ABSTRACT
Secretion of gelatinases A (MMP-2) and B (MMP-9) from 21 tumoral explants of squamous cell carcinoma (SCC) and five samples of normal mucosa of the oral cavity is demonstrated here. The explants were cultured into fetal bovine serum- and phenol red-deprived medium for 48 hours. The gelatinases secreted into the medium were revealed and quantified by zymography and densitometry, respectively. The results showed high medians of the 66 kDa forms of gelatinase A in tumoral explants, in comparison to normal explants: 31.0 vs 5.9 densitometric units (DU) (p <0.01). There was also a relatioship between clinical response to neo-adjuvant chemotherapy and low activity of 66 kDa form of gelatinase A, as well as 84 kDa and 92 kDa forms of gelatinase B. The median of gelatinolysis of the inactive form of gelatinase A (72 kDa form) was higher in those patients who exhibited a complete response to neo-adjuvant chemotherapy. We conclude that gelatinase A is a useful and objective tool to evaluate the response to chemotherapy and the aggressiveness of carcinomas of the oral cavity.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/enzymology , Chemotherapy, Adjuvant , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mouth Neoplasms/enzymology , Neoadjuvant Therapy , Neoplasm Proteins/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Culture Media, Conditioned/chemistry , Culture Media, Serum-Free , Electrophoresis, Polyacrylamide Gel , Female , Humans , Male , Mouth Neoplasms/drug therapy , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Treatment Outcome , Tumor Cells, Cultured/metabolismABSTRACT
Antecedentes. El carcinoma avanzado de pene es un tumor con un pronóstico malo con el tratamiento estándar por lo que la quimioterapia neoadyuvante se ha estado evaluando para mejorar la preservación del órgano y la supervivencia. Caso clínico. Paciente de 56 años visto en el Instituto Nacional de Cancerología en noviembre de 1993 siendo diagnosticado de cáncer de pene T3 N3 MO. El tratamiento consistió en cisplatino 100 mg/m2 cada 21 días por cinco ciclos alternados con metotrexato intravenoso a dosis de 250 mg/m2 más rescate con leucovorín oral a dosis de 10 mg/m2 cada ocho horas por seis dosis. El metotrexato y leucovorín se administraron cada 15 días en siete ocasiones. Además recibió interferón-alfa 4.5 x 10 6 U por vía subcutánea cada tercer día durante las 12 semanas del tratamiento. Resultados. El tratamiento fue bien tolerado alcanzando una respuesta clínica del 70 por ciento en el tumor primario y completa en los ganglios inguinales. Fue sometido a penectomía radical en abril de 1994 y actualmente está libre de enfermedad a los 61 meses de seguimiento. Conclusiones. Esta modalidad de quimioinmunoterapia parece ser muy activa en el cáncer de pene y debería evaluarse en un número mayor de pacientes con el fin de preservar el órgano e incrementar la supervivencia
Subject(s)
Humans , Male , Aged , Interferon-alpha/administration & dosage , Interferon-alpha/therapeutic use , Leucovorin/administration & dosage , Leucovorin/therapeutic use , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Penile Neoplasms/drug therapy , Chemotherapy, Adjuvant , SurvivorsABSTRACT
BACKGROUND: Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). METHODS: Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. Plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and bioavailability parameters were calculated. RESULTS: Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 +/- 0.30 micrograms/mL, AUC was 12.87 +/- 2.02 micrograms/mL and half-life was 6.72 +/- 0.97 h. CONCLUSIONS: Considering that the pharmacokinetic aim is to maintain plasma concentrations between 0.5 and 1.0 microgram/mL for several hours while avoiding high concentrations, i.e., of 10 micrograms/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Economics, Pharmaceutical , Etoposide/pharmacokinetics , Administration, Oral , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Biological Availability , Etoposide/administration & dosage , Etoposide/therapeutic use , Female , Humans , Injections, Intravenous , Male , Middle Aged , SolutionsABSTRACT
From April 1993 to September 1993, 15 patients with lymphoid or solid neoplasms underwent 16 non-cryopreserved peripheral stem cell transplantation courses using the ICE (ifosfamide, carboplatin, etoposide) program. They were randomized in a double-blind clinical trial to received oral misoprostol or placebo for mucositis prophylaxis. The active drug or placebo administration began jointly with chemotherapy at day -4 and was continued until day 16. The mucositis incidence and severity was significantly higher in patients who received misoprostol. We found no differences regarding myelosuppression, infections or other chemotherapy complications. Our results do not support the use of oral misoprostol as administered in this study, for high-dose chemotherapy-induced mucositis prophylaxis.
