RESUMEN
Interferon (IFN) has been shown to enhance the cytotoxic effects of 5-fluorouracil (5FUra) in colorectal cancer, and clinical trials with this combination resulted in higher response rate with respect to 5FUra alone. IFN is generally administered s.c. three times a week. This prolonged exposure could determine a block of tumor cells in the G0-G1 phase of the cell cycle, thus rendering tumor cells insensitive to 5FUra, an S-phase specific agent. In order to verify the presence of this block, 21 operable colorectal cancer patients were treated with IFN-alpha 2b at the dose of 3 megaunits every other day in the week before operation, while another 22 represented the control group. Samples of tumor tissue were taken at endoscopy and operation. [3H]Thymidine labeling index and flow cytometry were used to assess the S-phase fraction. In IFN treated patients, we found a significant statistical difference between the mean percentage of S-phase fractions evaluated either by labeling index (P = 0.00001) or by flow cytometry (P < 0.001). On the contrary, this difference was not present in the control group: labeling index, P = 0.06; flow cytometry, P = 0.08. Furthermore a significant increase in the G0-G1 phase of the cell cycle was found after IFN administration (P < 0.001) but not in the control group. Our results suggest that IFN reduces the S-phase fraction in colorectal cancer tumors. This action should be considered in the design of the 5FUra/IFN combination because it could decrease 5FUra activity, leading to a loss or a decrease in the advantage of 5FUra modulation by IFN.
Asunto(s)
Neoplasias Colorrectales/terapia , Fluorouracilo/farmacología , Interferón-alfa/farmacología , Adulto , Anciano , Ciclo Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Interacciones Farmacológicas , Citometría de Flujo , Humanos , Interferón alfa-2 , Persona de Mediana Edad , Proteínas Recombinantes , Fase S/efectos de los fármacosRESUMEN
PURPOSE: To evaluate the effect of exogenous recombinant human erythropoietin (rHuEPO) on the increase of hemoglobin levels and on the transfusion requirements in patients with cisplatin (CDDP)-induced anemia, we performed a double-blind randomized trial with placebo. PATIENTS AND METHODS: One hundred patients with CDDP-associated anemia (hemoglobin level < 90 g/L) were randomized to receive either placebo (saline solution) or rHuEPO (100 U/kg body weight subcutaneously) three times per week. The end points of this study were the increase in hemoglobin levels to greater than 100 g/L after 3, 6, and 9 weeks and the effect on transfusion requirements. RESULTS: Ninety-nine of 100 patients were assessable for response and toxicity. In the rHuEPO arm, mean hemoglobin levels were statistically significantly increased after the third, sixth, and ninth weeks of therapy (101.1 +/- 9.0, 102.4 +/- 6.6, and 105.1 +/- 9.4 g/L, respectively) compared with the mean baseline value (86.3 +/- 6.2 g/L). In the placebo arm, there were no increases in mean hemoglobin levels at the third, sixth, and ninth weeks (81.0 +/- 5.2, 81.3 +/- 9.2, and 81.2 +/- 11 g/L, respectively) compared with the mean baseline value (87.3 +/- 5.2 g/L). Furthermore only 20% of patients required blood transfusions in the rHuEPO arm versus 56% of patients in the placebo arm (P = .01), with a mean units of blood transfused per patient of 0.30 in the rHuEPO arm and 1.8 in the placebo arm (P = .01). Treatment was well tolerated, with no significant side effects. CONCLUSION: CDDP-induced anemia is corrected by rHuEPO, which results in reduced blood transfusion requirements.
Asunto(s)
Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Cisplatino/efectos adversos , Eritropoyetina/uso terapéutico , Adulto , Anciano , Anemia/sangre , Transfusión Sanguínea , Método Doble Ciego , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Placebos , Proteínas Recombinantes/uso terapéuticoRESUMEN
PURPOSE: We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity. PATIENTS AND METHODS: Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment. RESULTS: At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH. CONCLUSION: This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.
