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Anticancer Drugs ; 10(3): 257-61, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10327029


Cisplatin is the most important drug in the treatment of advanced ovarian cancer. The role of anthracyclines is controversial. We compared a combination of epirubicin plus cisplatin (EP) with a regimen of cyclophosphamide, epirubicin and cisplatin (CEP). Patients with stage Ic-IV ovarian cancer were randomized to receive either epirubicin 100 mg/m2 plus cisplatin 75 mg/m2 q 4 weeks or cyclophosphamide 500 mg/m2 plus epirubicin 75 mg/m2 plus cisplatin 50 mg/m2 q 4 weeks, which we considered the reference treatment based on our previous experience. Patients were initially debulked, followed by six cycles of chemotherapy, or in case primary debulking was insufficient or considered inappropriate, secondary debulking was attempted in selected cases after sufficient chemotherapy-induced regression. Optimal debulking was defined as residual lesions < or = 2 cm. A total of 210 patients (191 eligible) were randomized. Results did not show significant differences in all major endpoints (pathologically documented complete response and survival). The median survival for all patients was 34 months, for patients with stage III 26 months, for patients with stage IV 20 months and it has not been reached for patients with stage Ic-II. As no significant differences between an equitoxic regimen of EP and CEP were detected, it might be more useful to look again at the anthracyclines as part of combination chemotherapy instead of the alkylating agents.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Humanos , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Análisis de Supervivencia
Chem Phys Lipids ; 70(2): 133-45, 1994 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-8033285


In this study, 2H and 31P-NMR techniques were used to study the effects of trehalose and glycerol on phase transitions and lipid acyl chain order of membrane systems derived from cells of E. coli unsaturated fatty acid auxotroph strain K1059, which was grown in the presence of [11,11-2H2]-oleic acid or [11,11-2H2]-elaidic acid. From an analysis of the temperature dependence of the quadrupolar splitting it could be concluded that neither 1 M trehalose or glycerol generally had any significant effect on the temperature of the lamellar gel to liquid-crystalline phase transition. In the case of the oleate-containing hydrated total lipid extract, glycerol but not trehalose caused a 5 degrees C increase of this transition temperature. In general, both cryoprotectants induced an ordering of the acyl chains in the liquid-crystalline state. Trehalose and glycerol both decrease the bilayer to non-bilayer transition temperature of the hydrated lipid extract of oleate-grown cells by about 5 degrees C, but only trehalose in addition induces an isotropic to hexagonal (HII) phase transition. In the biological membranes, trehalose and not glycerol destabilised the lipid bilayer, and in the case of the E. coli spheroplasts, part of the induced non-bilayer structures is ascribed to a hexagonal (HII) phase in analogy with the total lipids. Interestingly, 1 mM Mg2+ was a prerequisite for the destabilisation of the lipid bilayer. In the hydrated total lipid extract of E. coli grown on the more ordered elaidic acid, both transition temperatures were shifted about 20 degrees C upwards compared with the oleate-containing lipid, but the effect of trehalose on the lipid phase behaviour was similar. The bilayer destabilising ability of trehalose might have implications for the possible protection of biological systems by (cryo-)protectants during dehydration, in that protection is unlikely to be caused by preventing the occurrence of polymorphic phase transitions.

Escherichia coli/efectos de los fármacos , Escherichia coli/ultraestructura , Membrana Dobles de Lípidos/química , Trehalosa/farmacología , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Fenómenos Químicos , Química Física , Frío , Deuterio , Ácidos Grasos/química , Glicerol/farmacología , Calefacción , Lípidos/química , Espectroscopía de Resonancia Magnética/métodos , Membranas Artificiales , Modelos Biológicos , Fosfolípidos/química , Fósforo
Ann Oncol ; 4(4): 295-301, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8518219


BACKGROUND: The Comprehensive Cancer Center trial 82-01 is a prospective randomized study to investigate the value of the addition of high-dose medroxyprogesterone acetate (MPA) to chemotherapy in patients with node-positive operable breast cancer. MPA may be of advantage in this setting because of its activity in estrogen receptor ER-positive as well as ER-negative tumors and since it may protect against chemotherapy-induced myelosuppression and thus enable maintenance of the appropriate chemotherapeutic scheduling. PATIENTS AND METHODS: Four hundred eight evaluable patients with node-positive (N+) operable breast cancer (T1-3, N1) were entered in a multicenter randomized trial. Two hundred nine patients were randomized in the MPA- arm and 199 in the MPA+ arm. CAF chemotherapy was given as a short i.v. bolus infusion: cyclophosphamide 500 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. day 1, and 5-fluorouracil 500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly (i.m.) 500 mg q d x 28 days, followed by 500 mg i.m. twice weekly during 5 months. RESULTS: The main side effects of MPA were weight gain with a mean of 5.5 kg as opposed to 1.8 kg in the control group (p = 0.01) and vaginal bleeding in 30/199 in the MPA+ group and 0 in the MPA- group. MPA ameliorated vomiting grade III, IV (45% vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p < 0.001) and leucocyte nadir grade III, IV (20% vs. 11%, p = 0.003). Disease-free survival (DFS) after 5 years was 59% in the MPA+ and 49% in the MPA- group (p = 0.12). Patients > or = 60 years benefitted most from MPA treatment, in particular if freedom from distant metastases was taken as the endpoint (p = 0.02). Overall survival (OS) was not significantly different between the two treatment groups (p = 0.18), but within subgroups analysed there was an advantage for MPA+ in patients > or = 55 years (p = 0.002) and in pT1 patients (p = 0.045). CONCLUSIONS: High-dose MPA ameliorates CAF side effects and reduces the risk of metastatic disease, especially in elderly breast cancer patients.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Acetato de Medroxiprogesterona/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia
Cancer Invest ; 11(1): 1-5, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8422593


Between January 1985 and May 1988, 87 patients with stage III-IV ovarian carcinoma were entered in a study assessing chemotherapy consisting of cyclophosphamide, 500 mg/m2, epirubicin, 75 mg/m2, and cisplatin, 50 mg/m2, intravenously (IV) on day 1, every 4 weeks (CEP-1). The results after a median follow-up of 4 years are presented. The pathologically complete remission rate was 36%. The median survival of all patients was 26 months. For patients with stage III disease debulked to lesions < or = 1.5 cm before the initiation of chemotherapy (n = 35), the median survival was 61+ months. These data are not clearly different from the results of a previous study conducted by our group utilizing CAP-1 chemotherapy.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología