There was no pharmacokinetic-sequence interaction between C and P in this study. A clear dose-response relation with respect to response rate and survival was observed. The pharmacokinetic parameter P-T > or = 0.1 mumol/L was related to improved survival in this study.
Summary The purpose of the study was to delineate the efficacy and toxicity of paclitaxel (Taxol, Bristol Myers Squibb) in the treatment of drug resistant small-cell lung cancer (SCLC). Patients with SCLC relapsing within 3 months of cytotoxic therapy received paclitaxel 175 mg m-2 intravenously over 3 h every 3 weeks. The dose of paclitaxel was adjusted to the toxicity encountered in the previous cycle. Of 24 patients entered into the study, 24 and 21 were assessable for response and toxicity respectively. There were two early deaths and two toxic deaths. No complete and seven partial responses (29%) (95%CI 12-51%) were observed and five patients had disease stabilization. The median survival (n = 21) was 100 days. Life-threatening toxicity occurred in four patients; in others (non)-haematological toxicity was manageable. Paclitaxel is active in drug-resistant SCLC. Further investigation in combination with other active agents in this poor prognosis group is appropriate.Keywords: small cell lung cancer; chemotherapy; early relapse With present-day chemo-and radiotherapy regimens, a major response with considerable prolongation of survival (Ihde, 1992) will be achieved in 90-95% of patients with small-cell lung cancer (SCLC). However, in the majority of these patients the tumour will relapse after a shorter or longer treatment-free period. In this situation, second-line treatment is necessary for adequate palliation. A multifocal relapse will usually lead to treatment with chemotherapy (Andersen et al, 1990). It is then necessary to distinguish between patients with tumours that are sensitive and patients with tumours presumably resistant to cytotoxic agents used in the induction phase (Giaccone, 1989). Patients relapsing within 3 months of induction chemotherapy are considered resistant to the drugs used in the induction regimen (Postmus et al, 1987;Smit et al, 1989). For such patients, second-line treatment should consist off non-cross-resistant drugs. The poor results currently obtained by second-line chemotherapy support the view that failure to identify real non-cross-resistant agents is the primary reason for lack of success (Andersen et al, 1990). Further evidence for this view comes from the fact that, although in most studies on second-line chemotherapy it is not specifically stated, most therapy-resistant patients responding to a second-line regimen have shown a previous response of short duration to first-line treatment (Smit et al, 1989;Postmus, 1993). Thus, there is a great need for new active agents in the setting of second-line treatment in so-called therapy-resistant patients. Moreover, identification of such agents may lead to the development of more potent first-line regimens.
Using EIT, determination of LIP and UDP from the regional PI curves is possible. The obtained information from the regional PI curves may help in understanding alveolar recruitment. The use of this new bedside technique for clinical decision making remains to be examined.
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