Asunto(s)
Cisplatino/efectos adversos , Glutatión/farmacología , Sistema Nervioso/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Cisplatino/administración & dosificación , Cisplatino/antagonistas & inhibidores , Método Doble Ciego , Esquema de Medicación , Femenino , Glutatión/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/patologíaRESUMEN
A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i.v. on days 1-4; 400 mg/m2 5-fluorouracil i.v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i.v. on days 2, 3, 5, and 6. Interferon-alpha 2b at a dose of 3 million U was given i.m. daily for the 6 days of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence interval 2-28%): In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to be effective, as it results in severe toxicity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Proyectos Piloto , Proteínas Recombinantes , Inducción de RemisiónRESUMEN
To evaluate the impact of chemotherapy in terms of feasibility and activity in elderly patients, we treated 120 patients aged 70 years or older with advanced cancer in six major organ sites (breast, colorectum, lung, stomach, ovary, and head and neck). Furthermore, we compared the results in this age group with those in 120 patients with similar clinical features receiving the same chemotherapeutic combinations but whose age was under 70. Our results show that chemotherapeutic regimens routinely used in younger patients yield the same benefits and levels of toxicity in older patients. In none of the different organ sites, in fact, did we observe a higher incidence or severity of side effects, nor were there differences in response rate and survival. In conclusion, elderly cancer patients who are not suffering from medical complications, which are generally increased in aged patients (e.g., cardiovascular, pulmonary, renal, or neurological diseases), can be considered candidates for full doses of chemotherapy, like their younger counterparts.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Actividades Cotidianas , Adulto , Factores de Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias del Colon/tratamiento farmacológico , Comorbilidad , Estudios de Factibilidad , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Incidencia , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Inducción de Remisión , Neoplasias Gástricas/tratamiento farmacológico , Tasa de SupervivenciaRESUMEN
Teniposide (VM26) has been claimed to be active with a moderate toxicity in elderly patients affected by small-cell lung cancer (SCLC). Twenty-two patients with SCLC older than 65 years received VM26 as first-line chemotherapy at a dose of 60 mg/m2 on 5 consecutive days every 3 weeks. Age distribution ranged from 67 to 80 years (median 72 years). Fourteen patients were men and eight were women. Twelve patients had limited disease (LD) and ten extensive disease (ED). One patient (LD) had a complete response, and four (3 LD, 1 ED) achieved a partial response for an overall response rate of 22.7% (95% CI 6-40%). The most frequent toxicity was myelosuppression: 20 and 15% of patients had grade 3 leukopenia and thrombocytopenia, respectively. Our results seem to suggest that VM26 by this schedule is moderately effective in elderly patients with SCLC, and it cannot be recommended as a routine treatment.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Tenipósido/uso terapéutico , Anciano , Anciano de 80 o más Años , Alopecia/inducido químicamente , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Médula Ósea/efectos de los fármacos , Carcinoma de Células Pequeñas/patología , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Leucopenia/inducido químicamente , Neoplasias Pulmonares/patología , Masculino , Náusea/inducido químicamente , Estadificación de Neoplasias , Inducción de Remisión , Tasa de Supervivencia , Tenipósido/administración & dosificación , Tenipósido/efectos adversos , Trombocitopenia/inducido químicamente , Vómitos/inducido químicamenteRESUMEN
To assess the possibility of increasing the detection rates of cytological examination in malignant effusions by the selection of specific tumor markers for a given type of tumor, we measured CEA, CA 19.9, CA 15.3, MCA, PSA, and AFP in malignant effusions from 89 patients with the following primary malignancies: colon, stomach, breast, liver, prostate, lung, and kidney. Cytological examination was positive in only 35 of 89 patients (40%), while the tumor markers were positive in 72 of 89 cases (80%). However, apart from small cell lung and kidney cancers, where the lack of a specific tumor marker resulted in no advantage, in the other types of tumors, the specific marker for each tumor identified correctly malignant effusions in 72 of 74 cases (97%). In fact, CEA was positive in 11 of 11 effusions induced by colorectal cancer; CA 19.9 in 28 of 30 gastric cancer effusions, while MCA and CA 15.3 were positive in breast cancer effusions (16/22 and 20/22). Finally, elevated AFP and PSA indicated hepatocellular and prostate cancer, respectively. In conclusion, in cancer patients with elevated effusion levels of specific tumor markers, the effusions could be considered of a malignant nature even without cytologically demonstrable tumor cells.
Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores , Líquido Ascítico/química , Biomarcadores de Tumor/análisis , Neoplasias/complicaciones , Derrame Pericárdico/química , Derrame Pleural Maligno/química , Adulto , Anciano , Antígenos de Neoplasias/análisis , Líquido Ascítico/etiología , Antígeno CA-19-9/análisis , Antígeno Carcinoembrionario/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Derrame Pericárdico/etiología , Derrame Pleural Maligno/etiología , Antígeno Prostático Específico/análisis , Sensibilidad y Especificidad , alfa-Fetoproteínas/análisisRESUMEN
A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN) was conducted in 15 advanced colorectal cancer patients refractory to a bolus regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600 mg/m2 administered concomitantly with LV at 500 mg/m2 over a 24 h period. IFN-alpha 2b was administered by 24 h infusion from the second cycle at escalating dose (4.5, 9, 18 and 27 MU/m2). The maximum tolerated dose of IFN was 18 MU/m2. At 27 MU/m2 two patients complained of diarrhea grade 3, so that the escalation of IFN dose was stopped. Two patients achieved a partial response (IFN level dose 9-18 MU/m2). Eight patients had stable disease. Pharmacokinetics of 5-FU were not influenced by IFN at any level dose. Our results show that doses of IFN of 18 MU/m2 given by a 24 h infusion can be administered safely to an established and active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been planned to define the level of activity of this regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Área Bajo la Curva , Carcinoma/patología , Neoplasias Colorrectales/patología , Diarrea/inducido químicamente , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacocinética , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Leucovorina/administración & dosificación , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Estomatitis/inducido químicamenteRESUMEN
Octreotide, a somatostatin analogue, has been shown to inhibit the growth of gastrointestinal cancers in vitro and in vivo. To assess the anti-tumour effect of octreotide, we performed a randomised trial comparing octreotide with best supportive care in advanced gastrointestinal cancer patients refractory to chemotherapy. A total of 107 patients with advanced gastrointestinal cancer refractory to chemotherapy were randomised to receive octreotide at the dose of 200 micrograms three times a day for 5 days a week, or the best supportive care only. The primary outcome variable was the survival duration. Response rate was an outcome variable of secondary importance. Fifty-five patients (15 stomach, 16 pancreas, 24 colon-rectum) received octreotide, while 52 (14 stomach, 16 pancreas, 22 colon-rectum) received the best supportive care. Patients treated with octreotide had a significant advantage in duration of survival with a median survival time of 20 weeks vs 11 in the control group (P < 0.0001). This advantage was present also considering the survival data for each tumour group. Twenty-five patients (45%) given octreotide showed stable disease vs only eight (15%) in the control group (P < 0.001). In conclusion, octreotide therapy seems to confer a survival benefit in advanced gastrointestinal cancer patients refractory to chemotherapy. Additional studies will be needed to confirm these results and to clarify other questions about dose and schedule of octreotide.
