Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Nov 2008
Phase-II study of weekly schedule of trastuzumab, paclitaxel, and carboplatin followed by a week off every 28 days for HER2+ metastatic breast cancer.
Addition of carboplatin (C) to trastuzumab (T) and paclitaxel (P) improves the efficacy in HER2+ metastatic breast cancer (MBC). The aim of this phase-II study was to evaluate the efficacy and safety of this combination given weekly (3x) followed by a week off. The primary endpoint was: objective response rate (ORR), and secondary endpoints were: time to progression (TTP), overall survival (OS), and toxicity profile. ⋯ The schedule showed an interesting activity, taking into account that 27% of patients had received previous treatment for MBC. One week of rest may benefit not only the patient but may also improve tolerability and efficacy of the combination.
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Cancer Chemother. Pharmacol. · Nov 2008
Interleukin-6 protects against paclitaxel, cisplatin and vincristine-induced neuropathies without impairing chemotherapeutic activity.
This study was conducted to investigate the potential neuroprotective effect of IL-6 on chemotherapy induced neuropathy (CIN). IL-6 was compared to four-methylcatechol (4-MC)-a known inducer of NGF secretion previously shown to exhibit neuroprotective effects in CIN models. ⋯ IL-6 at low doses (10 microg/kg) provided protection against the development of CIN without demonstrating interference with the anti tumoural activity of these anti-mitotic drugs.
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Cancer Chemother. Pharmacol. · Sep 2008
A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors.
This phase I study was conducted to evaluate the safety, tolerability, pharmacological properties and biological activity of the combination of the lonafarnib, a farnesylproteintransferase (FTPase) inhibitor, with gemcitabine and cisplatin in patients with advanced solid malignancies. ⋯ Lonafarnib 75 mg BID, gemcitabine 750 mg/m(2) days 1, 8, 15, and cisplatin 75 mg/m(2) day 1 on a 28-day schedule was established as the MTD. Lonafarnib did not demonstrate FTPase inhibition at these doses. Despite the observed efficacy, substantial toxicity and questionable contribution of anti-tumor activity of lonafarnib to gemcitabine and cisplatin limits further exploration of this combination.
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Cancer Chemother. Pharmacol. · Sep 2008
Antitumour effect of combination treatment with Sabarubicin (MEN 10755) and cis-platin (DDP) in human lung tumour xenograft.
Sabarubicin (MEN 10755), a new disaccaride anthracycline, has shown greater efficacy than Doxorubicin in a large panel of preclinical models and now it is in phase II clinical trials. Its promising antitumour activity promoted considerable interest to combine Sabarubicin with other antitumour agents. Thus, the purpose of this study was to evaluate in vitro cytotoxic effects and in vivo antitumour activities produced by the combination of Sabarubicin and cisplatin (DDP). ⋯ These preclinical results indicate the potential for a strong antitumour activity in lung tumours of the combination Sabarubicin and DDP. In particular, in SCLC the best response should be given by a sequence with administration of Sabarubicin followed 24 h later by that of DDP. Clinical trials based on these results are ongoing.
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Cancer Chemother. Pharmacol. · Aug 2008
Multicenter StudyTopotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study.
Second-line treatment with paclitaxel and carboplatin enhances survival of women with platinum-sensitive recurrent ovarian cancer (ROC). However, because of its cumulative neurotoxicity, there is a strong demand for platinum-combinations with better therapeutic index. Because of its pharmacological properties, topotecan is a good adjunct to carboplatin in this setting, but its safety and efficacy remains to be defined. ⋯ Topotecan and carboplatin is a well tolerated novel doublet option for women with platinum sensitive ROC. We encourage further studies on this approach, but to limit the doses of topotecan to 0.75 mg/m(2)/d1-3 and carboplatin AUC 5/d3.