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  • 1
    Electronic Resource
    Electronic Resource
    Treatment of poor-prognosis extensive disease small-cell lung cancer with an all-oral regimen of etoposide and cyclophosphamide – a Southwest Oncology Group clinical and pharmacokinetic study (1999)
    Springer
    Cancer chemotherapy and pharmacology 44 (1999), S. 461-468 
    Details
    ISSN: 1432-0843
    Keywords: Key words Etoposide ; Cyclophosphamide ; Oral chemotherapy ; Pharmacodynamics ; Small-cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: An all-oral regimen of etoposide and cyclophosphamide was developed for use in poor-prognosis extensive disease small-cell lung cancer. Limited pharmacokinetic sampling was used to derive a pharmacodynamic model predictive of myelosuppression early in the course of therapy. Patients and methods: Eligible patients were chemotherapy-naive and had extensive disease small-cell lung cancer with either SWOG performance status 2 or serum albumin 〈3.5 g/dl. The first cohort (n = 18) received etoposide orally at 50 mg daily and cyclophosphamide orally at 50 mg daily days 1–14 every 28 days. Due to good hematologic tolerance, the second cohort (n = 39) received both agents orally at 50 mg twice daily days 1–14 every 28 days. Plasma etoposide levels were determined in samples drawn at baseline, and at 1 h, 2 h, and 23.5 h (trough) after the first dose. Linear regression analysis was used to determine pharmacokinetic and demographic parameters predictive of myelosuppression. Results: A total of 173 treatment cycles were delivered. Patients on the daily regimen had a 22% response rate (complete and partial), a 22% unconfirmed response rate, and a 5-month median survival, while patients on the twice-daily regimen had a 28% response rate (complete and partial), a 13% unconfirmed response rate, and a 7-month median survival. Granulocytopenia and alopecia were the most common toxicities seen. Significant granulocytopenia could be predicted for the twice-daily regimen according to the formula ln(AGC nadir)=7.80 − 1.88(trough), with an increased incidence of granulocytopenia if the etoposide trough value was ≥1.49 μg/ml. Conclusion: Oral etoposide and oral cyclophosphamide given days 1–14 every 28 days is well tolerated and results in an acceptable response rate and median survival in poor-prognosis (poor performance status or low serum albumin) extensive disease small-cell lung cancer. A trough etoposide level obtained within 24 h of starting therapy can predict severe granulocytopenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051119
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  • 2
    Electronic Resource
    Electronic Resource
    Synchronous multicentric osteosarcoma: the case for metastases (1997)
    Springer
    Skeletal radiology 26 (1997), S. 569-578 
    Details
    ISSN: 1432-2161
    Keywords: Key words Osteosarcoma ; Multicentric ; Metastatic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. There is a current debate whether multicentric osteosarcoma represents synchronous multiple primary osteosarcomas or metastatic disease. The purpose of this report is to evaluate the etiology, presentation, and classification of this entity. Design and patients. Six patients ranging in age from 7 to 29 years were studied. The clinical, radiographic, and pathologic findings are reported. In addition, a review of the literature was undertaken. Results. The clinical courses of our six patients as well as a review of the literature suggest that multicentric osteosarcoma represent one extreme of a continuous scale of metastatic osteosarcoma rather than multiple synchronous primary tumors. The presentation is unusual and the clinical behavior distinctive, but the mechanism of spread remains the same: blood-borne and lymphatic-borne. Conclusions. Our experience with these six patients supports the concept in the recent literature that synchronous osteosarcoma is one extreme of the spectrum of metastatic osteosarcoma. Its unique features are: (1) multiple radiodense lesions that present simultaneously with or without pulmonary metastases; (2) a single ”dominant” lesion with multiple smaller lesions; and (3) a uniformly rapid, fatal prognosis. Osteosarcoma should be regarded as a metastatic disease, even when only a single primary lesion is found at the initial presentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560050289
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study (1997)
    Springer
    Cancer chemotherapy and pharmacology 41 (1997), S. 75-78 
    Details
    ISSN: 1432-0843
    Keywords: Key words Edatrexate ; Carboplatin ; Non-small-cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose-limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m2 (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m2 every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3–4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13%). The median survival time was 7 months, and 30% of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050710
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    A phase II trial of intravenous vinorelbine in previously untreated patients with extensive small cell lung cancer, a southwest oncology group study (1997)
    Springer
    Investigational new drugs 15 (1997), S. 153-156 
    Details
    ISSN: 1573-0646
    Keywords: Author, please supply keywords
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Twenty-two eligible patients with previously untreated extensive small cell lung cancer received intravenous vinorelbine 30 mg/M2 each week until progression. Response was assessed every 4 weeks by chest x-ray or every 8 weeks by CT scan. All responses had to be “confirmed” at all involved sites at least 4 weeks later. Fourteen patients were male and 8 were female with a Median age of 64.5 years (range 38-76). Fifteen patients were Caucasian and 7 were African-American. One patient had a ”confirmed” partial response, 3 had unconfirmed responses, 13 had stable or progressive disease, and 5 did not have adequate data. The median progression-free survival was 3 months with a median overall survival of 8 months. Thirteen patients experienced 22 episodes of grade 3 toxicity, more than half due to leukopenia and neutropenia, and 1 due to paresthesias. Of 4 episodes of grade 4 toxicity, 1 was due to leukopenia and 3 were due to hyponatremia which was not due to vinorelbine. Significant thrombocytopenia did not occur. The activity of single agent vinorelbine in untreated small cell lung cancer was disappointing when analyzed by Southwest Oncology Group (SWOG) criteria. The median survival in this trial was similar to that found in other SWOG trials using cisplatin based front line therapy and thus confirms previously reported findings that initial treatment with a phase II agent followed by a cisplatin based regimen at progression does not adversely affect overall survival in this population of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005869008452
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