RESUMEN

OBJECTIVE: Emergence of chemoresistance in the course of treatments with platinum drugs remains a major hurdle to ovarian carcinoma therapy. We have previously shown that acquisition of cisplatin resistance by OAW42-R ovarian carcinoma cells was associated with the loss of ERK activation in response to cisplatin. To try to sensitize this cell line by restoring ERK activation, we tested a new synthetic compound, 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol (2,3-DCPE), which was described to induce ERK activation and to display anticancer properties. METHODS: We treated four ovarian carcinoma cell lines with 2,3-DCPE, alone or combined with cisplatin. We characterized its effects on apoptosis induction and proliferation and correlated them with molecular modulations. RESULTS: We showed that 2,3-DCPE induced cell death and ERK phosphorylation in a time- and concentration-dependent manner in OAW42-R cells. 2,3-DCPE-triggered apoptosis was also associated with the inhibition of Bcl-2 expression and, to a less extent, with that of Bcl-xL. Treatment with 2,3-DCPE also elicited a strong G0/G1 cell cycle arrest, accompanied with p21WAF1/CIP1 up-regulation. All of these effects revealed to be irreversible. Moreover, 2,3-DCPE exerted a cytostatic effect on OAW42, IGROV1-R10 and SKOV3 ovarian carcinoma cells, the sensitivity to 2,3-DCPE appearing in particular linked with a low basal level of P-ERK. Finally, we showed that 2,3-DCPE increased the cytotoxic effect of cisplatin in OAW42-R resistant cells. CONCLUSION: Our results emphasized the potential interest of 2,3-DCPE, used alone or combined with cisplatin, for ovarian carcinoma treatment. The absence of basal P-ERK may constitute a predictive marker of response to this novel therapy.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Clorobencenos/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Etanolaminas/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína bcl-X/biosíntesis , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Clorobencenos/administración & dosificación , Cisplatino/administración & dosificación , Sinergismo Farmacológico , Activación Enzimática/efectos de los fármacos , Etanolaminas/administración & dosificación , Femenino , Fase G1/efectos de los fármacos , Humanos , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Proteína bcl-X/antagonistas & inhibidores

RESUMEN

A retrospective study evaluating the efficacy and tolerability of epirubicin-ifosfamide (EI) in patients with relapsed advanced ovarian cancer (ROC) after prior chemotherapy was conducted. A total of 93 patients received epirubicin (50 mg/m(2), day 1), ifosfamide (1500 or 2500 mg/m(2), days 1-3), and mesna monthly. Thirty-five percent had received one line of chemotherapy (platinum 100%, taxanes 8%); 38%, two lines; and 27%, more than two lines. Fifty-three percent received 2500 mg/m(2)/day ifosfamide and 47% received 1500 mg/m(2)/day ifosfamide. Ifosfamide was administered by continuous infusion in 12 patients. Mean number of courses was 4 (1-12). Grade 4 toxicity was 69% neutropenia and 12% thrombocytopenia. Three patients on high-dose ifosfamide as a short infusion had central nervous system dysfunction resulting in death. There were 84 assessable patients: 7 (8%), complete responses; 13 (15%), partial responses; and 20 (24%), stable disease. Median time to progression was 5 months (3 days to 36 months). The EI combination appears to be effective in ROC. However, toxicity with high-dose ifosfamide administered by short infusion is not acceptable. Tolerability can be improved using ifosfamide at 1500 mg/m(2) by continuous infusion. The combination of ifosfamide with newer anthracycline agents such as liposomal doxorubicin may be an alternative and needs further evaluation for use after first-line taxane-based chemotherapy.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/patología , Terapia Recuperativa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

