Monitoramento auditivo em adultos submetidos à quimioterapia com carboplatina / Auditory monitoring in adults undergoing chemotherapy with carboplatin / Monitoreo del oído en adultos sometidos a quimioterapia con carboplatino

Objetivo: Caracterizar a audição de pacientes adultos submetidos à quimioterapia com carboplatina por meio de exames audiológicos em dois momentos durante o tratamento quimioterápico. Métodos: Prospectivo e observacional. Participaram da pesquisa seis sujeitos adultos entre 53 e 59 anos e 11 meses, em tratamento quimioterápico com carboplatina submetidos a uma bateria de exames audiológicos. Os dados foram analisados por meio do teste ANOVA, teste z para proporções e Teste de Wilcoxon. O valor de significância adotado foi de 5% (p≤0,05). Resultados: Um aumento nos limiares auditivos foi observado, sobretudo nas frequências mais altas, porém não houve significância. Também foi observado aumento na relação sinal/ruído das emissões otoacústicas evocadas transientes e por produto de distorção, porém sem significância estatística. Conclusão: Não foram observadas mudanças estatisticamente significantes quanto aos limiares auditivos e as respostas das emissões otoacústicas, no entanto pode-se notar um aumento nos limiares audíveis, especialmente nas altas frequências, bem como aumento da amplitude de respostas nas emissões otoacústicas.

Purpose: To characterize the hearing of adult patients undergoing chemotherapy with carboplatin using two sequential audiological tests during chemotherapy treatment. Methods: Prospective and observational. The participants were six adult subjects between 53 and 59 years and 11 months, undergoing chemotherapy treatment with carboplatin subjected to a battery of audiological exams. Data were analyzed using the ANOVA test, z test for proportions and Wilcoxon signed-ranks test. The adopted significance was 5% (p ≤ 0.05). Results: An increase in hearing thresholds was observed, particularly in the higher frequencies, but there was no significance. It was also observed an increase in the signal / noise ratio of transient evoked otoacoustic emissions and for distortion product, but without statistical significance. Conclusion: No statistically significant changes regarding the hearing thresholds and responses of otoacoustic emissions were observed, however it could be noted an increase in hearing thresholds, especially at high frequencies, as well as the increased amplitude on the responses in otoacoustic emissions.

Objetivo: Caracterizar la audición de pacientes adultos sometidos a quimioterapia con carboplatino a través de pruebas audiológicas dos veces durante la quimioterapia. Métodos: Estudio prospectivo observacional. Los participantes fueron seis sujetos adultos de entre 53 y 59 años y 11 meses, sometidos a quimioterapia con carboplatino sometido a una batería de pruebas audiológicas. Los datos se analizaron mediante la prueba de ANOVA, prueba z para proporciones y prueba de los rangos con signo de Wilcoxon. La significancia fue del 5% (p ≤ 0,05). Resultados: fueron observados un aumento de los umbrales de audición, en particular en las frecuencias más altas, pero no identificaron significación. También se observó un aumento de la relación señal / ruido de emisiones otoacústicas evocadas transitorias y productos de distorsión, pero sin significación estadística. Conclusión: Los cambios estadísticamente significativos con respecto a los umbrales de audición y las respuestas de las emisiones otoacústicas, fueron observadas sin embargo es posible que observe un aumento de los umbrales audibles, especialmente a altas frecuencias, así como una mayor gama de respuestas de las emisiones otoacústicas.

the therapeutic index better with paclitaxel plus carboplatin than with paclitaxel plus cisplatin in initial treatment of advanced ovarian cancer?

Retrospective analysis and comparison of the side effects, efficacy and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. Between January 2001 and January 2006, 39 patients with advanced epithelial ovarian cancer were allocated to receive paclitaxel 175mg/m[2] intravenously as a 3-hour infusion followed by either cisplatin 75mg/m[2] or carboplalin [area under the plasma concentration-time curve of 5] both on day [1]. The schedule was repeated every 3 weeks for at least six cycles to the majority of the patients. The primary endpoint was the proportion of patients without progression at 2 years. Secondary endpoints included toxicity, tolerability, response to treatment, and overall and progression-free survival time. Kaplan-Meier method estimated overall and time to disease progression. Log rank test compared survival curves with p value 230 had 92.3% sensitivity and 100% specificity [p=<0.001] and tumor size at start of chemotherapy had 96.3% sensitivity and 100% specificity [p<0.001]. The 2-years progression-free survival [PFS] of all patients was 39.4% and the median time to disease progression was 23.3 months. While the median overall survival time of all patients was 37.5 months and the 2-years overall survival [OAS] was 62.9%. The 2-years PFS and OAS were 35.2% and 44.4%, respectively, for TC arm compared with 44.4% and 83.3%, respectively, for paclitaxel-cisplatin [TP] arm. The relative risk [RR] of progression for patients with incomplete response was 6.9 [95%- CI, 2.052 to 23.11] and the RR of death for TC arm was 6.3 [95% CI, 1.7 to 9.0]. The small number of patients entered onto the study caused wide CI around the hazards ratio for RR of death with delayed treatment [hazards ratio, 4.0; 95% CI, 1.7 to 23.3] and did not allow conclusions about efficacy. Age >60 [p=0.05], stage IIIB, IIIC and IV disease [p=0.02], and delayed treatment [0.001] had statistically significant adverse effect on the OAS, while response to chemotherapy [p=0.03] had statistically significant effect on prolonging the OAS. Presence of residual disease >1cm had borderline significance [p=0.06] on the OAS. However elevated level of CA[125] >230, tumor grade, pathological subtype, Karnofsky performance status [KPS] had no statistically significant effect on the OAS [all p=NS]. Univariate analysis of factors that might affect PFS showed that patients with a residual tumor of less than 1cm before chemotherapy [p=0.0003], KPS [p=0.0268], FIGO stage II or IIIa [p=0.0018], had statistically significant longer PFS while CA125 >230 [p=0.0012] and incomplete response [p=0.002] had a significant adverse impact on PFS. In patients with advanced ovarian cancer, a chemotherapy regimen consisting of TC results in less toxicity, is easier to administer, and has similar median time to disease progression [23.3 months], when compared with TP regimen, however a longer follow-up is required for a definitive statement on survival

