Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. Thirty women with advanced breast cancer undergoing chemotherapy were randomly assigned into two groups treated with either single agent Paclitaxel or Docetaxel. Sera from patients before the first and after the last treatment cycle and from normal donors were assayed by ELISA for IL-2, IL-1b, IFN-g, GM-CSF, IL-6, TNF-a, and PGE2 levels. In these same blood samples, NK and LAK cell activity was tested in the total PBMC population against NK-sensitive K562 tumour targets, respectively, and autologous mixed lymphocyte reaction was tested by 3 H-thymidine proliferation assays. All patients in both groups responded to therapy. Significant differences were observed in the following immune parameters between the control group of healthy blood donors and the pretreatment values of both taxane groups; IL-2, GM-CSF, IFN-g levels and NK and LAK cell cytotoxicity were depressed, whereas TNF-a and IL-6 levels were raised in breast cancer patients before treatment compared to controls. There were no significant differences between the two treatment groups regarding any of the parameters studied. Both drugs led to increases in MLR values, NK and LAK cell cytotoxicity, and IL-6, GM-CSF, IFN-g levels, and decreases for IL-1, TNF, and PGE2 levels. The percentage of these differences was greater for docetaxel in comparison to paclitaxel (P50.0001). More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-g, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-a levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-g, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-a. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel. Over the last decade, taxanes (namely paclitaxel and docetaxel) have emerged as effective antitumour agents in a variety of malignancies. Paclitaxel is a semi-synthetic taxane, isolated from the bark of the Pacific yew tree. Doxetaxel is a semi-synthetic taxane, derived from the needles of the European yew (Taxus Baccata). These compounds bind to tubulin, leading to microtubule stabilisation, mitotic arrest and, subsequently, cell death. Plasma clearance of paclitaxel exhibits non-linear kinetics, which results in ...

In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned.

. The present study indicates that, in patients with ACC who have relapsed after 5-FU plus LV, the administration of irinotecan fractionated into two doses every 21 days yields a similar efficacy to, but a much lower incidence of toxicity than, the same total dose of irinotecan administered once every 21 days.

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The purpose of the present study was to investigate the association between performance status (PS) and mean dose of irinotecan (CPT-11) in patients with recurrent advanced colorectal cancer relapsing after 5-fluorouracil and leucovorin chemotherapy. Patients who had completed their last chemotherapy course with 5-fluorouracil and leucovorin for at least 6 weeks and progressed were included. Based on PS, we administered a starting dose of 250 mg/m² in patients with a PS 70–80 (group A), and 350 mg/m² for those with a PS > 80 (group B). Of a total of 90 treated patients, all were evaluable, 18 had a partial response (PR) (20%), 39 stable disease (43%), and 15 progressed (37%). No significant difference was noticed between patients with PS ≧ 90 or ≤ 80 (p = 0.925), or between those who received a mean dose of CPT-11 ≧300 or ≤300 (p = 0.602), for response, survival and time to progression. Toxicity was increased in group B as expected, with significant differences for acute cholinergic syndrome (p = 0.02), diarrhea after the first 24 h (p = 0.03) and severe diarrhea (p = 0.03). According to these results, we conclude that response to CPT-11 is independent of its dose, and that a dose of 250 mg/m² every 3 weeks might be a cost-effective and less toxic alternative in this setting. However, further adequately powered phase II or III randomized studies might be required in order to confirm this observation.

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In an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel-ifosfamide-cisplatin (DIP) based on our previous experience with paclitaxel-ifosfamide-cisplatin. Patients with advanced NSCLC (stages III-IV), WHO-PS<2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80 -100 mg/m 2 day 1), ifosfamide (4 -5 g/m 2 ) and cisplatin (80 -100 mg/m 2 ), both divided over days 1 and 2 every 21 days. G-CSF (lenograstin) was administered from days 4 -13. Fiftyfive patients were accrued (phase I: 15; phase II: 40) and all are evaluable for response and toxicity: median age ‫؍‬ 58 (40 -72); PS ‫؍‬ 1 (0 -2); gender ‫؍‬ 48 males, 7 females; stages IIIA ‫؍‬ 8, IIIB ‫؍‬ 19, IV ‫؍‬ 28; and histologies were adenocarcinoma ( Key words: docetaxel; ifosfamide; cisplatin; chemotherapy; nonsmall cell lung cancerNonsmall cell lung cancer (NSCLC) has been considered traditionally refractory to cytotoxic chemotherapy. Cisplatin-based chemotherapy regimens have produced a small but finite chance of survival prolongation in a large meta-analysis of randomized clinical trials. 1 Introduction of newer agents with different mechanisms of antineoplatic activity have provided the opportunity to devise combinations of these drugs with platinum compounds. Docetaxel (Taxotere) has demonstrated a broad spectrum of activity against a variety of advanced solid tumors.The combination of another taxane, paclitaxel, with either cisplatin or carboplatin has shown encouraging activity in patients with advanced NSCLC, and randomized comparisons against standard previous generation cisplatin-based regimens with etoposide or teniposide have revealed its superiority. 2,3 Moreover, the prior popular 3-drug combination of mitomycin-ifosfamide-ciplatin (MIP) has demonstrated improved response rates and survival prolongation when compared to the early '90s standard: the cisplatin-etoposide regimen in a large cooperative European study. 4 However, it is not yet known whether triple drug combinations would be superior to current 2-drug regimens incorporating novel agents, such as paclitaxel, docetaxel, gemcitabine, vinorelbine in combination with platinum analogues. Ifosfamide, an oxazophosphorine alkylating agent with significant activity, as a single agent, in NSCLC has been successfully incorporated in the MIP regimen, yielding satisfactory activity and tolerability. 5,6 Combination of ifosfamide with paclitaxel and cisplatin (PIC) has been carried out in a previous phase I study by our group, and it has been demonstrated that high individual doses of each drug can be achieved, aided by G-CSF with acceptable toxicity in the outpatient setting. 7 Based on these, we demonstrated very high activity, prolonged TTP and survival in a phase II study of PIC in advanced NSCLC. 8 Docetaxel very likely represents the only new drug with significant single-agent activity in cisplatin-rela...