OBJECTIVE: Recurrence and cisplatin resistance that progressively develops in the course of treatments are major impediments in ovarian cancer therapy. We investigated the involvement of alterations of different signaling pathways in this acquired chemoresistance. METHODS: We studied the activation of these pathways in a model of progressive acquisition of resistance that we established, by discontinuously exposing a sensitive ovarian carcinoma cell line, OAW42, to increasing concentrations of cisplatin. RESULTS: OAW42-T1 and -T2 variants, which emerged after the first two treatments of OAW42 cells with 5 microg/ml cisplatin, showed enhanced but transient resistance. OAW42-R cells, obtained following successive reiterations of the treatment, displayed both a stronger resistance to cisplatin-induced apoptosis and an increased capacity to recover a normal proliferation after treatment. The measurement of DNA adducts demonstrated that the mechanisms leading to a decreased DNA platination could not explain the level of resistance of OAW42-R cells. The simultaneous study of activation pattern of key proteins of different signaling pathways revealed that cisplatin induced both activation of ERK and p38 and inhibition of P-FAK in the sensitive cells, whereas it progressively failed to elicit such a response in the resistant variants. In contrast, STAT3 and Akt did not seem to be involved in the acquired chemoresistance in our model. CONCLUSIONS: Our results suggested that emergence of chemoresistance was accompanied with the progressive loss of ERK and p38 activation and with the maintenance of FAK activation in response to cisplatin, and they demonstrated that these alterations were early events in the course of treatments.

Asunto(s)

Cisplatino/farmacología , Quinasa 1 de Adhesión Focal/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Línea Celular Tumoral , Cisplatino/administración & dosificación , Aductos de ADN/biosíntesis , ADN de Neoplasias/metabolismo , Resistencia a Antineoplásicos , Activación Enzimática/efectos de los fármacos , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos

RESUMEN

PURPOSE: To evaluate quality of life and social problems in long-term survivors of testicular cancer. PATIENTS AND METHODS: In 1998, 71 testicular cancer survivors (cases) identified from the Calvados General Tumor Registry were enrolled onto a case-control study. One hundred nineteen healthy control subjects (controls), matched by age and location of residence, were selected at random from electoral rolls. Three self-administered questionnaires were used: two health-related quality-of-life questionnaires (Short Form-36 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 core questionnaires) and one life situation questionnaire. Specific questions concerning sexuality were also added. RESULTS: With a mean follow-up of 11 years, health-related quality-of-life scores did not differ significantly between cases and controls, nor did general symptom scores. Psychosocial problems were reported equally by cases and controls. Cases reported more modification of sexual life (P =.04) with decreased sexual enjoyment (P <.01), decreased desire (P =.02), and infertility (P <.01). Cases did not report more divorce than controls; they reported fewer changes in relationships with friends (P =.03). Although a similar proportion of cases and controls were at work, cases expressed less ambitious professional plans (P =.002). Cases had greater difficulty in borrowing from banks (P <.001). CONCLUSION: French long-term survivors of testicular cancer do not express more impairment of health-related quality of life or familial or professional life in comparison with healthy men. They did have more sexual life problems and found difficulty in borrowing from banks. This information should be used by practitioners to help their patients cope with their disease and return to normal life.

Asunto(s)

Calidad de Vida , Ajuste Social , Sobrevivientes , Neoplasias Testiculares , Adulto , Anciano , Estudios de Casos y Controles , Familia/psicología , Francia , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sexualidad , Conducta Social , Estadísticas no Paramétricas , Neoplasias Testiculares/psicología

RESUMEN

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

Asunto(s)

Antineoplásicos/farmacología , Resistencia a Múltiples Medicamentos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacología , Topotecan/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Resistencia a Antineoplásicos , Europa (Continente)/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/mortalidad , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Estados Unidos/epidemiología

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the impact of platinum dose intensity on pathological response rate and overall survival in patients with advanced ovarian adenocarcinoma. METHODS: Between February 1992 and December 1996, 195 previously untreated patients with FIGO stage IIb-c, IIIb-c, or IV with macroscopic residual disease after suboptimal debulking surgery were randomized to receive CCC (100 mg/m(2) of cisplatin, 300 mg/m(2) of cyclophosphamide, 300 mg/m(2) of carboplatin, n = 96) or CC (100 mg/m(2) of cisplatin, 600 mg/m(2) of cyclophosphamide, n = 99) for six courses at 28-day intervals. A second-look laparotomy was planned at the end of chemotherapy. RESULTS: In the CCC arm, the platinum compound received dose intensity and relative total dose were 85 and 76%; in the CC arm, they were 94 and 85%. Grade 3-4 toxicity was more frequent in the CCC arm than in the CC arm for leukopenia (56% vs 26%, P < 0.001), febrile neutropenia (18% vs 4%, P = 0.002), anemia (31% vs 5%, P < 0.001), thrombopenia (55% vs 4%, P < 0.001), and ototoxicity (8% vs 0%, P < 0.001). The pathologic complete response rate was 22 and 14% in the CCC and CC arms, respectively (P = 0.19). With a median follow-up of 53 months, the median time to failure and the 3-year treatment failure-free survival rate were 17.4 months and 22% vs 13 months and 11% in the two arms, respectively (P = 0.01). The median survival time and the 3-year overall survival rate were, respectively, 30 months and 42% vs 25 months and 33% (P < 0.20). CONCLUSION: The platinum dose intensification (1.6-fold increase) obtained with the CCC association improves the treatment failure-free survival without significant impact on overall survival when compared with the CC regimen in suboptimal debulked ovarian adenocarcinoma. However, because of its high rate of hematologic toxicity and ototoxicity, this association cannot be recommended for routine practice.