Asunto(s)
Neoplasias Gastrointestinales/tratamiento farmacológico , Octreótido/uso terapéutico , Adulto , Anciano , Femenino , Neoplasias Gastrointestinales/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Somatostatina/fisiología , Tasa de SupervivenciaRESUMEN
It was our intention to verify if increases of granulocyte colony stimulating factor (G-CSF) dose were able to reduce treatment delays due to leukopenia in our weekly regimen of cisplatin (40 mg/m2), epidoxorubicin (35 mg/m2), 6S-leucovorin (250 mg/m2) and 5-fluorouracil (500 mg/m2), usually supported by G-CSF at a dose of 5 mu g/kg. Forty five patients with advanced gastric carcinoma (30 males and 15 females; median age 64 years) were randomized to receive three different doses of G-CSF (5, 8 and 10 mu g/kg) by s.c. injection. We did not observe any difference in the mean value of neutrophil counts at each of the 8 weeks of treatment; while we registered a higher incidence of severe neutropenia (< 500/mm3) in patients receiving higher G-CSF doses: two patients in the group at 5 mu g/kg, four in the group at 8 mu g/kg and seven in the group at 10 mu g/kg. Furthermore, low doses of G-CSF allowed a similar number of chemotherapeutic administrations in the eight study weeks. The results arising from our study do not seem to support the use of higher doses of G-CSF, at least in not such a weekly regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Cisplatino/administración & dosificación , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/patologíaRESUMEN
The non-pregnant uterus shows different patterns of contractility during the menstrual cycle. A renewed interest in uterine contractility has resulted from reports of non-invasive ultrasound (US) based studies. To clarify the changes in uterine contractility occurring throughout the menstrual cycle, we prospectively studied uterine contractions (UC) at six representative stages with US and intrauterine pressure (IUP) based approaches in 30 cycling volunteers. Results showed UC frequency could be measured by either US or IUP. UC amplitude and resting pressure tone could only be assessed by IUP. Conversely, direction of UC displacement could only be assessed by US. UC frequency increased at mid-cycle and decreased throughout the luteal phase suggesting oestradiol and progesterone exert positive and negative actions on uterine contractility, respectively. UC amplitude increased throughout the menstrual cycle to maximum values in the late luteal phase. Retrograde UC were most frequent at mid-cycle and convergent ('opposing') UC predominated during the luteal phase. While the former pattern ensures sperm transport, the latter may facilitate embryo implantation. In conclusion, UC changes throughout the menstrual cycle assessed by US and IUP emphasize the hormonal dependence of uterine contractility. Although UC patterns favouring sperm transport appear regulated by oestradiol, uterine quiescence and the dominance of convergent UC prevailing at the time of implantation are linked to progesterone. These data will serve to identify and treat possible dyskinetic changes in uterine contractility, particularly in women suffering from infertility, endometriosis, and dysmenorrhea.
Asunto(s)
Ciclo Menstrual/fisiología , Contracción Uterina , Adulto , Femenino , Humanos , Presión , Valores de Referencia , Ultrasonografía/métodosRESUMEN
BACKGROUND: Young patients with colorectal carcinomas are considered to have a worse prognosis than older patients. It was the goal of this study to assess if biologic characteristics of tumors in young patients differ from those observed in 2 different groups of patients with the same clinical characteristics but ranging in age either from 41 to 60 years or 61 years and older, respectively. METHODS: Colorectal carcinoma tumor samples were obtained from storage from patients age 40 years and younger and examined for tumor ploidy and S-phase fraction. For each younger patient, a control was selected among patients matched for Dukes stage, site of primary tumor, and sex, with the two age groups. RESULTS: Thirty-one of 1361 patients (2.2%) with colorectal carcinoma treated at our institution between 1984 and 1994 age 40 years or younger. Tumor aneuploidy was present in 3 younger patients, in 5 patients in the 41 to 60 years age group, and in 5 patients in the 61 years and older age group. S-phase fraction was 27.67 +/- 13.62 in patients younger than 40 years, 25.35 +/- 11.6 in the 40 to 61 years age group, and 22.45 +/- 8.48 in the 61 years and older age group. These differences were not statistically significant. CONCLUSIONS: It appears that there are no significant differences in S-phase fraction and tumor aneuploidy in patients younger or older than 40 years, suggesting that colorectal tumors arising in young people do not have different biologic properties.
