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  • Chronic myelogenous leukemia  (3)
  • chemotherapy  (3)
  • treatment toxicity and mortality  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Comparison of different ribozymes for efficient and specific cleavage of BCR/ABL related mRNAs
    Amsterdam : Elsevier
    FEBS Letters 338 (1994), S. 175-178 
    Details
    ISSN: 0014-5793
    Keywords: BCR/ABL ; Chronic myelogenous leukemia ; Ribozyme
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0014-5793(94)80359-5
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  • 2
    Electronic Resource
    Electronic Resource
    Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 57-64 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; non-small-cell lung cancer ; peripheral blood stem cell transplantation ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I/II trial to assess the feasibilityand activity of combination chemotherapy with etoposide, ifosfamide,cisplatin, and epirubicin in limited-stage (LS, stage I–IIIB) andextensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-pointswere treatment-related morbidity and mortality, response rate, duration ofresponse, and survival. Patients and methods: Chemotherapy followed by granulocytecolony-stimulating factor was given at a dose of etoposide (500mg/m2), ifosfamide (4000 mg/m2), cisplatin (50mg/m2), and epirubicin (50 mg/m2) (VIP-E) to107 patients with NSCLC. Twenty-five patients with qualifying responsesproceeded to high-dose chemotherapy with autologous peripheral blood stem celltransplantation after etoposide (1500 mg/m2), ifosfamide(12,000 mg/m2), carboplatin (750 mg/m2) andepirubicin (150 mg/m2) (VIC-E) conditioning. Results of conventional-dose VIP-E: 35 of 102 (34%) evaluablepatients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed nochange (NC); the remainder of patients progressed with therapy (PD). Objectiveresponse rate was 68% (4% CR, 64% PR) in LS-NSCLC and23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration ofsurvival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-yearsurvival was 26% in LS and 2% in ES-NSCLC. Results of high-dose VIC-E: 23 of 24 evaluable patients improved ormaintained prior responses (92%), 1 patient showed NC. Treatmentmortality was 4%. Median duration of survival was 17 months in LS-NSCLCand 10 months in ES-NSCLC. Two-year survival was 30% in LS and8% in ES-NSCLC. Conclusion: Response-rates and survival after conventional-dose VIP-Echemotherapy are comparable to other published trials of combinationchemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage,but unacceptably high in extensive stage NSCLC. Although better response-rateswere achieved in the high-dose arm, they did not translate into improvedsurvival. Most stage IV NSCLC-patients will neither benefit from VIP-Econventional dose, nor from VIC-E high dose chemotherapy. Whether selectedLS-patients with partial or complete responses to VIP-E induction chemotherapycould benefit from dose intensification in an adjuvant or neo-adjuvant settingremains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008209713568
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  • 3
    Electronic Resource
    Electronic Resource
    Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 49-56 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I/II trial to assess the feasibilityand activity of VIP-E chemotherapy in small-cell lung cancer. End-points weretreatment-related morbidity and mortality, response to treatment, duration ofresponse, and survival. Patients and methods: Two cycles of combination chemotherapy followedby granulocyte colony-stimulating factor (G-CSF) were given at a dose ofetoposide (500 mg/m2), ifosfamide (4000mg/m2), cisplatin (50 mg/m2), and epirubicin(50 mg/m2) to 100 consecutive patients with SCLC. Thirtypatients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dosechemotherapy with autologous peripheral blood stem cell transplantation(PBSCT) at a cumulative dose of etoposide 1500 mg/m2,ifosfamide 12,000 mg/m2, carboplatin 750 mg/m2and epirubicin 150 mg/m2 (VIC-E). Surgical resection ofprimary tumor was attempted at the earliest feasible point. Thoracicirradiation was given after completion of chemotherapy. Results of conventional-dose VIP-E: 97 patients were evaluable forresponse. Objective response rate was 81% in LD-SCLC (33% CR,48% PR; excluding patients in surgical CR) and 77% in ED-SCLC(18% CR, 58% PR). Treatment mortality was 2%. Mediansurvival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survivalwas 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: All 30 patients improved on or maintainedprior responses. Four patients (13%) died of treatment-relatedcomplications. Median survival was 26 months in LD-SCLC and 8 months inED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC. Conclusion: VIP-E chemotherapy is an effective induction therapy forSCLC. Compared with traditional protocols such as ACO orcarboplatin/etoposide, response rates are slightly improved, while survivalis not different. In the LD SCLC subgroup, high-dose chemotherapy improvedresponse rates and survival, especially for patients in surgical CR prior tohigh-dose therapy. In ED SCLC, however, higher response-rates did nottranslate into improved survival. Selected LD-SCLC patients with good partialor complete remissions after prior therapy may benefit from HDC and PBSCT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008232329498
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  • 4
    Electronic Resource
    Electronic Resource
    Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation (1991)
    Springer
    Annals of hematology 63 (1991), S. 189-194 
    Details
    ISSN: 1432-0584
    Keywords: Chronic myelogenous leukemia ; Allogeneic bone marrow transplantation ; Minimal residual disease ; BCR/ABL mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosomepositive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 104–5 to one cell in 105–6. Eight of 16 patients were negative by two-step PCR 1–39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01703441
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  • 5
    Electronic Resource
    Electronic Resource
    Bcl-2 mRNA-targeted ribozymes: effects on programmed cell death in chronic myelogenous leukemia cell lines (1998)
    Springer
    Annals of hematology 76 (1998), S. 117-125 
    Details
    ISSN: 1432-0584
    Keywords: Key words bcl-2 ; Ribozymes ; Programmed cell death ; Chronic myelogenous leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used synthetic RNA transcripts to prove the cleavage capability of ribozymes targeted against bcl-2-related RNAs. No cleavage occurred when control oligonucliotides were used. To assess the functional role of the specific ribozymes in chronic myelogenous leukemia (CML) cell lines we cultured K562, BV173, and Daudi cells for 48 h after lipofection with 10 μM oligonucleotide. An increase in apoptotic cells, dependent on ribozyme specificity, was shown in BV173 cells.This finding was underlined by the typical morphological changes, but there is no correlation with regard to the level of bcl-2 protein expressed. Though bcl-2 appears to interfere with cell death in myeloid cells, bcl-2-targeted ribozymes do not induce programmed cell death (PCD) by reducing bcl-2 protein levels, but rather by a presently unknown mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050375
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  • 6
    Electronic Resource
    Electronic Resource
    Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report (1999)
    Springer
    Annals of oncology 10 (1999), S. 561-567 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem-cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC. Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR 〉2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026453922931
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