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  • 1
    Electronic Resource
    Electronic Resource
    Etoposid (VP 16-213) (1981)
    Springer
    Journal of molecular medicine 59 (1981), S. 1177-1188 
    Details
    ISSN: 1432-1440
    Keywords: Etoposide ; Mechanisms of action ; Pharmacoclinetics ; Toxicity ; Clinical activity ; Cancer ; Etoposid ; Wirkungsmechanismus ; Pharmakokinetik ; Toxizität ; Klinische Aktivität ; Krebs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Etoposid ist ein halbsynthetisches Podophyllotoxinderivat mit einem breiten zytostatischen Wirkungsspektrum und relativ günstigem therapeutischen Index. Tierexperimentell zeigt diese Substanz einen Synergismus mitCis-Platin, Cyclophosphamid, BCNU und Cytosinarabinosid. Die Wirkmechanismen sind Hemmung des Nukleosidtransports in die Zelle, Störung der DNA- und RNA-Synthese, Einzelstrangbrüche, Störung der Proteinsynthese und Hemmung mikrotubulärer Proteine. In niedriger Konzentration wirkt Etoposid zellzyklusphasenspezifisch mit Akkumulation in der G2-Phase, in höherer Konzentration auch phasenunspezifisch. Am geeignetsten unter dem Aspekt von Wirkung und Toxizität ist die intravenöse oder orale Applikation in fraktionierten Dosen von 80–120 mg/m2 an 3–5 aufeinanderfolgenden Tagen und Wiederholung nach 21 [14–28] Tagen. Neben der dosislimitierenden Knochenmarkstoxizität sind weitere Nebenwirkungen Übelkeit, Erbrechen, Fieber, Kopfschmerz, Hypotension, Phlebitis, Mukositis, Neuropathie, Kardiotoxizität, Alopezie. Etoposid gehört zu den wirksamsten Substanzen beim kleinzelligen Bronchuskarzinom mit einer Ansprechrate von 37% (10% CR) und hat eine hohe Aktivität beim NHL (36%), Hodenkarzinom (37%), Chorion Karzinom der Frau (35%), beim Neuroblastom (29%) und bei der AMML (35%). Die Aktivität von Etoposid in Kombination mit anderen aktiven Substanzen bei diesen Tumoren wird in zur Zeit laufenden Studien untersucht; beim kleinzelligen Bronchuskarzinom sowie beim testikulären Karzinom und Non-Hodgkin-Lymphom wird Etoposid in Zukunft zu den Substanzen der ersten Wahl gehören können.
    Notes: Summary Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal withcis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect. Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80–120 mg/m2 on 3–5 consecutive days and repetition after 21 [14–28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01721212
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  • 2
    Electronic Resource
    Electronic Resource
    Combined radio-chemotherapy in advanced cervical cancer: a phase-II trial with weekly applied carboplatin, 5-fluorouracil and folinic acid (1996)
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachusetts, 02142, USA : Blackwell Science Inc.
    International journal of gynecological cancer 6 (1996), S. 0 
    Details
    ISSN: 1525-1438
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The 5-year survival of patients with advanced cervical cancer is poor. Major problems are the high frequency of pelvic recurrences and distant metastases. To prevent both, various efforts have been made to combine local radiotherapy with systemic chemotherapy. In this prospective study, 28 previously untreated patients with advanced cervical cancer (FIGO IIB-IVB) were treated with a newly designed therapy consisting of fractionated external beam irradiation (54 Gy) followed by two intracavitary cesium (Cs) applications (2 × 15 Gy), combined with carboplatin (70 mg m−2), 5-fluorouracil (5-FU) (400 mg m−2) and folinic acid (400 mg m−2). Cytotoxic agents were given intravenously on days 1, 8, 15, 22 and 29 as 1-day courses during external irradiation followed by three 3-day courses with carboplatin (100 mg m−2 i.v. daily), 5-FU (400 mg m−2 i.v. daily) and folinic acid (400 mg m−2 i.v. daily) after 8, 12 and 16 weeks of treatment.Acute toxicities ( 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1048891X:IJG06010020:ges" location="ges.gif"/〉 WHO grade 2) were leucopenia (27 of 28 patients), diarrhea (23/28), abdominal pain (19/28), nausea (14/28) and skin desquamation (12/28). Clinically diagnosed pelvic response was achieved in 88.5% (23/26) with a complete response of 34.5% (9/26). As yet, 19 of 26 patients (73.1%) are alive and well (persistent complete/partial remission), two patients (7.7%) are alive with local progression, four (15.4%) have died from pelvic and/or distal recurrence and one (3.8%) died some weeks after the start of therapy. The combined modality treatment concept has to be considered for the therapy of advanced cervical cancer and a prospective and randomized trial with a greater number of patients is warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1525-1438.1996.06010020.x
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  • 3
    Electronic Resource
    Electronic Resource
    Etoposide in patients with previously untreated non-small-cell lung cancer: a phase I study (1991)
    Springer
    Cancer chemotherapy and pharmacology 28 (1991), S. 59-62 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a phase I study, a range of doses of etoposide (200–370 mg/m2 given i. v. daily on 3 consecutive days) were evaluated for tolerance and response as first-line treatment in 26 patients with non-small-cell lung cancer. The dose-limiting toxicity was myelosuppression, especially leukopenia. At dose levels of 350 and 370 mg/m2 ctoposide per day, leukopenia of WHO grade 4 occurred in two and one of seven patients, respectively. No thrombocytopenia of this degree was observed. Myelosuppression was quickly reversible and noncumulative. Apart from alopecia, nonhematologic organ toxicities above WHO grade 2 were not seen. Toxicity analysis suggests that the recommended dose of single-agent etoposide for phase II studies in untreated patients is 330–370 mg/m2 given i. v. daily for 3 days. At the dose levels tested, 6 (23%) major responses could be induced. All responses were seen at a starting dose of 〉300 mg/m2 per day. The median duration of response was 4 months. The median survival for all patients was 8 months and that for responding patients was 15 months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684958
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  • 4
    Electronic Resource
    Electronic Resource
    Phase II study of carboplatin/ifosfamide in untreated advanced cervical cancer (1990)
    Springer
    Cancer chemotherapy and pharmacology 26 (1990), S. S33 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 32 patients with advanced squamous-cell carcinoma of the cervix were treated with 300 mg/m2 i. v. carboplatin and 5 g/m2 ifosfamide as a 24-h i. v. infusion, both given on day 1 every 4 weeks. In all, 3 (9%) complete responses (CRs) and 19 (59%) objective responses (CR+PR) were achieved in 32 patients. Myelosuppression with leukopenia and/or thrombocytopenia of WHO grade 4 in 28% and 13% of patients, respectively, was the main toxicity. The results of our study suggest that carboplatin/ifosfamide is active as neoadjuvant treatment in advanced cervical cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685414
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  • 5
    Electronic Resource
    Electronic Resource
    Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study (1998)
    Springer
    Annals of oncology 9 (1998), S. 45-50 
    Details
    ISSN: 1569-8041
    Keywords: metastatic breast cancer ; paclitaxel ; weekly 24-hour 5-FU/leucovorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC). Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m2, leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m2, weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m2 was administered additionally on days 1 and 22, q 50 days. Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting. Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008292332166
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  • 6
    Electronic Resource
    Electronic Resource
    High dose folinic acid/etoposide/5-fluorouracil in advanced gastric cancer — a phase II study in elderly patients or patients with cardiac risk (1990)
    Springer
    Investigational new drugs 8 (1990), S. 65-70 
    Details
    ISSN: 1573-0646
    Keywords: folinic acid ; etoposide ; fluorouracil ; gastric cancer elderly patients ; cardiac risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22–28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (⩾ 1 course). One patient was lost to follow up. The overall response rate was 48% (16/33) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216926
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