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  • 1
    Electronic Resource
    Electronic Resource
    Combination of daily 4-h infusion of 5-fluorouracil and cisplatin in the treatment of advanced head and neck squamous-cell carcinoma: A South-East European Oncology Group study (1993)
    Springer
    Cancer chemotherapy and pharmacology 31 (1993), S. 489-494 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between April 1986 and May 1989 a multicéntre study was conducted to evaluate the efficacy of a 4-h intravenous infusion of 1000 mg/m2 5-fluorouracil (5-FU) followed by a 1-h infusion of 25 mg/m2 cisplatin (CDDP) given for 4 consecutive days every 4 weeks to patients with advanced squamous-cell carcinoma of the head and neck. A total of 189 consecutive patients entered the study, including 106 who had previously undergone chemotherapy and 83 who were chemotherapy-naive. Of the 165 evaluable patients, 96 (58%) responded to treatment, including 22 (13%) who achieved a complete remission (CR). In the group of previously untreated patients an objective response (CR+PR) was seen in 78% (CR, 14%) whereas in pretreated patients the response rate (CR+PR) was 40% (CR. 13%). The median survival period was 10 months. No significant difference in the duration of survival or of remission was found between the two groups in relation to previous therapy, tumour localisation, disease stage or performance status. Almost half of the patients (49%) experimenced leucopenia but it was severe in only 11% of cases. Anemia (mainly WHO grades 1–2) occurred in 38% of the patients. Nausea and vomiting were common (84%). Nephrotoxicity (23%) was mild and of short duration. Moderate hair loss was seen in 42% of the patients, and phlebitis occurred in 8%. A few cases of cardiotoxicity and neurotoxicity were observed. This regimen is well tolerated and can be given even on an outpatient basis. The resultant response rate and side effects appear to be similar to those previously reported for combination chemotherapy with CDDP and continuous 5-FU infusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685041
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  • 2
    Electronic Resource
    Electronic Resource
    A phase II study of pirarubicin in patients with advanced recurrent head and neck squamous cell carcinoma (1994)
    Springer
    Cancer chemotherapy and pharmacology 33 (1994), S. 438-440 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Background: Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4′-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity in animal models. Patients and methods: Twenty-six patients with squamous cell carcinoma of the head and neck and documented progression after or during previous chemotherapy were entered into the study. Two patients were ineligible for evaluation. Pirarubicin was given at a dose of 70 mg/m2 every 3 weeks. Results: Partial remission was seen in 1 of the 24 evaluable patients. The predominant toxicity was bone marrow depression, with leucopenia in 62% of the patients. One patient died due to a gastrointestinal haemorrhage during a period with WHO grade IV thrombocytopenia. Conclusion: On the basis of these results, pirarubicin cannot be recommended as second-line treatment in patients with recurrent and metastatic HNSCC. Its possible relevance for first-line treatment cannot be judged from these data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686275
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  • 3
    Electronic Resource
    Electronic Resource
    A phase II study of pirarubicin in patients with advanced recurrent head and neck squamous cell carcinoma (1994)
    Springer
    Cancer chemotherapy and pharmacology 33 (1994), S. 438-440 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4′-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity in animal models. Patients and methods: Twenty-six patients with squamous cell carcinoma of the head and neck and documented progression after or during previous chemotherapy were entered into the study. Two patients were ineligible for evaluation. Pirarubicin was given at a dose of 70 mg/m2 every 3 weeks. Results: Partial remission was seen in 1 of the 24 evaluable patients. The predominant toxicity was bone marrow depression, with leucopenia in 62% of the patients. One patient died due to a gastrointestinal haemorrhage during a period with WHO grade IV thrombocytopenia. Conclusion: On the basis of these results, pirarubicin cannot be recommended as second-line treatment in patients with recurrent and metastatic HNSCC. Its possible relevance for first-line treatment cannot be judged from these data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686275
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  • 4
    Electronic Resource
    Electronic Resource
    Doxorubicin plus ifosfamide with rhGM-CSF in the treatment of advanced adult soft-tissue sarcomas: preliminary results of a phase II study from the EORTC Soft-Tissue and Bone Sarcoma Group (1991)
    Springer
    Journal of cancer research and clinical oncology 117 (1991), S. S193 
    Details
    ISSN: 1432-1335