Asunto(s)
Aneuploidia , Neoplasias del Colon/patología , Neoplasias del Recto/patología , Fase S , Adulto , Factores de Edad , Neoplasias del Colon/genética , Neoplasias del Colon/mortalidad , Femenino , Humanos , Masculino , Neoplasias del Recto/genética , Neoplasias del Recto/mortalidad , Fase S/genéticaRESUMEN
The efficacy of recombinant human erythropoietin (rHuEPO) on the increase in hemoglobin levels was assessed in patients with cisplatin (CDDP)-induced anemia older than 70 years. Furthermore, we compared the results obtained in this group of patients with those observed in other patients receiving rHuEPO for a CDDP-associated anemia with similar clinical features (chemotherapeutic regimen, primary tumor; CDDP cumulative dose) but of an age less than 70 years. Twenty patients older than 70 years with a CDDP-associated anemia (hemoglobin levels < 90 milligrams) received rHuEPO at the dose of 100 U/kg subcutaneously, three times a week. The control group consisted of 20 younger patients, anemic after CDDP chemotherapy, treated with rHuEPO. All patients were evaluable for response and toxicity. Hemoglobin concentrations showed a statistically significant increase after the 3rd, 6th and 9th week of therapy in both older (93.1 +/- 10.7, 103.5 +/- 8.2 and 102.7 +/- 8.2, respectively, vs. baseline, 84.6 +/- 4.9) and younger patients (95.3 +/- 11.7, 101.5 +/- 13.4 and 101.9 +/- 8.7, respectively, vs. baseline, 86.6 +/- 4.0). Furthermore, 30% of older patients required blood transfusions versus 35% of younger patients, with the mean unit of blood transfused per patient being 0.7 U in elderly and 0.65 U in younger patients. Treatment was well tolerated with no significant side effects. The CDDP-induced anemia seems to be corrected by rHuEPO also in elderly patients, without differences with respect to younger patients.
Asunto(s)
Anemia/tratamiento farmacológico , Cisplatino/efectos adversos , Eritropoyetina/uso terapéutico , Neoplasias/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anemia/inducido químicamente , Cisplatino/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
In an open prospective study. 40 patients with progressing painful bone metastases received 45 mg pamidronate by 1-h infusion every 3 weeks. A total of 27 patients (67%; 95% CI 53%-81%) experienced relief of pain as shown by the significant reduction of the bone pain score after three pamidronate administrations (from 2.25 +/- 0.64 to 1.15 +/- 0.36). Furthermore, 20 patients (60%) reduced their consumption of analgesics. We did not observe any objective response by skeletal radiological examination. In 11 patients presenting a skeletal progressive disease, bone pain improved, as well as their mobility score, but not their fatigue score. Treatment was well tolerated. Only 1 patient discontinued the treatment because of fever and cutaneous rash after the first administration. In conclusion, our results seem to confirm that pamidronate exerts a benefical effect on bone pain and mobility impairment in patients with painful osteolytic bone metastases.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Difosfonatos/uso terapéutico , Dolor/tratamiento farmacológico , Adulto , Anciano , Neoplasias Óseas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Cuidados Paliativos , Pamidronato , Estudios ProspectivosRESUMEN
Cancer patients with painful osteolytic bone metastases who had failed initial treatment with hormones and/or chemotherapy were each randomized to receive one of three pamidronate doses as outpatients: 45, 60, 90 mg given every 3 weeks for 12 weeks. Seventy patients were enrolled in this study, for a total of 265 infusions. There were 64 patients who completed 12 weeks of therapy. Forty-eight patients took nonsteroidal antinflammatory drugs, while 22 patients received morphine before pamidronate treatment. A reduction in bone pain and mobility scores was observed in all three different dose groups: in 11 of 23 patients (47%) at 45 mg; in 12 of 24 patients (50%) at 60 mg; and in 16 of 23 patients (69%) at 90 mg. However, while for patients receiving pamidronate at 90 mg median changes in pain and mobility were statistically significant at the 6th week, for patients receiving 45 mg they were not significant until the 12th week and for patients receiving 60 mg, until the 9th week. In weeks 0-6, the daily consumption of analgesics was reduced in 3 patients in the 45-mg arm, in 4 patients in the 60-mg arm, and in 7 patients in the 90-mg arm. In weeks 7-12, the daily consumption of analgesics was reduced in 8 patients receiving 45 mg, in 8 patients receiving 60 mg, and in 7 patients receiving 90 mg. No significant toxicity was recorded. In 2 patients (45 and 90 mg) fever (> 38 degrees C) and myalgia were observed after the first administration. In conclusion, our results seem to confirm the utility of higher doses of pamidronate in patients with painful bone metastases, because of the faster symptom relief achieved.