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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Illudins are a novel class of agents with a chemical structure entirely different from current chemotherapeutic agents. A new semisynthetic derivative, MGI 114 (NSC 683,863, 6-hydroxymethyl-acylfulvene, HMAF), is markedly effective in a variety of lung, breast and colon carcinoma xenograft models. This analogue, MGI 114, is currently in phase I human clinical trials, and is scheduled for two different phase II trials. ⋯ The parental MV522 xenograft is mildly responsive in vivo to mitomycin C and paclitaxel, as evidenced by partial tumour growth inhibition and a small increase in life span, whereas MV522/mdr1 xenografts were resistant to these agents. In contrast to mitomycin C and paclitaxel, MGI 114 produced xenograft tumour regressions in 32 of 32 animals and completely eliminated tumours in more than 30% of MV522/mdr1 tumour-bearing mice. Thus, MGI 114 should be effective in vivo against mdr1/gp170-positive tumours.
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Clinical Trial
Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer. A phase I/II dose escalation trial.
In this phase I/II study, we investigated the radiosensitising effects of docetaxel in non-small cell lung cancer (NSCLC). 30 patients with stage IIIb (18 patients) and IV (12 patients) NSCLC were treated with 64 Gy of accelerated chest radiotherapy (5-week schedule using a concomitant boost technique) and docetaxel on a weekly basis. The docetaxel starting dose level was 20 mg/m2/week and was escalated by 10 mg/m2 increments in cohorts of 10 patients. Dose-limiting toxicity (grade 3 asthenia) was observed in 6 of 10 patients treated at the 40 mg/m2/week dose level, enforcing a 50% dose reduction in 4 patients. ⋯ A partial response occurred in 15 of 30 patients (50%) for an overall response rate of 77% (95% confidence interval (CI) 60-92%). Radiosensitisation with docetaxel is feasible and the recommended dose for further phase II studies is 30 mg/m2/week. Further phase II studies are required to confirm the remarkably high response rate observed in the present trial.