Asunto(s)

Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Análisis de Supervivencia

RESUMEN

Our purpose was to evaluate the late physical and psychosocial difficulties of premenpausal patients treated for a localized breast cancer and to weigh the impact of chemotherapy on long-term quality of life. Two self-administered questionnaires, the EORTC core QLQ-C30 and the breast module (BR23) were mailed to 179 premenopausal node-negative women continuously disease-free, previously enrolled in a trial testing the efficacy of adjuvant CMF chemotherapy (Espié et al, 1997). The core questionnaire evaluates the physical, role, emotional, cognitive and social functioning and global health status. The breast module includes four functional scales: body image, sexual functioning, sexual enjoyment and future perspective. It also includes symptom scales such as arm or breast symptoms. Some specific professional and social states were added. 119 (68%) patients (mean age 54 years, range 30-69) participated. Mean follow-up time since diagnosis was 9.6 years (4-16). 68% had conservative and 32% radical surgery (with reconstructive surgery in 50%). CMF was given to 77 (65%) patients. Irradiation was administered in 75% of patients irrespective of adjuvant therapy. QLQ-C30 scale scores were similar in patients who had or had not received chemotherapy. Disturbance in body image, sex life and breast symptoms did not differ between patients who had or had not received adjuvant CMF. No major socioprofessional difficulties were reported except problems in borrowing from banks not related to past chemotherapy. With long follow-up, most premenopausal women treated for a localized breast cancer cope with the disease and its treatments. Adjuvant CMF chemotherapy does not appear to impair quality of life nor social and professional life in these patients.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Calidad de Vida , Adulto , Anciano , Neoplasias de la Mama/psicología , Neoplasias de la Mama/cirugía , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Metástasis Linfática , Metotrexato/uso terapéutico , Persona de Mediana Edad , Premenopausia/psicología , Encuestas y Cuestionarios , Sobrevivientes/psicología , Factores de Tiempo

RESUMEN

PURPOSE: To evaluate late physical and psychosocial sequelae in patients treated with an association of external beam irradiation (EBI) and brachytherapy (BT) for localized prostate cancer. PATIENTS AND METHODS: Seventy-one patients free of disease, treated at the Centre François Baclesse from 1988 to 1992, were enrolled in a case-control study. Seventy-one healthy controls, matched on age and residence, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in January 1996. The French translation of the Nottingham Health Profile questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire were used to evaluate physical, role, emotional, cognitive and social functioning, global health status as well as energy and sleep disturbance. Specific problems related to prostate cancer were explored using the prostate specific module developed by the EORTC Genito-Urinary Tract Cancer Cooperative Group. Concordance between clinical complications reported by patients and those reported by physicians was also analyzed. RESULTS: General health quality of life scale scores did not significantly differ between patients and controls, nor did general symptom scale scores. Furthermore, no more late psychosocial sequelae were reported by patients than by controls. No major digestive complications were observed among patients. However, statistical differences were observed concerning interest in sex (P = 0.016) and sexual activity (P < 0.001), urinary incontinence (P < 0.001) and cystitis (P = 0.01). Late subjective morbidity (dysuria, nocturia, urinary incontinence, pelvic pain) appraisal differed slightly between patients and physicians who generally underestimate its severity. While nocturia was reported more often by physicians than by patients (P = 0.0016), patients reported urinary incontinence and pelvic pain more often than physicians (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The study demonstrates that survivors from localized prostate cancer treated with an association of BT and EBI have good global health status. Major problems that persist are sexual disorders, urinary incontinence and cystitis while digestive disorders were rare. This association could be an alternative to standard EBI in patients with localized prostate cancer. Whatever the treatment choice, patients should be involved in the therapeutic decision which should consider not only expected survival rate but also quality of life.

