[Show abstract][Hide abstract] ABSTRACT: Advanced biliary tract carcinomas (BTCs) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) has shown promising activity in this setting. This international phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTC received gemcitabine 1000 mg m(-2) (day 1) and oxaliplatin 100 mg m-2 (day 2), every 2 weeks. Seventy patients were enroled; 72.9% had metastatic disease. Sixty-seven patients were treated. There were 10 confirmed partial responses (14.9%; 95% confidence interval (CI), 7.4-25.7%) in the treated population (RECIST). Twenty-four patients (35.8%) had stable disease. The objective response rate was 20.5% in patients with non-gallbladder cancers (9/44 patients) and 4.3% in patients with gallbladder cancers (1/23). Median overall survival for the intent-to-treat population was 8.8 months (95% CI, 6.9-11.1%) and progression-free survival was 3.4 months (95% CI, 2.5-4.6%). Grade 3/4 toxicities included thrombocytopenia (14.9% of patients), alanine aminotransferase elevation (13.4%), anaemia (10.4%), neutropenia (11.9%) and pain (1 1.9%). In this study, GEMOX demonstrated activity in non-gallbladder carcinoma, but poor activity in gallbladder carcinoma. GEMOX is well tolerated in advanced BTCs.
British Journal of Cancer 10/2008; 99(6):862-7. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with advanced (stage IIIb/IV) NSCLC, the addition of cetuximab to chemotherapy has demonstrated increased activity compared with chemotherapy alone. Furthermore, the addition of cetuximab to RT in patients with locally advanced squamous cell head & neck carcinoma significantly prolongs the duration of locoregional control and median overall survival compared to radiotherapy alone. Therefore, the SCRATCH study was designed to assess the safety of synchronous cetuximab with radical RT in patients with Stage III NSCLC. The safety results of cohort 1 from this phase I study are presented below.
Twelve patients with inoperable stage III NSCLC were enrolled into cohort I. Inclusion criteria were performance status 0-1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria were previous malignancy, thoracic RT or treatment with EGFR (epidermal growth factor receptor) targeted therapy. Patients received platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m2; maintenance dose 250 mg/m2) and concomitant Rt (64Gy/32 fractions/45 days). The primary end-point was toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments were preformed weekly during radiotherapy, and at regular follow-up visits.
9 out of 12 patients completed the concomitant therapy as planned, with no dose reductions. 3 patients did not complete the full schedule. One died from bronchopneumonia mid-treatment; one experienced grade 3 lethargy following the first cetuximab dose and declined further cetuximab; one experienced a grade 2 skin reaction following the third dose of cetuximab and declined further treatment. On follow-up only one patient has developed a grade III reaction - pneumonitis - which settled on steroids with intermittent oxygen. Three patients have died on follow-up (2 from disease progression and one from thromboembolic disease). Of the 12 patients entered ito the study, 8 have survived at least 1 year, measured from the first day of induction chemotherapy.
The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2008; 3(6):648-51. · 4.55 Impact Factor