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  • 1
    ISSN: 1432-0843
    Keywords: 5-Fluorouracil ; Interferon ; Colorectal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standard treatment approach in patients with metastatic colorectal cancer. Modulation of FUra with interferon alfa has also shown some promise. Laboratory data have demonstrated increased cytotoxicity when FUra is combined with both LV and interferon. The current study examined the effects of double modulation of FUra using LV and interferon. Patients with measurable advanced colorectal cancer received bolus FUra 375 mg/m2 plus LV 20 mg/m2 daily for 5 days, repeated every 28 days. Recombinant human interferon alfa-2a, 3 million IU/m2 subcutaneously, was given daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% CI 12.0–40.0%). Overall, 70% of patients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P〈0.0001). Improvements in tumor-related symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressive changes in FUra metabolism from interferon usage.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: Key words 5-Fluorouracil ; Interferon ; Colorectal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standard treatment approach in patients with metastatic colorectal cancer. Modulation of FUra with interferon alfa has also shown some promise. Laboratory data have demonstrated increased cytotoxicity when FUra is combined with both LV and interferon. The current study examined the effects of double modulation of FUra using LV and interferon.Patients with measurable advanced colorectal cancer received bolus FUra 375 mg/m2 plus LV 20 mg/m2 daily for 5 days, repeated every 28 days. Recombinant human interferon alfa-2a, 3 million IU/m2 subcutaneously, was given daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% CI 12.0–40.0%). Overall, 70% of patients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P〈0.0001). Improvements in tumor-related symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressive changes in FUra metabolism from interferon usage.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-7339
    Keywords: Key words Quality of life ; Chemotherapy ; Cancer ; Nausea ; Vomiting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose was to measure the effects of postchemotherapy nausea and vomiting (PCNV) on health-related quality of life (HQL) in patients receiving either moderately or highly emetogenic chemotherapy. The study sample consisted of 832 chemotherapy-naive patients with cancer who received either moderately or highly emetogenic chemotherapy as part of multicenter trials of new antiemetics. The patients completed the self-report European Organization for Research and Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) before chemotherapy (baseline) and 1 week (day 8) and 2–4 weeks after chemotherapy. They also completed a self-report nausea and vomiting (NV) diary for 5–7 days after chemotherapy. To determine the effects of PCNV on HQL, the change in scores between the baseline and day 8 HQL assessments was calculated for each domain and symptom in the QLQ-C30 and compared in four subgroups of patients: those with both nausea and vomiting, those with nausea but no vomiting, those with no nausea but with vomiting, and those with neither nausea nor vomiting. The group with both nausea and vomiting showed statistically significantly worse physical, cognitive and social functioning, global quality of life, fatigue, anorexia, insomnia and dyspnea as compared to the group with neither nausea nor vomiting (0.0001〈P〈0.05). Patients with only nausea but no vomiting tended to have less worsening in functioning and symptoms than those having both nausea and vomiting. Increased severity of vomiting (〉2 episodes) was associated with worsening of only global quality of life and anorexia as compared with 1–2 episodes of vomiting (0.0001〈P〈0.01). By 2–4 weeks after chemotherapy all HQL scores had either returned to their baseline levels or were better than baseline. PCNV adversely affects several quality-of-life domains, but patients with only nausea experience less disruption than do those with both nausea and vomiting. Patients with 1–2 episodes of vomiting experience almost the same degree of disruption of HQL as do patients with more than 2 episodes of vomiting.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; hormone independent ; liarozole ; metastatic breast cancer ; RAMBA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three phase II studies were conducted to determine the efficacy and tolerability of liarozole fumarate (R85246; liarozole), a retinoic acid metabolism blocking agent (RAMBA) and aromatase inhibitor. Additionally, animal experiments in the MNU-induced rat mammary tumor model and in immature ovariectomized rats were conducted to further elucidate liarozole's mechanisms of action. Patients were postmenopausal with either: ER negative disease in first relapse (Group 1; n = 16); ER positive or unknown disease refractory to tamoxifen (Group 2; n = 16); ER positive, negative or unknown disease resistant or refractory to chemotherapy (Group 3; n = 27). Treatment was liarozole (150–300 mg) twice daily orally until disease progression. Response rates were: 25% in group 1 (95% CI 11.0–52.3%; median duration (MD) 20 months; range 2–36.5); 25% in group 2 (95% CI 11.0–52.3%; MD 6.5 months; range 3.5–38); 11% in group 3 (95% CI 4.2–29.2%; MD 7 months; range 3–8.5). No significant improvement in quality of life scores (FLI-C) was noted. Toxicities observed were predominantly dermatological (skin disorders: 88%; dry mouth/eyes/lips: 69%). Plasma estradiol decreased from mean pre-treatment levels of 72.7 pM (9.1–1839 pM) to below detection (9.2 pM) after 1 month. Liarozole, but not vorozole, partially inhibited estradiol induced uterine hypertrophy and demonstrated dose-dependent anti-tumor effects in the rats, only partially overcome by coadministration of estradiol. The clinical responses observed, together with our preclinical results, confirm liarozole's dual mechanism of action and provide a rationale for further evaluation of RAMBAs in the treatment of breast cancer.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; folinic acid ; 5FU ; metastatic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Standard combination chemotherapy for metastatic breast cancer produces response rates between 30–60% with limited impact on survival. We undertook a phase II trial to determine the activity of 5 fluorouracil (5FU) and folinic acid (FA) in patients with measurable metastatic or recurrent breast cancer who had received no prior chemotherapy. Patients meeting the eligibility criteria received 5FU 370 mg/m2/day and FA 200 mg/m2/day for 5 days repeated every 28 days, toxicity allowing. Response defined by standard criteria was assessed every 8 weeks and toxicity according to WHO criteria was determined on every course. Thirty-three patients were entered on trial. Thirty-two patients were evaluable for response and 33 for toxicity. The dose limiting toxicity was stomatitis with 7/32, 19/32, and 5/32 patients experiencing grade 1, 2, and 3 toxicity. Grades 1 and 2 diarrhea occurred in 17/32 and 11/32 patients respectively. Myelosuppression was not significant. Two complete and 11 partial responses were observed. The overall response rate was 41% (95% CI, 24–58%). Responses were seen in soft tissue and visceral sites. Patients who had received adjuvant chemotherapy more than 6 months prior to receiving 5FU and FA responded also. Six of 29 patients receiving standard combination chemotherapy as second line treatment responded subsequently. We concluded: 1) 5FU and FA is an active combination in the treatment of breast cancer warranting further evaluation in combination with other drugs; 2) the dose-limiting toxicity of stomatitis is tolerable; 3) patients receiving 5FU and FA as first line therapy can respond to conventional combination chemotherapy as second line treatment.
    Type of Medium: Electronic Resource
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