Asunto(s)

Neoplasias de la Próstata/radioterapia , Calidad de Vida , Anciano , Braquiterapia/efectos adversos , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios

RESUMEN

BACKGROUND: The efficacies of granisetron plus dexamethasone and dexamethasone alone in controlling delayed nausea and vomiting after cisplatin chemotherapy (> or = 69 mg/m2) were compared in a multicentre, double-blind, placebo-controlled comparative study. PATIENTS AND METHODS: In all, 654 patients (of whom 619 were evaluable) received prophylactic granisetron plus dexamethasone before chemotherapy on day 0; on day 1 complete responders and non-responders were randomized separately to receive dexamethasone, 8 mg b.d. p.o., with either granisetron, 1 mg b.d. p.o., or matching placebo for six days. RESULTS: Over days 1-6 the complete response rates were 54.5% (dexamethasone group) and 52.1% (dexamethasone plus granisetron group). Response rates were higher over days 4-6 (71.8% and 70.7%, respectively) than over days 1-3 (60.4% and 57.9%, respectively). Significantly more patients who responded to antiemetic treatment during day 0 were responders over days 1-6 (63% vs. 17%; P < 0.001). No other treatment-related differences were found. Adverse events tended to be minor, with constipation and headache the most common. Overall, there were no significant differences in the safety profiles of the two regimens, but constipation and abdominal pain were significantly more common in the dexamethasone plus granisetron group. CONCLUSIONS: Granisetron plus dexamethasone did not appear to confer additional benefit over use of dexamethasone alone in controlling delayed nausea and vomiting following cisplatin chemotherapy. Control of acute nausea and vomiting, however, appeared to be an important factor influencing delayed nausea and vomiting.

Asunto(s)

Dexametasona/administración & dosificación , Granisetrón/administración & dosificación , Náusea/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/administración & dosificación , Antieméticos/efectos adversos , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Dexametasona/efectos adversos , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Granisetrón/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Vómitos/inducido químicamente

RESUMEN

PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.

Asunto(s)

Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel/efectos adversos , Análisis de Supervivencia , Topotecan

RESUMEN

This phase I trial was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin (400 mg/m2) as first-line chemotherapy for stage IIIC/IV ovarian adenocarcinoma. After premedication, paclitaxel was infused over 3 hours, followed by carboplatin infused over 30 minutes on day 1 of a 28-day cycle (group 1, with 28 patients accrued and 150 evaluable cycles) or on day 1 of a 21-day cycle (group 2, with 16 patients accrued and 55 evaluable cycles). Dose-limiting toxicities assessed after the first course included grade 4 neutropenia lasting longer than 7 days, febrile grade 4 neutropenia requiring intravenous antibiotics, grade 4 thrombocytopenia, mucositis greater than grade 2 for more than 7 days, grade > or = 3 nonhematologic toxicity (excluding alopecia, vomiting, and muscular pain), no hematologic recovery on day 42 (for group 1) or on day 35 (for group 2), neurotoxicity above grade 2, and persistence of nonhematologic toxicity (excluding alopecia, nausea/vomiting, and musculoskeletal pain) grade > or = 2 at scheduled re-treatment. If any of the events occurred during the first cycle in three or more of six patients, maximum tolerated dose was considered to have been reached. The hematologic toxicity associated with the two treatment schedules was mainly neutropenia, but it was of short duration. Very few dose reductions or dose delays were necessary. Until now, the six planned courses have been administered without colony-stimulating factors. No toxic death has occurred. Grade 2 or 3 peripheral neuropathy has occurred in 12% of patients, mainly with high doses of paclitaxel. At this time, the maximum tolerated dose has not been reached at paclitaxel 275 mg/m2 every 4 weeks or 225 mg/m2 every 3 weeks, and enrollment continues.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/efectos adversos , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/efectos adversos

Asunto(s)

Oncología Médica , Neoplasias , Guías de Práctica Clínica como Asunto , Técnicas de Apoyo para la Decisión , Francia , Humanos , Oncología Médica/normas , Neoplasias/diagnóstico , Neoplasias/terapia , Guías de Práctica Clínica como Asunto/normas , Práctica Profesional , Garantía de la Calidad de Atención de Salud , Sociedades Médicas

