Concurrent twice-a-week docetaxel and radiotherapy: a dose escalation trial with immunological toxicity evaluation.

Abstract

In vitro studies show that docetaxel (Taxotere) is potent radiosensitizer. In a previous study we observed a 27% complete response rate after radiotherapy and weekly docetaxel for non-small-cell lung cancer. In this dose escalation study we investigated the feasibility of a twice-a-week docetaxel regimen together with conventionally fractionated radiotherapy for brain, chest, and pelvic tumors. Nine patients with stage IIIb lung cancer, 9 with stage IVa pelvic tumors, and 9 with brain glioblastoma were recruited. The starting dose was 15 mg/m2 (twice a week) and was escalated by 4 mg/m2 increments every 3 patients with chest, pelvic, and brain tumors. The maximum tolerated dose of docetaxel was 15 mg/m2 (twice a week) for chest and pelvic cancer patients. The dose-limiting toxicity (DLT) was asthenia and mucosal toxicity (esophagitis or diarrhea in chest and pelvic tumors, respectively). Patients with glioblastomas received 23 mg/m2 (twice a week) without toxicity. Complete response of the chest disease was observed in 3/9 (33%) patients and partial response in 4/9 (44%). Three patients with glioblastoma had a partial response. In pelvic malignancies a high complete response rate was observed (4/9; 45%). Severe monocytopenia and lymphocytopenia were observed during the fourth week of treatment. IgG and IgA immunoglobulins were also reduced. This coincided with the onset of asthenia and severe mucosal toxicity. Asthenia was absent in patients treated for brain tumors, and lymphocyte toxicity was less pronounced. Docetaxel radiochemotherapy is a promising therapeutic approach for locally advanced cancer. The recommended dose of docetaxel for chest and pelvic cancer patients is 15 mg/m2 twice a week. Patients with brain tumors can be safely treated with higher doses of docetaxel (23 mg/m2 twice a week) without toxicity. The severe immunologic toxicity observed suggests that granulocyte-macrophage colony-stimulating factor (GM-CSF) and immunoglobulin administration may be important in the efficacy and tolerance of taxane-based radiochemotherapy. Randomized trials are required to assess whether the efficacy of docetaxel radiochemotherapy depends on the frequency of docetaxel administration during radiation treatment.