No abstract

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m À2 ) plus FA (500 mg m À2 , 2-h infusion) followed by 5-FU (2000 mg m À2 , 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39 -69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2 -26.2 months), median survival is 11.4 months (95% CI, 8.0 -14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9 -9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.

Based on the small number of patients and low statistical power of our study definite conclusions regarding efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer cannot be drawn.

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m À2 twice daily on days 1 -14) plus intravenous docetaxel (75 mg m À2 on day 1) every 3 weeks as first-(n ¼ 16) or second-line (n ¼ 8) therapy. Patients received a median of four cycles of treatment (range, 0 -6). The median follow-up is 16.5 months (range, 7.9 -21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5 -7.7 months). The meian survival was 15.8 months (95% CI, 7.8 -23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.

This phase II trial assessed the toxicity and efficacy of irinotecan plus docetaxel in cisplatin-pretreated oesophageal cancer. Irinotecan 160 mg m À2 plus docetaxel 65 mg m À2 once every 3 weeks led to severe myelosuppression in four patients, all of whom experienced neutropenic fever. After amendment of this regimen, 24 patients (male/female ¼ 18/6; median age ¼ 58.5 years; ECOG performance status 0/1/2 ¼ 9/11/4) with advanced oesophageal cancer (adenocarcinoma/epidermoid carcinoma ¼ 13/11) received irinotecan 55 mg m À2 plus docetaxel 25 mg m À2 on days 1, 8 and 15 of a 28-day cycle. Serious adverse events occurred in five patients, one with lethal outcome (pneumonia). Haematological toxicity X31 was rare, whereas nonhaematological toxicity X31 was noted in nine out of 24 patients (asthenia in five patients, diarrhoea in three patients, nausea/emesis in two patients, constipation in one patient). Median survival time was 26 (range 2 -70) weeks. Response rate, assessed according to the WHO criteria, was 12.5% (95% CI 2.7 -32.4%); rate of disease stabilisation (partial remission and stable disease) was 33.3% (95% CI 15.6 -55.3%) with a median duration of 18.5 (range 16 -51) weeks. Although the nonhaematological toxicity proved to be considerable, weekly irinotecan plus docetaxel is feasible and shows some activity in extensively pretreated patients with oesophageal cancer. British Journal of Cancer (2003) Owing to early lymphogenic and haematogenous spread, most patients with oesophageal cancer are diagnosed with advanced disease. These patients receive multimodal treatment if the tumour is deemed to be resectable, or systemic chemotherapy if palliation is the goal. Cisplatin has been the mainstay of chemotherapy and chemoradiotherapy protocols during the last decade (Herskovic et al, 1992;Bleiberg et al, 1997). In case of resistance to cisplatin-based therapy, no evidence-based recommendations regarding second-line treatment exist, but many patients ask for more than measures of best supportive care. Thus, there is a need for tolerable and active protocols beyond cisplatin-based therapy. Irinotecan and taxanes proved to induce remissions in oesophageal cancer (Ilson et al, 1998(Ilson et al, , 1999 although single-agent docetaxel revealed only moderate activity (Heath et al, 2002). The combination of irinotecan and docetaxel has been investigated in phase I studies in patients with pretreated solid tumours (Adjei et al, 2000;Couteau et al, 2000). The recommended phase II dose on this schedule was irinotecan 160 mg m À2 followed by docetaxel 65 mg m À2 administered every 3 weeks (Adjei et al, 2000). This phase II trial was designed to assess the activity and toxicity of the combination of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer. METHODS Patient populationPatients with histologically confirmed adenocarcinoma or epidermoid carcinoma of the oesophagus were enrolled at a single site (Klinikum rechts der Isar, Technical University of Munich). Eligible patients with...