Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer

Abstract

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...

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

“…In patients with pretreated oesophageal cancer, the reported response rates vary between 0 and 16% (Conroy et al, 1996;Heath et al, 2002;Lordick et al, 2003;Muro et al, 2004). In our study, the response rate of 25% in patients with prior chemotherapy was encouraging compared to findings reported from other second-line trials.…”

“…Single-agent docetaxel has revealed only moderate activity in patients with previously untreated adenocarcinoma of the upper gastrointestinal tract (Einzig et al, 1996;Heath et al, 2002), but combination regimens, for example, docetaxel plus irinotecan, have been shown to induce remissions in oesophageal cancer (Ilson et al, 1998Lordick et al, 2003). Capecitabine is an oral fluoropyrimidine designed to generate 5-FU preferentially in tumour tissue while minimising systemic 5-FU exposure.…”

Biweekly Docetaxel-Irinotecan Treatment with Filgrastim Support Is Highly Active in Antracycline-Paclitaxel-Refractory Breast Cancer Patients

“…During the 3 years which elapsed from then, several studies have been published, which evaluated the activity of this combination in a wide range of solid tumors; however, data concerning its use in BC patients have not been reported yet [18,19,20,21,22,23,24,25]. …”

The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

“…Docetaxel is used as monotherapy or in combination with other agents to treat ESCC, but its activity is far from satisfactory (20,21). Therefore, identifying and targeting genes conducive to the treatment of ESCC, such as enhancement of conventional chemotherapy, is necessary to improve the survival of patients with this type of refractory cancer.…”