European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Cremophor EL (CrEL) is a formulation vehicle used for various poorly-water soluble drugs, including the anticancer agent paclitaxel (Taxol). In contrast to earlier reports, CrEL is not an inert vehicle, but exerts a range of biological effects, some of which have important clinical implications. Its use has been associated with severe anaphylactoid hypersensitivity reactions, hyperlipidaemia, abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral neuropathy. ⋯ In addition, it has been shown that CrEL, as an integral component of paclitaxel chemotherapy, modifies the toxicity profile of certain anticancer agents given concomitantly, by mechanisms other than kinetic interference. A clear understanding of the biological and pharmacological role of CrEL is essential to help oncologists avoid side-effects associated with the use of paclitaxel or other agents using this vehicle. With the present development of various new anticancer agents, it is recommended that alternative formulation approaches should be pursued to allow a better control of the toxicity of the treatment and the pharmacological interactions related to the use of CrEL.
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Comparative Study
In vivo antitumour efficacy of MGI-114 (6-hydroxymethylacylfulvene, HMAF) in various human tumour xenograft models including several lung and gastric tumours.
MGI-114 (6-hydroxymethylacylfulvene, HMAF) is a semi-synthetic analogue of the cytotoxic sesquiterpenoid illudins. In the present study, the in vivo antitumour efficacy of MGI-114 was examined in a panel of human tumour xenograft models consisting mainly of human lung and gastric tumours, and compared with that of other antitumour drugs such as irinotecan, paclitaxel, cisplatin, doxorubicin, vindesine, etoposide and 5-fluorouracil (5-FU). When different administration schedules were compared, daily administration of MGI-114 was found to be more effective than intermittent administrations. ⋯ Moreover, in four human lung and three gastric tumour xenograft models, MGI-114 showed a strong antitumour activity with complete tumour regression being observed in some of the models. The antitumour efficacy of MGI-114 was generally higher than or equivalent to that of other antitumour drugs such as irinotecan and paclitaxel. These results support the potential utility of MGI-114 in the treatment of a variety of human solid tumours.
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Multicenter Study Clinical Trial
A phase II trial of oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma.
Only a minority of patients with hepatocellular carcinoma (HCC) may benefit from curative treatments, whereas there is no standard therapy for the remaining patients. The objective of this multicentre, open label phase II study was to estimate the objective tumour response rate of a 28-day regimen of oral eniluracil/5-fluorouracil (5-FU) in patients with chemotherapy-naïve, or anthracycline-refractory, inoperable HCC. 45 patients received courses of twice daily oral 5-FU (1.0 mg/m(2)) and eniluracil (10 mg/m(2)) for the first 28 days of each 5-week course. Patients were assessed at regular intervals to determine the tumour response and to evaluate toxicity. ⋯ The combination of eniluracil/5-FU was well tolerated and had an acceptable safety profile. Only 7 patients (16%) reported at least one adverse event (AE) of grade 3 or 4 intensity considered reasonably attributable to the study medication. In conclusion, oral eniluracil/5-FU had minimal, if any, activity in patients with inoperable HCC, but the safety profile was acceptable.
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Randomized Controlled Trial Clinical Trial
A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.
The aim of this study was to examine the strategy, feasibility and outcome of neo-adjuvant chemotherapy, with doxorubicin and ifosfamide, in adult patients with 'high-risk' soft-tissue sarcomas. Patients with 'high-risk' soft-tissue sarcomas, defined as tumours > or =8 cm of any grade, or grade II/III tumours <8 cm, or grade II/III locally recurrent tumours, or grade II/III tumours with inadequate surgery performed in the previous 6 weeks and therefore requiring further surgery, were randomised between either surgery alone or three cycles of 3-weekly doxorubicin 50 mg/m(2) intravenous (i.v.) bolus and ifosfamide 5 g/m(2) (24 h infusion) before surgery. The type of surgery had to be planned at randomisation. ⋯ The 5 year overall survival for both arms is 64 and 65%, respectively (standard error 7%) (P=0.2204). Neo-adjuvant-chemotherapy with doxorubicin and ifosfamide at these doses and with this schedule was feasible and did not compromise subsequent treatment, surgery with or without radiotherapy. Although not powered to draw definitive conclusions on benefit, but with an at least 7 year median follow-up, the results render it less likely that major survival benefits will be achieved with this type of chemotherapy.