Weekly paclitaxel and paraplatin as first line chemotherapy in patients with advanced NSCLC

Optimal platinum based combination regimen for advanced NSCLC remains to be defined. Weekly Taxol and paraplatin is an effective and generally well tolerated regimen for first line treatment for stage III and IV NSCLC and affords potential for lower toxicity and increases exposure to drugs with alternative cytotoxic/cytostatic mechanisms. Thirty patients with histologically or cytologically proven NSCLC stages IIIb and IV were included during the period between March 2001-March 2003 with the following criteria, median age was 55 years, measurable or evaluable disease, PS

Acute renal toxicity of 2 conditioning regimens in patients undergoing autologous peripheral blood stem-cell transplantation. Total body irradiation-cyclophosphamide versus ifosfamide, carboplatin, etoposide

To compare acute renal toxicity of 2 conditioning regimens of total body irradiation/cyclophosphamide TBI-Cy and Ifosfamide, Carboplatin, and Etoposide ICE. Between August 1996 and February 2004, patients treated with autologous peripheral stem cell transplantation in the Department of Medical and Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey with 2 different conditioning regimens was comparatively analyzed for acute renal toxicity in the early post-transplant period. Forty-seven patients received ICE regimen with 12 g/m2; 1.2 g/m2; and 1.2 g/m2 divided to 6 consecutive days, whereas 21 patients received 12 Gy TBI 6 fractions twice daily in 3 consecutive days and 60 mg/m2/day cyclophosphamide for 2 days. Sixty-eight patients were evaluated in this study. There was no significant difference in baseline renal function between patients in the ICE and TBI-Cy groups. Eleven patients developed nephrotoxicity 23.4% in the ICE group while one patient 4.8% in the TBI-Cy group developed nephrotoxicity p=0.06. Five out of 11 patients developing nephrotoxicity in ICE group required hemodialysis and subsequently 4 8.5% of them died. In contrast, one patient 4.8% died due to nephrotoxicity despite hemodialysis in the TBI-Cy arm. This study reveals that the TBI-Cy conditioning regimen seems no more nephrotoxic than an ICE regimen particularly in patients who had used cisplatin prior to transplantation

Concurrent weekly paclitaxel and carboplatin with thoracic radiation followed by consolidation chemotherapy for locally advanced non-small cell lung cancer [NSCLC]

To assess the feasibility and activity of chemoradiation program using paclitaxel and carboplatin-based combined-modality therapy based on the unique radiation-sensitizing properties of these agents in locally advanced unresectable stage III NSCLC. Twenty-seven patients with unresectable NSCLC were evaluable, with a median age of 54 years [range 44-69]. Eleven patients [41%] had stage IIIA and 16 [59%] had stage IIIB. Treatment consisted of paclitaxel [50 mg/m[2] i.v. infusion over 1 hour] followed by carboplatin [AUC 2.0 i.v. bolus infusion over 30 min.] administered weekly concurrently with radiation on days 1,8,15,22,29,36. Thoracic radiation was delivered in daily doses of 2 Gy to a total dose of 65 Gy over 6.5 weeks. Consolidation chemotherapy: After chemoradiation therapy, patients received an additional 4 cycles of paclitaxel 175 mg/m[2] I.V infusion over 3 hours and carboplatin at AUC 6 every 3 weeks. The overall response rate was 77.8% with CR in 7 patients [25.9%] PR in 14 patients [51.9%], SD in 5 patients [18.5%] and 1 patient [3.7%] showed progressive disease. The median overall survival was 13.5 months and 1 year and 2 year survival rates were 58% and 26% respectively. The most frequent and significantly noted toxicity in this study was esophagitis [85.2%]. The other nonhematologic toxicities included nausea and vomiting [59.2%], peripheral neuropathy [25.9%], fatigue [33.3%] and pneumonitis [11.1%]. Hematologic toxicity consisted of anemia in 12 patients [44.4%], leucopenia in 8 patients [29.6%] and thrombocytopenia in 6 patients [22.2%]. These data together with our experience suggest that, in patients with unresectable stage IIIA-IIIB NSCLC, concomitant weekly chemoradiotherapy with paclitaxel and carboplatin, followed by consolidation chemotherapy with the same regimen is feasible, generally well tolerated, and yields therapeutic results that compare favorably to those reported for other regimens. However, further randomized studies are needed to identify the optimal chemoradiotherapy regimens and schedules for treatment of unresectable stage IIIA-IIIB NSCLC patients