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Óseas/secundario , Carcinoma/secundario , Difosfonatos/administración & dosificación , Dolor Intratable/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Intratable/terapia , Pamidronato , Resultado del TratamientoRESUMEN
BACKGROUND: Inactivation of the p53 gene has been reported to be associated with resistance to chemotherapy. The authors evaluated the significance of p53 status to the clinical outcomes of patients with locally advanced, unresectable gastric carcinoma (LAGC) who received chemotherapy. METHODS: Thirty chemotherapy-naive patients with LAGC received weekly administration of cisplatin 40 mg/m2, epi-doxorubicin 35 mg/m2, 5-fluorouracil 500 mg/m2, 6S-leucovorin 250 mg/m2, and glutathione 1500 mg/m2. After eight administrations of these agents, patients were assessed for response. Biopsy specimens of primary tumors were analyzed for p53 status using monoclonal antibody Bp53-12. RESULTS: Characteristics of patients were as follows: The median age was 66 years (range, 44-70 years); 18 were males and 12 were females. Eastern Cooperative Oncology Group performance status was 0 for 14 patients and 1 for 16. Histology was intestinal for 13 patients; for 17, it was diffuse. The site of the primary tumor was the cardia in 8 patients, the body of the stomach in 13, and the antrum in 9. The response rate (assessed with CT scan and endoscopy) for patients with p53 negative tumors was significantly higher than for those with overexpression of p53 (71% vs. 12%, P=0.004). CONCLUSIONS: p53 status analyzed before chemotherapy seems to be associated with response to treatment in patients with LAGC. This may provide a useful guide to selecting neoadjuvant chemotherapy for these patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Cuidados Preoperatorios/métodos , Neoplasias Gástricas/tratamiento farmacológico , Proteína p53 Supresora de Tumor/biosíntesis , Adulto , Anciano , Cisplatino/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Adjuvant chemotherapy for colorectal carcinoma was found to improve survival of patients with American Joint Committee on Cancer/International Union Against Cancer Stage III disease. The usefulness of chemotherapy in patients with Stage II disease continues to be debated, and it is likely that only those patients with a poor prognosis should receive adjuvant chemotherapy. Biologic prognostic factors may allow further insight into the optimal treatment strategy for patients with Stage II or earlier disease. In this study the prognostic role of S-phase fraction (SPF) determined by flow cytometry was assessed in patients with Stage I-II colorectal carcinoma. METHODS: Specimens of surgically resected colorectal carcinoma were examined for SPF by flow cytometric DNA analysis. Consecutive patients referred to the study institution were considered eligible for this study. The main inclusion criteria were a Stage I-II tumor together with sufficient tumor material and adequate follow-up information. For each stage of disease, SPF data were associated with the recurrence rate and the disease free survival (DFS). RESULTS: Analysis was performed on 167 patients (65 with Stage I disease and 102 with Stage II disease). Among Stage I patients, SPF was high in 20 patients and low in 45 patients. In Stage II patients, there were 36 patients with low SPF and 66 patients with high SPF. In both stages, the recurrence rate and DFS were significantly worse for the subgroups of patients with high SPF. CONCLUSIONS: SPF has revealed prognostic differences among patients with surgically resected Stage I-II colorectal carcinoma. These data should be considered for planning future trials in the adjuvant setting because patients with high SPF may benefit from adjuvant chemotherapy.
