid) [FU+LV] in patients with Dukes' C colorectal cancer. We used the X-ACT results to determine the cost effectiveness of capecitabine compared with FU+LV from the perspective of the Italian National Health Service (NHS). METHODS: Medical resource use data were collected throughout the treatment period. Unit costs for drug administration, hospitalization, emergency room visits and concomitant medications were obtained using Italian published sources. A health-state transition model was used to estimate the incremental cost-effectiveness ratio per quality-adjusted life-month (QALM) gains in the intent-to-treat population (1004 and 983 patients in the capecitabine and FU+LV arms, respectively). Costs and effectiveness were discounted at 3.5%. Costs were calculated in euros (2005 values). RESULTS: Administration of capecitabine required fewer clinic visits per patient than FU+LV (7.35 vs 28.0, respectively). Mean acquisition costs per patient for capecitabine were higher than for FU+LV (euro 2533 vs euro 231, respectively), but this difference was offset by the difference in mean chemotherapy administration costs per patient for FU+LV (euro 4338, compared with euro 152 for capecitabine). Mean total hospital days and medication costs for treatment-related adverse events were higher for FU+LV than for capecitabine (euro 352 vs euro 78, respectively). The cost of emergency room visits for the treatment of adverse events did not differ between the treatment groups. With respect to the lifetime horizon, compared with FU+LV, capecitabine is projected to increase QALMs by a mean 6.5 months, with overall cost savings of euro 2234 over the treatment period. These findings show that capecitabine is an economically dominant treatment in this setting. CONCLUSIONS: Adjuvant capecitabine for patients with Dukes' C colon cancer has the same activity in terms of outcome when compared with FU+LV but is a lower cost option from the economic perspective of the Italian NHS.
Abstract: BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of a novel combination of paclitaxel (P) and gemcitabine (G) in an every 2 weeks schedule followed by weekly paclitaxel (P) as first-line treatment in elderly patients with locally advanced or metastatic NSCLC. METHODS: Elderly patients (>/=65 years of age) with 1997 TNM stage IIIB (pleural effusion)/stage IV NSCLC, performance status (PS) of 0-2 and normal organ function were eligible. Therapy consisted of P at 150mg/m(2) and G at 2000mg/m(2) administered every 2 weeks for 3 cycles followed, in progression-free patients, by P at 80mg/m(2) every week for 6 consecutive weeks every 8 weeks for 2 cycles. RESULTS: Fifty-three eligible patients were enrolled: M/F 51/2; stage IIIB/IV 8/45; PS 0, 40%, PS 1 51%, PS 2 9%; median age, 73 years (range 67-82). The overall response rate was 32% (95% confidence interval [CI]: 19-45). The median overall survival was 7 months (95% CI: 5-9); the median progression-free survival was 5 months (95% CI: 3-6); and the 1- and 2-year survivals were 28.3% and 10.1%, respectively. Both phases of the treatment protocol were well tolerated. CONCLUSIONS: Biweekly P/G followed by weekly P is well tolerated and active as first-line therapy for elderly NSCLC patients.
Abstract: BACKGROUND: For patients with stage IV nonsmall cell lung cancer (NSCLC) who present with brain metastasis (BMs), standard platinum-based chemotherapy regimens have challenged the role of up-front whole-brain radiotherapy (WBRT). METHODS: In this survey, the authors analyzed the decision tree by which 6 oncologic centers guided the pattern of care in an unselected population of patients with NSCLC who presented with BMs at first diagnosis. The impact of front-line, platinum-based chemotherapy also was evaluated. Individual data were reviewed from 156 eligible patients who were referred to participating centers. RESULTS: Up-front treatment included chemotherapy in 110 patients and WBRT followed by chemotherapy in 46 patients. The selection of first treatment was guided based mainly on the presence of by BM symptoms, with chemotherapy selected for 24% of patients in the chemotherapy cohort and for 76% of patients in the chemotherapy and WBRT cohort. Regardless of treatment, the brain response was 29% (27% and 35% for the chemotherapy and WBRT cohorts, respectively; P value not significant). For the entire population, the overall response rate was 37%, progression-free survival was 6 months, and the median survival was 11 months. At multivariate analysis, significant predictors for survival were: brain response (hazard ratio [HR], 2.59; P = .0001), modified Radiation Therapy Oncology Group class (HR, 0.87; P = .003), and Eastern Cooperative Oncology Group performance status (HR, 1.49; P = .04). CONCLUSIONS: For patients with NSCLC who present with BMs at first diagnosis, the results of the current survey confirmed that the expected benefit of platinum-based chemotherapy may be translated into clinical practice and that selected subsets of patients who receive frontline chemotherapy (ie, patients in whom BM symptoms are absent or are controlled by supportive therapy) may be spared from WBRT. Further prospective studies evaluating different approaches and interventions are warranted.