Simposio. Avances recientes con ifosfamida/mesna en el tratamiento de tumores sólidos malignos: estudio fase II con ifosfamida, mesna y carboplatino en el tratamiento del cáncer cervicouterino etapa IIB / Symposium. Recent Advances with ifosfamide/Mesna in the treatment of malignant solid tumors: Phase II study in carcinoma of the uterine cervix clinical stage IIB with ifosfamide, mesna and carboplatin

Los casos de carcinoma cervicouterino se diagnostican en la mayoría de las pacientes en etapas localmente avanzadas. Esto evita el abordaje quirúrgico. La quimioterapia combinada neoadyuvante ha demostrado reducción tumoral en más de la mitad de los casos tratados. En el Instituto Nacional de Cancerología, elaboramos un estudio fase II con objeto de determinar la eficacia y la toxicidad de la combinación de ifosfamida+mesna+carboplatino. También se evaluó la posibilidad de intervenir quirúrgicamente a las enfermas con carcinoma cervicouterino etapa IIB. Se incluyeron 20 pacientes sin tratamiento previo y con edad promedio de 42 años. Todas recibieron tres ciclos de quimioterapia cada cuatro semanas con carboplatino 300 mg/m² el día 1+ifosfamida 3g/m²/día por dos días en infusión contínua de 24 horas; mesna 600mg por vía intravenosa (bolo) directo antes de ifosfamida; 3,000 mg en la solución de la ifosfamida en infusión de 24 horas por dos días. Al término de ésta se administró 1,500 mg de mesna en 1,00 ml de solución glucosada en infusión de 12 horas. Se obtuvieron cuatro respuestas completas y nueve parciales; tres pacientes cursaron con enfermedad estable y cuatro progresaron. En dos enfermas sometidas a cirugía, los especímenes mostraron: carcinoma in situ residual en una mujer y en la otra no hubo actividad tumoral. De 18 pacientes que recibieron radioterapia posterior a la quimioterapia, 13 tuvieron respuesta completa, una mostró respuesta parcial y cuatro progresaron. La toxicidad para 54 ciclos de quimioterapia fue predominantemente medular; neutropenia grado 1-2 (6 por ciento), grado 3-4 (62 por ciento); plaquetopenia grado 0 (90 por ciento), grado 1-2 (44 por ciento) y grado 3 (4 por ciento). No se observó ningún proceso séptico asociado a la neutropenia. Se presentó emesis grado 2-3 en el 42 por ciento y alopecia grado 3 en el 75 por ciento. El seguimiento promedio para todas la pacientes fue de 12 meses. El intervalo libre de progresión en 14 casos con respuesta completa (13 con quimioterapia+radioterapia y uno con quimioterapia+cirugía) fue de 14.3 meses promedio (extremos 6-19 meses). Los resultados obtenidos con esta combinación confirman un alto índice de respuestas objetivas (65 por ciento) y completas (20 por ciento) con toxicidad moderada. La quimioterapia neoadyuvante puede reducir suficientemente el volumen tumoral; esto permite la cirugía en pacientes tradicionalmente consideradas con enfermedad irresecable

Carboplatino (JM8) en el tratamiento del cáncer metastásico: estudio preliminar sobre toxicidad, tolerabilidad y eficacia / Carboplatinum (JM8) in the treatment of metastatic cancer: preliminary study over toxicity, tolerability and efficacy

Los autores han tratado 31 pacientes afectados con cáncer metastásico (13 cánceres de mama; cuatro de testículo; 14 misceláneos) y parcialmente ya tratados (17 con quimioterapia; cuatro también con radioterapia y cuatro también con hormonoterapia), con un derivado del platino, el carboplatino, solo (400 mg/m* cada 21 días) o en asociación (300 mg/m*) con otros antineoplásicos. Fueron suministrados en total 104 ciclos y la evaluación fue hecha después de por lo menos dos ciclos. En los 31 pacientes tuvimos cinco remisiones completas y siete parciales. En los 13 pacientes con cáncer de mama obtuvimos 46 porciento de remisiones parciales. Recordemos que después de dos ciclos no se evaluaron respuestas a nivel óseo. La mielosupresión fue la toxicidad más alta y frecuente (leucopenia en 54.8 porciento; plaquetopenia 9.6 porciento; anemia 22.5 porciento). La náusea y el vómito fueron bien controlados con los antieméticos usuales. Dos casos de presuntas reacciones alérgicas se resolvieron con el uso oportuno de cortisona y antihistamímicos. Dado que el carboplatino no demostró ser nefrotóxico y no necesitó de terapia hidratante, puede ser usado en pacientes ambulatorios. El estudio se encuentra aún abierto.