Asunto(s)
Carcinoma/patología , Neoplasias del Colon/patología , Neoplasias del Recto/patología , Fase S , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos ProporcionalesRESUMEN
Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer; thus its inhibition can arrest tumor growth and decrease metastatic potential. Octreotide has been shown to inhibit growth of colorectal tumors in vitro and in vivo. Part of the antiproliferative activity of octreotide could be related to its antiangiogenic properties. Effects of octreotide on VEGF expression were evaluated in 35 patients with operable colorectal cancer receiving octreotide for 2 weeks before surgery. Tissue VEGF expression and serum VEGF concentrations were determined before and after treatment with octreotide. There was a statistically significant reduction in the tissue VEGF expression both considering the percentage of VEGF positive cells (P = 0.006) and the intensity of VEGF staining (P = 0.003). A similar significant reduction was observed in serum values of VEGF (P = 0.03). The present study indicates that octreotide inhibits expression of VEGF in colorectal cancer patients, and, furthermore, that serum VEGF expression correlates with tissue VEGF, representing a safe method to monitor the activity of antiangiogenic agents.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Factores de Crecimiento Endotelial/antagonistas & inhibidores , Linfocinas/antagonistas & inhibidores , Octreótido/farmacología , Anciano , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND & AIMS: Octreotide was shown to inhibit the growth of colon cancer and to reduce serum concentrations of tumor growth factors such as insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) in vitro and in animal models. Effects of octreotide on tumor cell kinetics and serum concentration of IGF-I and EGF in patients with colorectal cancer were evaluated. METHODS: Seventy-five patients with colorectal cancer were randomized to receive octreotide (200 micrograms daily) in the 2 weeks before surgery or the usual medications. Samples of tumor tissue were taken at endoscopy and at surgery. [3H]Thymidine labeling index and flow cytometry were used to assess the S-phase fraction. In octreotide-treated patients, plasma levels of IGF-I, EGF, and growth hormone were assessed before and after treatment. RESULTS: There was a statistically significant reduction in the mean percentage of the S-phase fraction as a result of octreotide treatment measured by both [3H]thymidine labeling index (P = 0.001) and flow cytometry (P = 0.001). No reduction in the percentage of the S-phase fraction was observed in the control group patients. Serum values of IGF-I were significantly reduced by octreotide, whereas EGF and growth hormone levels were not affected. CONCLUSIONS: Octreotide reduces the proliferative activity of tumor cells and the serum IGF-I levels in patients with colorectal cancer. This activity may have a role in the treatment of colorectal cancer.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Factor I del Crecimiento Similar a la Insulina/análisis , Octreótido/uso terapéutico , Cuidados Preoperatorios , Adulto , Anciano , Ciclo Celular , Neoplasias Colorrectales/sangre , Factor de Crecimiento Epidérmico/sangre , Citometría de Flujo , Hormona de Crecimiento Humana/sangre , Humanos , Persona de Mediana Edad , Fase S , Timidina/metabolismoRESUMEN
Diarrhea is one of the dose-limiting toxicities for administration of fluorouracil (5FU) in patients with colorectal cancer and can result in severe morbidity and mortality. No well-defined prognostic factors influencing 5FU-associated diarrhea have been identified, which means its occurrence is unforeseeable. The aim of this study was to check whether any characteristics related to patients or chemotherapy could allow the identification of subsets of patients at higher risk of developing diarrhea while receiving a regimen containing 5FU. A logistic regression analysis was performed with age, sex, site of primary tumor, presence of primary tumor, presence of colostomy, time since surgery, number of courses of chemotherapy, diarrhea in previous courses, season of treatment, and chemotherapeutic regimens used as model parameters to predict occurrence of diarrhea in 258 colorectal cancer patients receiving a 5FU-containing regimen. Presence of primary tumor (P = 0.004), previous episodes of chemotherapy-related diarrhea (P = 0.00005) and summer season (P = 0.014) were found to be significant risk factors for developing diarrhea. The other variables examined, such as age, sex, chemotherapeutic regimen, site of primary tumor, presence of colostomy, and time since surgery, were not significantly correlated to diarrhea. Chemotherapeutic regimen was the only parameter that allowed prediction of the severity of diarrhea: 5FU/6S-leucovorin/interferon caused more severe diarrhea, followed by 5FU/leucovorin weekly. Although the analysis of these clinical features does not seem to allow the definition of a well-defined subset of colorectal cancer patients at higher risk of 5FU-induced diarrhea, it can be recommended that patients with primary tumor, or who have experienced diarrhea in earlier courses of chemotherapy or are receiving treatment in summer should be carefully monitored, especially in the first cycles.