    Keywords: Doxorubicin plus ifosfamide ; rhGM-CSF ; Soft-tissue sarcoma ; Advanced disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Doxorubicin and ifosfamide are the two most active agents used in the treatment of advanced inoperable soft-tissue sarcoma, but their use in combination produces dose-limiting myelosuppression. To explore the feasibility of combining optimal doses of both drugs, doxorubicin (75 mg/m2) and ifosfamide (5 g/m2) were given every 3 weeks with recombinant human granulocyte/macrophage-colony-stimulating factor (rhGMCSF; 250 μg m−2 day−1) by subcutaneous injection for up to 14 days after each course. A total of 52 patients with progressive metastatic soft-tissue sarcoma were entered, none having received prior chemotherapy. One patient was ineligible and received no treatment after registration. Preliminary analysis of six cycles of chemotherapy revealed that the full protocol dose intensity had been administered to the majority of patients. Although the median leucocyte and neutrophil counts did not fall with subsequent courses of chemotherapy, the duration of neutropenia increased with each course delivered. Cumulative thrombocytopenia was a major dose-limiting toxicity and was the main reason for any dose modifications that occurred. Although 26 patients experienced infections after one or more courses of treatment, in only 7 was admission required for parenteral antibiotics. One patient died as a result of septicaemia after the first cycle of treatment. To date, there have been 22 responses (43%) with 8% complete remissions. It appears that the administration of rhGM-CSF allows this high-dose regime of chemotherapy to be given safely and the early encouraging response rate adds support to the concept that increasing the dose of doxorubicin improves the outlook for patients with advanced soft-tissue sarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01613226
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  • 5
    Electronic Resource
    Electronic Resource
    Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear (1991)
    Springer
    Pharmacy world & science 13 (1991), S. 1-6 
    Details
    ISSN: 1573-739X
    Keywords: Drug therapy ; Neoplasms ; Neurophysiology ; Pathology ; Receptors, dopamine ; Receptors, serotonin ; Vomiting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Both radiotherapy and chemotherapy for cancer are capable of causing severe nausea and vomiting, which formerly often interfered with the patient's compliance to treatment. The basic pathway and pharmacological mechanisms involved in this are still poorly understood. The recent discovery, however, that 5-HT3 receptor antagonists can prevent or greatly reduce chemotherapy-induced emesis led to a re-evaluation of the sequence of events occurring in the protective emetic reflex, which are reviewed in this paper. The vomiting centre co-ordinates the incoming and outgoing information, and is thought to be represented by complex interactions between different adjacent areas in the brainstem. Whether the main role in the emetic reflex arch is accomplished by either the central part (chemoreceptor trigger zone) or the peripheral part (gastro-intestinal tract) needs further confirmation. A more important role, however, of the vagal nerve and the gastro-intestinal tract is generally accepted. The neurotransmitter serotonin (5-HT) appears to play a major role in chemotherapy-induced emesis via the 5-HT receptor. These indications could form the basis for further investigations into the involvement of other neurotransmitters, and the character of their interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01963876
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  • 6
    Electronic Resource
    Electronic Resource
    Abstracts of papers clinical pharmacological meeting (1993)
    Springer
    Pharmacy world & science 15 (1993), S. 1-7 
    Details
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01876624
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  • 7
    Electronic Resource
    Electronic Resource
    Controlling cancer chemotherapy-induced emesis (1991)
    Springer
    Pharmacy world & science 13 (1991), S. 189-197 
    Details
    ISSN: 1573-739X
    Keywords: Adrenal cortex hormones ; Antineoplastic agents ; Benzodiazepines ; Cannabinoids ; Clinical trials ; Dopamine antagonists ; Methods ; Metoclopramide ; Nausea ; Serotonin antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3–6 mg·kg−1·d−1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01988874
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  • 8
    Electronic Resource
    Electronic Resource
    Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer (1992)
    Springer
    Breast cancer research and treatment 21 (1992), S. 133-138 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; doxorubicin ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18–67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+–60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16–20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01836959
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