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Purpose: Docetaxel is highly active in the treatment of patients with breast cancer. The principal dose-limiting toxicities of the 3-weekly regimen are neutropenia and febrile neutropenia. In a previous phase I dose-escalation study with granulocyte colony-stimulating factor (G-CSF) support, the recommended dose was determined to be docetaxel 160 mg/m(2) 3-weekly. The objectives of this phase II study were to determine the response rate and toxicity of this dose and schedule, given as first-line in patients with advanced breast cancer. Mobilisation of peripheral blood stem cells (PBSCs) was also investigated., Patients and Methods: Eligible women had metastatic breast cancer and were aged 18-75 years with ECOG performance status < or =2. Strict criteria for liver function were followed, and adjuvant chemotherapy must have been completed at least 6 months previously. Treatment was docetaxel 160 mg/m(2) over 60-90 min every 21 days with G-CSF 5 micro g/kg/day until neutrophil recovery, for up to six cycles. A 3-day corticosteroid prophylaxis was given. Bloods samples to determine PBSC levels [CD34+, granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming units-erythroid (BFU-E)] were taken on days 6, 8, 9 and 11 following docetaxel., Results: Twenty-five women with median age 50 years (range 35-66) were included. Seventeen (68%) had previously received adjuvant chemotherapy. In total, 112 cycles were delivered (median four per patient), with dose reductions required in 12.5% of cycles. G-CSF was given for a median of 6 days. The median neutrophil nadir was 0.5 x 10(9)/l and occurred a median 5 days after treatment. The median duration of grade 3 or 4 neutropenia was 2 days (range 1-7). Grade 4 neutropenia occurred in 44% of patients, but there was only one episode of febrile neutropenia. Five patients were taken off study due to toxicities that included oedema, neurosensory toxicity and asthenia. Confirmed partial response was seen in nine patients (37.5%; 95% confidence interval 19% to 59%). CD34+ cells, GM-CFC and BFU-E levels peaked at day 8 following docetaxel administration. The median CD34+ cell peak was 6.5 x 10(4)/ml, with only 20% of patients <2 x 10(4)/ml, a level below which leukapheresis is not usually attempted., Conclusions: Docetaxel 160 mg/m(2) was delivered with G-CSF support with a very low rate of febrile neutropenia. Non-haematological toxicity was significant, causing five patients to go off study. Effective mobilisation of PBSCs was seen. The response rate of 37.5% was less than that obtained in first-line studies using standard-dose docetaxel 100 mg/m(2), suggesting that there is no additional benefit in dose escalation of this cytotoxic agent in breast cancer patients using this schedule.

Background: Docetaxel is a widely active cytotoxic agent. The principal dose-limiting toxicities (DLTs) of the 3-weekly regimen are neutropenia and febrile neutropenia. Use of prophylactic granulocyte colony-stimulating factor (G-CSF) may allow higher doses of docetaxel to be administered with potentially greater anticancer efficacy. The objectives of this study were to determine the maximum tolerated dose (MTD) and toxicity profile of docetaxel given with G-CSF support., Patients and Methods: Eligible patients had solid tumours and were aged 18-75 years with a WHO performance status of up to 2. Strict criteria for liver function were followed. Patients may have received one previous regimen of chemotherapy in addition to adjuvant chemotherapy. Cohorts of three to six patients received docetaxel over 60-90 min every 3 weeks, commencing at 110 mg/m(2) and escalating at 10 mg/m(2) increments. Patients also received G-CSF 5 micro g/kg/day until neutrophil recovery. A 3-day corticosteroid prophylaxis was given., Results: Twenty-nine patients with median age 55 years (range 29-75) were included. Fourteen (48%) had previously received chemotherapy. At the 170 mg/m(2) dose level (the MTD), two of three patients had DLTs and 160 mg/m(2) was determined to be the recommended dose. The principal DLTs were skin and neurosensory toxicity. Asthenia was frequent, especially at dose levels >/=140 mg/m(2). Grade 4 neutropenia occurred in only 10 patients (35%) and was not dose related, with febrile neutropenia in three patients (10%)., Conclusions: Docetaxel may be escalated considerably above standard doses when administered with G-CSF support. The recommended dose for phase II studies is 160 mg/m(2). With escalated-dose docetaxel, DLTs were non-haematological and qualitatively similar to the toxicity profile at standard doses.

Background: Raltitrexed ('Tomudex') is a folate based inhibitor of thymidylate synthase which has been registered in Europe and Australia for the treatment of advanced colorectal cancer. In a European phase I trial of raltitrexed anti-tumour activity was seen in two patients with head and neck cancer, prompting the current study., Patients and Methods: From November 1996 to December 1998, 24 patients with metastatic or recurrent squamous-cell carcinoma of the head and neck from 7 Australian centres received raltitrexed, 3 mg/m2 given intravenously over 15 minutes every 3 weeks, for a maximum of 6 cycles. Patients were required to be chemotherapy naïve and have measurable disease, age > 18 years, WHO performance status initially < or = 2, no significant intercurrent illness or organ dysfunction and a life expectancy > 12 weeks., Results: Twenty-two men and two women, median age 65 years, median performance status 1 were enrolled. Fifteen patients (63%) had received both prior surgery and radiotherapy. In 15 patients (63%) there was recurrent locoregional disease only. Twelve patients (50%) received one cycle of treatment with only four patients (17%) receiving four or more cycles of treatment. No patient achieved a complete or partial response, although 5 patients experienced stable disease which lasted a median of 188 days (range 61-436). The median survival for the whole group was 101 days (range 20436). Raltitrexed was generally well tolerated with minimal antiproliferative toxicity., Conclusions: Single-agent raltitrexed does not demonstrate significant anti-tumour response rates in patients with predominantly locally recurrent head and neck cancer.