Activity of pemetrexed against brain metastases in a patient with adenocarcinoma of the lung.

A 53-year-old woman was with adenocarcinoma of the lung metastatic to the brain was treated after several lines of chemotherapy with pemetrexed. After six cycles an impressive regression of the brain metastases was documented. A brief review of the literature on response of cerebral metastases to chemotherapy is added.

Two-weekly gemcitabine fixed dose rate and oxaliplatin combination chemotherapy for advanced non-small-cell lung cancer.

PURPOSE: Combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) is active in patients with advanced non-small-cell lung cancer (NSCLC). Oxaliplatin has a favourable toxicity profile compared to cisplatin. Gemcitabine's cellular uptake mechanism is saturable and fixed dose rate (FDR) infusion results in higher intracellular concentrations. We evaluated the feasibility, response rate and toxicity of bi-weekly GEMOX. PATIENTS AND METHODS: Eligible patients with inoperable stage IIIB and IV NSCLC were treated with gemcitabine 1200mg/m(2) FDR and oxaliplatin 85mg/m(2), both given on d1 and d15 every 4 weeks for a maximum of six cycles. Tumour response was assessed every 8 weeks using RECIST criteria. RESULTS: Forty eligible patients initiated treatment between December 2002 and December 2004. There were nine partial responses (23%). An additional 23 patients (58%) had stable disease, resulting in a disease stabilization rate of 81%. The time to progression was 7.3 months (95% CI, 6.0-8.2 months). Median survival time was 10.4 months (95% CI, 8.7-13.2 months). The 1 and 2-year survival rates were 42% and 12%, respectively. The time to treatment response was 2.2 months (95% CI, 1.8-3.5 months) with a median response duration of 4 months. The most common grade 3 or higher toxicities were leucopenia (20%), asthenia (15%) and neurotoxicity (10%). There were no treatment-related deaths. Patients with performance status (PS) of 0 had a significantly longer survival than patients with higher PS (12.9 months versus 9.4 months, HR 0.45, P=0.03). CONCLUSION: Bi-weekly GEMOX is active and well tolerated for chemotherapy-naïve patients with advanced NSCLC. This regimen merits consideration for further investigation.

Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.

BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.

Feasibility and toxicity of weekly Paclitaxel-Carboplatin in 131 patients with pretreated and non-pretreated solid tumors.

BACKGROUND: Chemotherapy with paclitaxel and carboplatin 3-weekly is active in many tumors. Major toxicities are myelosuppression and neurotoxicity. Weekly administration of taxanes allows high dose intensity with reduced toxicity. PATIENTS AND METHODS: 131 patients with solid tumors were treated as outpatients with paclitaxel 75 mg/m(2) and carboplatin AUC 2-3 days 1, 8, 15 every 4 weeks irrespective of pretreatment and partly in neoadjuvant and multimodal concepts. RESULTS: 125 patients (median age 58 years) were evaluable for response and toxicity, of whom 45 suffered esophageal carcinoma (19 patients in neoadjuvant treatment) and 31 non-small cell lung cancer. 49 patients were pretreated. 23 patients received concomitant radiotherapy of esophagus or lung in doses ranging from 40 to 60 Gy. We observed a low hematologic toxicity with 15.2% grade-III/IV leukopenia/granulocytopenia and 3.2% thrombocytopenia grade III/IV. Neurotoxicity grade II was reported in 14 patients. Main toxicity with radiotherapy was esophagitis grade II or III in 7 out of 23 patients. Overall response rate was 54.2%. 5 out of 19 patients treated neoadjuvantly for esophageal cancer reached a pathological complete response. CONCLUSIONS: Weekly paclitaxel and carboplatin is safe and feasible in outpatients and a high dose intensity can be achieved. The favorable toxicity profile allows treatment of elderly and pretreated patients. Response rate is high including pathological complete responses and responses appear quickly, making this therapy most suitable for multimodal and neoadjuvant treatments.

Bilateral internal mammary artery grafting: midterm results of pedicled versus skeletonized conduits.

BACKGROUND: To increase the number of anastomoses per patient, bilateral internal mammary arteries (BIMAs) were harvested with a skeletonized approach instead of a pedicled one. METHODS: One thousand one hundred forty-six patients underwent isolated myocardial revascularization using BIMAs, 304 receiving pedicled grafts (group A, October 1991 through May 1994) and 842 receiving skeletonized conduits (group B, June 1994 through June 1998). Group B had a higher incidence of patients with diabetes (223 versus 40, p < 0.001). RESULTS: The number of BIMA anastomoses per patient was significantly higher in group B (2.4 +/- 0.3 versus 2.1 +/- 0.4, p < 0.001), as well as the number of sequential grafts (288 versus 42, p < 0.001). Twenty-three patients (2.0%) died in the first 30 days after surgery, 5 in group A (1.6%) and 18 in group B (2.1%) (not significant). Postoperative complications were similar in both groups; the incidence of sternal wound healing problems was higher as a whole and with regard to diabetic patients (4 of 40 [10%] versus 5 of 223 [2.2%], p < 0.05) in group A. Seventy-one patients in group A and 133 (15.8%) in group B underwent a postoperative angiography. Patency rate was similar, both early (100% in group A versus 98.6% in group B, not significant) and late (98.6% in group A versus 98.4% in group B, not significant). CONCLUSIONS: The use of skeletonized BIMA conduits allowed us to increase the number of BIMA anastomoses per patient with a lower rate of sternal wound complications and angiographic results similar to those obtained with pedicled BIMA conduits.

The edge-to-edge technique: a simplified method to correct mitral insufficiency.

OBJECTIVE: Repair of mitral regurgitation (MR) is more demanding in case of prolapse of the anterior leaflet, posterior leaflet with calcified annulus, or prolapse of both leaflets. We evaluated a repair which consists of anchoring the free edge of the prolapsing leaflet to the corresponding free edge of the facing leaflet: the 'edge-to-edge' (E-to-E) technique. The correction results in a double orifice valve when the prolapse is in the middle portion of the leaflet and in a smaller valve orifice when the prolapse is close to a commissure. METHODS: Out of 432 patients with MR submitted to valve repair between January 1991 and September 1997, 121 (mean age 56 +/- 15.8 years) underwent E-to-E correction. The most prevalent etiology was degenerative disease (82 patients, 68%). The mechanism of MR was anterior leaflet prolapse (61 patients), posterior leaflet prolapse (24 patients), prolapse of both leaflets (28 patients) and other complex mechanisms (8 patients). In 72 patients, a double orifice was created, the paracommissural repair was done in 49 patients. RESULTS: Hospital mortality was 1.6%. Overall survival was 92 +/- 3.1% at 6 years with 95 +/- 4.8% freedom from reoperation. Mortality was unrelated to the type of repair. Mitral stenosis was never observed after the correction. At the follow-up (mean 2.2 +/- 1.5 years), all patients but 15 are class I or II. Symptoms at the follow-up are not related to residual MR. CONCLUSIONS: Midterm results of this alternative repair technique are promising, considering the high prevalence of complex anatomical lesions. The technique is simple, easily reproducible and rapidly feasible also when mitral exposure is suboptimal.