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1.
J Chemother ; 23(6): 362-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22233822

RESUMO

Mitomycin C (MC) is used as therapy against solid tumors, also combined with other chemotherapeutic agents or radiotherapy. It may cause acute, subacute, or chronic anemia capable of modifying the results of chemo- and radiotherapy. Erythropoietin may be lowered by cancer itself or because of chemoradiotherapy. There are few studies investigating the relationship between erythropoietin and chronic anemia.We prospectively analyzed the chronic anemia and erythropoietin in 38 patients with solid cancer. Patients were 40 to 82 years of age. MC was randomly given every 3 weeks as a single drug at 10 or 20 mg/m². When myelotoxicity occurred the next therapy cycle was delayed until recovery. RBC indices, hemolysis, erythropoietin, liver and kidney function were studied. MC cycles were 136 (3.6 ± 1.4 per pt), 32 being delayed because of myelotoxicity.Hematocrit, hemoglobin and RBC were inversely related to the cumulative dose (r = 0.70 to 0.86; p 0.03 to 0.01) of MC. Other tests remained stable. Anemia occurred almost twofold earlier in the 20 mg/m² group (p=0.049). basal erythropoietin, already lower than in age and sex watched 81 non cancerous subjects (p<0.001), decreased during MC therapy (p<0.01). For each given MC mg/m² a 0.0372 Hb mg/dl reduction occurred. Chronic anemia due to MC is accompanied by erythropoietin reduction. These results can help in designing chemoradiotherapy.


Assuntos
Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Eritropoetina/sangue , Mitomicina/efeitos adversos , Neoplasias/sangue , Neoplasias/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Doença Crônica , Progressão da Doença , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritropoetina/análise , Feminino , Hematócrito/métodos , Hemoglobinas/análise , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Estudos Prospectivos
2.
Ann Oncol ; 17 Suppl 5: v25-28, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16807458

RESUMO

BACKGROUND: The pyrimidine antimetabolite Gemcitabine (G) (2',2'-difluorodeoxycytidine) is used against several malignancies G exerts its antitumour effect mainly by incorporation of its triphosphate metabolite (dFdCTP) into DNA. Subsequently, DNA polymerase adds one additional deoxynucleotide and DNA synthesis is interrupted. The nuclear enzymes topoisomerase I and II (TPs) are critical for DNA function and cell survival; they control, maintain and modify DNA topology during both replication and translation of genetic materials. These enzymes induce cuts in one or both strands of DNA, allowing strands to pass through the nick and then rejoining the nicked strand of DNA. Anti-topoisomerase (TPs-inhibitors) drugs exist and are largely used in chemotherapy, however, most often blindly of the cancer TPs status. AIM: To understand the best association between G and TPs-inhibitors, we studied: (a) Topoisomerases I, II alpha and II beta mRNA expression in Peripheral Mononuclear Blood Cells (PBMCs) of patients with solid tumor, after 1, 2, 3, 4, 5, 6 h after treatment with Gemcitabine (G); b) in vivo expression of TPs genes after administration of Gemcitabine (a topoisomerases up-regulating drug) combined with the TPs inhibitors drugs (TID) Topotecan (T) and Etoposide (E), added to the culture beneath 1 h after TPD treatment. TPs mRNA expression was measured by quantitative real-time RT-PCR in PBMCs. RESULTS: The administration of 1-h infused G is followed by a fast rise of TPs expression (P > 0.0001 Student's t test, paired data, each patient control of himself); TPs inhibitors, sequentially given after G, highly reduced the TPs rising (P > 0.0001). CONCLUSIONS: G induces a TPs increase. A rationale might be available for combination chemotherapy (G plus TPs inhibitors). The study is ongoing to enroll further patients.


Assuntos
Antígenos de Neoplasias/genética , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo I/genética , Proteínas de Ligação a DNA/genética , Desoxicitidina/análogos & derivados , Neoplasias/tratamento farmacológico , Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Esquema de Medicação , Inibidores Enzimáticos/administração & dosagem , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/metabolismo , Pessoa de Meia-Idade , Neoplasias/metabolismo , RNA Mensageiro/metabolismo , Fatores de Tempo , Inibidores da Topoisomerase I , Inibidores da Topoisomerase II , Gencitabina
3.
Ann Oncol ; 17 Suppl 5: v47-51, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16807462

RESUMO

BACKGROUND: Chemotherapy of non-small-cell lung cancer (NSCLC) has been improved by the use of cis-platin (P) and the pyrimidine antimetabolite gemcitabine (G) (2',2'-difluorodeoxycytidine). GP regimens currently used in Italy for NSCLC were and are mainly based on G day 1, 8 and 15; P on day 2, every 28 days (4 Day-Hospital admissions per cycle). However, the third G dose is frequently omitted because of myelo-toxicity, with a consistent dose decrease of both G and P in comparison with the intended dose. The 24-h lag time from 1(st) G and P has not reasonable clinical pharmacology base. AIM OF THE STUDY: To have a simplified GP regimen based on two Day-Hospital admissions per cycle, with G on day 1 and 8, P after G on day 8; every 21 days, with the goal to use it in the neoadjuvant setting. MATERIAL AND METHODS: The study was designed as a controlled, prospective, multicentre investigation, based on G (1500 mg/m(2)) on day 1 and 8, and P (100 mg/m(2)) on day 8 immediately following G, administered on a 3-week cycle. Quality of life (EORTC) was valuated in 46 patients out of 95 valuable patients. Restaging procedures were repeated after the 3rd and the 6th cycle. RESULTS: Enrolled patients were 105 (stage IV: 63: IIIB: 29; IIIA: 13). GP cycles were 488 (1 to 6 per patient) 95 patients had at least 3 cycles and 59 of them had further 3 cycles. Myelotoxicity >or= g3 was mainly neutropenia, easily amenable with symptomatic and GCSF therapies (12.6% neutropenic fever); PNS toxicity occurred in 17.9% of patients. QoL was ameliorated (P < 0.05). Therapy was tolerable and gave a Response Rate (RR) of 52.3% after 3 cycles (Intention-to-treat analysis) and of 57.9% in 95 valuable patients who received at least 3 therapy cycles. CONCLUSION: Present results confirm a good efficacy and/or synergism of G to P, with G on day 1 and 8 and P on day 8. This two day-hospital admissions regimen is at least as good as more complex GP regimens, and may be proposed in the neoadjuvant setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/psicologia , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Qualidade de Vida , Gencitabina
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