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Oncología Médica , Neoplasias/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Instituciones Oncológicas , Estudios de Seguimiento , Francia , Humanos , Relaciones Interprofesionales , Oncología Médica/normas , Educación del Paciente como Asunto , Práctica Profesional , Relaciones Profesional-Paciente , Garantía de la Calidad de Atención de Salud , Calidad de Vida , Sociedades Médicas

Asunto(s)

Cisplatino/efectos adversos , Dexametasona/administración & dosificación , Granisetrón/uso terapéutico , Metoclopramida/administración & dosificación , Vómitos/prevención & control , Enfermedad Aguda , Administración Oral , Adulto , Anciano , Método Doble Ciego , Quimioterapia Combinada , Femenino , Granisetrón/administración & dosificación , Granisetrón/efectos adversos , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

PATIENTS AND METHODS: Three anti-emetic treatment regimens were compared in 357 patients receiving cisplatin therapy (mean dose 81 mg/m2) in this double-blind randomized study. Regimens studied were i) granisetron 1 mg bd orally for 7 days (granisetron alone); ii) gran 1 mg bd orally for 7 days plus prophylactic dexamethasone (12 mg i.v.) on the first day only (gran/dex); iii) metoclopramide (3 mg/kg i.v. loading dose; 4 mg/kg i.v. infusion) plus dex (12 mg i.v.) on the first day followed by met 10 mg orally tds for a further 6 days (met/dex). RESULTS: At 24 hours, gran/dex was significantly superior to met/dex in terms of total anti-emetic control, defined as no nausea, no vomiting, no rescue anti-emetic therapy, not withdrawn (54.7% gran/dex vs. 37.2% met/dex; P < 0.01). There was also a significant delay in time to onset of nausea (P < 0.01) and vomiting (P < 0.01) following gran/dex compared with met/dex. Oral granisetron alone was as effective as met/dex in control of acute emesis in all parameters examined. There were no significant differences between the three groups in the control of delayed nausea and vomiting. The most common adverse experiences in both granisetron groups were headache and constipation, both characteristic of 5-HT3 antagonists. Agitation, somnolence, diarrhoea and decreased appetite were reported more frequently by the met/dex group. CONCLUSIONS: Oral granisetron as a single agent is as effective as high doses of i.v. met/dex in preventing cisplatin-induced emesis. Oral granisetron in combination with a corticosteroid provides superior anti-emetic control to the met/dex regimen in patients undergoing highly emetogenic chemotherapy.

Asunto(s)

Cisplatino/efectos adversos , Dexametasona/uso terapéutico , Granisetrón/uso terapéutico , Metoclopramida/uso terapéutico , Vómitos/prevención & control , Administración Oral , Adulto , Anciano , Distribución de Chi-Cuadrado , Estreñimiento/inducido químicamente , Método Doble Ciego , Quimioterapia Combinada , Europa (Continente) , Femenino , Granisetrón/administración & dosificación , Granisetrón/efectos adversos , Cefalea/inducido químicamente , Humanos , Masculino , Metoclopramida/administración & dosificación , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/prevención & control , Pronóstico , Sudáfrica , Vómitos/inducido químicamente

RESUMEN

BACKGROUND: Because of its antitumour activity and its pharmacological advantage when administered by the intraperitoneal route, carboplatin was studied in a phase II multicentric trial. The aim of the study was to determine the response rate and the toxicity of carboplatin administered intraperitoneally and to determine if pathological complete response could be attained in women with macroscopic residual ovarian cancer at second-look laparotomy after intravenous cisplatin chemotherapy. PATIENTS AND METHODS: Twenty-nine patients with macroscopical residual disease after intravenous cisplatin-based chemotherapy at second-look laparotomy, were treated at that time with 300 mg/m2 of carboplatin administered in the abdominal cavity every four weeks for six cycles. In instances of negative findings at physical and CT scan examination, laparotomy evaluation was performed and the catheter was removed. The dose of carboplatin was increased or decreased according to hematological toxicity. RESULTS: Efficacy is evaluable in 25 pts: 2 pts had pathological complete responses and 1 pt had microscopic disease (12% response rate of evaluable patients). Toxicity is evaluable for 135 cycles in 29 patients. No grade 4 hematological toxicity was observed, 2 pts had grade 3 leukopenia and 3 pts had grade 3 thrombocytopenia; grade 3 vomiting was observed in 11% of cycles. No peritoneal complication was observed; catheter dysfunction occurred after the first cycle in one patient who refused a surgical procedure to remove the catheter and to pursue treatment. CONCLUSION: Intraperitoneal carboplatin demonstrates efficacy in patients with macroscopical residual disease at second-look laparotomy after first-line cisplatin chemotherapy. The recommended dose for further studies is 300 mg/m2 administered every 4 weeks. A low response rate does not favour a randomised study.