Abstract: PURPOSE: The selection of effective schedules of treatment for metastatic non-small cell lung cancer still remains a challenge for the oncologist. The present multicentric phase II study was designed in order to investigate the activity and safety of the combination of weekly paclitaxel and celecoxib as second-line treatment for non-small cell lung cancer. As a secondary endpoint, the possible correlation of biomarkers with objective response was investigated in a subset of patients. PATIENTS AND METHODS: Patients with platinum-refractory non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0-2 entered the present phase II study. Paclitaxel was administered at the dose of 80 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week rest, and celecoxib, 400 mg p.o. b.i.d. administered continuously. A cycle consisted of 8 weeks of treatment. Determination of circulating vascular endothelial growth factor and interleukin 6 was performed at baseline and every two cycles. RESULTS: Fifty-eight patients were enrolled: median age, 60 years (range, 30-77 years); male/female ratio = 44/14; performance status, 0, 31 patients; 1, 25 patients; and 2, two patients. Predominant histotype was adenocarcinoma (34 cases), and most patients had at least two sites of disease. According to the intent-to-treat analysis, 14/58 objective responses (24.1%) and 24/58 (41.3%) stabilizations of disease were observed, with a median duration of 4 months (range, 2-22+ months) and 5 months (range, 1-13 months), respectively. Median time to progression and median overall survival were 5 and 11 months, respectively. One-year survival was 42.5%. The main toxicity was neuropathy (4% of grade 3). Preliminary results suggest that decrease in serum vascular endothelial growth factor level is significantly associated with clinical response. DISCUSSION: Combination of celecoxib and weekly paclitaxel is safe and active new regimen in pretreated non-small cell lung cancer. Toxicity appears not to be worsened by the addition of celecoxib. According to preliminary results, serum vascular endothelial growth factor level seems to be predictive of response, suggesting that it should be further investigated as a surrogate marker of response.
Abstract: The aim of the current study was to evaluate the activity and toxicity of a combination of oxaliplatin with bolus fluorouracil and leucovorin in colorectal cancer (CRC) patients pretreated for advanced disease with various schedules including continuous fluorouracil infusion. Thirty consecutive patients with pretreated advanced CRC received oxaliplatin 130 mg/m2 by 2-h infusion dl, leucovorin 100 mg/m2 by 1-h infusion followed by fluorouracil 425 mg/m2 i.v. bolus from day 1 to 3 every 3 weeks for a maximum of 6 cycles. The best overall response rate in an intent-to-treat analysis was 13% (2 complete responses and 2 partial responses) (95% CI, 1.2-25.5%) and 37% of patients obtained stable disease with a tumor growth control rate of 50% (95% CI, 32.1-67.9%). The median progression-free survival was 4.0 months (95% CI, 1.4-6.5 months) and median overall survival was 12.0 months (95% CI, 9.9-14.1 months). The independent prognostic factors for improved overall survival were a good performance status and a response/stabilization of disease to chemotherapy. Severe neutropenia was quite common (43.3% of patients and 14.4% of cycles), although complicated by fever only in one case (3.3% of patients). There was one toxic death. In conclusion, the study combination showed an interesting rate of tumor growth control in a cohort of patients previously treated for advanced disease with various schedules including continuous fluorouracil infusion.
Abstract: Thymoma is the most common neoplasm of the anterior mediastinum and is frequently associated with paraneoplastic syndromes. Surgery is the first therapeutic option, but in advanced disease a multidisciplinary approach is feasible, because of chemosensitivity and radiosensitivity of the disease. The natural history of thymoma after surgery points to local recurrence. Adjuvant radiotherapy seems to improve local control and survival. Chemotherapy based on cisplatin plus anthracyclines could be performed in advanced and metastatic disease. The optimal sequence of chemotherapy, radiation therapy and surgery is yet to be defined. In our experience, primary chemotherapy seems to give best results in advanced thymoma with good tolerability.
