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  • anthracyclines  (1)
  • clinical trials  (1)
  • mitoxantrone
  • Springer  (3)
  • 1995-1999  (3)
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Keywords
Publisher
  • Springer  (3)
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Year
  • 1
    Electronic Resource
    Electronic Resource
    Activity of the morpholino anthracycline 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming unitsin vitro (1995)
    Springer
    Investigational new drugs 13 (1995), S. 125-131 
    Details
    ISSN: 1573-0646
    Keywords: anthracyclines ; cloning assay ; morpholino anthracyclines ; MX2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 μg/ml either for 1 hour (201 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19%in vitro response at 0.05 μg/ml and 69% at 0.5 μg/ml) than with 1-hour exposure (1.3% at 0.05 μg/ml and 12% at 0.5 μg/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 μg/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity in patients with those tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00872860
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  • 2
    Electronic Resource
    Electronic Resource
    Activity of gemcitabine in a human tumor cloning assay as a basis for clinical trials with gemcitabine (1996)
    Springer
    Investigational new drugs 14 (1996), S. 265-270 
    Details
    ISSN: 1573-0646
    Keywords: gemcitabine ; clinical trials ; human tumor cloning assay (HTCA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2′,2′-difluorodeoxycytidine (LY 188011, Gemcitabine, Gemzar®) has recently been approved both in Europe for the treatment of patients with non-small cell lung cancer and in the United States for patients with pancreatic cancer. Since the initial discovery of the compound, we have been evaluating the in vitro activity of gemcitabine against human tumor colony-forming units taken directly from patients and growing in soft agar (in the human tumor cloning assay — HTCA). A total of 315 specimens have had gemcitabine tested against them with 44% giving evaluable results. Gemcitabine has been found to be active against colony-forming units from patients with non-small cell lung, breast, ovarian, and pancreatic cancers. A concentration-dependent in vitro response was noted with a higher in vitro response rate noted at 20 μg/ml than at 2.0 μg/ml. Based on subsequent clinical phase II data, the HTCA correctly predicted the wide spectrum of the clinical activity of gemcitabine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194529
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  • 3
    Electronic Resource
    Electronic Resource
    A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors (1998)
    Springer
    Investigational new drugs 16 (1998), S. 37-43 
    Details
    ISSN: 1573-0646
    Keywords: vinorelbine ; vinca-alkaloids ; mitoxantrone ; anthracenedione-derivative ; phase I ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Vinorelbine (Navelbine®) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone®) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016075126007
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