Australian researchers find Ifosfamide and Docetaxel effective in treating advanced cancer

Australian researchers have conducted a phase I trial to identify the maximum tolerated dose of Docetaxel plus Ifosfamide (manufactured by Baxter) with and without granulocyte-colony stimulating factor (G-CSF) support, and to characterise the toxicity profile of the combination in 31 patients with advanced malignancies.

Docetaxel and Ifosfamide have both demonstrated significant single agent anti-tumour activity in a number of tumours.

Patients were treated with Docetaxel 75 mg/m2 intravenously on days 1, and Ifosfamide at increasing dose levels from 1500 mg/m2 /day to 2750 mg/m2 /day as a continuous infusion from day 1-3, every 3 weeks.

The dose limiting toxicity without G-CSF support was grade 4 neutropenia greater than 5 days at a dose of Docetaxel 75 mg/m2 on day 1 and Ifosfamide 1500 mg/m2 /day on days 1-3. When patients received G-CSF, the dose limiting toxicities included Ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. The maximum tolerated dose was Docetaxel 75 mg/m2 on day 1 and Ifosfamide 2750 mg/m2 /day on days 1-3.

Researchers found the ‘anti-tumour activity was seen at all dose levels’ and that ‘complete response was achieved in three patients adenocarcinoma of oesophagus (duration of response 12 months), non-small cell lung cancer (18 months), and breast cancer (8 months). Three patients had a partial response adenocarcinoma of oesophagus (6 months), adenocarcinoma of unknown primary (7 months) and non-small cell lung cancer (3 months)’.

‘Of particular interest were the responses seen in two of four patients with adenocarcinoma of the oesophagus, and in two of four patients with non-small cell lung cancer’.

Researchers concluded, ‘the combination of Docetaxel and infusional Ifosfamide for patients with advanced cancer is tolerable and effective. The recommended dose for phase II studies is Docetaxel 75 mg/m2 day 1 and Ifosfamide 2500 mg/m2 on days 1-3 for previously untreated, good performance status patients, and Docetaxel 75 mg/m2 and Ifosfamide 2250 mg/m2 for previously treated patients’.

‘This schedule is worthy of further exploration in non-small cell lung cancer and upper gastro-intestinal malignancies’.

(Source: OMNUS Oncology & British Journal of Cancer)