Asunto(s)

Carboplatino/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma/mortalidad , Carcinoma/patología , Femenino , Humanos , Inyecciones Intraperitoneales , Laparotomía , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Tasa de Supervivencia

RESUMEN

Present chemotherapy, with cisplatin combinations, currently offers the possibility of seeking adjuvant therapy in locally advanced and bulky carcinomas of the cervix, which have an unfavorable prognosis (nodal involvement). This initial adjuvant chemotherapy may improve the results of classical pelvic irradiation. From 1982 to 1987, a randomized phase III trial was performed in order to determine the long term effect of induction chemotherapy before irradiation in stage IIb-N1, III, M0 squamous cell carcinomas of the cervix. Radiotherapy (R) for all patients consisted in 50 Gy in the pelvis with a boost by external irradiation of the brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen (C + R group) was an association of methotrexate, chlorambucil, vincristine and cisplatin, given every 3 weeks, at least two courses were to be given before assessing efficacy and two more courses were given to patients who responded. After a follow up of 5-10 years, 76 patients were fully evaluable in the R arm and 75 in the C + R arm. The response rate (> 50%) to chemotherapy was 42.5% and after completion of treatment, remission rate was 93% in the R arm and 96% in the C + R arm. The disease-free survival was 40% in the C + R group and 35% in the R group, and the median survival was 42 and 45 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group when they are responding to chemotherapy, than in R group (P < 0.05). Radiotherapy was not modified whether patients had an initial chemotherapy or not; tolerance was not significantly different between the two groups. Efficacy of induction chemotherapy is an available test for long term results. This approach has the potential for improving the outlook in patients with high-risk primary cancer: earlier use and higher dose intensity of chemotherapy may be associated with a better cytoreduction, and probably a better survival. Further controlled investigations are warranted to confirm the value of adjuvant chemotherapy in cervical cancer.

Asunto(s)

Carcinoma de Células Escamosas/terapia , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Dosis de Radiación , Análisis de Supervivencia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapia

Asunto(s)

Neoplasias de la Mama/genética , Receptores Androgénicos/genética , Secuencia de Aminoácidos , Andrógenos/fisiología , Cromosomas Humanos Par 17 , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Células Tumorales Cultivadas

RESUMEN

Sixty patients with advanced carcinoma of the cervix were treated with 3-week cycles of chemotherapy consisting of bleomycin (10 mg/m2, D1, 2, 3), mitomycin (10 mg/m2, D1), cisplatin (80 mg/m2, D3), etoposide (100 mg/m2, D1, 2, 3). Twenty-six patients had prior therapy. Toxicities noted were primarily nausea, vomiting, asthenia, fever and myelosuppression, especially in the pre-treated patients. One patient died of pulmonary toxicity. Of the 34 untreated patients, 25 objective responses (74%) were observed, with two complete responses (6%) and among the 26 pre-treated patients, ten objective responses (39%) with only one complete response. The mean duration of response was 3.8 months [2-14]. These data indicate that combination chemotherapy regimen is active against advanced and recurrent cervical cancer but caution is required for administration and continuation of treatment after four cycles. This method of chemotherapy has significant potential for primary treatment in patients with locally advanced disease.

Asunto(s)

Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/fisiopatología , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/fisiopatología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Evaluación de Medicamentos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Mitomicinas/administración & dosificación , Mitomicinas/efectos adversos , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/fisiopatología

RESUMEN

One case of hepatoid carcinoma of the ovary is described, and a review of the literature is performed. This tumor is now considered as a variety of common epithelial tumor of the ovary and must be distinguished from other ovarian-neoplasms, especially from hepatoid yolk sac tumors.

Asunto(s)

Carcinoma Hepatocelular/patología , Neoplasias Ováricas/patología , Diferenciación Celular , Femenino , Humanos , Persona de Mediana Edad